The document describes the cellular changes that occur during apoptosis, including condensation of chromatin, fragmentation of DNA and the nucleus, shrinkage of the cell, breakdown of mitochondria, fusion of the cell membrane with the plasma membrane, formation of apoptotic bodies that are engulfed by nearby cells. It also discusses the significance of apoptosis for maintaining normal tissue development, disposing of damaged or unwanted cells, avoiding autoimmunity, eliminating virus-infected cells, and preventing tumor formation by balancing cell division and cell death.
Apoptosis is a tightly regulated process of programmed cell death that removes unnecessary or damaged cells. It is mediated by caspases, cysteine-dependent aspartate-directed proteases, that cleave key cellular proteins and lead to cell death. Apoptosis occurs through the intrinsic mitochondrial pathway or the extrinsic death receptor pathway and plays an important role in development, tissue homeostasis, and defense against infection and cancer. Defects in apoptosis can lead to neurodegenerative diseases, autoimmunity, and cancer.
DNA repair mechanisms are indispensable for cell maintenance. The most common repair mechanisms are base excision repair (BER) and nucleotide excision repair (NER). Deficiencies in repair can lead to diseases like cancer or myelodysplastic syndrome. Studies have found that some viruses like murine polyomavirus activate DNA damage repair proteins like ATR and MRE11 to promote viral replication. Understanding DNA repair is important for developing new treatments for diseases linked to repair deficiencies and viral infections.
Sperm DNA fragmentation can negatively impact fertility and pregnancy outcomes. DNA becomes vulnerable during spermatogenesis when protamine replaces histones in chromatin compaction. Tests can evaluate sperm DNA fragmentation levels, which are correlated with lower fertilization and implantation rates. Factors like oxidative stress, temperature, and infections can intrinsically or extrinsically damage sperm DNA. Repair mechanisms attempt to resolve DNA double-strand breaks, but extensive unrepaired damage may be incompatible with embryo development. Treatments aim to address underlying causes of DNA fragmentation or use testicular sperm or ICSI to bypass ejaculated sperm issues.
Apoptosis is a form of programmed cell death that is mediated by activation of caspases. It plays an important role in both physiological processes like development and pathological conditions like DNA damage. The key features of apoptosis include cell shrinkage, chromatin condensation, formation of apoptotic bodies, and phagocytosis of cell fragments without eliciting inflammation. The intrinsic and extrinsic pathways initiate apoptosis through an imbalance of survival and death signals within cells.
Introduction to CELL APOPTOSIS
Including Definition
Micro-organism which cause CELL APOPTOSIS
Mechanism by which some bacteria lead to CELL APOPTOSIS
Some factors which facilitate microbes to present CELL APOPTOSIS
Sequence effects of Cell-Apoptisis
there are s many methods are used in diagnosis of human gene mutation which occur disorders ,here u get information about the diagnostic method for genetic mutation detection
The document describes the cellular changes that occur during apoptosis, including condensation of chromatin, fragmentation of DNA and the nucleus, shrinkage of the cell, breakdown of mitochondria, fusion of the cell membrane with the plasma membrane, formation of apoptotic bodies that are engulfed by nearby cells. It also discusses the significance of apoptosis for maintaining normal tissue development, disposing of damaged or unwanted cells, avoiding autoimmunity, eliminating virus-infected cells, and preventing tumor formation by balancing cell division and cell death.
Apoptosis is a tightly regulated process of programmed cell death that removes unnecessary or damaged cells. It is mediated by caspases, cysteine-dependent aspartate-directed proteases, that cleave key cellular proteins and lead to cell death. Apoptosis occurs through the intrinsic mitochondrial pathway or the extrinsic death receptor pathway and plays an important role in development, tissue homeostasis, and defense against infection and cancer. Defects in apoptosis can lead to neurodegenerative diseases, autoimmunity, and cancer.
DNA repair mechanisms are indispensable for cell maintenance. The most common repair mechanisms are base excision repair (BER) and nucleotide excision repair (NER). Deficiencies in repair can lead to diseases like cancer or myelodysplastic syndrome. Studies have found that some viruses like murine polyomavirus activate DNA damage repair proteins like ATR and MRE11 to promote viral replication. Understanding DNA repair is important for developing new treatments for diseases linked to repair deficiencies and viral infections.
Sperm DNA fragmentation can negatively impact fertility and pregnancy outcomes. DNA becomes vulnerable during spermatogenesis when protamine replaces histones in chromatin compaction. Tests can evaluate sperm DNA fragmentation levels, which are correlated with lower fertilization and implantation rates. Factors like oxidative stress, temperature, and infections can intrinsically or extrinsically damage sperm DNA. Repair mechanisms attempt to resolve DNA double-strand breaks, but extensive unrepaired damage may be incompatible with embryo development. Treatments aim to address underlying causes of DNA fragmentation or use testicular sperm or ICSI to bypass ejaculated sperm issues.
Apoptosis is a form of programmed cell death that is mediated by activation of caspases. It plays an important role in both physiological processes like development and pathological conditions like DNA damage. The key features of apoptosis include cell shrinkage, chromatin condensation, formation of apoptotic bodies, and phagocytosis of cell fragments without eliciting inflammation. The intrinsic and extrinsic pathways initiate apoptosis through an imbalance of survival and death signals within cells.
Introduction to CELL APOPTOSIS
Including Definition
Micro-organism which cause CELL APOPTOSIS
Mechanism by which some bacteria lead to CELL APOPTOSIS
Some factors which facilitate microbes to present CELL APOPTOSIS
Sequence effects of Cell-Apoptisis
there are s many methods are used in diagnosis of human gene mutation which occur disorders ,here u get information about the diagnostic method for genetic mutation detection
Cancer is caused by uncontrolled cell growth and can spread through the body. There are many types of cancer and symptoms vary by type. Treatments include chemotherapy, radiation, and surgery. Cancer treatments work by manipulating DNA, blocking cell metabolism and growth, disrupting cell division, altering hormone balance, and restricting amino acid supply to cancer cells.
1) The study analyzed the long-term effects of polychlorinated biphenyl (PCB) exposure on cell lines by continuously treating two cell lines with PCBs over 50 generations.
2) The PCB-treated cell lines displayed accelerated growth rates compared to control cells. One cell line (293T) also showed significantly higher levels of aneuploidy, indicating increased genetic instability from long-term PCB exposure.
3) The results suggest that prolonged PCB exposure can promote carcinogenesis by enhancing chromosomal instability and faster cell growth, two hallmarks of cancer.
This document discusses genetic instability. It defines genetic instability as an increased rate of genomic alterations ranging from point mutations to chromosome rearrangements. It describes three main types: nucleotide instability, microsatellite instability, and chromosomal instability. Causes of genetic instability include replication errors, defects in DNA repair pathways, and issues during cell division. Methods for detecting instability include karyotyping, FISH, and array technologies. Genetic instability is a hallmark of cancer and helps accelerate tumor genesis by increasing mutations. Cells use mechanisms like DNA proofreading and cell cycle checkpoints to maintain stability.
The document discusses cancer and cancer care. The theme for World Cancer Day 2022 is "Close the care gap" which aims to raise awareness about differences in access to cancer prevention and treatment. Cancer rates have been increasing exponentially. While India's cancer burden is lower than other countries, it is estimated that 1 in 9 Indians will develop cancer in their lifetime. Common cancers in India vary by sex, with breast cancer being most common among women and lung cancer among men. Treatment options discussed include surgery, chemotherapy, radiotherapy, and genomic therapy.
This document discusses various methods for mutation detection including:
- Single-stranded conformation polymorphism (SSCP) which detects differences in DNA secondary structure between mutant and wild-type sequences.
- Denaturing gradient gel electrophoresis (DGGE) which separates DNA fragments based on their melting properties.
- Oligonucleotide ligation assay (OLA) which detects mutations by hybridizing PCR primers and ligating probes.
- Restriction fragment length polymorphism (RFLP) which identifies polymorphisms by cleaving DNA with restriction enzymes.
Simple sequence repeat (SSR) markers consist of di- or tri-nucleotide repeats and have many advantages as genetic markers. They display high diversity and have many possible alleles per locus. While SSR markers are useful, single nucleotide polymorphism (SNP) markers are becoming more widely used due to their greater reliability and cost-effectiveness. Microsatellites can be amplified using PCR to analyze relatedness and identify individuals, but they have limitations such as null alleles occurring when primers don't correctly amplify loci.
This document summarizes three research studies on skin and keratinocytes:
1) The first study found elevated expression of osteopontin splice variants in nonmelanoma skin cancers compared to normal skin and adult keratinocytes. It also found that human adult keratinocytes expressed basal or induced levels of only two osteopontin variants.
2) The second study generated a mouse model lacking the desmoglein 1 protein and found it led to perinatal lethality and impaired skin barrier formation. Desmoglein 1 appears essential for normal epidermal morphogenesis.
3) The third study used fluorescence polarization microscopy and magnetic tweezers to investigate protein organization and force transmission at
Genomic instability plays an important role in cancer development by accelerating the accumulation of genetic changes in cancer cells. Several mechanisms can cause genomic instability, including defects in DNA repair pathways like base excision repair, mismatch repair, and double-strand break repair. Loss of function in DNA repair genes like MLH1 and MSH2 can lead to hypermutation and microsatellite instability in colorectal cancer. Other causes include problems with DNA replication, chromosome segregation, and telomere dysfunction. Genetic disorders involving genomic instability include ataxia-telangiectasia, neurofibromatosis type 1, Bloom syndrome, and ring chromosomes.
Genomic instability can occur at both the chromosomal and nucleotide levels and plays an important role in cancer development. Chromosomal instability results in gains and losses of whole chromosomes and structural changes, while instability at the nucleotide level is caused by defects in DNA repair pathways like mismatch repair and base excision repair. Many mechanisms help maintain genomic stability during cell division, including DNA repair pathways, epigenetic modifications, telomere protection, and proteins like ATM, ATR, BRCA1 and BRCA2. Cancer arises through a multi-step process as mutations accumulate in single cells, allowing their uncontrolled growth and proliferation into malignant tumor masses.
It describes about Structure and function of telomere, Telomerase enzyme, How does telomerase works?, Telomere replication, What happens to telomeres as we age?, Factors contribute to telomere shortening
Genomic instability refers to changes in chromosome structure and number that can lead to cancer. It is caused by failures in DNA replication, damage sensing and repair, and cell cycle checkpoints. There are several types of genetic instability, including chromosomal instability (CIN), microsatellite instability (MIN), and DNA replication errors. CIN results in chromosome gains and losses, while MIN causes repetitive DNA expansions and contractions. Genomic instability can arise from defects in DNA damage response genes like p53 and ATM, problems with DNA replication, fragile sites in the genome, and DNA secondary structures. While genetic instability promotes evolution, it also contributes to pathological conditions like cancer by enabling the accumulation of mutations needed for malignant transformation.
This document provides information on mitochondria and mitochondrial DNA. It discusses:
1) The structure and functions of mitochondria, including that they contain DNA (mtDNA) and encode proteins involved in oxidative phosphorylation.
2) The properties of mtDNA, including that it is circular, double-stranded, and encodes 37 genes including tRNAs and rRNAs.
3) Mitochondrial mutations and diseases, noting that mutations in mtDNA or nuclear genes can cause disorders by disrupting oxidative phosphorylation or mtDNA maintenance mechanisms. Common mtDNA disorders discussed include MELAS, MERRF, and LHON.
4) Methods for diagnosing mitochondrial disorders, including biochemical tests, imaging,
Ibica2014 p(8) visualizing and identifying the dna methylationAboul Ella Hassanien
DNA methylation is an epigenetic mechanism that cells use to control
gene expression. DNA methylation has become one of the hottest topics in cancer
research, especially for abnormally hypermethylated tumor suppressor genes
or hypomethylaed oncogenes research. The analysis of DNA methylation data
determines the differential hypermethlated or hypomethylated genes that are candidate
to be cancer biomarkers. Visualization the DNA methylation status may
lead to discover new relationships between hypomethylated and hypermethylated
genes, therefore this paper applied a mathematical modelling theory called formal
concept analysis for visualizing DNA methylation status.
Liposomal gene delivery is an important non-viral gene delivery method. Cationic liposomes are used because the cationic lipid molecules can bind to the negatively charged DNA via electrostatic interactions. This forms lipoplexes that can enter cells via fusion or endocytosis. Liposomal gene delivery offers advantages over viral vectors like lower toxicity, but has lower gene transfer efficiency. It has potential applications in treating diseases by fixing or replacing defective genes.
Mutations and detection of mutation using AuNPRahul Mitra
This document discusses mutations and techniques for detecting mutations using gold nanoparticles. It begins with definitions of genetic terminology and describes the different types of mutations including point mutations, frameshift mutations, and chromosomal mutations. It then explains that gold nanoparticles are well-suited for mutation detection due to their chemical inertness, biocompatibility, and surface plasmon resonance properties. The document outlines a method using gold nanoparticles for colorimetric detection of point mutations based on changes in nanoparticle aggregation and color. It concludes that gold nanoparticle detection of mutations provides sensitive, specific, low-cost analysis with naked-eye results.
DNA repair systems help maintain the integrity of genetic material by correcting damage from mutagens. There are several types of DNA repair mechanisms, including direct damage reversal, mismatch repair, base excision repair, nucleotide excision repair, and recombination repair. Key DNA repair proteins like p53 play an important role in recognizing DNA damage and initiating cell cycle arrest to allow time for repair or inducing apoptosis if damage is irreparable. Double strand breaks are the most difficult to repair and can lead to chromosomal rearrangements if unrepaired.
Telomeres play an important role in cellular aging and division. A study found that women with phobic anxiety had shorter telomeres, suggesting anxiety is a risk factor for accelerated aging. In cancer cells, telomerase remains active, allowing indefinite division by regenerating telomeres. Researchers discovered a protein complex that normally inhibits telomerase; in cancer it is delayed, allowing telomerase to extend telomeres and confer immortality. Understanding these processes may lead to new prevention and treatment strategies for diseases of aging and cancer.
This document summarizes different types of cell death including apoptosis and necrosis. It describes the morphology and causes of apoptosis and discusses examples of apoptosis occurring in physiological and pathological situations. It also discusses various mechanisms of intracellular accumulations including lipids, proteins, glycogen, and pigments. Finally, it outlines the morphology and patterns of cell injury and necrosis.
PARENCHYMAL CELL INJURY AND THEIR ULTRASTRUCTURESwatichaudhary2
This document summarizes a seminar presentation on the molecular mechanisms of parenchymal cell injury and their ultrastructure. It begins by introducing the concept that disease begins at the cellular level. It then discusses various methods for studying pathology, including light and electron microscopy. It describes the ultrastructure of typical animal cells and organelles. It explains the different types of cell injury including necrosis, apoptosis, and pyroptosis. The major causes and molecular mechanisms of cell injury are outlined. Finally, it discusses the ultrastructural changes that occur in cells during reversible and irreversible injury.
CHI's Targeting Stromal Cells in Cancer and Inflammatory Diseases Conference ...James Prudhomme
This virtual meeting will highlight cutting-edge science and provide insight into recent developments towards therapeutic stromal cell targeting in cancer and chronic inflammatory diseases. View full details and register: https://www.healthtech.com/stroma-conference
Cancer is caused by uncontrolled cell growth and can spread through the body. There are many types of cancer and symptoms vary by type. Treatments include chemotherapy, radiation, and surgery. Cancer treatments work by manipulating DNA, blocking cell metabolism and growth, disrupting cell division, altering hormone balance, and restricting amino acid supply to cancer cells.
1) The study analyzed the long-term effects of polychlorinated biphenyl (PCB) exposure on cell lines by continuously treating two cell lines with PCBs over 50 generations.
2) The PCB-treated cell lines displayed accelerated growth rates compared to control cells. One cell line (293T) also showed significantly higher levels of aneuploidy, indicating increased genetic instability from long-term PCB exposure.
3) The results suggest that prolonged PCB exposure can promote carcinogenesis by enhancing chromosomal instability and faster cell growth, two hallmarks of cancer.
This document discusses genetic instability. It defines genetic instability as an increased rate of genomic alterations ranging from point mutations to chromosome rearrangements. It describes three main types: nucleotide instability, microsatellite instability, and chromosomal instability. Causes of genetic instability include replication errors, defects in DNA repair pathways, and issues during cell division. Methods for detecting instability include karyotyping, FISH, and array technologies. Genetic instability is a hallmark of cancer and helps accelerate tumor genesis by increasing mutations. Cells use mechanisms like DNA proofreading and cell cycle checkpoints to maintain stability.
The document discusses cancer and cancer care. The theme for World Cancer Day 2022 is "Close the care gap" which aims to raise awareness about differences in access to cancer prevention and treatment. Cancer rates have been increasing exponentially. While India's cancer burden is lower than other countries, it is estimated that 1 in 9 Indians will develop cancer in their lifetime. Common cancers in India vary by sex, with breast cancer being most common among women and lung cancer among men. Treatment options discussed include surgery, chemotherapy, radiotherapy, and genomic therapy.
This document discusses various methods for mutation detection including:
- Single-stranded conformation polymorphism (SSCP) which detects differences in DNA secondary structure between mutant and wild-type sequences.
- Denaturing gradient gel electrophoresis (DGGE) which separates DNA fragments based on their melting properties.
- Oligonucleotide ligation assay (OLA) which detects mutations by hybridizing PCR primers and ligating probes.
- Restriction fragment length polymorphism (RFLP) which identifies polymorphisms by cleaving DNA with restriction enzymes.
Simple sequence repeat (SSR) markers consist of di- or tri-nucleotide repeats and have many advantages as genetic markers. They display high diversity and have many possible alleles per locus. While SSR markers are useful, single nucleotide polymorphism (SNP) markers are becoming more widely used due to their greater reliability and cost-effectiveness. Microsatellites can be amplified using PCR to analyze relatedness and identify individuals, but they have limitations such as null alleles occurring when primers don't correctly amplify loci.
This document summarizes three research studies on skin and keratinocytes:
1) The first study found elevated expression of osteopontin splice variants in nonmelanoma skin cancers compared to normal skin and adult keratinocytes. It also found that human adult keratinocytes expressed basal or induced levels of only two osteopontin variants.
2) The second study generated a mouse model lacking the desmoglein 1 protein and found it led to perinatal lethality and impaired skin barrier formation. Desmoglein 1 appears essential for normal epidermal morphogenesis.
3) The third study used fluorescence polarization microscopy and magnetic tweezers to investigate protein organization and force transmission at
Genomic instability plays an important role in cancer development by accelerating the accumulation of genetic changes in cancer cells. Several mechanisms can cause genomic instability, including defects in DNA repair pathways like base excision repair, mismatch repair, and double-strand break repair. Loss of function in DNA repair genes like MLH1 and MSH2 can lead to hypermutation and microsatellite instability in colorectal cancer. Other causes include problems with DNA replication, chromosome segregation, and telomere dysfunction. Genetic disorders involving genomic instability include ataxia-telangiectasia, neurofibromatosis type 1, Bloom syndrome, and ring chromosomes.
Genomic instability can occur at both the chromosomal and nucleotide levels and plays an important role in cancer development. Chromosomal instability results in gains and losses of whole chromosomes and structural changes, while instability at the nucleotide level is caused by defects in DNA repair pathways like mismatch repair and base excision repair. Many mechanisms help maintain genomic stability during cell division, including DNA repair pathways, epigenetic modifications, telomere protection, and proteins like ATM, ATR, BRCA1 and BRCA2. Cancer arises through a multi-step process as mutations accumulate in single cells, allowing their uncontrolled growth and proliferation into malignant tumor masses.
It describes about Structure and function of telomere, Telomerase enzyme, How does telomerase works?, Telomere replication, What happens to telomeres as we age?, Factors contribute to telomere shortening
Genomic instability refers to changes in chromosome structure and number that can lead to cancer. It is caused by failures in DNA replication, damage sensing and repair, and cell cycle checkpoints. There are several types of genetic instability, including chromosomal instability (CIN), microsatellite instability (MIN), and DNA replication errors. CIN results in chromosome gains and losses, while MIN causes repetitive DNA expansions and contractions. Genomic instability can arise from defects in DNA damage response genes like p53 and ATM, problems with DNA replication, fragile sites in the genome, and DNA secondary structures. While genetic instability promotes evolution, it also contributes to pathological conditions like cancer by enabling the accumulation of mutations needed for malignant transformation.
This document provides information on mitochondria and mitochondrial DNA. It discusses:
1) The structure and functions of mitochondria, including that they contain DNA (mtDNA) and encode proteins involved in oxidative phosphorylation.
2) The properties of mtDNA, including that it is circular, double-stranded, and encodes 37 genes including tRNAs and rRNAs.
3) Mitochondrial mutations and diseases, noting that mutations in mtDNA or nuclear genes can cause disorders by disrupting oxidative phosphorylation or mtDNA maintenance mechanisms. Common mtDNA disorders discussed include MELAS, MERRF, and LHON.
4) Methods for diagnosing mitochondrial disorders, including biochemical tests, imaging,
Ibica2014 p(8) visualizing and identifying the dna methylationAboul Ella Hassanien
DNA methylation is an epigenetic mechanism that cells use to control
gene expression. DNA methylation has become one of the hottest topics in cancer
research, especially for abnormally hypermethylated tumor suppressor genes
or hypomethylaed oncogenes research. The analysis of DNA methylation data
determines the differential hypermethlated or hypomethylated genes that are candidate
to be cancer biomarkers. Visualization the DNA methylation status may
lead to discover new relationships between hypomethylated and hypermethylated
genes, therefore this paper applied a mathematical modelling theory called formal
concept analysis for visualizing DNA methylation status.
Liposomal gene delivery is an important non-viral gene delivery method. Cationic liposomes are used because the cationic lipid molecules can bind to the negatively charged DNA via electrostatic interactions. This forms lipoplexes that can enter cells via fusion or endocytosis. Liposomal gene delivery offers advantages over viral vectors like lower toxicity, but has lower gene transfer efficiency. It has potential applications in treating diseases by fixing or replacing defective genes.
Mutations and detection of mutation using AuNPRahul Mitra
This document discusses mutations and techniques for detecting mutations using gold nanoparticles. It begins with definitions of genetic terminology and describes the different types of mutations including point mutations, frameshift mutations, and chromosomal mutations. It then explains that gold nanoparticles are well-suited for mutation detection due to their chemical inertness, biocompatibility, and surface plasmon resonance properties. The document outlines a method using gold nanoparticles for colorimetric detection of point mutations based on changes in nanoparticle aggregation and color. It concludes that gold nanoparticle detection of mutations provides sensitive, specific, low-cost analysis with naked-eye results.
DNA repair systems help maintain the integrity of genetic material by correcting damage from mutagens. There are several types of DNA repair mechanisms, including direct damage reversal, mismatch repair, base excision repair, nucleotide excision repair, and recombination repair. Key DNA repair proteins like p53 play an important role in recognizing DNA damage and initiating cell cycle arrest to allow time for repair or inducing apoptosis if damage is irreparable. Double strand breaks are the most difficult to repair and can lead to chromosomal rearrangements if unrepaired.
Telomeres play an important role in cellular aging and division. A study found that women with phobic anxiety had shorter telomeres, suggesting anxiety is a risk factor for accelerated aging. In cancer cells, telomerase remains active, allowing indefinite division by regenerating telomeres. Researchers discovered a protein complex that normally inhibits telomerase; in cancer it is delayed, allowing telomerase to extend telomeres and confer immortality. Understanding these processes may lead to new prevention and treatment strategies for diseases of aging and cancer.
This document summarizes different types of cell death including apoptosis and necrosis. It describes the morphology and causes of apoptosis and discusses examples of apoptosis occurring in physiological and pathological situations. It also discusses various mechanisms of intracellular accumulations including lipids, proteins, glycogen, and pigments. Finally, it outlines the morphology and patterns of cell injury and necrosis.
PARENCHYMAL CELL INJURY AND THEIR ULTRASTRUCTURESwatichaudhary2
This document summarizes a seminar presentation on the molecular mechanisms of parenchymal cell injury and their ultrastructure. It begins by introducing the concept that disease begins at the cellular level. It then discusses various methods for studying pathology, including light and electron microscopy. It describes the ultrastructure of typical animal cells and organelles. It explains the different types of cell injury including necrosis, apoptosis, and pyroptosis. The major causes and molecular mechanisms of cell injury are outlined. Finally, it discusses the ultrastructural changes that occur in cells during reversible and irreversible injury.
CHI's Targeting Stromal Cells in Cancer and Inflammatory Diseases Conference ...James Prudhomme
This virtual meeting will highlight cutting-edge science and provide insight into recent developments towards therapeutic stromal cell targeting in cancer and chronic inflammatory diseases. View full details and register: https://www.healthtech.com/stroma-conference
Merkel cells are specialized mechanoreceptor cells found in the basal layer of the epidermis that respond to light touch. They are innervated by sensory nerves. Merkel cells help transmit information about pressure and touch sensations to the central nervous system. Merkel cell carcinoma is a rare but aggressive form of skin cancer that is associated with Merkel cell polyomavirus (MCV). MCV infects most children asymptomatically but can later reactivate and integrate into the host cell genome if immune surveillance is compromised. This can lead to mutations that inactivate tumor suppressors and allow cells to proliferate uncontrollably, resulting in Merkel cell carcinoma.
This document discusses cell injury, adaptations, and degenerations in pathology. It begins by defining key terms like etiology, pathogenesis, and morphology. It then explains the causes of cell injury including hypoxia, physical agents, chemicals, microbes, and immune reactions. The document delves into the pathogenesis of cell injury, noting factors like the type, duration, and severity of the injurious agent and target cell characteristics. It also describes the mechanisms of cell injury such as ATP depletion, mitochondrial damage, calcium influx, oxidative stress, and membrane permeability defects. Finally, it distinguishes between reversible and irreversible cell injury.
The complement system refers to a series of >20 proteins that are normally inactive but become sequentially activated in an enzyme cascade in response to microorganisms. Complement activation can lead to cytolysis, opsonization, and stimulation of inflammation. The classical, lectin, and alternative pathways activate the complement cascade through different mechanisms but all lead to formation of the membrane attack complex. Complement proteins are regulated to prevent attack of host cells but deficiencies can lead to diseases like hereditary angioedema where swelling occurs.
1) The document discusses apoptosis and necrosis, two types of cell death. Apoptosis is programmed cell death where cells shrink and fragment in an orderly process. Necrosis is unprogrammed cell death caused by external injury or damage where cells swell and leak.
2) Apoptosis can be triggered internally through mitochondrial pathways or externally through death receptor pathways and leads to caspase activation and cell fragmentation. Cancer cells develop ways to avoid apoptosis like inhibiting proteins in these pathways.
3) Necrosis occurs when cells are damaged by external factors like toxins and involves cell and organelle swelling without fragmentation. Cancer cells and viruses can interfere with apoptosis to allow cancer progression.
Anti radiation vaccine molecular mechanisms and immune protection against rad...Dmitri Popov
Anti Radiation Vaccine, like vaccines against infectious disease and some vaccines against cancer, are administered prophylactically , however most vaccines against cancer usually administered after the onset of disease.
So, vaccines against infections and cancer considerably divided for prophylactic vaccines and therapeutic vaccines.
Anti Radiation Vaccine belonging to group vaccine which administered prophylactically.
Prophylactic use of Anti Radiation Vaccine very important because irreversible damage for cells compartments of irradiated organisms developed in first hours after irradiation
Leukocyte and lymphocyte: Cytotoxicity. Dmitri Popov
This document discusses leukocytes and lymphocytes and their response to acute radiation exposure. It provides background on these immune cells, noting that leukocytes include both myeloid cells and lymphocytes. It then discusses how radiation can functionally alter the immune system by breaking self-tolerance and damaging these cells, with implications for immune responses and treatment of radiation sickness. Specific cell types like polymorphonuclear leukocytes are also examined in terms of their roles and enzyme contents.
The Discovery Of Vesicle Transportation System EssayMichelle Singh
The 2013 Nobel Prize in Physiology or Medicine was awarded to three researchers who discovered the machinery that regulates vesicle traffic in cells. Vesicles are small cellular bodies that transport hormones, enzymes, and other chemicals throughout the cell. Much of this transport is mediated by the Golgi apparatus, which contains many vesicles and sorts molecules into vesicles that deliver them to the cell membrane or other parts of the cell. The researchers' discoveries explained the previously unknown process by which vesicles transport essential molecules within and between cells.
This document summarizes recent research on how breast cancer cells evade detection and killing by natural killer (NK) cells. It discusses three main mechanisms: 1) Breast cancer patients have NK cells with decreased activity and altered receptor expression, induced by tumor-produced TGFβ1. 2) Breast cancer cells modulate their immunogenicity by expressing ligands for inhibitory NK receptors and decreasing ligands for activating receptors. They also release immunosuppressive molecules like TGFβ1. 3) Breast cancer cells influence the terminal maturation of NK cells, increasing poorly differentiated and non-cytotoxic NK subsets in patients' blood and tumors. This may explain the poor cytotoxic functions observed in patients and highlights NK cell plasticity.
monoclonal antibodies and engineered antibodiesMunawar Ali
This document provides an overview of monoclonal antibodies and engineered antibodies. It discusses the advantages and disadvantages of monoclonal versus polyclonal antibodies. Production methods like hybridoma technology and fermentation are described. Problems associated with monoclonal antibody therapy like HAMA response are covered. Applications in diagnosis, therapy and analytical uses are mentioned. Finally, the document discusses engineering antibodies by modifying regions to reduce immunogenicity and enhance functions.
The document summarizes different types of cell death including programmed cell death (PCD), apoptosis, necrosis, and autophagy. It describes key aspects of apoptosis such as the intrinsic and extrinsic pathways, the role of caspases and Bcl-2 proteins, mitochondrial involvement, and morphological changes cells undergo during apoptosis. Necrosis is described as unprogrammed cell death caused by external factors like trauma or infection. Autophagy is noted as another form of programmed cell death.
Molecular Mechanisms of Radiation Damage. Dmitri Popov
Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005).
Conclusion: Specific antibodies – possible antagonists of Toll like receptors and can inhibit massive activation of lysosomal hydrolytic enzymes and prevent radiation toxicity after high doses of Radiation.
This document provides an overview of monoclonal antibodies and gene therapy. It discusses the discovery of monoclonal antibodies by Kohler and Milstein in 1975. It also describes the multi-step process of producing monoclonal antibodies through cell fusion and hybridoma technology. Several types of monoclonal antibodies are outlined, along with their purification techniques and therapeutic applications in cancer treatment and other diseases. Gene therapy approaches including ex vivo and in vivo methods are briefly introduced.
ESCOZINETM is an innovative polarized, potentiated bio-active peptide extracted from the Blue Caribbean Scorpion (Rhopularus Princeps) which contains amino acids, proteins and minerals. Medolife filed a patent in 2012 for its ESCOZINETM and polarization technology (Patent # US 8,097,284 B2). The polarization technique acts as a delivery system and additionally, amplifies the highly positive
Compliment system, Cellular immunity and Humoral immunity, Immune mechanism...Vamsi kumar
The complement system is part of the immune system and consists of proteins that interact in a regulated cascade to eliminate pathogens. There are three pathways of complement activation: classical, alternative, and mannose-binding lectin. The classical pathway is activated by antigen-antibody complexes, the alternative pathway by microbial surfaces, and the mannose-binding lectin pathway by lectins binding mannose residues on microbes. All three pathways result in the formation of the membrane attack complex that lyses microbes. Complement proteins also promote inflammation, antibody production, immune complex clearance, and phagocytosis of pathogens. Deficiencies or dysregulation of the complement system can cause various infectious and autoimmune diseases.
This document provides an overview of monoclonal antibodies (MAbs), including their definition, development, mechanisms of action, pharmacokinetics, adverse effects, and various therapeutic applications. Some key points discussed include:
- MAbs are antibodies produced from a single clone that are more uniform and abundant than natural antibodies. They can be produced in large quantities in the laboratory.
- Therapeutic uses of MAbs include immunosuppression for transplant rejection, treatment of autoimmune diseases by inhibiting cytokines like TNF-α, and various forms of cancer therapy by targeting cell surface antigens.
- Adverse effects are usually mild and related to cytokine release during infusion, but long-term suppression of physiological functions can also occur depending on
Similar to Radiation toxicity: complement system activation. (20)
Protection of humans during long space flight. using cannabis to reduce biol...Dmitri Popov
Protection of humans during long space flight. using cannabis to reduce biological consequences of high doses of radiation, treat stress, anxiety, and depression Associated with Long-term Space Flight to Mars.
The document discusses an anti-radiation antidote developed using antibodies against the membrane attack complex (MAC). MAC is activated after irradiation and plays a toxic role in acute radiation syndromes. Rabbits were inoculated with "specific radiation determinants" from irradiated animals to produce hyper-immune serum with high levels of IgG antibodies against MAC. Animals treated with these antibodies before and after lethal irradiation showed 60-75% survival rates and reduced radiation sickness symptoms compared to untreated controls where all animals died. The results suggest targeting MAC with specific antibodies may provide significant but incomplete protection against high radiation doses.
Marihuana acute intoxication: express diagnosis with ELISADmitri Popov
This document discusses using an ELISA test to detect acute marijuana intoxication. It describes how ELISA tests work to detect THC metabolites in urine or saliva, which can confirm a diagnosis of acute marijuana intoxication. ELISA tests have detection limits of 20-100 ng/mL in urine and can detect THC and its metabolites for several hours after marijuana use. The document also provides background information on the pharmacokinetics of THC and discusses symptoms of acute marijuana intoxication.
Polyclonal/ monoclonal antibodies to serotonin receptors as a therapeutic age...Dmitri Popov
Polyclonal/monoclonal antibodies to serotonin receptors have potential as therapeutic agents. Serotonin receptors mediate effects of serotonin and are targets of many drugs. Antibodies to specific serotonin receptors could modulate receptor signaling and impact conditions like depression, anxiety, nausea, and pain. Developing therapeutic antibodies requires overcoming challenges but may help treat diseases influenced by the serotonin system.
Polyclonal, monoclonal antibodies to serotonin receptors as a therapeutic age...Dmitri Popov
Polyclonal/monoclonal antibodies to serotonin receptors have potential as therapeutic agents. Serotonin receptors mediate effects of serotonin and are targets of many drugs. Antibodies to specific serotonin receptors could modulate receptor signaling and impact conditions like depression, anxiety, nausea, and pain. Developing therapeutic antibodies requires overcoming challenges but may help treat diseases influenced by the serotonin system.
Comprehensive toxicology: Ionized Radiation as Carcinogen.Dmitri Popov
This document provides the full text of a chapter from the book "Comprehensive Toxicology" on ionizing radiation as a carcinogen. The chapter is copyrighted material provided for non-commercial educational use. It discusses the mechanisms of radiation damage at cellular and molecular levels, evidence of radiation-induced cancer from human populations and animal/in vitro studies, and models for assessing radiation cancer risk.
Polyclonal/Monoclonal antibodies to histamine receptors as a selective hista...Dmitri Popov
Polyclonal/monoclonal antibodies to histamine receptors have potential as selective antihistamine agents. They may block the inflammatory and immune effects of histamine by targeting its four receptor types: H1, H2, H3, and H4. Developing monoclonal antibodies as antagonists/agonists of these receptors could provide effective therapies for conditions like allergies, asthma, gastrointestinal issues, and cognitive disorders. Several companies produce antibodies to the different histamine receptors for research applications.
ANTIOXIDANTS AND POTASSIUM FERROCYANIDE, APROPHYLACTIC AND THERAPEUTIC MIXTU...Dmitri Popov
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This document discusses research on developing an anti-radiation T cell vaccine. It describes T cells and their role in cell-mediated immunity, including recognizing radiation antigens created by radiation damage. The proposed anti-radiation T cell vaccine would generate immunological memory to radiation antigens, protecting against future radiation exposure through memory T cells that can quickly respond. It would work by modulating cytotoxic T cells to induce apoptosis in cells displaying radiation epitopes, without causing necrosis.
Implications for Immunotherapy of Acute Radiation Syndromes. Part 2.Dmitri Popov
Research Proposal: Implications for Immunotherapy of Acute Radiation Syndromes. Part 2.
Dmitri Popov
Full-text available · Research Proposal · Feb 2017
File name: Implications for Immunotherapy of ARS. Part 2.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
1. Dmitri Popov. PhD, Radiobiology.
MD (Russia)
Advanced Medical Technology and Systems Inc.
Canada.
intervaccine@gmail.com
Radiation toxicity: Complement system
activation, Membrane Attack Complex.
2. Radiation Toxicity: Complement
Cascade Activation, MAC formation
Activation of the complement system is,
however, also involved in the pathogenesis of the
systemic Acute Radiation Syndromes.
3. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
Complement system is composed of more than
25 different proteins produced by hepatocytes,
macrophages and intestinal epithelial cells.
Fibroblasts and intestinal epithelial cells make C1,
while the liver makes C3, C6, and C9.
Complement proteins are present in the
circulation as inactive molecules.
4. Radiation Toxicity: Complement
Cascade Activation, MAC formation
Complement is part of the innate immune system.
Its major function is recognition and elimination of
pathogens via direct killing and/or stimulation of
phagocytosis.
Activation of the complement system , however,
also involved in the pathogenesis of the systemic
autoimmune diseases.
Activation of the complement system also
involved in the pathogenesis of the Acute
Radiation Syndromes, Membrane Attack Complex
formation and cell necrosis after irradiation.
5. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
Activation of the complement system involves participation of
a large number of plasma proteins including C1q, C1r, C1s, C2
through C9, factor B, factor D, and properdin. There are three
pathways of complement activation, i.e. the classical, alternative
and lectin pathway. All three pathways are activated in a
sequential manner, with activation of one component leading to
activation of the next.
Min Chen a,b, Mohamed R. Daha c, Cees G.M. Kallenberg a,*
a Department of Rheumatology and Clinical Immunology,
University Medical Center Groningen, University of Groningen,
The Netherlands
b Renal Division, Peking University First Hospital, Beijing
100034, China
c Department of Nephrology, Leiden University Medical Center,
The Netherlands.
6. Membrane Attack Complex.
The membrane attack complex (MAC) is
typically formed on the surface
of pathogenic bacterial cells as a result of the
activation of the host's alternative pathway and
the classical pathway of the complement system,
and it is one of the effector proteins of
the immune system. The membrane-attack
complex (MAC) forms transmembrane channels.
These channels disrupt the phospholipid bilayer
of target cells, leading to cell lysis and death
7. Membrane Attack Complex.
A number of proteins participate in the assembly
of the MAC. Freshly activated C5b binds to C6 to
form a C5b-6 complex, then to C7 forming the
C5b-6-7 complex. The C5b-6-7 complex binds to
C8, which is composed of three chains (alpha,
beta, and gamma), thus forming the C5b-6-7-8
complex. C5b-6-7-8 subsequently binds to
C9 and acts as a catalyst in the polymerization of
C9.
Active MAC has a subunit composition of C5b-
C6-C7-C8-C9.
9. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
An essential aspect of innate immunity is
recognition of molecular patterns on the surface
of pathogens or altered self through the lectin and
classical pathways, two of the three well-
established activation pathways of the
complement system.
Altered self – after irradiation.
10. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
The ability of pattern-recognition molecules to
bind foreign markers such as pathogen-
associated molecular patterns is central to the
innate immune defense. One such defense
mechanism is complement, which is capable of
recognizing molecular patterns associated with
microbes and apoptotic or necrotic cells
11. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
Recognition causes activation of proteolytic enzyme
cascades, resulting in cleavage of the complement
proteins C3, C4, and C5. Fragments of these proteins
have important effector functions through binding to
host cell receptors and pathogen surfaces.
Rune T. Kidmosea,1, Nick S. Laursena,1, József
Dobób , Troels R. Kjaerc , Sofia Sirotkinaa , Laure
Yatimea , Lars Sottrup-Jensena , Steffen Thielc ,
Péter Gálb , and Gregers R. Andersena,2
Departments of a Molecular Biology and Genetics and
c Biomedicine, Aarhus University, DK-8000 Aarhus,
Denmark; and b Institute of Enzymology, Research
Centre for Natural Sciences, Hungarian Academy of
Sciences, H-1113, Budapest, Hungary
12. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
Complement is traditionally thought of as a pro-
inflammatory effector mechanism of antitumor immunity.
However, complement is also important for effective
clearance of apoptotic cells, which can be an anti-
inflammatory and tolerogenic process. We show that
localized fractionated radiation therapy (RT) of
subcutaneous murine lymphoma results in tumor cell
apoptosis and local complement activation. Cotreatment of
mice with tumor-targeted complement inhibition markedly
improved therapeutic outcome of RT, an effect linked to
early increases in apoptotic cell numbers and increased
inflammation.
Complement-dependent modulation of antitumor
immunity following radiation therapy.
Elvington M1, Scheiber M1, Yang X1, Lyons K2, Jacqmin
D2, Wadsworth C1, Marshall D2, Vanek K2, Tomlinson S3.
13. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
In cells irradiation by heavy ions has been hypothesized to produce
microlesions, regions of local damage. In cell membranes this damage
is thought to manifest itself in the form of holes. The primary evidence
for microlesions comes from morphological studies of cell membranes,
but this evidence is still controversial, especially since holes also have
been observed in membranes of normal, nonirradiated, cells. However,
it is possible that damage not associated with histologically discernable
disruptions may still occur. In order to resolve this issue, we developed
a system for detecting microlesions based on liposomes filled with
fluorescent dye. We hypothesized that if microlesions form in these
liposomes as the result of irradiation.
Detection of microlesions induced by heavy ions using liposomes filled
with fluorescent dye
Original Research Article
Pages 1373-1377
J.P. Koniarek, J.L. Thomas, M. Vazquez
14. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
Damage of cell membranes after irradiation
possible occur after membrane attack complex
action.
Proteins of the complement membrane attack
complex (MAC) and the protein perforin (PF)
share a common MACPF domain that is
responsible for membrane insertion and pore
formation (Cajnko et al. 2014)
15. Radiation Toxicity: Complement
Cascade Activation, MAC formation.
Appropriate complement inhibition with
monoclonal antibodies playing a promising
strategy to enhance a mainstay of treatment for
Acute Radiation Syndromes.