Study Of Human Pathology Research Articles

Apoptosis in neurodegenerative disorders.

We review here recent reports pertaining to the issue of apoptosis in neurodegenerative diseases. Tissue culture models, animal models and human pathological studies are discussed. At present, there is supportive, but not definitive, evidence for apoptosis in a number of neurodegenerative disorders.

44]Detection and analysis of mitochondrial DNA and RNA in muscle by in situ hybridization and single-fiber PCR

This chapter discusses the detection and analysis of mitochondrial DNA and RNA in muscle by in situ hybridization and single-fiber polymerase chain reaction (PCR). The power of in situ hybridization (ISH) in providing spatial information of gene location and expression is unique. ISH provides a wealth of information on the intercellular distribution of heteroplasmic mitochondrial DNA (mtDNA) populations, with its usefulness particularly evident in the study of human pathologies. The technique has been used extensively to correlate mitochondrial abnormalities with the presence of mutated mtDNAs—an analysis that provides strong support for a pathogenetic role of a specific mitochondrial genotype. Despite its qualitative nature, ISH can be used for semiquantitative determinations, if certain precautions are taken. This approach has been used to determine the ratio of rRNA and heavy-strand-encoded mRNAs in muscle of patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Although ISH utilizing RNA probes are more widely used in typical cell and molecular biology applications, most of the experience derives from the use of DNA probes. The use of RNA probes—although requiring special care—may yield better signal-to-background results when the levels of the target sequence are low.

Neocortical Pathology in Chronic Murine Retroviral Encephalitis

Retroviral infection of the central nervous system (CNS) causes chronic functional and morphological damage in a wide variety of mammals. Neuropathological studies have focused on subcortical pathology, however, the neocortex is also affected. Because studies of human CNS pathology have been limited to the use of material from terminal stages of disease, we used two neuropathogenic murine leukemia virus (MuLV) models to study the development of neocortical damage. MuLV infection caused spongiform change in the spinal cord, brainstem and cerebellum but not in the cerebrum. However, over the course of disease, we observed a reduction of neocortical thickness, accompanied by diminished neuronal and dendritic spine density. Electron microscopic studies showed minimal to no ultrastructural alterations of dendritic spines. Since there was no evidence of extensive direct viral infection of the neocortical neurons or glia at the ultrastructural level, we hypothesize that neocortical damage may be an indirect effect of subcortical retroviral infection.

Blastocystis hominis--past and future

The history of B. hominis is unique. Few infectious agents have provoked the many misconceptions that plague this enigmatic parasitic ameba. Conflicting descriptions of its nature and pathogenesis have continued throughout the 20th century. As seen by the greatly expanded number of reports in recent years, B. hominis is now a major subject of study, particularly for evidence of disease causation. Physicians are treating patients with intestinal disease caused by B. hominis. Many mild cases resolve in about 3 days without treatment, but others are acute and chronic disease is common. As with E. histolytica, the carrier state is often seen without symptoms. Treatment is usually with metronidazole, but emetine (for refractory infections), trimethoprim-sulfamethoxazole, and pentamidine are also effective. In fecal samples, this complex protozoan appears in a variety of cell forms which makes microscopic diagnosis difficult. As yet, no specific fluorescent-antibody test is available for diagnosis. A culture method to demonstrate the more easily recognized CB form is available, but probably not feasible for most diagnostic laboratories. The common cell forms are the CB form, the granular (mitochondria) form, and the ameba form. The unexpected size range of these forms in clinical material, from yeast size (ca. 7 microns) to giant cells of 20 to 40 microns, makes diagnosis difficult Pseudopodia may be demonstrated by the ameba form in heated microscope stage culture chambers. The anaerobic B. hominis has no cyst form. Its mitochondria are uniquely anaerobic and have no cytochrome protein or oxidative mitochondrial enzymes. Because of its many cell forms and anaerobic mitochondria, B. hominis is an organism of great interest for morphologic and biochemical study. Reproduction is asexual, usually by binary fission. Shizogony occurs in cultured cells. The CB appears to be an organelle whose specific purpose is for reproduction by shizogony. From 2 to 30 progeny are derived from schizogony. The ameba form reproduces by plasmotomy; it has no CB. The pathology of B. hominis infections has been studied in gnotobiotic guinea pigs in which inflammation of the intestinal mucosa and invasion of the superficial layers were seen. Only limited studies of human pathology are available. Those who have studied mucosal histopathology report inflammation and cellular changes that resolve after treatment. More study in this area is strongly indicated (32, 44, 57, 62, 67, 75). Ultrastructural details of B. hominis major forms, except for the schizont, are complete. The organism has no cell wall. The concentric CB takes up as much as 95% of the cell. The major organelles, which include multiple nuclei, Golgi apparatus, mitochondria, endoplasmic reticulum, fat, and other inclusions, are confined in two or four opposed pods in a thin band of peripheral cytoplasm between the spherical entire plasma membrane and the CB membrane. The pods buldge the CB membrane inward. There is evidence of a bacteroid endosymbiont. Education about B. hominis is needed. Entry of recent findings into new textbooks is imperative for its understanding among medical practitioners. Laboratory workers need to be aware of it for many reasons. The College of American Pathologists includes B. hominis in its proficiency testing samples and requires that it be reported from clinical samples.

Phosphorus-31 MRS of human testicular function and viability.

The current clinical use of magnetic resonance spectroscopy (MRS) is explored with attention to testicular function and pathology. Magnetic resonance spectroscopy provides insights into metabolic processes that are occurring in vivo. Information on these processes were, until now, only obtained through the use of invasive procedures such as biopsy, with the attendant undesired side effects. Phosphorus-31 (31P) MRS of the testes can provide unique metabolic information noninvasively and may provide clinicians with an alternative to the invasive procedures. The practical applicability of 31P MRS to the study of human infertility and testicular pathologies is described in some very preliminary studies.

Mechanism of angioplasty and its relation to restenosis

Balloon angioplasty enlarges atherosclerotic narrowings in the vast majority of patients in whom it is attempted at an acceptably low complication rate. Experimental and human pathologic studies have confirmed that angioplasty enlarges the lumen by stretching the vessel wall. Often this stretching process causes plaque fracture due to inelastic components of the atheroma. Denudation of the endothelium is also a consistent observation. While enlarging the lumen, this vascular trauma promotes marked platelet adhesion and aggregation that is dependent on the degree of vascular damage. Most platelets accumulate early within the first few hours. Subsequently, thrombus formation and smooth muscle cell proliferation can occur with the formation of a new fibrocellular occlusive process. Experimentally, anti-platelet therapy can significantly reduce platelet deposition and can reduce the incidence of restenosis. Although restenosis is a multifactoral process, prevention seems possible when platelet accumulation, thrombus formation and smooth muscle cell proliferation can be inhibited through drug or mechanical means.

Magnetic resonance imaging of the fetal temporal bone.

Magnetic resonance imaging (MRI) is a powerful new tool for the study of human anatomy and pathology. By various MRI techniques, the structure of the middle and inner ears of aborted 20-week fetuses is defined and compared to gross anatomic sections. MRI's potential for evaluating temporal bone development and diseases of the ear is discussed.

Retinal Pigment Epithelium and Endothelium

To the Editor. —The recent reports on the interactions between retinal pigment epithelium (RPE) and endothelium in vitro point out that an RPElocated inhibitor of neovascularization and an endothelium-located chemoattractant for RPE cells explain only part of the story of how neovascularization and the status quo at Bruch's membrane are controlled.1,2I would like to point out the following evidence derived from experimental animals and human pathologic studies that suggest interesting and relevant interactions between RPE and endothelium in vivo. Animal experiments have shown that choriocapillaris atrophies (its endothelium thickens and loses its fenestrae; endothelial cells die, and the capillary plexus retracts) when and where RPE is destroyed. This is seen, for example, in rabbits that receive sodium iodate intravenously.3The chemical destroys the RPE in a patchy manner. Choriocapillary atrophy ensues at sites of RPE loss—and only there. In histologic studies of human eyes with RPE degeneration

Studies of human temporal bone pathologies: the NIH perspective.

The study of human inner ear pathology, necessarily tied to autopsy studies in general, is influenced in the United States at the present time by a number of factors (and I imagine that much the same influences are at work in Europe). Virchow would turn in his grave were we even to suggest that the study of human tissue pathology and its comparison with the normal is a practice that has outlived its usefulness. Nevertheless, there are those in our field or in closely related fields who believe that light microscopic studies of human temporal bone pathology represent a pasture whose previous yield, in the ~O’S, 40’s and ~O’S, was rich, but which has by now been so thoroughly plowed that productivity is diminished to the point of cost ineffectiveness. Certainly many spectacularly effective and clinically valuable studies were carried out in those decades, but the list of otologic problems whose etiology and treatment continue to defy us and whose solutions could come from further studies of the human temporal bone, is even more impressive. A second factor influencing the study of the human inner ear is the falling autopsy rate. Numerous explanations for this decline have been offered. These include the improvements in our capability of seeing inside the intact human patient by such techniques as ultrasonography, scintigraphy , computerized tomography and now nuclear magnetic resonance scanning. In other words, we are told, disorders are now so much more readily studied during the life of the patient that an autopsy can add little more information. Would that this were true of the inner ear! Another factor influencing the autopsy rate and therefore temporal bone studies in particular, and whose full effect may not yet have been realized, is the direct result of the rising cost of medical care and the cost of maintaining teaching hospitals. Autopsies are expensive-an expense that must be born by the institution since we would find it dificult to ask patients’ relatives or medical insurance carriers to meet this particular expense. No matter how informative and fascinating autopsies can prove to be, the cold facts of current fiscal problems must be faced. Many institutions must now eliminate such sources of financial loss or face bankruptcy. This inevitably makes physicians, no matter what their past opinions may have been, far less likely than ever to urge an autopsy. Those of us who study the human inner ear, particularly its sensory epithelia, have so far benefited little from advances in in vivo clinical examination methods. But there will continue to be advances in diagnostic and therapeutic skills from which we will benefit and there will be improvements in the methods we have for harvesting and preserving and for examining human temporal bones. These advances will demand and permit, respectively, new approaches to the study of human inner ear pathology. Surface preparations are now in extensive use (these actually represent a revival of a much earlier method of examination); the micro slicing technique of Michaels will be discussed during this meeting, as will freeze fracturing; and transmission and scanning electron microscopy are beginning to be applied to studies of human inner ear material. In general terms, there is a growing and very logical tendency for the type of study proposed to determine the technique to be used. Changes in the focus of studies of the histopathology of the human inner ear are well

Animal models of hydrocephalus: recent developments.

The presence of a watery fluid that could also be found in large amounts within the brain has been known for many centuries. The idea that this fluid circulated was inspired largely by investigations of the 19th century anatomists. According to Cushing (1) the modern era in research on cerebrospinal fluid (CSF) circulation began with Magendie who was probably the first to fully appreciate the physiological importance of the fluid. Magendie and Luschka described in the roof of the fourth ventricle of the brain, the foramina which bear their names and through which CSF can flow into the subarachnoid space. The existence of these openings may not be present in all animal species. In one investigation in the mid-19th century, they were not found in human pathological studies by Hilton (2); in this particular case, there was an abnormal accumulation of fluid in the interior of the brain.The source of the CSF had been relegated to the choroid plexus, a view favored by Faivre and by Luschka but not by some who r...

Development of a nude mouse model to study human sebaceous gland physiology and pathophysiology.

Study of human sebaceous gland physiology and pathophysiology is limited by lack of an adequate animal model. This study was designed to develop an animal model using human face skin grafted onto the nude mouse to study human sebaceous glands. Full-thickness human face skin was grafted onto 60 adult male nude mice. 4 wk after grafting, androgens, which are known to stimulate sebaceous glands, were administered to test the system. Androgens were administered to 21 animals by implanted catheters that were filled with testosterone (T) or dihydrotestosterone (DHT). Empty catheters were implanted in 15 control animals. Graft biopsies and blood for androgen levels were obtained at time 1 (pre-catheter) and time 2 (26 d after catheter implantation). Three assessments were made on each biopsy: sebaceous gland volume, using an image analyzing computer; sebaceous cell size; and sebaceous gland labeling index. 29 mice completed the study through time 2. In the androgen-treated group, T levels (nanogram per milliliter) five times increased to 4.92 +/- 0.35, and DHT levels (nanogram per milliliter) increased 50 times to 16.70. In the androgen-treated group, sebaceous gland volume (micron 3 X 10(-3) increased from 896 +/- 194 to 3,233 +/- 754 (P less than 0.001), sebaceous cell area (micron 2) increased from 167 +/- 12 to 243 +/- 19 (P less than 0.001), and labeling index (percentage) increased from 2.7 +/- 0.7 to 6.4 +/- 0.9 (P less than 0.01). In the control group, sebaceous gland volume fell from 1,070 +/- 393 to 417 +/- 99 (NS), sebaceous cell size remained the same, and the labeling index fell from 5.1 +/- 1.9 to 3.2 +/- 1.1. After androgen administration, Halowax N-34, a known comedogen, or its vehicle, was applied to 15 grafts for 2-6 wk. Twice as many microcomedones were seen in the Halowax-treated grafts, compared with vehicle-treated grafts at the end of this time period. No visible comedones were produced. This study demonstrated that: (a) human sebaceous glands can be successfully transplanted and studied on the nude mouse; (b) after androgen stimulation, sebaceous gland volume, cell size, and labeling index increase; (c) microcomedones can be produced in the human skin grafts by the application of a comedogenic substance. Thus, this model demonstrates significant potential for the future study of human sebaceous gland physiology and pathology.

Evaluation of Mixed Exposure to Carcinogens and Correlations of in vivo and in vitro Systems

The biological evaluation of air pollutants is an example of the difficulties of evaluating the effects of mixed concurrent exposures to multiple agents, such as combinations of carcinogens with other carcinogens of the same or different chemical class, with incomplete carcinogens and cocarcinogens, with particulate materials and other factors that modify tissue distribution and retention, and with modifiers of metabolic pathways of activation and detoxication. A research approach is outlined to investigate such interactions in a series of biological systems of increasing complexity but closely related to each other in a step-by-step sequence, e.g., bacterial mutagenesis; mammalian cell mutagenesis, toxicity and neoplastic transformation, including embryo cells, fibroblasts and epithelial cells; organ cultures of target epithelia; in vivo animal systems for short-term and long-term studies, including animal models closely comparable to human pathology; observational studies of human pathology and histopathogenesis; experimental studies of corresponding human target tissues using organ and cell culture methods for metabolism, toxicity, mutagenicity and possibly neoplastic cell transformation. Respiratory carcinogenesis models were successfully used for studies of mixed exposures to different carcinogens and cofactors. The role of particulates has been found to be important but needs to be further characterized. Quantitative variations in the response to carcinogens and cofactors among different biological test systems and among different individuals in the human population make quantitative risk estimation very difficult, but studies in a sequence of related biological systems including human tissues indicate the importance of qualitative risk evaluation.

Evaluation of mixed exposure to carcinogens and correlations of in vivo and in vitro systems.

The biological evaluation of air pollutants is an example of the difficulties of evaluating the effects of mixed concurrent exposures to multiple agents, such as combinations of carcinogens with other carcinogens of the same or different chemical class, with incomplete carcinogens and cocarcinogens, with particulate materials and other factors that modify tissue distribution and retention, and with modifiers of metabolic pathways of activation and detoxication. A research approach is outlined to investigate such interactions in a series of biological systems of increasing complexity but closely related to each other in a step-by-step sequence, e.g., bacterial mutagenesis; mammalian cell mutagenesis, toxicity and neoplastic transformation, including embryo cells, fibroblasts and epithelial cells; organ cultures of target epithelia; in vivo animal systems for short-term and long-term studies, including animal models closely comparable to human pathology; observational studies of human pathology and histopathogenesis; experimental studies of corresponding human target tissues using organ and cell culture methods for metabolism, toxicity, mutagenicity and possibly neoplastic cell transformation. Respiratory carcinogenesis models were successfully used for studies of mixed exposures to different carcinogens and cofactors. The role of particulates has been found to be important but needs to be further characterized. Quantitative variations in the response to carcinogens and cofactors among different biological test systems and among different individuals in the human population make quantitative risk estimation very difficult, but studies in a sequence of related biological systems including human tissues indicate the importance of qualitative risk evaluation.

Application of analytical subcellular fractionation techniques and tissue enzymic analysis to the study of human pathology.

Other| December 01 1977 Application of Analytical Subcellular Fractionation Techniques and Tissue Enzymic Analysis to the Study of Human Pathology T. J. Peters T. J. Peters 1Department of Medicine, Royal Postgraduate Medical School, London Search for other works by this author on: This Site PubMed Google Scholar Clin Sci Mol Med (1977) 53 (6): 505–511. https://doi.org/10.1042/cs0530505 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation T. J. Peters; Application of Analytical Subcellular Fractionation Techniques and Tissue Enzymic Analysis to the Study of Human Pathology. Clin Sci Mol Med 1 December 1977; 53 (6): 505–511. doi: https://doi.org/10.1042/cs0530505 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search Keywords: coeliac disease, congestive cardiomyopathy, enzyme analysis, granulomatous This content is only available as a PDF. © 1977 The Biochemical Society and the Medical Research Society1977 Article PDF first page preview Close Modal You do not currently have access to this content.

Coronary Collateral Circulation

Collateral coronary channels represent obvious compensatory mechanisms for the delivery of nutrients to the myocardium. In spite of extensive basic research, we are still unaware of the factors determining adequate compensatory adjustments. Extensive human pathologic studies have presented a quantitative overall view, but have said little about the individual stages of adaptation. Complex multidisciplinary studies in animals have played a role but have emphasized great species variation. Human angiography is establishing a large data base but one strongly biased by clinical and therapeutic considerations. Meanwhile, clinical research is aimed at establishing the sequential morphologic changes in the development of angina, insufficiency, and infarction. Final answers concerning the significances of the collateral circulation will very likely parallel our deeper investment in research into the basic problems of the atherosclerotic process.

In Vitro Studies of the Human Mammary Gland: Effect of Hormones on Proliferation in Primary Cell Cultures

Epithelial cells from the human mammary gland were propagated up to 40 days in vitro as primary cell cultures. Large and medium-sized ducts, dissected from 4 different glands, served as a specific source of the epithelial cells. Ducts were opened, cut in small pieces, and were treated with trypsin-EDTA. The loosened epithelial cells were obtained in suspension and inoculated into Petri dishes where they attached, maintained their epithelial shape and grew as cohesive sheets of cells. The cultured cells had certain ultrastructural features in common with control uncultured cells of the ducts. In cultures from 2 mammary glands, addition of insulin or prolactin to serum-containing culture fluid did not result in any increase in the mitotic index or number of cells synthesizing DNA. Hydrocortisone, on the other hand, suppressed mitosis and DNA synthesis. This system should make possible additional studies of human mammary gland biology and pathology.

Intracellular Electromyography

IN THE STUDY of human muscle pathology the nature of possible pathophysiological disorders of the muscle cell has been inferred from clinical, biochemical, and conventional (extracellular) electromyographic evidence. Intracellular (IC) recording with glass microelectrodes offers the possibility of studying the muscle cell directly. This can be done without exposing the muscle and thus resting membrane potentials (RMP) in normal human muscle and in several pathological conditions have been measured. 1-4 Most data upon activity in human muscle fibers derive from in vitro studies of normal and pathological biopsy material, especially the intercostal muscle preparation. 5-8 The in vivo study of the action potential has proved more difficult largely due to the inability to maintain the microelectrode's IC location during stimulation, although action potentials evoked by current passed through the recording micropipette have been reported. 1,4 By this method it is possible to obviate the movement occasioned by voluntary contraction