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At least 37 records · Page 2Linked to original sources
PubMed1975

Pathogenesis of diastematomyelia and spina bifida.

Three cases of spina bifida (SB) associated with diastematomyelia (DM) are described and possible differences in pathogenesis are discussed. The frequent simultaneous occurrence of both malformations and the possibility that the cord can be split above, at the level of or below the SB indicate a common pathogenesis for SB and DM. Splitting of the cord symmetrically, asymmetrically, bilateraly or even antero-posteriorly can be explained only by the existence of a destructive phenomenon which is responsible for the bifurcation of the neural tube or its anlage. The existence of such a phenomenon indicates that myelocele can develop due to re-opening of a previously closed neural tube. Meningocele may be a manifestation of early embryonic antero-posterior DM in which the anterior tubule develops into an almost normal spinal cord, whereas the posterior tubule provides the wall of the cystic sac of meningocele in which most or all the neural tissue undergoes fibrous replacement.

Humans↗
PubMed1977

The mechanism of palatal shelf elevation and the pathogenesis of cleft palate.

Both normal Wistar rat fetuses and those with cleft palate induced by 5-Fluoro-2-Desoxyuridine were studied with a view to elucidating the mechanism of palatal shelf elevation and the pathogenesis of cleft palate. It was postulated that normal shelf elevation is brought about rapidly by an intrinsic turgor shelf force generated by binding of water to mucopolysaccharides. Interference with mucopolysaccharide synthesis would seem to be an important factor in the pathogenesis of some types of cleft palate.

Animals↗
PubMed1978

Heterotopic brain tissue in the submandibular region and lung. Report of two cases and comments about pathogenesis.

Two cases of extracranial heterotopia of the brain are reported. Case 1, in an otherwise normal female baby, had a brain heterotopia in the submandibular region. Case 2, in a still-born female baby with anencephaly, had the heterotopia in the lung. The lesion in case 1 is believed to be an encephalocele that has been pinched off through a cleft in the bone or through a foramen of the skull; the pathogenesis is similar to that of the so-called "nasal glioma". Concerning the pathogenesis of case 2, contrary to the generally supported embolism theory, observation of serial sections of the tumor in the lung favors the aspiration theory according to which amniotic brain tissue fragments, which are dislocated into the amnion because of nonclosure of the ventricle or following destruction of the fetal brain, are aspirated by fetal respiratory movements in the 4th to 6th month of intra-uterine life.

Anencephaly↗
PubMed1979

Pathogenesis of duodenal ulceration produced by cysteamine or propionitrile: influence of vagotomy, sympathectomy, histamine depletion, H-2 receptor antagonists and hormones.

Insight into the pathogenesis and etiology of experimental duodenal ulceration was sought by studying the modulation of this disease in rats by selective vagotomy, chemical sympathectomy, histamine depletion, histamine H-2 receptor antagonists (eg, metiamide, cimetidine), or endocrine ablations. Gastric secretion was examined in intact and pylorus-ligated animals. The formation of duodenal ulcers induced by the administration of propionitrile or cysteamine was abolished by vagotomy, decreased by sympathectomy, histamine depletion, histamine H-2 receptor antagonists, hypophysectomy, thyroidectomy, or adrenalectomy. Cimetidine and metiamide exerted a dose-dependent antiulcer effect, but metiamide enhanced the mortality of rats given propionitrile or cysteamine. The non-ulcerogen derivative of cysteamine, ethanolamine, did not increase mortality when given in combination with metiamide. The gastric hyperacidity elicited by cysteamine was reduced by metiamide or vagotomy, the latter being more effective in this respect. Thus, the chemically induced duodenal ulcer in rats resembles the human peptic ulcer disease in sensitivity to therapeutic modalities and may serve as an appropriate model to study the role of neural, hormonal, and other factors in the etiology and pathogenesis of this disorder.

Adrenalectomy↗
PubMedDate not supplied

Morphological alterations of non-varicose and varicose veins. (A morphological contribution to the discussion on pathogenesis of varicose veins).

Venous valves do not play a role in pathogenesis of primary varicose veins. Their number remains constant during life time. In varicose veins their insufficiency is secondary. Intimal fibrosis is no prerequisite for the development of varicose veins. It is a frequent finding in non-varicose veins of all age groups. Fibrosis of media and adventitia is no early morphological alteration in varicose veins. Fibrotic replacement of smooth muscles represents a late stage of varicosis. Degenerative lesions of deep leg veins are rare even at old age. The deep veins are not influenced by sclerotic lesions of the adjacent arteries. Preexisting intimal fibrosis in autogenous graft veins may be one of several factors which induce an overshooting intimal proliferation. Degenerative alterations (fibrotic lesions of the wall layers, insufficiency of the valves) are secondary phenomena in pathogenesis of varicose veins which follow a functional deficiency of the smooth musculature.

Adolescent↗
PubMed1992

Isolated rat pancreatic acini as a model to study the potential role of lipase in the pathogenesis of acinar cell destruction.

We have recently reported that lipase may play a role in the pathogenesis of acute pancreatitis by its ability to release fatty acids from triglycerides. The aim of this study was to further investigate the effect of lipase and its various digestive products on the integrity of isolated pancreatic rat acini. Pancreatic acini were prepared by collagenase digestion and their newly synthesized proteins labeled with 35S-methionine. Acini were later incubated in buffer to which various factors were added: Products of lipolytic digestion, such as various fatty acids and monoglycerides, fat tissue, nonactivated or trypsin activated homogenized pancreatic tissue, and a specific lipase inhibitor (THL, tetrahydrolipstatin). Cellular destruction was quantified by the degree of radiolabeled proteins released. Short chain fatty acids and monoglycerides (up to C-12) caused cellular destruction, whereas long chain fatty acids and their respective monoglycerides were not harmful. With regard to unsaturated fatty acids, long chain fatty acids (C-18 to C-22) were also able to destroy cells. The degree of cellular necrosis correlated with incubation time and fatty acid concentration. The cellular damage caused by incubation of acini with either inactive or trypsin activated pancreatic homogenates together with triglycerides could be completely inhibited by the specific lipase inhibitor THL. Bile alone caused no damage. When bile was combined with activated-pancreatic homogenates, about 25% of newly synthesized proteins were released by acini within 30 min. Incubation with a combination out of bile activated pancreatic homogenates and triglycerides resulted in the most pronounced damage. This acinar destruction could only be partly inhibited by THL. These studies suggest that both lipase and phospholipase-A2 may play an important role in the pathogenesis of acinar cell destruction.

Animals↗
PubMed1975

Pathogenesis of gangrene following intra-arterial injection of drugs: a new hypothesis.

We have demonstrated the toxicity of diazepam and the safety of ketamine hydrochloride following intra-arterial injection in an anaesthetized animal model. The pathogenesis of gangrene following intra-arterial injection of drugs is unclear. Clinical reports and this experiment suggest that it only follows injection of highly membrane-soluble drugs. Early swelling and disruption of capillary endothelial cells were demonstrated after intra-arterial injection of diazepam and thiopentone. We believe that a theory of pathogenesis based on this finding is consistent not only with our experimental findings, but with known in vitro effects of membrane soluble drugs on cell membranes and the clinical features following intra-arterial injections in both human subjects and in animals.

Animals↗
PubMed1978

Membranes nephropathy associated with renal cell carcinoma. Evidence against a role of renal tubular or tumor antibodies in pathogenesis.

A patient with the nephrotic syndrome due to membranous nephropathy was found to have renal cell carcinoma. Since membranous nephropathy in patients with malignancies has been attributed to a tumor antigen-antibody complex form of glomerulonephritis, an attempt was made to implicate tumor antigens and/or renal tubular epithelial antigens in the pathogenesis of membranous nephropathy in our patient with renal cell carcinoma. Antibodies directed against tumor antigens and renal tubular antigens and renal tubular eipthelial antigens were sought in his serum and in eluates of his glomeruli; no such antibodies were found. The concurrence of the two renal lesions may have been fortuitous in this patient. However, their association temporally suggests that they were related, and our immunologic studies demonstrate that tumor antigen-antibody complexes are not invariably involved in the pathogenesis of malignancy-associated membranous nephropathy.

Adenocarcinoma↗
PubMed1975

The pathogenesis of the Treacher Collins syndrome (mandibulofacial dysostosis).

Numerous synonyms have been used to describe syndromes affecting structures derived from the first and second branchial arches. These conditions are most conveniently grouped into the asymmetrical anomalies of hemifacial microsomia and the symmetrical syndrome of mandibulofacial dysostosis. By examination of animal models of these conditions it can be demonstrated that the pathogenesis is distinct but different for each group. The characteristic facies of mandibulofacial dysostosis suggests a mechanism of malformation which operates early in embryogenesis, acting uniformly on parts which are derived from neural crest cells. In the serial examination of a phenocopy of mandibulofacial dysostosis, induced in the rat by the teratogen vitamin A, focal death of pre-otic neural crest cells is observed to occur, creating both a spatial rearrangement of the developing ears and a paucity of ectomesenchyme in the first and second branchial arches. The result of these deviations from normal morphogenesis is the development of a facial skeleton which is symmetrical but distinctly different in form from that in the normal animal. Microscopic study of the induced ear and jaw defects revealed that the animal model was closely comparable in all respects to human mandibulofacial dysostosis. The specific nature of the interaction between teratogen and migrating neural crest cells is not yet clear; nor is it known whether these cells are attacked before or after their specific destination is determined. The greater part of the damage is inflicted in a general fashion and leads to symmetrical abnormal development. Minor examples of dyssymmetry do occur, however, in the animal model and man, but these are compatible with the hypothesis of a pathogenetic mechanism which is initiated centrally and symmetrically but modified locally at a later stage. A description of the pathogenesis of these two conditions, scientific predictions can be made with respect to the timing and technique of reconstruction of the orofacial defects, and the effects of surgery on growth and development.

Abnormalities, Multiple↗
PubMed2026

Novel HLA class I and II insights into the pathogenesis of systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the leading cause of mortality in systemic sclerosis (SSc), yet its genetic architecture remains incompletely understood. Therefore, given the key role of the major histocompatibility complex (MHC) in SSc, we aimed to perform a comprehensive MHC-wide association study in the largest SSc-ILD cohort to date. METHODS: We analysed 2412 patients with SSc-ILD⁺, 3550 patients with SSc-ILD⁻, and 15,076 controls of European ancestry from 10 international cohorts. After quality control, the MHC region was imputed, and inverse variance weighted meta-analysis was performed. Subsequently, conditional stepwise analyses, adjustment for antitopoisomerase autoantibody (ATA) status, and functional annotation of significant single-nucleotide polymorphisms were performed. Finally, we constructed a composite score combining genetic, clinical, and demographic variables to predict SSc-ILD. RESULTS: After conditional analysis, we detected 12 significant associations within class I and class II human leukocyte antigen (HLA) genes. ATA adjustment reduced the significance of class II HLA variants, whereas class I HLA variants remained unaffected. Finally, the built composite score had an area under the curve of 0.754, significantly outperforming the models including any of the variables alone. CONCLUSIONS: In this study, we identify genetic mechanisms underlying SSc-ILD that support the potential implication of CD8+ T cells and ATAs in its pathogenesis. Moreover, we also demonstrate the enhanced efficacy of integrating genetic information into predictive models to detect patients at high risk of SSc-ILD. These findings provide new insights into disease pathogenesis and suggest potential biomarkers and therapeutic targets for improved patient management.

Humans↗
PubMed1977

Pathogenesis of dissecting aneurysm of aorta. Comparative histopathologic study of significance of medial changes.

In previous investigation of the normal aging aorta, the claimed specificity of alterations in the media in the pathogenesis of dissecting aneurysm of the aorta was challenged. The concept was promoted that these changes are nonspecific and caused by general hemodynamic events within the aorta. In this investigation the aortic media was studied in patients with a dilated ascending aorta, whose hemodynamic profile is known to be altered. The results were compared with data obtained from the study of aortas with complete or incomplete dissection and aortas from patients with Marfan's syndrome, a condition known to predispose to dissection. Only quantitative differences were found between the normal "aging" aorta and the overtly abnormal aorta. The pathogenesis of dissected aneurysm, therefore, is considered to be initiated by processes if injury and repair within the aortic wall, consequent to hemodynamic forces. The histologic features of the media previously implicated as the specific underlying defect appear to represent the morphologic substrate of this traumatizing and reparative process. This process may gradually lead to dilatation of the aorta and, according to Laplace's law, a vicious cycle may ensue that may lead to further complications. Local circumstances determine whether a dilated aorta will rupture or whether an incomplete or complete dissection will occur. The fact that the aorta in patients with Marfan's syndrome shows basically the same structural alterations supports the concept proposed. The underlying connective tissue disorder in these patients will lead to complications at an earlier age. Dissecting aneurysm therefore is part of a spectrum of lesions that have as a common denominator the process of injury and repair.

Adolescent↗
PubMed1978

Congenital diaphragmatic hernia associated with homolateral upper limb malformation: a study of possible pathogenesis in four cases.

Four cases of congenital diaphragmatic hernia associated with homolateral upper limb reduction deformities are presented and are analyzed in terms of their pathogenesis. Diaphragm and upper limb are supplied by adjacent segments of cervical neural crest, and the sensitive period for upper limb formation occurs during early neural crest development. The evidence supports the possibility of cervical neural crest injury as the underlying pathogenesis.

Arm↗
PubMed1977

Intrathymic pathogenesis and dual genetic control of myasthenia gravis.

We propose a two-step model for the pathogenesis of myasthenia gravis. In the first step, primitive intrathymic stem-cells are induced by abnormal stimuli to differentiate to (abnormal?) myogenic cells. In the second step, immunocompetent T lymphocytes start an autoimmune reaction against these newly differentiated myogenic cells. The clinical stage is reached when autosensitised effector T lymphocytes leave the thymus and either infiltrate the synaptic spaces of peripheral muscles or participate in the formation of autoantibodies, causing the neuromuscular symptoms. At two points the pathogenesis is under genetic control--the first at the differentiation of the stem-cells to myogenic cells and the second at the immune responsiveness of the lymphocytes to these atypical intrathymic muscle cells.

Animals↗
PubMed1978

Possible role for impaired renal prostaglandin production in pathogenesis of hyporeninaemic hypoaldosteronism.

A 57-year-old woman with hypertension and moderate renal insufficiency had chronic unexplained hyperkalaemia. Metabolic balance studies confirmed a diagnosis of hyporeninaemic hypoaldosteronism. Two observations suggested that impaired renal prostaglandin production contributed to the pathogenesis of the patient's disorder. Baseline renal-prostaglandin synthesis (as determined by urinary excretion of P.G.E and P.G.F) was was substantially depressed when compared with that in nine normal females. Infusion of low doses of P.G.A1 produced a significant increase in serum-aldosterone and urinary potassium excretion; it also led to a dramatic fall in blood-pressure and serum-potassium. It appears from these studies that a defect in renal prostaglandin synthesis has an important role in the pathogenesis of hyporeninaemic hypoaldosteronism.

Adrenal Insufficiency↗
PubMed1976

Pathogenesis of the glomerulopathy associated with renal infarction in rats.

The present studies were designed to characterize the extent and pathogenesis of the glomerular lesions which occur in the viable portion of the kidney following partial renal infarction in rats. Control rats with two normal kidneys had a mean blood pressure of 112 mm Hg, minimal proteinuria and no glomerular pathology on light (LM), electron (EM) or immunofluorescence microscopy (IFM). Rats with two-thirds infarction of one kidney (stage II) became hypertensive, although less than 4% of the glomeruli from either kidney were abnormal. Rats with two-thirds infarction of one kidney and contralateral nephrectomy (stage III) developed proteinuria and hypertension whether fed a normal, low or high Na+ diet. By light microscopy 37% of glomeruli were abnormal 28 days after partial infarction and contralateral nephrectomy and thereafter the percent of abnormal glomeruli increased. Detectable amounts of immunoglobulin and complement (C3) were present in kidneys of stage II or III rats but were always accompanied by more extensive albumin and fibrin deposits. Basement membrane deposits characteristic of immune complexes were not seen on EM. Administration of antihypertensive medication to stage III rats significantly lowered blood pressure and reduced the number of abnormal glomeruli on LM; however, IFM abnormalities remained prominent. Platelet thrombi seen by EM and abundant glomerular fibrin deposits seen on IFM suggested that coagulation mechanisms may be prominent in the pathogenesis of the renal lesion. Heparin-treated stage III rats had significantly lower blood urea nitrogen concentrations, blood pressures and proportion of abnormal glomeruli although glomerular deposition of serum proteins was still present on IFM. These observations suggest that this glomerulopathy is initiated by an unknown agent(s) which increased capillary permeability. This lesion progresses via thrombotic mechanisms which are prevented by heparin administration.

Aneurysm↗
PubMed2026

EIF4H and YBX1 are essential host factors for hepatitis E virus replication and pathogenesis.

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, responsible for approximately 20 million infections annually. Despite the availability of a vaccine in China, no direct-acting antivirals are approved, and host factors required for HEV replication remain poorly defined. Here, using a genome-wide CRISPR/Cas9 knockout screen in a replicon system, we identified Eukaryotic Translation Initiation Factor 4H (EIF4H) and Y-Box Binding Protein 1 (YBX1) as essential host factors for HEV replication and pathogenesis. Knockout of either factor markedly impaired replication of HEV genotypes 1, 3, and 4, as well as HEV infection and production in hepatocellular carcinoma cells and human induced pluripotent stem cell-derived hepatocyte-like cells, while leaving SARS-CoV-2, hepatitis B virus, hepatitis C virus, and Zika virus unaffected, underscoring their HEV-specific roles. Mechanistically, EIF4H interacts with ORF1 via its methyltransferase-Y-papain-like protease region, and EIF4H deficiency alters the composition of the ORF1-associated replication complex. By contrast, YBX1 is dispensable for ORF1 translation and RNA binding but is specifically required for ORF1 proteolytic processing, a prerequisite for assembling a functional replication machinery. EIF4H knockout rats and liver-specific YBX1 knockout rats were largely resistant to rat HEV-C1 infection, showing profound reductions in viral shedding, suppressed hepatic and intestinal viral loads, and protection from liver pathology. Together, our findings establish EIF4H and YBX1 as essential host factors for HEV infection and pathogenesis and reveal potential targets for antiviral intervention.

Virus Replication↗
PubMed2026

Impact of pH and Mycoplasma hominis endosymbiosis on Trichomonas vaginalis pathogenesis.

The parasite Trichomonas vaginalis colonizes the human vaginal tract and adheres to and lyses epithelial cells causing an inflammatory infection. The vaginal tract is typically acidic, ranging from pH 3.8 to 5.1; however, pathogenesis studies have previously been conducted on parasites grown at pH 5.9 to 6.2. Here we compared the adherence and cytotoxicity of T. vaginalis grown at pH 5.1 and pH 5.9, identifying changes in the surface proteome that contribute to increased pathogenesis of the parasite at pH 5.1. We show that growth of the parasite at pH 5.1 significantly enhances adherence to and lysis of host cells and that this is strongly amplified by the presence of a common bacterial endosymbiont, Mycoplasma hominis. Quantitative proteomics revealed the upregulation of putative surface proteins, three of which were found to be involved in increased parasite adherence and host cell killing. Mechanistic assays demonstrated that a Ricin B-like protein mediates parasite adherence dependent on host glycosaminoglycans via its carbohydrate-recognition domain, while an EF-hand-like protein is shown to promote Ca2+dependent adherence. Ricin B overexpression was found to reprogram host metabolism, activating ERK1/2 and HIF-1α and driving a Warburg-like glycolytic shift with greatly increased lactate release, which may create a nutrient-rich niche that supports parasite persistence and host cell cytotoxicity. These studies demonstrate a coordinated upregulation of multiple adhesins rather than a single factor at pH 5.1 in the presence of M. hominis and explore the mechanisms underlying the interaction of parasite surface proteins with the host cell.

Trichomonas vaginalis↗
PubMed1976

Pathogenesis of cutaneous lesions in acute meningococcemia in humans: light, immunofluorescent, and electron microscopic studies of skin biopsy specimens.

Biopsy specimens of the skin were taken from 10 patients with acute meningococcemia who exhibited mainly maculopurpuric lesions. The specimens were studied by light, electron, and immunofluorescent microscopy in an attempt to obtain information on the pathogenesis of vascular injury. Light microscopy disclosed a large number of Neisseria meningitidis organisms, both in the endothelial cells and being phagocytized by neutrophils. Vascular injury was characterized (by means of both light and electron microscopy) by endothelial necrosis, thrombosis, and necrosis of other elements of the vascular wall, such as muscle cells and pericytes. Immunoglobulins and complement were also found in the vascular wall in most cases. Hypercoagulability was demonstrated in some patients. These findings suggest that the cutaneous lesions of meningococcemia fulfill most of the gross and histologic criteria of the local Shwartzman reaction, but that immunological factors probably contribute to pathogenesis.

Blood Coagulation Tests↗