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At least 937 records · Page 52Linked to original sources
PubMed1992

Experimental studies on the pathogenesis of the gastric mucosal lesions induced by whole-body vibration.

In order to determine the pathogenesis of gastric mucosal lesions induced by whole-body vibration (WBV), the effects of WBV (3.0 G, 10 Hz, 90 min) on gastric mucosal blood flow (GMBF), plasma corticosterone (COR) and catecholamines (CA), and gastric ulcer formation were investigated in relation to the effects of forced water-immersion stress (FWI) upon the same parameters. While WBV increased GMBF during the exposure, FWI decreased it both during and after the stress. No difference in the severity of ulcer formation between the WBV and the FWI groups was seen. Both WBV and FWI increased plasma COR and CA, although the degree of the increase in COR that accompanied WBV was less than that associated with FWI. Truncal vagotomy attenuated the reduction of GMBF and the extent of ulcer formation that occurred with FWI, but promoted a reduction of GMBF with WBV. These findings indicate that ulceration induced by WBV may be caused primarily by its direct and specific mechanical actions and not by indirect, central nervous system effects known to be important in the pathogenesis of ulcerations produced by mental stress.

Animals↗
PubMed2003

Smooth muscle cells and the pathogenesis of cerebral microvascular disease ("angiomyopathies").

Many forms of human cerebral microvascular disease result from abnormal proliferation and/or degeneration of smooth muscle cells (SMC) in the vessel wall of arteries and arterioles. Human cerebral microvessel-derived smooth muscle cells (MV-SMC) in culture can be used to study the pathogenesis of microvascular disease. Primary cultures were established from nonneoplastic human brain specimens surgically resected and characterized as to their growth properties and phenotype. The cultures have been used to study various factors that may be relevant in the pathogenesis of microangiopathies, in particular cerebral amyloid angiopathy (CAA), to help determine mechanisms of SMC degeneration in these disorders. Factors investigated have included cellular growth rate, response to hypoxia and amyloidogenic peptides, and telomerase activity. MV-SMC appear to behave differently than aortic SMC with regard to proliferation and telomerase activity. These differences may play a role in the responses to MV-SMC in the evolution of CAA and other microangiopathies (cerebral arteriosclerosis/lipohyalinosis) and provide insight into mechanisms of degeneration of these cells within vessel walls.

Aging↗
PubMed2001

Decreased expression of the heat shock protein hsp70-2 is associated with the pathogenesis of male infertility.

OBJECTIVE: To examine the expression of the heat shock protein hsp70-2, and the possible relationship with the pathogenesis of male infertility. DESIGN: Prospective study. SETTING: Reproductive testing laboratory in a university hospital. PATIENT(S): Men undergoing testicular biopsy during an investigation of subfertility. INTERVENTION(S): Testicular tissues were obtained from biopsies of men undergoing infertility evaluation and subdivided into three groups: normal testes, maturational arrest and Sertoli cell-only syndrome. Immunostaining and Western blotting techniques determined expression of the heat shock protein hsp70-2 MAIN OUTCOME MEASURE(S): Expression of the heat shock protein hsp70-2 in the testes. RESULT(S): The experimental data demonstrated that the heat shock protein hsp70-2 was expressed in the normal and maturation arrest testicular specimens. The heat shock protein hsp70-2 was strongly present in the cytoplasm of spermatocytes and spermatides in the adluminal compartment of the seminiferous epithelium in normal testis. However, maturation arrest testis tissue demonstrated light staining in spermatocytes and spermatides, and Sertoli-only specimens demonstrated no staining for the heat shock protein hsp70-2. The Western blotting data showed a 70-kDa heat shock protein in the normal and maturation arrest testicular tissues, but not in the Sertoli-only tissues. CONCLUSIONS: These results suggest that the heat shock protein hsp70-2 is expressed in spermatocytes and spermatides in normal and maturation arrest tissues. However, the expression of the heat shock protein hsp70-2 was low in maturation arrest, and no heat shock protein hsp70-2 was demonstrated in Sertoli-only specimens. Therefore the decreased expression of the heat shock protein hsp70-2 is associated with the pathogenesis of male infertility.

Adult↗
PubMed2000

Contribution of nitric oxide to the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats.

BACKGROUND & AIMS: Decreased cardiac contractility and beta-adrenergic responsiveness have been observed in cirrhosis, but the etiology remains unclear. We aimed to test the role of nitric oxide (NO), a negative inotropic agent, in the pathogenesis of cirrhotic cardiomyopathy in a rat model. METHODS: Cirrhosis was induced by bile duct ligation. Four weeks after ligation or sham operation, cardiac levels of tumor necrosis factor (TNF)-alpha, guanosine 3,5'-cyclic monophosphate (cGMP), inducible NOS (NOS2), and endothelial constitutive NOS (NOS3) messenger RNA (mRNA) and protein were determined. Serum nitrite/nitrate level was measured. Cardiac contractile function was evaluated in isolated left ventricular papillary muscles in the absence and presence of the NOS inhibitor nitro-L-arginine methyl ester (L-NAME). RESULTS: Cardiac TNF-alpha, NOS2 mRNA and protein, cGMP, and serum interleukin (IL)-1beta and nitrite/nitrate levels were significantly higher in cirrhotic rats than sham controls. No significant differences in NOS3 mRNA or protein were found between cirrhotic and sham control rats. Baseline isoproterenol-stimulated papillary muscle contractile force was significantly lower in the cirrhotic group; with L-NAME incubation, contractile force increased significantly in cirrhotic rats but was unaffected in the controls. In normal papillary muscles, IL-1beta attenuated the contractility, but coincubation with L-NAME again reversed this attenuation. Incubation with the exogenous NO donor S-nitroso-N-acetyl-penicillamine also blunted papillary muscle contractility. CONCLUSIONS: These results suggest that cytokine-induced stimulation of NOS2 plays a significant role in the pathogenesis of cirrhotic cardiomyopathy.

Animals↗
PubMed2004

Silent peptic ulcer disease: frequency, factors leading to "silence," and implications regarding the pathogenesis of visceral symptoms.

BACKGROUND: Peptic ulcer disease may occur in the absence of dyspeptic symptoms. The pathogenesis of dyspepsia in peptic ulcer disease is unclear. Whether the presence of Helicobacter pylori infection or use of non-steroidal anti-inflammatory drugs affects dyspeptic symptoms in patients with peptic ulcer disease has not been determined. The aim of the study was to determine the frequency and risk factors for peptic ulcer disease in a cohort of asymptomatic, unselected patients undergoing routine screening EGD. METHODS: This was a prospective study of a cohort of Chinese subjects undergoing screening EGD as part of a routine health maintenance program. Routine EGD screening was performed in 6457 consecutive subjects who underwent a self-paid, health evaluation. Those with endoscopy-confirmed peptic ulcer disease were enrolled to assess the risk factors that distinguish asymptomatic patients with peptic ulcer disease from patients with symptoms because of peptic ulcer disease. RESULTS: A total of 704 (10.9%) patients were found to have peptic ulcer disease, of which two thirds (n=496) were asymptomatic. Both uni- and multivariate analysis showed that the asymptomatic patients tended to have a larger body mass index, to be habitual tea drinkers, and to have an ulcer that was less than 1 cm in diameter and in a healing stage. Gender, blood group, history of hypertension and/or diabetes, ulcer location, Helicobacter pylori status, use of non-steroidal anti-inflammatories or sedative medications, habitual coffee drinking, and habits with respect to smoking of tobacco or ingestion of alcohol, had no association with symptoms. CONCLUSIONS: The results of this study suggest that silent peptic ulcer disease is common in Taiwan. Dyspeptic symptoms because of peptic ulcer disease may be influenced by intrinsic (body mass index and ulcer characters) and extrinsic (habitual tea drinking) factors. Non-steroidal anti-inflammatory drug use and Helicobacter pylori status had no significant effect on the symptomatology of peptic ulcer disease. These findings may contribute to the understanding of the pathogenesis in the visceral symptoms of peptic ulcer disease.

Adult↗
PubMed2002

New considerations for the pathogenesis of endometriosis.

OBJECTIVES: To review the available evidence regarding the immunological, epidemiological and other factors involved in the pathogenesis of endometriosis. METHODS: Literature review. RESULTS: Endometriosis remains a poorly-understood disease of unknown etiology and pathogenesis. CONCLUSIONS: There is evidence to suggest that alterations in the immune response, whether genetically transmitted or environmentally induced, predispose women to the ectopic implantation of endometrial cells transported into the peritoneal cavity by way of retrograde menstruation. This predisposition may exist because of an impaired peritoneal clearing of endometrial cells and fragments or because of pathological angiogenesis.

Choristoma↗
PubMed2001

The role of endothelin in the pathogenesis of Chagas' disease.

Infection with Trypanosoma cruzi causes a generalised vasculitis of several vascular beds. This vasculopathy is manifested by vasospasm, reduced blood flow, focal ischaemia, platelet thrombi, increased platelet aggregation and elevated plasma levels of thromboxane A(2) and endothelin-1. In the myocardium of infected mice, myonecrosis and a vasculitis of the aorta, coronary artery, smaller myocardial vessels and the endocardial endothelium are observed. Immunohistochemistry studies employing anti-endothelin-1 antibody revealed increased expression of endothelin-1, most intense in the endocardial and vascular endothelium. Elevated levels of mRNA for prepro endothelin-1, endothelin converting enzyme and endothelin-1 were observed in the infected myocardium. When T. cruzi-infected mice were treated with phosphoramidon, an inhibitor of endothelin converting enzyme, there was a decrease in heart size and severity of pathology. Mitogen-activated protein kinases and the transcription factor activator-protein-1 regulate the expression of endothelin-1. Therefore, we examined the activation of mitogen-activated protein kinases in the myocardium by T. cruzi. Western blot demonstrated an extracellular signal regulated kinase. In addition, the activator-protein-1 DNA binding activity, as determined by electrophoretic mobility shift assay, was increased. Increased expression of cyclins A and cyclin D1 was observed in the myocardium, and immunohistochemistry studies revealed that interstitial cells and vascular and endocardial endothelial cells stained intensely with antibodies to these cyclins. These data demonstrate that T. cruzi infection of the myocardium activates extracellular signal regulated kinase, activator-protein-1, endothelin-1, and cyclins. The activation of these pathways is likely to contribute to the pathogenesis of chagasic heart disease. These experimental observations suggest that the vasculature plays a role in the pathogenesis of chagasic cardiomyopathy. Additionally, the identification of these pathways provides possible targets for therapeutic interventions to ameliorate or prevent the development of cardiomyopathy during T. cruzi infection.

Animals↗
PubMedDate not supplied

The pathogenesis of neosporosis in pregnant cattle: inoculation at mid-gestation.

To investigate the pathogenesis of bovine neosporosis, 14 pregnant cattle were each inoculated subcutaneously with either 10(7) or 5 x 10(8) Neospora caninum (strain NC1) tachyzoites at 140 days' gestation. Serial necropsies were then carried out over an 8-week period. In the placenta, Neospora DNA and histopathological changes were observed in samples taken 14 days post-inoculation (dpi), with focal necrosis of maternal caruncular septa and fetal placental villi, serum leakage, and a maternal and fetal inflammatory response. At subsequent samplings, pathological changes in the placenta showed signs of resolution. No parasitaemia was detected in the dams in the two weeks following inoculation. In the fetus, Neospora DNA was detected at 14 dpi, and histopathological changes in the fetal central nervous system at 28 and 42 dpi consisted of small foci of necrosis and inflammation. Resolution of placental lesions during the experiment indicated that the disease was being controlled, and fetal infection, although established, did not appear to be progressing to a fatal outcome. The two doses of tachyzoites produced similar results, but the higher dose elicited earlier and more extensive lesions in the placenta and fetus. Control animals remained negative for all parameters recorded. It is concluded that in bovine neosporosis the placenta plays a central role in the pathogenesis and epidemiology of the infection, and that while primary tissue destruction by the parasite may endanger the fetus, the maternal and fetal inflammatory responses may also be damaging.

Animals↗
PubMed2003

The pathogenesis and diagnosis of foot-and-mouth disease.

The pathogenesis of foot-and-mouth disease (FMD) is reviewed, taking account of knowledge gained from field and experimental studies and embracing investigations at the level of the virus, the cell, the organ, the whole animal and the herd or flock. The review also addresses the immune response and the carrier state in FMD. Progress made in understanding the pathogenesis of the disease is highlighted in relation to developments in diagnosis and methods of control.

Animals↗
PubMed1997

The role of inflammatory cytokines and nitric oxide in the pathogenesis of necrotizing enterocolitis.

PURPOSE: The role of inflammatory cytokines in the pathogenesis of necrotizing enterocolitis (NEC) is still undefined. Elevated levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha have been measured in infants with NEC, while elevated levels of nitric oxide (NO) have been reported in newborn infants with clinical sepsis. However, the cellular source of the NO or cytokines is unknown. The authors hypothesized that local intestinal production of NO induced by cytokines may contribute to the pathogenesis of bowel necrosis in NEC by inducing apoptosis (programmed cell death) or necrosis of the enterocytes. We examined the levels of inflammatory cytokines and NO in the intestine of infants undergoing surgical resection for NEC, and the cellular localization of human inducible NO synthase (NOS-2) in the inflamed gut. METHODS: We compared 15 patients undergoing bowel resection for NEC, with six infants (of similar age) undergoing intestinal resection for ileal atresia or stricture, meconium peritonitis, intussusception, or cecal perforation (control). Diagnosis of NEC was confirmed histologically. Representative segments of the surgical specimen were examined for messenger RNA (mRNA) for NOS-2 by Northern blotting and in situ hybridization. Cytokine mRNA was measured by polymerase chain reaction (PCR) because mRNA could not be detected by Northern blotting. The site of NO production was determined by in situ hybridization and immunohistochemistry. Apoptosis was measured using in situ DNA strand break extension (TUNEL). Nitrotyrosine immunoreactivity was assessed to determine if NO mediates cellular injury via peroxynitrite formation. RESULTS: Messenger RNA for NOS-2 was detected in nearly all patients with NEC except for one infant who underwent proximal diverting jejunostomy alone, and who did not have histological evidence of NEC at that site. NOS-2 mRNA was detected less frequently in control patients. In situ hybridization and immunohistochemistry showed that the enterocytes were the predominant source of NOS-2 activity in the intestine of NEC patients. Extensive apoptosis was seen in enterocytes in the apical villi of infants with NEC, and correlated with nitrotyrosine staining. NOS-2 activity was markedly diminished at the time of stoma closure, but remained elevated in infants who died from progressive disease. PCR showed variable cytokine mRNA expression in the intestine. Transforming growth factor (TGF)-beta expression was nearly identical in NEC and control. However, interferon (IFN)-gamma was present in 9 of 10 NEC, but only in one of six control patients. CONCLUSION: The data show that NO is produced in large quantity by enterocytes in the intestinal wall of infants with NEC and leads to apoptosis of enterocytes in apical villi through peroxynitrite formation.

Cytokines↗
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↗
PubMed1982

Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection.

In order to determine the role of parainfluenza virus-specific IgE antibody production and release of histamine in the pathogenesis of lower respiratory disease caused by parainfluenza virus infection, we studied 84 infants and children at the time of parainfluenza virus infection. Parainfluenza virus-IgE antibody was detected in samples of nasopharyngeal secretions by means of an enzyme-linked immunosorbent assay, and histamine content of nasopharyngeal secretions was determined by a fluorometric technique. Virus-specific IgE responses appeared earlier and were of greater magnitude in patients with croup, wheezing, and croup with wheezing caused by parainfluenza virus infection than in patients with parainfluenza virus-induced upper respiratory illness. Histamine was detectable in nasopharyngeal secretions of patients with parainfluenza virus-related croup significantly more often than in patients with upper respiratory illness caused by parainfluenza virus. These observations suggest a role for immunologic mechanisms in the pathogenesis of severe forms of respiratory illness caused by parainfluenza virus infection.

Antibodies, Viral↗
PubMed1998

The protein tyrosine kinase p60c-Src is not implicated in the pathogenesis of the human autosomal recessive form of osteopetrosis: a study of 13 children.

Osteopetrosis has been described in mice generated by homozygous gene disruption of c-src gene encoding for the p60c-Src protein tyrosine kinase (Src-/- mice). The similarities of bone histologic findings in this murine model to those observed in some patients first seen with autosomal recessive osteopetrosis, "malignant" osteopetrosis, led us to investigate the potential role of p60c-Src in the pathogenesis of malignant osteopetrosis in 13 children. In 4 patients a c-src mutation was ruled out by an intragenic microsatellite segregation study. In the other 9 we analyzed p60c-Src expression and function, as well as c-src sequence. The expression was normal in all of the patients tested. In addition, the tyrosine phosphorylation and kinase activity of p60c-Src were also normal in all of the patients. Moreover, in these patients, sequences of the coding region of c-src were identical to the published sequence of the human c-src complementary DNA. These results exclude a role for c-src in the pathogenesis of human malignant osteopetrosis in the 13 patients analyzed.

Antibodies, Monoclonal↗
PubMed2003

Differential interactions within the Caenorhabditis elegans-Pseudomonas aeruginosa pathogenesis model.

A pathogenesis model based on the interaction between Caenorhabditis elegans and bacterial opportunistic pathogens has recently been developed. In the case of Pseudomonas aeruginosa, the model is based on three different modes of nematode killing (fast killing, slow killing and lethal paralysis) by virulent bacteria that has been incubated in different nutrient media. Using parametric statistics and Probit analysis, we test the reliability of the three different killing systems with respect to bacterial virulence. To accomplish this, we use three P. aeruginosa strains, each with a different level of virulence and one strain of non-virulent Escherichia coli. Probit function proved to be effective in quantifying the virulence of P. aeruginosa. The results of the killing curve analysis using the Probit function demonstrates that the slow-killing test is the most reliable method for quantifying virulence using the C. elegans model of bacterial pathogenesis. Although the greatest virulence differences are observed after long periods of incubation, the Probit analysis clearly shows that the death kinetics of C. elegans depend on the first hours of nematode/bacteria interaction. In contrast, fast killing seems to be non-specific, at least under our experimental conditions, since the killing rates of virulent P. aeruginosa and non-virulent E. coli strains were indistinguishable.

Animals↗
PubMed1999

Molecular pathogenesis of lung cancer.

Lung cancer is the largest cancer killer of men and women in the united states. In addition to the progress made from antismoking primary prevention measures, new tools to help treat patients with lung cancer are emerging from the rapid advances in knowledge of the molecular pathogenesis of lung cancer. These tools include molecular and cellular biology and are starting to provide an insight into how the tumor cell, by altering oncogenes and tumor suppressor genes, achieves growth advantage, uncontrolled proliferation and metastatic behavior via disruption of key cell-cycle regulators and signal transduction cascades. Moreover, new knowledge is being developed in terms of the molecular definition of individual susceptibility to tobacco smoke carcinogens. These tools are being translated into clinical strategies to complement surgery, radiotherapy, and chemotherapy and also to assist in primary and secondary prevention efforts. This review summarizes current knowledge of the molecular pathogenesis of lung cancer. From this we know that respiratory epithelial cells require many genetic alterations to become invasive and metastatic cancer. We can detect cells with a few such changes in current and former smokers, offering the opportunity to intercede with a biomarker-monitored prevention and early detection effort. This will be coupled with new advances in computed tomography-based screening. Finally, because the molecular alterations are known, new mechanism-based therapies are being developed and brought to the clinic, including new drugs, vaccines, and gene therapy, which also must be integrated with standard therapies.

Biomarkers, Tumor↗
PubMed1991

Evidence in favor of the mechanical (intrauterine torsion) theory over the endocrinopathy (cryptorchidism) theory in the pathogenesis of testicular agenesis.

There are 2 competing theories regarding the pathogenesis of testicular agenesis--the endocrinopathy/cryptorchidism and the mechanical/intrauterine torsion theories. We compare the number of Leydig cells, total number of germ cells and the transformation of adult dark spermatogonia into primary spermatocytes in semithin sections of testicular biopsies from 59 contralateral descended testes of patients with testicular agenesis with those in the contralateral descended testes from 250 patients with unilateral cryptorchidism. The contralateral descended testes from boys with testicular agenesis demonstrated higher numbers of Leydig cells, higher numbers of total germ cells and a higher rate of transformation of adult dark spermatogonia into primary spermatocytes than did the contralateral descended testes from the patients with unilateral cryptorchidism. These findings favor the mechanical/intrauterine torsion theory over the endocrinopathy/cryptorchidism theory in the pathogenesis of testicular agenesis.

Biopsy↗
PubMed1988

The role of androgens and estrogens in the pathogenesis of experimental nonbacterial prostatitis.

The etiology and pathogenesis of nonbacterial prostatitis remains unclear. This study provides evidence that genetic background, advancing age, and hormonal imbalance are important etiologic factors for prostatitis in rats. It also demonstrates that Lewis and Wistar rats develop a spontaneous nonbacterial prostatitis with advancing age, making them good animal models for the laboratory investigation of this disease. Spontaneous nonbacterial prostatitis is much more common in Lewis rats (72%) than in Wistar rats (27%, p less than .05), and does not occur in Sprague-Dawley rats. The incidence of spontaneous prostatitis is significantly higher in older animals than in younger animals (72% old adult Lewis rats vs. 30% young adult Lewis rats, p less than .05). Administration of exogenous 17 beta-estradiol increases the incidence and severity of prostatitis in old Wistar rats (100% treated vs. 27% control, p less than .01). Castration has a similar effect. Testosterone can block the effect of estradiol on prostatitis, however treatment with an anti-estrogen or an aromatase inhibitor to block estrogen action does not improve prostatitis in the rat. The major finding of this study is the demonstration that severe prostatitis can be induced in young adult Wistar rats by neonatal treatment with 17 beta-estradiol followed several months later in adulthood by testosterone administration. The results of this study suggest that genetic background, advancing age, and hormonal imbalance contribute to the pathogenesis of nonbacterial prostatitis in rats.

Aging↗
PubMed1999

Some state space models of HIV pathogenesis under treatment by anti-viral drugs in HIV-infected individuals.

In this paper we have extended the model of HIV pathogenesis under treatment by anti-viral drugs given by Perelson et al. [A.S. Perelson et al., Science 271 (1999) 1582] to a stochastic model. By using this stochastic model as the stochastic system model, we have developed a state space model for the HIV pathogenesis under treatment by anti-viral drugs. In this state space model, the observation model is a statistical model based on the observed numbers of RNA virus copies over different times. For this model we have developed procedures for estimating and predicting the numbers of infectious free HIV and non-infectious free HIV as well as the numbers of different types of T cells through extended Kalman filter method. As an illustration, we have applied the method of this paper to the data of patient Nos. 104, 105 and 107 given by Perelson et al. [A.S. Perelson et al., Science 271 (1999) 1582] under treatment by Ritonavir. For these individuals, it is shown that within two weeks since treatment, most of the free HIV are non-infectious, indicating the usefulness of the treatment. Furthermore, the Kalman filter method revealed a much stronger effect of the treatment within the first 10 to 20 h than that predicted by the deterministic model.

CD4 Lymphocyte Count↗