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At least 811 records · Page 45Linked to original sources
PubMed1996

Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Studies on the pathogenesis of Parkinson's disease in Japan.

Studies on the pathogenesis of nigral cell death in Parkinson's disease (PD) are reviewed. Discussions are focused mainly on studies performed by Japanese investigators because of the purpose of this issue. We and other groups found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with PD, and in addition to complex I deficiency, we reported loss of alpha-ketoglutarate dehydrogenase complex of the tricarboxylic acid cycle (TCA cycle) by immunohistochemistry. Thus mitochondrial respiratory failure and resultant energy crisis appear to be one of the most important mechanisms that lead nigral neurons to cell death. The primary cause of mitochondrial respiratory failure has not been elucidated yet; however, environmental neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) may be responsible for nigral cell death in PD; in this respect a number of candidate toxins including tetrahydroisoquinolines and beta-carbolines have extensively been studied for nigral as well as mitochondrial toxicity. Recent progress in this field is also reviewed. Even if an environmental neurotoxin is involved in PD, exposure to such a neurotoxin alone may not account for its pathogenesis, as most of us are probably being exposed to the same toxin. Therefore, genetic predisposition appears to be essential for the development of PD. The genetic predisposition may involve hepatic detoxifying enzymes for such neurotoxins, the transport mechanism of those toxins to the brain, bioactivation of those toxins in the brain, the uptake mechanism to the nigral neurons, and the activity levels of target enzymes or proteins; all of these factors are being extensively studied in many laboratories at a molecular level.

Journal Article↗
PubMed1994

Localized cellular responses to Ichthyophthirius multifiliis: protection or pathogenesis?

The ciliate Ichthyophthirius multifiliis is an economically important parasite in aquaculture as well as in the ornamental fish trade. The parasite has been well studied and details of life cycle, host response and pathogenesis have been characterized. Parasite development within host epithelial tissues initiates localized leukocytic infiltrations, although the relationship between these responses and host resistance is uncertain, and whether or not leukocyte responses play a role in protective immunity is unclear. Here Frank Cross outlines the character of localized cellular responses during I. multifiliis infection and discusses the contribution of such responses to protective immunity and pathogenesis.

Journal Article↗
PubMed1995

Clinical disease and pathogenesis in malaria.

This is the report of a meeting held in Ahungalla, Sri Lanka, 16-19 January 1994, under the sponsorship of the Rockefeller Foundation, Health Sciences Division. The meeting was initiated jointly by the Rockefeller Foundation and the TDR Special Programme of the World Health Organization in order to bring together scientists with a wide spectrum of experience relating to malarial disease and pathogenesis. The objective was to generate interdisciplinary discussion ranging from the clinical pictures of malarial infections and their impact in different parts of the world, to current investigations on mechanisms of pathogenesis and clinical immunity and the genetic determinants in human and parasite populations affecting the nature of the disease.

Journal Article↗
PubMed1996

Leishmania and the pathogenesis of HIV infection.

Acquired immunodeficiency syndrome (AIDS) and leishmaniasis overlap in several parts of the world, and microorganisms responsible for these human diseases infect and replicate within the macrophage. Therefore, the opportunity that the pathogenesis of the human immunodeficiency virus (HIV) and Leishmania infections could be modulated within dually infected individual is optimized. The most prominent clinical feature of AIDS is the development of debilitating secondary infections induced by several opportunistic microorganisms, including protozoa. Michel Tremblay, Martin Olivier and Richard Bernier here focus on the recently reported information on the putative cofactor role that the intracellular pathogen of the genus Leishmania may play in the pathogenesis of HIV infection.

Journal Article↗
PubMed1993

A radical proposal for the pathogenesis of scleroderma.

Because the etiology and pathogenesis of scleroderma are largely speculative, effective therapy is not available for this debilitating condition and its variants. This article reviews current concepts in the etiology and pathogenesis of scleroderma and suggests a unifying hypothesis involving the generation of free radicals. The role of specific free radical scavengers should be tested both in vitro and in clinical trials of patients with scleroderma.

Capillaries↗
PubMed1993

Kaposi's sarcoma. Epidemiology, pathogenesis, histology, clinical spectrum, staging criteria and therapy.

The acquired immunodeficiency syndrome (AIDS) epidemic has had a profound impact on our understanding of Kaposi's sarcoma (KS). Epidemiologic features suggest a sexually transmitted cofactor in the pathogenesis of AIDS-associated KS (AIDS-KS), and several putative agents have received intense scrutiny. Cell culture studies suggest that the angiogenesis of AIDS-KS is stimulated by both human immunodeficiency virus proteins and growth factors that may be involved in the development and progression of AIDS-KS, thereby providing a rationale for new therapeutic interventions. The dermatologist is uniquely qualified to provide care for the majority of patients with KS, as many patients have cutaneous lesions amendable to local therapy (cryotherapy, intralesional therapy, simple excision). Patients requiring more aggressive local therapy (radiation therapy) or systemic therapies (interferon, chemotherapy) can be easily recognized. Standardized staging criteria provide assistance for determining appropriate local or systemic therapy and for evaluating and comparing responses to new therapies. This article reviews the epidemiology, pathogenesis, histologic features, clinical spectrum, staging criteria, and treatment of KS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

The role of cortical connectivity in Alzheimer's disease pathogenesis: a review and model system.

Here we review current evidence in support of the cortical disconnection/cortical connectivity model of Alzheimer disease (AD) pathogenesis, a model which predicts that one of the first events in AD is damage to the entorhinal cortex and/or subiculum resulting in the disconnection of the hippocampal formation and neocortex, and the subsequent progression of the disease in a stepwise fashion along cortico-cortical connections. Much of the evidence for this model has been obtained from studies involving the limbic system where investigators have demonstrated a precise correspondence between established patterns of connectivity and the degenerative changes associated with AD. In addition, some studies of the distribution of neuritic plaques (NP) and neuro-fibrillary tangles (NFT) in the neocortex and subcortical structures have yielded corroborative data. The validity of the cortical disconnection/connectivity model in the neocortex remains to be established or refuted. We propose that testing of this model can be accomplished with systematic studies of the laminar and regional distribution of NP and NFT in a series of sequentially interconnected cytoarchitectural regions that also form part of two functional hierarchies--the paralimbic and occipitotemporal visual systems. To adequately control for variation between brains affected by AD, it is imperative that such studies be conducted in a large but varied population of AD cases exhibiting differences in several variables, including clinical and/or neuropathological severity of the disease, temporal duration of the disease, and clinical/neuropsychological profile. We believe that further understanding of the relationship between characteristic AD pathology and intrinsic anatomico-functional circuits will contribute not only to our comprehension of AD pathogenesis but also to our general knowledge of the human brain.

Alzheimer Disease↗
PubMedDate not supplied

Inflammation and Alzheimer's disease pathogenesis.

Appreciation of the role that inflammatory mediators play in Alzheimer's disease (AD) pathogenesis continues to be hampered by two related misconceptions. The first is that to be pathogenically significant a neurodegenerative mechanism must be primary. The second is that inflammation merely occurs to clear the detritis of already existent pathology. The present review addresses these issues by showing that 1) inflammatory molecules and mechanisms are uniquely present or significantly elevated in the AD brain, 2) inflammation may be a necessary component of AD pathogenesis, 3) inflammation may be sufficient to cause AD neurodegeneration, and 4) retrospective and direct clinical trials suggest a therapeutic benefit of conventional antiinflammatory medications in slowing the progress or even delaying the onset of AD.

Alzheimer Disease↗
PubMed1989

Oxygen-derived free radicals in the pathogenesis of experimental shock.

Oxygen-derived free radicals are naturally produced in biological systems mostly in ischemia and hypoxia related conditions. Imbalance of physiological defenses against oxygen-derived free radicals causes cellular damage. In our laboratory the role of oxygen radicals in the pathogenesis of circulatory shock was studied by exploiting the scavenging action of the spin-trapping compound phenyl-butyl-nitrone (PBN) in experiments concerning: (1) survival after shock, (2) microcirculatory derangements in endotoxin shock, (3) fluidity modifications of cell membranes during shock, (4) exhalation of ethane as non-invasive marker of shock. In some experiments the steroid methylprednisolone was used. Results showed that administration of PBN and of the steroid (1) ensures survival after otherwise lethal shock as confirmed by decreased ethane exhalation, (2) prevents microcirculatory troubles, (3) maintains stability of cell membranes. These findings strongly support the role of oxygen-derived free radicals in the pathogenesis and pathophysiology of circulatory shock.

Animals↗
PubMed1992

Pathogenesis of intestinal cryptosporidiosis in conventional and gnotobiotic piglets.

The pathogenesis of intestinal cryptosporidiosis was studied in 52 conventionally reared and 20 gnotobiotically reared piglets by inoculation with different doses of Cryptosporidium parvum oocysts. The prepatent period of C. parvum in both groups of animals were variable, depending on the number of oocysts administered. The patent period of C. parvum in conventionally reared piglets was 8 or 9 days; in gnotobiotic piglets cryptosporidia were found in feces until Day post infection (DPI) 16, when the last piglet was necropsied. Cryptosporidiosis in conventionally reared piglets is a self-limited diarrheal disease associated with morphological changes within the intestine. The most severe lesion was seen in the posterior jejunum and ileum from DPI 3 to DPI 7, and consisted of villous atrophy, crypt hyperplasia and inflammatory infiltration in the lamina propria. In gnotobiotic piglets cryptosporidia induced severe enterocolitis which occurred at least until DPI 16. The characteristics of enteric lesions were similar to those found in conventionally reared piglets. Intestinal cryptosporidiosis in both groups of animals shifted in the course of infection in the caudal direction and terminated in the large intestine. Examination by scanning electron microscope showed that infected absorptive cells had thicker and longer microvilli than those on non-infected cells; neighboring non-infected cells were hypertrophic, bulbously protuberant with minute microvilli with no distinct intercellular borders. Numerous cryptosporidia in the heterotopic glandular epithelium in the submucosa of cecum and colon on DPI 9 and 10 were found. No differences in the location and degree of cryptosporidial infection between colostrum-fed and colostrum-deprived conventionally reared piglets were found. Sow's colostrum does not appear to protect piglets from C. parvum infection. The role of intestinal microflora in the pathogenesis of cryptosporidiosis in piglets is discussed.

Animals↗
PubMed1989

Understanding the pathogenesis of the restless legs syndrome at the level of the dopamine receptor. Are we about to identify the neurochemical deficiency causing schizophrenia?

According to a recent hypothesis, the restless legs syndrome is thought to be due to a caffeine-like substance produced by the human body (1). Some researchers have reported a case of familial restless legs that had high concentration of free dopamine in the cerebrospinal fluid (2). Other researchers have noticed the beneficial effect of opioids in the treatment of the restless legs syndrome (3). In this article, I am compiling information reconciling the findings of those researchers with the hypothesis that proposes that the restless legs syndrome is due to a caffeine-like substance produced by the human body. Also, I am addressing the pathogenesis of the restless legs syndrome at the level of the dopamine receptors in the central nervous system. Understanding this pathogenesis probably will help in identifying the neurochemical deficiency causing schizophrenia.

Brain↗
PubMed1992

Possible role of histamine in pathogenesis of autoimmune diseases: implications for immunotherapy with histamine-2 receptor antagonists.

The immunosuppressive chemical drugs cyclosporine A (CsA) and methotrexate (Mx) have recently been shown to be of benefit in several different diseases of autoimmune origin. Cellular immune responses may play a major role in autoimmunity as autoreactive T lymphocytes appear to recognize autoantigens and major histocompatibility complex (MHC) class II restriction molecules presented by non-immune, aberrant cells, subsequently leading to damage on healthy tissues. Psoriasis is suggested to be an autoimmune disease and in severe, uncontrollable psoriasis CsA and Mx are of value in reducing disease activity. Histamine is suggested to be involved in the pathogenesis of psoriasis and the histamine-2 receptor antagonist ranitidine has been shown to be of value to reduce severe psoriatic disease. The finding that CsA and Mx efficiently reduce histamine formation and release raises the possibility, that histamine is one of the molecules involved in pathogenesis of autoimmune diseases. T cell mediated regulation and suppression of autoreactive T cells seem to be ineffective in controlling the enhanced immune reaction in patients where the discrimination between self and non-self is changed. A consequence of this may be induction of interferon-gamma (IFN-g) production and release by cytotoxic T cells, subsequently leading to expression of MHC II molecules on non-immune tissues. As immunotherapy may be of value in some autoimmune diseases the use of histamine-2 receptor antagonists should be evaluated in patients where conventional therapy is ineffective to reduce disease activity.

Autoimmune Diseases↗
PubMed1992

The role of reactive oxygen species in the pathogenesis of multiple sclerosis.

Although reactive oxygen species are thought to mediate cellular damage in many disease states the role of reactive oxygen species in the pathogenesis of multiple sclerosis is unknown. Data from biochemical, histochemical and pharmacological studies have been evaluated to determine if the necessary conditions exist for the formation of reactive oxygen species during a demyelination episode of multiple sclerosis. This evaluation found that not only do the necessary conditions exist for the formation of reactive oxygen species but that these species may play a significant pathogenic role in this disease. A hypothesis describing a detailed role of reactive oxygen species in the pathogenesis of multiple sclerosis is put forth.

Free Radicals↗
PubMed1994

Short note: possible role of macrophage metabolic products including quinolinic acid and neopterin in the pathogenesis of inflammatory brain diseases.

It is hypothesized that macrophage metabolic products, including the possible neurotoxic NMDA receptor agonist quinolinic acid, and neopterin, may play a role in the pathogenesis of inflammatory brain diseases. It is suggested that the production of neopterin may have physiological roles, including to inhibit folate synthesis in intracellular pathogenic microorganisms and to inhibit viral nucleic acid synthesis. The possible role of excess neopterin production during chronic infection in the pathogenesis of inflammatory brain diseases is discussed.

Biopterins↗
PubMed1995

Pantothenic acid deficiency as the pathogenesis of acne vulgaris.

For years, the pathogenesis of acne vulgaris has been known to be strongly influenced by hormonal factors. However, the exact role of and the interrelationship among the various hormones in question have not been well elucidated. Here, I wish to suggest a radically different theory for its pathogenesis and relate its basic pathology to a deficiency in pantothenic acid, a vitamin hitherto not known to cause any deficiency syndrome in humans. Hence, the effect of hormonal factors in this disease entity becomes secondary to that of the availability of pantothenic acid. A complete cure of this condition is effected by a very liberal replacement therapy with the vitamin.

Acne Vulgaris↗
PubMed1990

Pathogenesis of mucosal disease and molecular aspects of bovine virus diarrhoea virus.

Studies carried out over three decades, on the pathogenesis and epidemiology of bovine virus diarrhoea virus (BVDV), have provided the basis for our understanding of the aetiology of mucosal disease. Experimental reproduction of the disease has demonstrated the mechanism of sequential infection and the role of the two virus biotypes. The need for "homogeneity" between the biotypes, causing mucosal disease, has demonstrated the precision of immunotolerance. The origin of the cytopathogenic biotype remains unclear but molecular studies may provide the solution. Recent findings have revealed the absence of an 80 kDa polypeptide in the non-cytopathogenic isolates. This protein is related to the 120 kDa polypeptide that is present in both biotypes. Genomic sequences for two isolates have been reported. An extensive homology to the protein ubiquitin has been identified only within the Osloss sequence in the region flanking coding sequences for the 80 kDa and 120 kDa proteins. Advances in the development of molecular gene probes and monoclonal antibodies will provide new tools for furthering our understanding of the pathogenesis, epidemiology and interrelationships of pestiviruses that infect pigs, cattle and sheep.

Animals↗
PubMed1991

Perspectives on the epizootiology of feline enteric coronavirus and the pathogenesis of feline infectious peritonitis.

This review presents some current thoughts regarding the epizootiology of the feline coronaviruses; feline infectious peritonitis virus (FIPV) and feline coronavirus (FECV) with primary emphasis on the pathogenesis of these viruses in nature. Although the mechanism(s) whereby FIPV causes disease are still incompletely understood, there have been significant contributions to the literature over the past decade which provide a framework upon which plausible explanations can be postulated. Two concepts are presented which attempt to clarify the pathogenesis of FIPV and at the same time may serve as an impetus for further research. The first involves the hypothesis, originally promulgated by Pedersen in 1981, that FIPV is derived from FECV during virus replication in the gastrointestinal tract. The second involves a unique mechanism of the mucosal immune system referred to as oral tolerance, which under normal conditions promotes the production of secretory immunity and suppresses the production of systemic immunity. In the case of FIPV infection, we propose that oral tolerance is important in the control of the virus at the gastrointestinal tract level. Once oral tolerance is disrupted, FIPV is capable of systemic spread resulting in immune-mediated vasculitis and death. Thus, it may be that clinical forms of FIP are due to a combination of two events, the first being the generation of FIPV from FECV, and the second being the capacity of FIPV to circumvent oral tolerance.

Animals↗