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Biomedical subjects

A J Pinching

Publications and source records attributed to A J Pinching.

At least 91 records · Page 5Linked to original sources

Defective signal transduction--a common pathway for cellular dysfunction in HIV infection?

Qualitative defects in immune responsiveness after human immunodeficiency virus (HIV) infection have been well characterized and may play a key role in the development of HIV disease. However, no clear picture of the underlying mechanism of the functional deficiencies has yet emerged. In this article, Anthony Pinching and Keith Nye suggest that HIV or HIV proteins can sabotage transmembrane signalling and that this is of primary importance to the alterations in immune responsiveness.

CD4-Positive T-Lymphocytes↗

Visceral leishmaniasis in HIV infection and AIDS: clinical features and response to therapy.

The development of visceral leishmaniasis with atypical features in an AIDS patient, and the recent flurry of reports of visceral leishmaniasis in HIV-infected individuals prompted the review of its manifestations in the 47 reported cases. Splenomegaly, which is almost always a feature of visceral leishmaniasis in the immunocompetent host, was absent in eight. Antibodies to Leishmania donovani, which are present in approximately 95 per cent of immunocompetent patients with visceral leishmaniasis, were absent in 29 of 45 (66 per cent) of HIV-infected patients tested. Nine HIV-positive patients with visceral leishmaniasis did not exhibit a primary clinical response to therapy with antimonials and of those who did show a response, relapse occurred in 13, at a mean 4.5 months after stopping therapy. Seventeen patients are known to have died often in association with respiratory disease; Leishmania was seen in one bronchial lavage specimen and in lung tissue in one post-mortem performed. In order to improve the prognosis of visceral leishmaniasis in HIV-infected patients diagnosis will have to be made earlier, taking account of the atypical features, and treatment will need to be improved, both initially and perhaps also by the use of long-term maintenance therapy.

Acquired Immunodeficiency Syndrome↗

HIV infection of H9 lymphoblastoid cells chronically activates the inositol polyphosphate pathway.

Infection with HIV causes a reduction in the numbers and function of CD4+ lymphocytes and functional abnormalities of other cells. We have studied the effect of HIV infection on signal transduction in the H9 lymphoblastoid CD4+ cell line. Resting HIV-infected H9 cells show evidence of chronic activation with raised levels of InsP3 and InsP4, the active metabolites of the inositol polyphosphate pathway, and a consequently raised intracellular free calcium concentration. Stimulation of HIV-infected H9 cells with phytohemagglutinin (PHA) leads to a fall in the previously raised levels of InsP3 but a further rise in InsP4, whilst an attenuated intracellular calcium rise is seen with both PHA and anti-CD3 antibody. The observed effects of HIV infection on signal transduction provide a mechanism to explain the functional defects in CD4+ lymphocytes and, possibly, other cell types.

CD4-Positive T-Lymphocytes↗

Alveolar macrophages in AIDS patients: increased spontaneous tumour necrosis factor-alpha production in Pneumocystis carinii pneumonia.

In order to assess the role of alveolar macrophages and their products in the control of Pneumocystis carinii pneumonia (PCP) and other infections in AIDS, bronchoalveolar lavage cells and peripheral blood mononuclear cells from HIV-positive AIDS/ARC patients (with and without PCP) and HIV-negative patients were counted and cultured in vitro; spontaneous and LPS-induced tumour necrosis factor-alpha (TNF-alpha) production was measured. Markedly increased spontaneous TNF-alpha production by alveolar macrophages and, to a lesser extent, peripheral blood monocytes was found in HIV-positive patients with active PCP but not in patients without the infection. Higher TNF production was associated with lower counts of Pneumocystis in the bronchoalveolar lavage fluid. These results suggest that TNF-alpha production by macrophages may play an important role in the control of Pn. carinii infection in AIDS.

Bronchoalveolar Lavage Fluid↗

Epstein-Barr virus associated oesophageal ulcers in AIDS.

Epstein-Barr virus (EBV) associated ulceration has not previously been included in the differential diagnosis of oesophageal ulcers in AIDS. We report five cases of oesophageal ulceration in homosexual men with advanced human immunodeficiency virus infection in whom this was considered to be the most likely cause. DNA in situ hybridisation studies showed EBV in biopsy material from three of four patients with oesophageal ulcers and in none of three controls. Of other viruses studied, only human papillomavirus was present, and this was found in both patients and control subjects. These findings support the hypothesis that EBV is an aetiological factor in some cases of AIDS-associated oesophageal ulceration.

Acquired Immunodeficiency Syndrome↗

Campylobacter pylori in the upper gastrointestinal tract of patients with HIV-1 infection.

Fifty one patients with human immuno-deficiency virus (HIV-1) infection who had been consecutively endoscoped for upper gastrointestinal symptoms were biopsied (stomach or duodenum, or both) and compared with 59 age and sex matched controls for the presence of Campylobacter pylori. In 28 (47%) of the control group but in only seven (14%) of the HIV seropositive patients were C pylori seen on histological examination (p less than 0.001, odds ratio 5.6, 95% confidence interval 2.2-14.5). Sixteen patients who were HIV antibody positive had other index diseases for the diagnosis of AIDS in the biopsy material and, when these were excluded, comparison with the control group still showed a significant difference; p less than 0.01, odds ratio 3.6, 95%, confidence interval 1.4-9.6. In this series, therefore, C pylori were far less common in HIV antibody positive patients than in controls. Among the HIV positive patients, a higher proportion of C pylori negative cases had AIDS but this trend was not significant. The findings of this study indicate that whatever abnormalities of cell mediated mucosal immunoregulation are caused by HIV infection, they do not seem to be important in the response to infection by C pylori.

Acquired Immunodeficiency Syndrome↗

An update on HIV-testing at a London sexually transmitted diseases clinic: long-term impact of the AIDS media campaigns.

Trends in the number of tests for HIV-1 antibody at a London sexually transmitted diseases clinic showed substantial changes between September 1985 and June 1988. From an average of 100 tests per month between September 1985 and August 1986, the average increased to 365 tests per month for September 1986 to August 1987. This levelled off at 243 tests per month between September 1987 and June 1988. The average number of positive tests per month between September 1985 and June 1988 remained constant, though the number of seropositive tests in females increased. Male and female populations displayed similar temporal patterns. The greatest increase was seen in the tests generated by heterosexual males and females with no other risk factors. This group generated 42% of the 8012 tests performed during the study period. The Clinic's catchment area predominantly included London and surrounding areas and temporal patterns were similar for residents from each of the Thames Regions. The temporal patterns observed coincided with periods of increased media attention on HIV infection/AIDS and involved campaigns by the popular press, television, Department of Health Education Authority. The increase in tests during the time of maximum media exposure, the subsequent plateau at a level substantially higher compared with the period preceding the media campaigns and the large increase in heterosexual males and females tested, all suggest that the campaigns have contributed to increasing awareness of HIV infection/AIDS as a major contemporary public health problem.

AIDS Serodiagnosis↗

Mycobacterial infection in patients infected with the human immunodeficiency virus.

Of 207 homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS), 24 with the AIDS related complex, and 39 with asymptomatic HIV infection, 32 patients were found to have mycobacterial infection. Mycobacterium tuberculosis was found in 13 patients with AIDS and in two with the AIDS related complex. M avium-intracellulare was found in 15 patients with AIDS and was disseminated in 12. One patient was infected with M kansasii and one with M ulcerans. Invasive procedures were frequently required to obtain positive bacteriological results. Subclinical carriage of M avium-intracellulare and other mycobacteria thought to be nonpathogenic was common in patients seronegative for the human immunodeficiency virus and at all stages of human immunodeficiency virus infection. All but one isolate of M tuberculosis were fully sensitive to standard antimycobacterial antibiotics. Response to treatment was usually rapid. M avium-intracellulare isolates were all resistant to first line agents in vitro, and antibiotics such as ansamycin and amikacin were required to obtain a clinical response.

AIDS-Related Complex↗

HIV-related enteropathy in Zambia: a clinical, microbiological, and histological study.

To investigate the etiology of chronic diarrhea associated with human immunodeficiency virus (HIV) infection in Lusaka, we studied 63 HIV-positive patients and 36 seronegative controls clinically and endoscopically. Stools were studied for morphology and for opportunist infections. Fifty-five percent of patients seropositive for HIV who presented with a history of chronic diarrhea had parasites; the most common were Cryptosporidium (32%), Isospora belli (16%), and Strongyloides stercoralis (6%). As indicated by villous blunting and inflammation on duodenal histology, those with diarrhea and parasites showed the most severe damage. We could not implicate mycobacteria or bacterial overgrowth as causes for the enteropathy associated with HIV.

Chronic Disease↗

Dendritic cell infection, depletion and dysfunction in HIV-infected individuals.

Immune responses in resting T cells are initiated by the presentation of antigen by bone marrow-derived dendritic cells (DC). Normal DC are susceptible to infection with human immunodeficiency virus (HIV) in vitro (Patterson & Knight, 1987) and this blocks their capacity to stimulate T-cell responses to other antigens (Macatonia, Patterson & Knight, 1989a). To study the relationship between HIV and DC in patients and its relevance to the pathogenesis of disease, DC have been isolated from the blood of individuals in the different clinical categories, counted, examined for the presence of virus genome and their antigen-presenting capacity measured. Infection, depletion and impaired function of DC occur in early HIV infection. HIV seropositive patients who were asymptomatic and those with symptoms of disease had significantly reduced numbers of DC, but patients with persistent generalized lymphadenopathy had normal numbers. Between 3% and 21% of DC, identified as large low-density cells not bearing monocyte, lymphocyte or natural killer cell markers, were infected with HIV, as indicated by in situ hybridization. Less than 0.12% of the lymphocytes or monocytes were infected. The DC from infected individuals were poor at enhancing responses to the mitogen concanavalin A (Con A). They also caused low levels of stimulation in allogeneic lymphocytes in mixed leucocyte cultures. By contrast, T cells from asymptomatic patients gave normal T-cell responses to uninfected allogeneic DC, although those from acquired immunodeficiency syndrome (AIDS) patients did show reduced responsiveness. Defects in DC thus precede both the appearance of symptoms and changes in T cells and may be instrumental in the development of AIDS. Furthermore, since DC numbers and function differ at different stages of disease, monitoring these may contribute to clinical assessment and lead to new therapeutic approaches.

Cell Count↗

Clinical immunology.

Clinical immunology is a medical specialty with a pathogenetic rather than organ-based focus. The main clinical areas covered are allergic disease, autoimmune disease, lymphoproliferative disease, transplantation and immunodeficiency. The role and training of the physician immunologist and the organ-based specialist with an interest are outlined.

Allergy and Immunology↗

Fat absorption and exocrine pancreatic function in human immunodeficiency virus infection.

Exocrine pancreatic function and fat absorption were determined using a 'tubeless' test in 25 human immunodeficiency virus (HIV) antibody positive subjects (23 males, two females), CDC criteria groups II (four), III (one), and IV (20). In 12 fat absorption was poor but in only three of these were the results indicative of pancreatic insufficiency and in all three this was mild. In nine of the cases the results were compatible with small intestinal malabsorption. Mild, but not severe, exocrine pancreatic insufficiency may occur in acquired immune deficiency syndrome; however fat malabsorption is more commonly associated with a small intestinal cause.

4-Aminobenzoic Acid↗