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Biomedical subjects

J Gaub

Publications and source records attributed to J Gaub.

At least 37 records · Page 2Linked to original sources

Markers of human immunodeficiency virus infection in high-risk individuals seronegative by first generation enzyme-linked immunosorbent assay.

A total of 228 stored serum samples from 140 high risk individuals was examined for serological markers of human immunodeficiency virus (HIV) infection by second generation enzyme-linked immunosorbent assay, immunoblot, and HIV antigen assay. All the samples were negative in first generation enzyme-linked immunoassay (ELISA). Seventy-four of the serum samples had been obtained from 40 sexual partners of HIV antibody positive individuals. Two of the samples were reactive for p24 in immunoblot, but no other markers of HIV infection were found. From 80 sexually active male homosexuals, 117 serum samples were obtained. They were all negative by the tests employed. Further, 37 serum samples from 20 seroconverters were studied. Four patients had antigenaemia 6-12 months before seroconversion was detected by first generation ELISA. Our data do not support the notion that serological signs of HIV infection are common in high risk individuals seronegative by first generation ELISA. However, HIV infection do occur in subjects negative by first generation ELISA, which emphasises the need for more sensitive screening assays and/or the use of antigen detection as part of screening in high risk individuals. The advent of second generation ELISAs has not in a substantial way reduced this demand.

Biomarkers↗

The value of lymph node histology in human immunodeficiency virus related persistent generalized lymphadenopathy.

Histological changes in lymph nodes were evaluated in a prospective study of 124 homosexual men who presented with generalized lymphadenopathy. The histological changes were classified according to a classification system with three stages. HIV antibodies were present in 88% of the patients. The finding of one of the three histopathological stages was highly indicative--although not absolutely pathognomonic--for HIV infection. The subsequent course of HIV infection after biopsy was significantly correlated to the histopathological changes, but it was not possible to evaluate if the biopsy added new information to that already available. Among the group of HIV infected, immediate clinical consequences of lymph node biopsy were not observed (95% confidence limits 0-3.3%). In a retrospective investigation of 123 consecutive AIDS patients, it was found that lymph node histopathology had been able to identify secondary infections and neoplasms among 10%. It is concluded that lymph node biopsy is indicated in the HIV infected patients with unexplained generalized symptoms or with atypical enlargement of the lymph nodes. The prognostic significance of lymph node histology compared to other prognostic parameters of HIV infection, remains to be determined.

AIDS-Related Complex↗

Clinical and electrophysiological studies of human immunodeficiency virus-seropositive men without AIDS.

Motor weakness and ataxia of lower limbs and abnormalities of somatosensory evoked potentials occur in many patients with the acquired immunodeficiency syndrome (AIDS). We studied 15 human immunodeficiency virus-seropositive subjects without AIDS and found no clinical neurological abnormalities. The mean latency of the brainstem auditory evoked potential (peak V) was increased, suggesting a central defect. Despite normal peripheral nerve conduction along the tibial nerve, the mean latency of the spinal cord potential of the twelfth thoracic vertebra was increased compared with normal, possibly indicating an incipient conduction defect at or near the spinal root ganglion or lumbar spinal cord.

Acquired Immunodeficiency Syndrome↗

Antibody to HIV in patients with acute hepatitis B in the period 1975-1984.

In order to elucidate the time when HIV was introduced into a population of patients with acute hepatitis B, serum samples collected in the period 1975-1984 from 331 patients with hepatitis B were analysed for the presence of antibody to HIV (anti-HIV). Anti-HIV was not detected in any of the serum samples from 97 females. 5/234 serum samples from males (2%) were repeatedly positive. Anti-HIV was first demonstrated in 1978, 3 years before the first patients with AIDS were recognized in Denmark. None of the 4 Danish patients with anti-HIV developed AIDS during a follow-up period of 1-7 years. However, at the time of follow-up in 1985 3 had decreased cell mediated immunity. The hepatitis B infection had an uncomplicated course in 4/5 patients with anti-HIV. One patient had a protracted delta hepatitis and was a HBsAg carrier before as well as after the acute hepatitis. Thus, the HIV infection did not cause any complicated course in this study.

Acquired Immunodeficiency Syndrome↗

The immunological and clinical outcome of HIV infection: 31 months of follow-up in a cohort of homosexual men.

T-cell subsets, antibodies (Ab) against human immunodeficiency virus (HIV) and clinical status were evaluated during a 31 (24-35) month follow-up study of homosexual men. The study group included 50 homosexual men, with many sexual partners, who by 1982-83 were without symptoms and had a prevalence of HIV Ab of 38%. Among the men who were seropositive on the initial investigation a significant decrease occurred in the absolute number of CD4+ lymphocytes (p less than 0.01). 88% of these men experienced a decrease, and by follow-up 59% had CD4+ lymphocytes below the normal range. Also the men who seroconverted during the study had a significant decrease in CD4+ lymphocytes, while no changes were observed in the seronegative group. None of the subgroups had significant changes in CD8+ lymphocyte number. AIDS or AIDS related complex developed in 33% of the men seropositive at inclusion. None of these clinical syndromes developed in the seroconverting or the seronegative group. The men who eventually developed clinical symptoms did not differ significantly from the healthy HIV Ab positive persons, with respect to lifestyle parameters, presence of lymphadenopathy and isolation of cytomegalovirus. However, they had significantly lower CD4+ cells and CD4/CD8 ratio (p less than 0.01) at inclusion. It is concluded that in the majority of persons infected with HIV, phenotypic T-cell alterations will occur with a latency of years, but it remains to be seen if the alterations necessarily will result in clinical manifestations. Further, T-cell subset determination among healthy HIV Ab positive persons will provide prognostic information.

AIDS-Related Complex↗

The effect of foscarnet (phosphonoformate) on human immunodeficiency virus isolation, T-cell subsets and lymphocyte function in AIDS patients.

Foscarnet was administered by continuous intravenous infusion in 15 patients with the acquired immunodeficiency syndrome (AIDS) in an open, uncontrolled study. Mean steady state serum concentrations of foscarnet was 261 mumol/l. Treatment was given for 6-21 days, median 14 days, being interrupted prematurely due to renal function impairment in seven patients, and due to other reasons in three patients. Foscarnet therapy was accompanied by improvement of some, probably cytomegalovirus (CMV) related, symptoms but did not otherwise affect the clinical condition of the patients. The occurrence of positive CMV cultures decreased significantly during therapy. Human immunodeficiency virus (HIV) detection by culture was positive in 70-80% of cultures and was unaffected by foscarnet treatment. Eight patients had detectable, free HIV antigen in serum before therapy, and in five of these HIV antigen disappeared during therapy, but reappeared 4-23 weeks after therapy. No patient lost HIV antigen, except during foscarnet therapy. No patient became HIV antigen positive during foscarnet therapy. Immunological parameters did not change during or after foscarnet therapy. Renal function impairment was seen in 9 patients (95% confidence limits, 32-84%), apparently due to reversible tubular damage. At follow-up, serum creatine was normal in all surviving patients. Concomitant medication may have contributed to the renal side-effects. Severe renal function impairment, i.e. serum creatinine above 0.25 mumol/l, was only seen in patients who at the start of foscarnet therapy were chronically affected by their disease. Thus, foscarnet reduces HIV antigen production in AIDS patients. Renal function impairment limits foscarnet use in AIDS patients, but in individuals with less severe manifestations of HIV infection, this side effect may be less frequent.

Acquired Immunodeficiency Syndrome↗

Immunological studies in acquired immunodeficiency syndrome: effect of TCGF and indomethacine on the in vitro lymphocyte response.

We studied the effects of exogenous T cell growth factor (TCGF) (= interleukin-2) and indomethacine on the lymphocyte transformation response in vitro to allogeneic cells, mitogens, and antigens in AIDS patients, those with AIDS-related complex (ARC), and in healthy controls. While low amounts of TCGF reduced the response of peripheral blood mononuclear cells (PBMC) to allogeneic cells in both healthy controls and AIDS patients, large amounts of TCGF augmented the response in both groups, although the response of the patients' cells were still subnormal. By depleting the PBMC for either CD4-positive or CD8-positive cells, the effect of TCGF on suboptimally mitogen-stimulated PBMC from controls was shown to be due to an increased response in both the CD4-positive and the CD8-positive cells. In contrast, with patient cells, TCGF only increased the response of the CD4-positive cells, while that of the CD8-positive cells was largely unchanged. Thus, the lack of normalization of the mitogen response of patient cells upon addition of TCGF may be largely due to unresponsiveness of CD8-positive cells to TCGF. This observation further supports the idea that CD8-positive cells are abnormal. To investigate the role of the inhibitor of TCGF production, PGE2, in AIDS, indomethacine was added to cultures of mitogen-stimulated PBMC from controls and patients. No differences were found between the three groups: the responses to PHA were slightly increased and those to Con A were unchanged.

AIDS-Related Complex↗

Immunological studies in homosexual men with and without antibodies to human T-cell lymphotropic virus type III.

T-cell subsets were studied in 559 homosexual or bisexual men attending outpatient clinics for AIDS-screening in Copenhagen during the period July 1984 to April 1985. Of the 559 individuals studied, HTLV III antibodies were found in 161 (29%). Persistent generalised lymphadenopathy (PGL) defined as the presence of lymph nodes greater than 1 cm in diameter at two or more extrainguinal sites for at least three months were found in 91 patients, 72 (79%) of whom had HTLV III antibodies. The seropositive group had lower counts of T-helper/inducer cells (p less than 0.001), higher counts of T-suppressor/cytotoxic cells (p less than 0.001), lower T-helper/T-suppressor ratios (p less than 0.001) and higher levels of IgG (p less than 0.001), compared to the seronegative group. Compared to seropositive men without PGL, seropositive men with PGL had higher levels of IgA and IgG (p less than 0.05) and lower T-helper/T-suppressor ratios (p less than 0.05), the latter primarily caused by an elevated number of T-suppressor/cytotoxic cells. It is concluded that HTLV III infection is accompanied by a number of immunological abnormalities, including depletion of T-helper/inducer cells and B-lymphocyte activation. A subgroup of patients is characterised by having PGL and increased serum concentrations of IgA and IgG. The clinical and prognostic importance of PGL and B-cell activation is unknown. To study this more closely, prospective studies are needed.

Acquired Immunodeficiency Syndrome↗

The LAV/HTLV-III screening in Copenhagen. Epidemiological results from four clinics over the period 1 July 1984 to 1 April 1985.

Over the nine month period from 1st July 1984 to 1st April 1985, 737 persons attended the four AIDS-screening clinics in Copenhagen. The attendance was unconditional, and the examination free of charge. All were examined clinically and serologically for LAV/HTLV-III infection. Ninety-seven percent were males; 490 (68%) and 198 (28%) described themselves as homosexual or bisexual respectively. This study presents epidemiological data on that group. As in other studies, we found a relationship between anti-LAV/HTLV-III and male homosexual promiscuity, i.e. trends towards higher antibody prevalences, the higher the number of different sexual partners annually and the number of previous sexually transmissible diseases. The occurrence of 18 percent seropositivity in a group with no previous sexually transmissible disease indicate a dissemination of the infection to a subpopulation of Danish homosexuals with a nonpromiscuous lifestyle. Night sweats and lymph node enlargement as subjective complaints along with lymphadenopathy and anal pathology on objective examination were significantly (p less than 0.025) related to positive LAV/HTLV-III serology. Fifty-one percent (337 persons) had neither subjective symptoms nor objective signs, and 50 of these (28% of this asymptomatic group) were seropositive. At this stage of the AIDS epidemic, it is important for surveillance purposes that anti-LAV/HTLV-III testing is made available to all members of risk groups. The establishment of the screening clinics with unconditional attendance and ensured anonymity seems to be an important step in this effort.

Acquired Immunodeficiency Syndrome↗

Changes in quantitative measures of hepatic function after 90% hepatectomy in rats.

Quantitative measures of liver functions were investigated in rats up to 360 h after 90% hepatectomy and related to total hepatic DNA. Galactose elimination capacity (cytosolic phosphorylation of carbohydrate), p-nitro-anisole demethylase activity (endoplasmic drug hydroxylation) and prothrombin index (protein synthesis at rough endoplasmic membranes) were initially reduced as much as the liver weight, but recovered differently. During hepatic regeneration prothrombin index and galactose elimination were back to control values after an interval of 360 h, while p-nitro-anisole demethylase activity was about 0.4 times control value after that interval. The correlation between total hepatic DNA and liver weight, and between total hepatic protein and liver weight was 0.92 in both cases, indicating their close relationship during hepatic regeneration. Compared to earlier studies on 70% hepatectomy the recovery of metabolic functions after 90% hepatectomy is delayed, as compared to regeneration of total hepatic DNA. The compensatory hyperfunction observed after 70% hepatectomy was not found after 90% hepatectomy, indicating a lost ability to hyperfunction when hepatic function is reduced close to the minimal residual function. This is suggested to be important for the sudden onset of hepatic insufficiency.

Animals↗

Quantification of nuclear non-histone proteins by Feulgen--Naphthol Yellow S cytophotometry.

Owing to the accumulation of nuclear non-histone protein (NHP) (a) in cells entering the cell cycle from the quiescent state and (b) in continuously cycling cells during G1 phase, a simultaneous determination of DNA and nuclear NHP is of high potential utility in cell kinetic studies. This paper provides guidelines for a Feulgen--Naphthol Yellow S staining technique for this purpose. It discusses details of the preparation and quantification procedures, and reviews the evidence for a quantitative relationship between nuclear Naphthol Yellow S binding and nuclear NHP.

Animals↗