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Biomedical subjects

A L Cunningham

Publications and source records attributed to A L Cunningham.

At least 109 records · Page 6Linked to original sources
PubMed1992

Recombinant interleukin 4 stimulates human immunodeficiency virus production by infected monocytes and macrophages.

Recombinant interleukin 4 (IL-4) stimulated extracellular (EC) and intracellular (IC) production of human immunodeficiency virus (HIV) from infected human blood-derived monocytes and macrophages when incubated with the cells after but not before virus inoculation. Significant stimulation was observed in 20 of 27 experiments with monocytes (inoculated with HIV immediately after adherence) and 10 of 13 experiments with macrophages (inoculated after 5 days adherence) using a total of 30 normal donors of monocytes and macrophages, and 11 recent isolates of monocytotropic HIV strains (after one passage in mononuclear cells). Marked increases in EC and IC HIV antigen were observed in some experiments, which were comparable with the maximal stimulatory effects of other cytokines such as IL-2. IL-4 also had similar effects on infectious HIV concentration as measured by reverse transcriptase and TCID50 assays. Antibody to IL-4 prevented the stimulatory effect of the cytokine. The proportion of monocytes and macrophages infected by HIV, as determined by in situ hybridization, also increased after incubation with IL-4 for 7 days. The most marked effects were observed with HIV-infected macrophages, for which the proportion of unstimulated infected cells was lower (35 to 45% increasing to 66 to 70% with IL-4 treatment). There was also an increased proportion of cells with high granule concentrations, suggesting that IL-4 increases the intracellular concentration of viral nucleic acids. This was supported by semi-quantitative hybridization experiments showing that total HIV RNA increased in IL-4-stimulated monocytes 48 to 96 h after HIV inoculation. A marked increase in aggregates was observed on day 7 in HIV-infected monocytes treated with IL-4, compared to that in HIV-infected cells alone or IL-4-treated uninfected monocytes. These findings suggest that IL-4 stimulates HIV replication in the early phases of infection and may also facilitate virus transmission by aggregate formation.

Base Sequence↗
PubMed1992

Concurrent zidovudine-induced myopathy and hepatoxicity in patients treated for human immunodeficiency virus (HIV) infection.

Myopathy and hepatic toxicity are important complications of zidovudine (3'-azido-3'-deoxythymidine therapy) in patients infected with the human immunodeficiency virus (HIV) both may also occur in HIV infection in the absence of zidovudine therapy. We report 2 cases of myopathy caused by zidovudine, occurring within 16 wks of initiation of therapy, and a case of concurrent hepatic and muscle toxicity. In one case, electron microscopy demonstrated characteristic enlarged mitochondria with paracrystalline inclusions. This technique can distinguish the myopathies caused by either HIV or zidovudine. Both zidovudine-induced myopathy and hepatoxicity require discontinuation of the drug if severe.

Adult↗
PubMed1992

The diagnosis of recent herpes simplex virus type 2 genital infections by the simplex-2 test.

The prevalence of complement-fixing (CF) antibody against the AG-4 early antigen of herpes simplex virus (HSV) type 2 (HSV-2) was determined in patients with culture confirmed HSV-2 genital herpes and control groups using a commercial HSV-2 early antigen (Simplex-2; Gene Link Australia Ltd). Eighty seven per cent of 39 sera collected between 14 and 28 days after confirmed primary and recurrent HSV-2 infection were positive. In acute sera collected between 2-10 days after onset the Simplex-2 test was negative in all 90 patients with presumed primary infection but positive in 53% of 230 sera from recurrent infection. A specificity of 90-94.5% was obtained by testing 36 patients with recent proven HSV-1 infection and 331 control group patients. The Simplex-2 test may be useful in some cases of culture-negative, clinically suspected genital HSV-2 lesions only when sera are collected between 14-28 days after primary and recurrent infection. Its lack of specificity makes it unsuitable for the routine diagnosis of recent HSV-2 infection in the general population.

Adult↗
PubMed1992

HIV infection of monocytes inhibits the T-lymphocyte proliferative response to recall antigens, via production of eicosanoids.

Human monocytes infected in vitro with human immunodeficiency virus (HIV) soon after adherence to plastic substrate demonstrated a significantly decreased ability to restimulate autologous immune T-lymphocyte proliferation after exposure to soluble (tetanus toxoid) and particulate [herpes simplex virus (HSV)] antigen. Incubation with the cyclo-oxygenase inhibitor, indomethacin (2-5 microM), prevented inhibition of antigen-stimulated lymphocyte proliferation. The inhibitory activity was identified in ultrafiltrates containing the low molecular weight fraction (less than 3000 MW) of supernatants from HIV-infected monocyte cultures. This activity was significantly and markedly reduced in similar ultrafiltrates prepared from indomethacin-treated cultures. Increased concentrations of prostaglandin E2 (PGE2) were detected in ultrafiltrates from HIV-infected monocyte cultures compared with uninfected cultures and cultures preincubated with indomethacin. Ultrafiltrates were inhibitory when added during the presentation of antigen to T lymphocytes but not when removed from monocyte cultures prior to the addition of lymphocytes. In addition, ultrafiltrates inhibited antigen-stimulated lymphocyte proliferation and PHA-induced lymphocyte proliferation to the same extent. These data indicate that cyclo-oxygenase products of arachidonic acid, including PGE2, are produced in excess by HIV-infected monocytes and that PGE2 and perhaps other cyclo-oxygenase products are implicated in the inhibition of antigen-stimulated lymphocyte proliferation via a direct effect on T lymphocytes.

Cell Division↗
PubMed1991

The validity of parental report of vaccination as a measure of a child's measles immunisation status.

OBJECTIVE: To determine the validity of parental report of vaccination as a measure of a child's measles immunisation status. DESIGN: Cross-sectional survey. SETTING: Four 24-hour medical centres in western Sydney. PATIENTS: Parents of children aged 12-36 months were approached in the clinic waiting room. Of the 160 parents approached, 137 agreed to be interviewed and a successful venepuncture to yield a 2 mL blood sample was achieved with 128 children. MAIN OUTCOME MEASURES: Measles IgG antibody, determined by means of an indirect ELISA, was compared with parental report of measles vaccination status by McNemar's chi 2 test. RESULTS: Parental report significantly over-estimates the immunisation status of children. Eighty-four per cent of the parents in the sample stated that their child had been vaccinated, but only 74% were immune (95% confidence interval, 65%-81%). A positive predictive value of 84% meant that only 84% of children who were reported to have been vaccinated were immune to measles. Further, of all those who were not immune to measles, only one half would have been identified by asking the parents. Failed seroconversion may have accounted for up to 70% of cases of non-immunity in children reported to have been vaccinated. CONCLUSIONS: Parental report is limited as a measure of a child's measles immunisation status.

Child, Preschool↗
PubMed1991

Influenza A(H1N1): a widening spectrum?

OBJECTIVE: To study the incidence of H1N1 influenza from 1977 to 1988 in unvaccinated volunteers and the effects of continuing minor antigenic change (antigenic drift) in the virus. DESIGN: Prospective study by a group of general practitioners, backed up by virological findings. PARTICIPANTS: Mainly patients of the general practitioner group, also some doctors and members of staff. There were 287 participants during 1977-1981, and 207 at the end of 1988. INTERVENTION: Any participant deemed to be "at risk" was encouraged to be vaccinated and to withdraw from the study. BACKGROUND: In 1957, H1N1 subtype influenza had been displaced by H2N2 (Asian) subtype. In 1968, H2N2 was displaced by H3N2 (Hong Kong) subtype. During 1977, H1N1 influenza unexpectedly reappeared in Asia, and spread widely. The resurgent strain, designated A/USSR/90/77(H1N1), caused world pandemics, attacking (almost exclusively) persons who had been born since the 1950-1951 northern winter and causing negligible mortality. It did not displace the current H3N2 strain, and strains of both subtypes have continued to emerge independently. HYPOTHESIS: Antigens of A/USSR resembled closely those of the 1950-1951 H1N1 strain, which apparently was rendered antigenically inert between 1951 and 1976 (possibly frozen) and was reactivated during 1977. Antigenic drift was then resumed. MAIN OUTCOME MEASURE: The A/USSR/90/77 strain and its close successor, A/Brazil/11/78, attacked mainly the young, whose previous exposure to H1N1 antigens had been minimal or zero. Mortality during the A/USSR pandemics was negligible because death from influenza in people aged less than 30 years is rare. Would continuing antigenic drift ultimately widen the H1N1 spectrum of attack? RESULT: During the epidemic of 1988, A/Taiwan/1/86(H1N1) attacked a wider range of age groups than had A/USSR or A/Brazil. CONCLUSION: Assuming that H1N1 viruses continue to undergo further antigenic drift, an ever widening age spectrum of H1N1 attack may be expected.

Antibodies, Viral↗
PubMed1991

Contralateral hemiplegia following thoracic herpes zoster.

OBJECTIVE: To suggest interim therapeutic guidelines for stroke following truncal herpes zoster on the basis of the first reported Australian case, in a patient who showed good clinical response related temporally to antiviral therapy. CLINICAL FEATURES: A 70-year-old patient with no known underlying immune disorder presented with left-sided hemiplegia one week after right-sided truncal herpes zoster. In all probability the neurological deficit was due to large artery vasculopathy with thrombosis. INTERVENTION AND OUTCOME: Clinical improvement (not to pre-morbid levels) was noted soon after commencement of antiviral therapy with acyclovir. CONCLUSION: Stroke following herpes zoster may be a treatable condition. In view of the previously described occurrence of viral antigen within the walls of intracerebral vessels, the occasional progression of the syndrome over months, the generally low toxicity of acyclovir and the clinical response of the few patients treated with antiviral agents to date, early antiviral therapy in patients presenting with delayed contralateral hemiplegia associated with herpes zoster is recommended as prudent.

Acyclovir↗
PubMed1990

Does hepatitis C virus play a role in "non-viral" chronic liver disease?

It has recently been suggested that the hepatitis C virus may play a significant role in chronic liver diseases, such as autoimmune chronic active hepatitis, which are usually attributed to non-viral causes. We tested for antibodies to hepatitis C virus (anti-HCV) in sera from 140 patients with well characterised "non-viral" chronic liver diseases as well as sera from 51 patients thought to have chronic non-A, non-B (NANB) hepatitis (acting as positive controls) and 25 patients with non-hepatic autoimmune disorders. As expected, 45 of 51 patients (88%) diagnosed as having chronic NANB hepatitis were anti-HCV seropositive. Among 26 patients with cryptogenic cirrhosis, 8 were anti-HCV seropositive; in 5 patients (22%) there was no apparent risk factor for parenteral transmission. In the remaining 114 patients with chronic liver disease, 10 patients (9%) were seropositive for anti-HCV. However, 5 of these patients had a significant risk factor for parenteral transmission of hepatitis C virus, leaving only 5 of 106 (4.7%) with unexplained positive anti-HCV test results. Among patients with high titres of circulating autoantibodies but no liver disease, no positive results occurred. It is concluded that hepatitis C virus infection may account for some cases of cryptogenic cirrhosis. Although anti-HCV occurs more commonly in patients with other "non-viral" chronic liver diseases than has been reported in the community (0.5%-1.2%), the low prevalence of the antibodies indicates that hepatitis C virus infection is unlikely to be important in the aetiology or pathogenesis of autoimmune chronic active hepatitis and other poorly understood chronic liver diseases.

Autoimmune Diseases↗
PubMed1990

Hepatitis C virus in intravenous drug users.

Sera from 172 intravenous drug users were tested for the presence of antibodies to hepatitis C virus (anti-HCV). The results were analysed in relation to aspects of the history of drug use and evidence of liver disease. The presence of anti-HCV was strongly associated with duration of intravenous drug use. Two-thirds of patients were anti-HCV seropositive within two years of commencing regular intravenous drug use, and there was 100% seropositivity among people injecting drugs for more than eight years. Seropositivity for hepatitis C virus closely paralleled exposure to hepatitis B virus, which was also endemic in this population. In contrast, only one patient tested positive for antibodies to the human immunodeficiency virus. The presence of anti-HCV correlated poorly with biochemical markers of hepatitis. About half the patients with anti-HCV had normal serum levels of alanine aminotransferase, whereas an abnormal liver biochemistry was frequently observed in anti-HCV seronegative subjects. Previous studies of non-A, non-B hepatitis that have used abnormal liver biochemistry as a marker have underestimated the prevalence of chronic hepatitis among intravenous drug users; the use of a specific screening test reveals that infection with hepatitis C virus is very common in this population.

Adult↗
PubMed1990

A polyanion binding site on the CD4 molecule. Proximity to the HIV-gp120 binding region.

Recent studies have demonstrated that sulfated polyanions (SP) are potent inhibitors of HIV infection in vitro, appearing to inhibit virus attachment. To understand the mode of action of these compounds a large panel of SP were examined for their ability to inhibit HIV infection, block anti-CD4 mAb binding and, when immobilized, bind soluble CD4 and virion gp120. Based on anti-CD4 mAb binding-inhibition studies a SP binding site was identified on the CD4 molecule. Dextran sulfate (DXS)-500 kDa, polyvinylsulfate (PVS), and polyanethole sulfonate were particularly potent SP inhibitors, blocking the binding of 11 of the 12 anti-CD4 mAb tested. These 11 mAb are known to interact with the two amino-terminal Ig-like domains of CD4. In fact, DXS-500 kDa exhibited an hierarchy of inhibition of anti-CD4 mAb which suggests that SP bind to a conformational site incorporating the first two Ig-like domains of CD4. This SP binding site is clearly distinct but closely associated with the gp120 binding region of CD4. In terms of anti-HIV activity there was no evidence that SP act at the virion level as rgp120 did not bind to immobilized SP and preincubation of virions with SP did not affect infectivity. In contrast, many of the SP tested showed some affinity for CD4 based on anti-CD4 mAb blocking studies and binding of soluble CD4 to immobilized SP. The most active in this regard were DXS-500 kDa and PVS, whose anti-HIV activity could be entirely due to disruption of the CD4-gp120 interaction. However, with SP such as heparin, fucoidan, the carrageenans, and polyanethole sulfonate, although CD4 blocking may contribute to anti-HIV activity, some other anti-viral mechanism is also operating. Finally, pentosan sulfate, a SP with anti-HIV activity comparable to DXS-500 kDa and PVS, showed little or no reactivity with CD4 and must inhibit HIV infection by a totally CD4-independent mechanism.

Antibodies, Monoclonal↗
PubMed1990

Serological diagnosis of infection with human herpesvirus type 6.

OBJECTIVE: To identify clinical consequences of acute human herpesvirus type 6 infection by hypothesising that the virus will induce similar clinical syndromes to cytomegalovirus. DESIGN: Examination of consecutive serum samples from patients with illnesses compatible with acute cytomegalovirus infection or exanthem subitum by indirect immunofluorescence for the presence of antibodies to human herpesvirus type 6. An IgG absorption step was included to avoid false positive and negative results for IgM. The criterion standard for diagnosis of human herpesvirus type 6 infection was the presence of IgM human herpesvirus type 6 antibody (titre greater than 20) and a rising titre of IgG human herpesvirus type 6 antibody without serological evidence of alternative infection. SETTING: Routine viral diagnostic and reference laboratory in the largest teaching hospital in Sydney. PATIENTS: 341 Consecutive serum samples were analysed from patients with hepatitis (147 samples); infectious mononucleosis-like illness (106); screens for toxoplasma, other viruses, rubella, cytomegalovirus, and herpesvirus (38); fever in an immunocompromised patient (eight); unusual neurological (nine) or haematological syndromes (14); splenomegaly (six); and rash in a child (13). RESULTS: Three cases of acute human herpesvirus type 6 infection were identified: in one patient aged 65 with a previous diagnosis of acute non-A non-B hepatitis, one aged 25 with a glandular fever-like illness, and one aged 6 with a glandular fever-like illness. All three illnesses resolved completely. 15 Further serum samples were positive for human herpesvirus type 6 antibody but were also diagnostic for acute infection with other viruses (cytomegalovirus (nine), Epstein-Barr virus (three), and HIV (one] or had a titre of IgM human herpesvirus type 6 antibody less than 20 (two). CONCLUSIONS: Acute human herpesvirus type 6 infection in immunocompetent patients may result in a mononucleosis-like illness or an acute but self limiting hepatitis.

Adult↗
PubMed1990

Dual antibody rises to cytomegalovirus and human herpesvirus type 6: frequency of occurrence in CMV infections and evidence for genuine reactivity to both viruses.

The frequency of high (greater than 256) IgG anti-human herpesvirus type 6 (HHV-6) titers in sera known to be positive for IgM anti-cytomegalovirus (CMV) or IgM anti-Epstein Barr virus (EBV) was significantly greater than in sera from healthy controls or from a group of ill patients who were CMV and EBV IgM-negative (15/25 and 17/25 vs. 1/25 and 2/25, respectively, P less than .001). There was serologic evidence of simultaneous HHV-6 infection or reactivation (a rise in IgG anti-HHV-6 titer or the presence of IgM anti-HHV-6) in sera from 14 of 17 primary CMV infections. In 5 of the 10 patients with concurrent rises in IgG titers to both viruses, the rise in IgG anti-HHV-6 preceded that of IgG anti-CMV. Complete removal of IgG anti-CMV reactivity from 5 sera from patients who had a primary CMV infection with a rise in IgG anti-HHV-6 titer had no effect on the IgG anti-HHV-6 titer of those sera, demonstrating that the rise in HHV-6 IgG titer was not a consequence of anti-CMV antibodies cross-reacting in the HHV-6 IgG assay.

Adult↗