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Biomedical subjects

D A Cooper

Publications and source records attributed to D A Cooper.

At least 289 records · Page 16Linked to original sources

Epidemiology of acquired immunodeficiency syndrome in Australia .

Since 1982, when the first case of acquired immunodeficiency syndrome (AIDS) was diagnosed in Australia, a total of 373 cases has been reported to the NHMRC Special Unit in AIDS Epidemiology and Clinical Research to December 19, 1986. Analysis of the data shows that 70% of cases were diagnosed in NSW and of all cases 88% were found to be in homosexual or bisexual men, with the majority aged between 30 and 39 years. Opportunistic infections were found in nearly three-quarters of cases. A mathematical model which has been developed predicts that 1000 cases will have been diagnosed by mid-1988 and nearly that many again in 1990 alone. The absence of a treatment or vaccine, the likelihood that current Australian resources will be inadequate to deal with the predicted number of cases, and the urgent need to establish measures that are aimed at controlling the extent of the disease are emphasized.

Acquired Immunodeficiency Syndrome↗

Requests for psychiatric consultation concerning 22 patients with AIDS and ARC.

Psychiatric consultation was requested for 22 of 150 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) admitted to St Vincent's Hospital, Sydney. The mean age of the patients was 35 years and all were homosexual or bisexual men. Ten patients had an organic brain syndrome: six as a result of cerebral opportunistic infection, two due to metabolic or iatrogenic causes and two apparently due to the direct neurotropic effects of the human immunodeficiency virus (HIV). Hallucinations and delusions were documented in five patients, of whom two had symptoms that fulfilled the criteria for a diagnosis of functional psychosis. Four patients were diagnosed as having adjustment disorder-depressive mood and one patient may have had a major depressive illness. Marked denial of illness was seen in two patients and four had markedly slow mentation with only mild or no evidence of cognitive impairment. It is concluded that patients with AIDS may have a wide variety of neuropsychiatric manifestations.

AIDS-Related Complex↗

Antibody response to human immunodeficiency virus after primary infection.

The antibody response to human immunodeficiency virus (HIV) after primary infection was monitored in eight homosexual men with the acute mononucleosis-like illness associated with seroconversion. Multiple sera from each subject, taken at frequent intervals after onset of acute illness, were tested for antibody to HIV by IgM and IgG immunofluorescent assays (IFAs), four commercial enzyme-linked immunosorbent assays (ELISAs), and Western immunoblot (WB). Antibody to HIV was detected first by IgM IFA (mean +/- SD, 5 +/- 3 days), followed by IgG IFA (11 +/- 3 days); the IgM antibody titer peaked at 24 +/- 17 days and disappeared by 81 +/- 27 days, whereas the IgG antibody titer peaked at 133 +/- 63 days and has not disappeared in any subject. Antibody to HIV was first detected by ELISA from 31 +/- 14 to 58 +/- 32 days, depending on the assay kit used. Antibody to p24 and gp41 was first detected by WB at 24 +/- 10 days, followed by antibody to p55 (40 +/- 20 days), p68 (57 +/- 19 days), and p34 (71 +/- 22 days).

Acquired Immunodeficiency Syndrome↗

Factors influencing the level and interanimal variability of retinyl ester hydrolase activity in rat liver.

Retinyl ester hydrolase activity was studied in 25 7-wk-old rats that had been previously fed no vitamin A for 1 wk and then were fed 0, 5, 24, 60 or 240 micrograms retinol/d for 2 wk. This treatment produced rats with vitamin A reserves from depleted to normal (0.03 to 184 micrograms/g) and serum retinol concentrations of 4-67 micrograms/dl. Hydrolase activity in liver homogenates was optimal when assayed with 275 mM CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), 2 mg/ml Triton X-100 and 5 mM retinyl palmitate at pH 7.0. By use of these concentrations and conditions, retinyl ester hydrolase activity displayed relatively low interanimal variability (fivefold). Furthermore, activity was independent of serum or liver vitamin A concentrations. When CHAPS in the assay was replaced with equimolar sodium cholate, or with reduced concentrations of CHAPS and retinyl palmitate, retinyl ester hydrolase activity was more variable, i.e., 37- and 23-fold, respectively. Furthermore, in the latter case, hydrolase activity was threefold higher in rats with liver vitamin A reserves less than 10 micrograms/g. Thus, the type and concentration of bile salt used to assay retinyl ester hydrolase affect its interanimal variability. Furthermore, hydrolase activity measured in reduced concentrations of substrate and detergent is elevated in rats with low liver reserves of vitamin A.

Animals↗

Pulmonary manifestations of the acquired immunodeficiency syndrome.

Between 1983 and 1985, 71 patients with the acquired immunodeficiency syndrome (AIDS) were evaluated. Pulmonary manifestations were present in 42 patients (59%). Pneumocystis carinii pneumonia (PCP) was the most common pulmonary manifestation, present in 32 patients (45%). Other pulmonary findings were cytomegalovirus pneumonia (one patient), Candida pneumonia (one patient), cryptococcal pneumonia (one patient), bacterial pneumonia (three patients), nonspecific pneumonitis (three patients), Kaposi's sarcoma (one patient), and non-Hodgkin's lymphoma (one patient). The presenting features of PCP were reviewed and in seven patients the chest X-ray and blood gases were normal at the time of diagnosis of PCP. Bronchoscopy was a safe and useful technique for obtaining specimens for diagnosis promptly, and a combination of samples obtained by bronchial washings/brushings and transbronchial biopsy was found to give a higher diagnostic yield than any single sample. Drug side-effects were common during therapy, requiring change of therapy in 16 patients. At one month after diagnosis 16% of patients with PCP had died. PCP is a common pulmonary manifestation in patients with AIDS which is treatable and has an initially favourable outcome.

Acquired Immunodeficiency Syndrome↗

Properties of liver retinyl ester hydrolase in young pigs.

A new sensitive method for the assay of retinyl ester hydrolase in vitro was developed and applied to liver homogenates of 18 young pigs with depleted-to-adequate liver vitamin A reserves. Radioactive substrate was not required, because the formation of retinol could be adequately quantitated by reversed-phase high-performance liquid chromatography. Optimal hydrolase activity was observed with 500 microM retinyl palmitate, 100 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, and 2 mg/ml Triton X-100 at pH 8.0. The relative rates of hydrolysis of six different retinyl esters by liver homogenate were: retinyl linolenate (100%), myristate (99%), palmitate (47%), oleate (38%), linoleate (31%), and stearate (29%). The enzyme was found primarily in the membrane-containing fractions of liver (59 +/- 3%, S.E.) and kidney (76 +/- 3%), with considerably lower overall activity in kidney (57-375 nmol/h per g of tissue) than in liver (394-1040 nmol/h per g). Retinyl ester hydrolase activity in these pigs was independent of serum retinol values, which ranged from 3 to 24 micrograms/dl, and of liver vitamin A concentrations from 0 to 32 micrograms/g. Pig liver retinyl ester hydrolase differs from the rat liver enzyme in its substrate specificity, bile acid stimulation, and interanimal variability.

Animals↗

AIDS and prostitutes.

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Acquired Immunodeficiency Syndrome↗

Separation of retinyl esters by non-aqueous reversed-phase high-performance liquid chromatography.

Rapid separation and sensitive quantitation of vitamin A esters can be achieved by use of an acetonitrile-dichloromethane (80:20) mobile phase with a 5-microns C18 column (15 cm X 4.6 mm) and absorbance detection at 325 nm. Either a Waters Resolve or a Rainin Microsorb column was used satisfactorily. Retinyl palmitate is eluted at about 7 min (capacity factor, k' = 5.5) at a flow-rate of 1.5 ml/min; retinyl palmitate and retinyl oleate, which are usually difficult to separate, are well resolved (resolution 1.2). Sensitivity (at a signal-to-noise ratio of 10:1) is 8 pmol retinyl palmitate (equivalent to 2.5 ng retinol). Quantitation of total retinyl esters is identical to that determined by a gradient high-performance liquid chromatographic technique over the range 30-1000 ng retinyl esters. Retinyl ester peaks in rat liver extracts were identified by their characteristic light absorption spectra, susceptibility to saponification, and by co-chromatography with authentic standards. Nine vitamin A ester peaks were identified and quantitated in rat liver extracts. A 10-microns Whatman Partisil 10/25 ODS-2 column was used with the same mobile phase to obtain partial resolution of retinyl esters (resolution 1.05 between retinyl oleate and retinyl palmitate; k' = 11.0 for retinyl palmitate) and improved retention for retinol (k' = 2.5, compared with k' = 0.6 for retinol on the 5-microns column).

Animals↗

Clinical and immunologic sequelae of AIDS retrovirus infection.

The Sydney AIDS Project is a prospective immunoepidemiological study of 911 homosexual and bisexual men enrolled between February 1984 and January 1985. Clinical, immunological, and serological studies are performed on these subjects every six months. At enrollment, 39.9% of subjects were seropositive for antibodies to AIDS retrovirus (ARV). Of these 352 seropositive subjects, 28.1% were symptomless with normal immune profiles, 23.6% were symptomless with an immunodeficiency, 18.8% had a clinical illness but normal immune profile, and 29.6% had a clinical illness and immunodeficiency. Of the symptomless subjects, 27.8% were seropositive for antibodies to ARV. Clinically, seropositivity was significantly associated with enlargement of three or more non-inguinal lymph node groups, splenomegaly, and hepatomegaly. Immunologically, seropositivity was significantly associated with lower absolute numbers of lymphocytes and T4+ lymphocytes and a lower T4+ : T8+ ratio, compared with seronegative subjects. Seropositive subjects with a clinical illness had a significantly lower percentage of T4+ lymphocytes and lower T4+ : T8+ ratio than did those who were symptomless. However, the absolute number of T4+ cells was not significantly different between subjects with a clinical illness and those who were symptomless. Subjects whose sera were positive by immunofluorescence and enzyme-linked immunosorbent assay but were negative by radioimmune precipitation assay had a lower number and percentage of T4+ lymphocytes than subjects who were positive by all three tests. These results demonstrate a wide variety of clinical and immunological responses to ARV infection. Prospective study of these subjects will enable us to define further the natural history of ARV infection and factors associated with progression.

Acquired Immunodeficiency Syndrome↗

Seroimmunology of AIDS retrovirus infection. I. Use of immunofluorescence assay to confirm sera with ELISA reactivity.

One thousand sera shown to be reactive by one of two commercial enzyme linked immunosorbent assays (ELISA) for antibodies to the AIDS virus were referred to the NSW State Reference Laboratory for confirmatory assays. Each serum was retested by two commercial ELISA systems (Abbott and ENI), the ENI exclusionary H9 ELISA and an immunofluorescence assay. Three hundred and twenty four sera were reactive by all 3 tests whereas 244 demonstrated concordant non-reactivity. Three hundred and seventy seven sera were reactive by Abbott EIA only and could not be confirmed positive by the ENI ELISA incorporating exclusionary testing, immunofluorescence or Western immunoblot of representative sera. Sera obtained from teaching hospital laboratories were more likely to be positive and less likely to be negative by all 3 tests, and were also less likely to be Abbott EIA reactive only compared with sera obtained from the blood transfusion service. Of the remaining 55 sera, 52 demonstrated a negative immunofluorescent reaction or a pattern of equal fluorescence on AIDS virus infected and control cells. Representative sera were shown to be negative on Western immunoblot analysis. Of the 3 sera which demonstrated immunofluorescence reactivity, one was positive and one was negative by Western immunoblot, and one could not be determined. We conclude that a combination of two ELISAs, one with an exclusionary ELISA test and an immunofluorescence assay is a reliable and simple means of confirming reactive sera for AIDS virus antibodies.

Acquired Immunodeficiency Syndrome↗

Postnatal transmission of AIDS-associated retrovirus from mother to infant.

The third child of a previously healthy woman was delivered by caesarean section. Because of intraoperative blood loss, a blood transfusion was given after the delivery. The baby was breast-fed for 6 weeks. One unit of blood came from a male in whom the acquired immunodeficiency syndrome (AIDS) developed 13 months later. On recall, the mother proved to have lymphadenopathy, serum antibody to the AIDS virus, and a reduced T4/T8 ratio. The infant, who failed two thrive and had atopic eczema from 3 months, has likewise proved to have antibody to the AIDS virus. Since his mother was transfused after his birth, he is presumed to have been infected via breast milk or by way of some other form of close contact with his mother.

Acquired Immunodeficiency Syndrome↗

Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion.

In the course of a prospective immunoepidemiological study of homosexual men in Sydney, seroconversion to the AIDS-associated retrovirus (ARV) was observed in 12 subjects. Review of the clinical files defined an acute infectious-mononucleosis-like illness in 11 subjects. The illness was of sudden onset, lasted from 3 to 14 days, and was associated with fevers, sweats, malaise, lethargy, anorexia, nausea, myalgia, arthralgia, headaches, sore throat, diarrhoea, generalised lymphadenopathy, a macular erythematous truncal eruption, and thrombocytopenia. In 1 subject an incubation period of 6 days after presumed exposure to ARV was determined and in 3 subjects seroconversion took place 19, 32, and 56 days after onset. Comparison of T-cell subsets before and after the acute illness showed inversion of T4:T8 ratio in 8 subjects, due to increased numbers of circulating T8+ cells. These findings support the notion of an acute clinical, immunological, and serological response to infection with ARV which should be considered in the differential diagnosis of mononucleosis-like syndromes in groups at high risk for the development of AIDS.

Acquired Immunodeficiency Syndrome↗

A monoclonal antibody-based radioimmunoassay for the in vitro production of IgE by lymphocyte cultures.

Very sensitive radioimmunoassay systems have been described for the measurement of IgE produced in cultures of human peripheral blood mononuclear cells. However, differing results have been reported when cultures from non-atopic donors are stimulated with pokeweed mitogen, which may be due to cross-reactivity of anti-IgE antibodies with IgG. A monoclonal antibody specific for the Fc region of human IgE, and two polyclonal affinity-purified antibodies to IgE were tested for binding to 125I-labelled IgE myeloma proteins and polyclonal IgG in a sensitive double antibody precipitation assay. The monoclonal antibody and one of the polyclonal antibodies bound only IgE, whereas the other polyclonal antibody bound a significant proportion of labelled IgG. A solid phase radioimmunoassay was developed which combined the specificity of the monoclonal antibody with the sensitivity of the first polyclonal antibody as radioactive tracer. A second assay system was also tested using the cross-reacting antibody as tracer. Supernatants of pokeweed mitogen-stimulated peripheral blood mononuclear cell cultures from non-atopic donors were examined for IgE synthesis using both assays. The assay based on the monoclonal antibody did not detect IgE synthesis, whilst the second assay, based on the cross-reacting antibody indicated that spurious IgE had been produced in the same cultures. This study shows that protein-binding assays provide a simple means for checking the specificity of antibodies in solid phase radioimmunoassays, and confirms that pokeweed mitogen does not stimulate IgE production by cells from non-atopic donors when measured by a specific radioimmunoassay.

Antibodies, Monoclonal↗

Suppression of IgE synthesis in vitro by allogeneic T cells from atopic and non-atopic subjects.

The role of T cells in the regulation of IgE synthesis by human PBMC was studied. PBMC or separated and recombined populations of T and B cells from both normal and atopic donors were cultured for 10 days with and without cycloheximide. IgE and IgG synthesis were determined by specific RIA. IgE synthesis was detected in 0/30 non-atopic, 6/34 mildly atopic and 25/31 severely atopic subjects. Autologous T cells from 10/26 atopic donors, whose B cells synthesised IgE, significantly suppressed this IgE synthesis. The addition of allogeneic T cells from atopic or non-atopic subjects to atopic B cells resulted in greater suppression of IgE synthesis than the addition of autologous T cells. These data support the notion that atopic subjects have naturally occurring IgE isotype-specific suppressor T cells as well as suppressor T cells which can be activated during incubation with alloantigen.

Adult↗

1H nuclear magnetic resonance of heroin's D ring.

The 1H nuclear magnetic resonance (NMR) chemical shifts and coupling constants of heroin's D ring H-15 alpha, H-15 beta, and H-16 alpha, and H-16 beta are presented. These assignments were accessible through the introduction of a double bond (delta 15,16) in heroin. The resulting compound, delta 15,16 didehydroheroin, was subjected to deuterium exchange or stereoselective reduction or both. Reduced products d1-16 alpha heroin d2-15 alpha, 15 beta-heroin, and d3-15 alpha, 15 beta, 16 alpha-heroin are presented. Heroin with deuterated acetyls is also presented for 1H NMR spectral clarity in the D ring area.

Chemical Phenomena↗