Biomedical subjects
A G Dalgleish
Publications and source records attributed to A G Dalgleish.
HTLV-III serology distinguishes atypical and endemic Kaposi's sarcoma in Africa.
Serum samples from African patients with Kaposi's sarcoma and acquired-immuno-deficiency-syndrome-related (AIDS-related) disorders and from normal subjects in Uganda and Zambia were tested for antibodies to the human T-lymphotropic retroviruses (HTLV) types I, II, and III. Nearly 90% of patients with AIDS-related disorders or with atypical, aggressive Kaposi's sarcoma were seropositive for HTLV-III in both countries, whereas only 17% of patients with classic endemic Kaposi's sarcoma were seropositive. Among the controls 20% were seropositive for HTLV-III in Uganda but only 2% in Zambia. None of the subjects tested had antibodies to HTLV-I or HTLV-II. These results are further evidence of the emergence of a clinically atypical form of Kaposi's sarcoma in Africans, which resembles that seen in American patients with AIDS, and which is associated with HTLV-III infection. The low frequency of antibodies to HTLV-III in the normal Zambian population together with the first appearance of HTLV-III-associated diseases during the past 2 years suggests that this virus is new to Zambia, although it may have been present in Uganda for longer.
Central nervous system echovirus infection in Bruton's X-linked hypogammaglobulinemia.
A patient with Bruton's X-linked hypogammaglobulinemia, who developed the typical syndrome associated with systemic echovirus 3 infection whilst on routine intramuscular gammaglobulin replacement therapy, is described. Following regular infusions of specific antibody-containing plasma from his spouse, he has shown sustained clinical improvement over a period of two years, and is, therefore, one of the very rare cases with this syndrome to survive for more than a few months.
Human retroviruses.
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Sexual transmission of AIDS.
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Lacticacidosis of thiamine deficiency.
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Refractory hypercalcaemia. Parathyroid adenoma or multiple myeloma?
A case of multiple myeloma in which hypercalcaemia persisted despite an otherwise good response to conventional treatment is described. The hypercalcaemia was eventually found to be due to a parathyroid adenoma. Despite the frequent association of hypercalcaemia and malignant disease, and the relative frequency of primary hyperparathyroidism as a cause of hypercalcaemia, there are very few reports of multiple myeloma and parathyroid adenoma occurring together. This case emphasizes the need to be aware that there may be more than one cause of hypercalcaemia in a patient with multiple myeloma.
Bleomycin pulmonary toxicity: its relationship to renal dysfunction.
Two hundred seventy-five patients who had received bleomycin were examined for evidence of pulmonary toxicity. Twenty-six patients were diagnosed as having bleomycin pulmonary toxicity and, of these, 20 (77%) were documented as having renal dysfunction without other features recognized to be associated with the development of pulmonary toxicity. In this study renal dysfunction was a most important factor in the development of bleomycin pulmonary toxicity. As bleomycin is often administered with nephrotoxic drugs, it is suggested that renal function should be checked prior to each administration of bleomycin. It is proposed that appropriate dose modifications could significantly reduce the morbidity and mortality associated with bleomycin administration.
Hepatocellular carcinoma associated with hepatitis B in a renal graft recipient.
Hepatitis B virus (HBV) infection, which is common in renal dialysis and transplant units, has been shown to be associated with the development of hepatocellular carcinoma. We report the case of a patient in whom HBV infection was detected after renal transplantation, and who developed a hepatocellular carcinoma 12 years later. The availability of effective preventive and surveillance techniques offers a potential means of reducing the development of hepatocellular carcinoma in these patients.
Acquired immune deficiency syndrome. A prodromal form.
Only one case of the acquired immune deficiency syndrome (AIDS) has been conclusively documented in Australia despite a large at-risk population and the endemic nature of the syndrome in the United States. In this article, the cases of two homosexual men who had the clinical and laboratory features of a prodromal form of AIDS are presented. Such cases should serve to alert the medical profession and public health authorities to the possible existence of the syndrome in Australia.
The role of hepatitis B virus in the etiology of hepatocellular carcinoma in Australia.
Fifty-three patients with Hepatocellular Carcinoma (HCC) from three Sydney teaching hospitals were examined for possible evidence of Hepatitis B virus (HBV) infection. Hepatitis Surface Antigen (HBsAg) was positive in 38% of those in whom it was sought, a higher incidence than previously reported in an Australian series. A further 13 patients had antibody to Hepatitis B core (Anti-HBc), but negative HBsAg, confirming past exposure to HBV. Where serum was available evidence of HBV infection was obtained in 62% of patients. It is argued that the incidence of HBV infection may be shown to be higher still with the advent of new technology as applied to HBV assays and tissue stains. The need to be aware of the growing evidence of a strong association between Hepatitis B virus and the development of HCC is stressed and the clinical implications are discussed.
Hypertrophic pulmonary osteoarthropathy: response to chemotherapy without documented tumour response.
A case is reported of severe hypertrophic pulmonary osteoarthropathy associated with bronchogenic carcinoma which successfully responded to chemotherapy, despite the fact there was no objective response in the primary lesion. Previous treatment and responses are briefly reviewed. The method or methods by which chemotherapy may alleviate HPOA in the absence of response to the primary lesion are discussed. The marked discrepancy between progression of the HPOA and progression of the clubbing is noted. The fact that HPOA is potentially treatable despite the prognosis of the primary is emphasised.
Concurrent hydatid disease and cryptococcosis in a 16-year-old girl.
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Quantitation of HIV-1 activity in tissue culture supernatants: effects of culture condition on syncytial assays and virus production.
We have compared the infectivity titres, reverse transcriptase levels and antigen titres in the supernatants from persistently infected cell lines that produce a variety of HIV-1 isolates. We found a poor correlation between the different assays, and a variability in viral activity dependent on culture medium.
Characteristics and growth patterns of human peritoneal mesothelial cells: comparison between advanced epithelial ovarian cancer and non-ovarian cancer sources.
OBJECTIVE: To compare the characteristics and growth patterns of human peritoneal mesothelial cells (HPMCs) from advanced epithelial ovarian cancer (EOC) patients with those from non-EOC patients. METHODS: Peritoneal and omental biopsies were obtained from treatment-naïve patients. Formalin-fixed biopsies and cytologic touch preparations were studied immunochemically. HPMCs were isolated from tissue biopsies or malignant ascites and cultured with or without growth factors. Cell growth was determined by the MTT assay. Cultured HPMCs were further characterised by flow cytometry analysis (FACS). RESULTS: Peritoneal biopsies showed a continuous flat mesothelial cell layer in non-EOC patients, whereas in advanced EOC, the mesothelium was a discontinuous layer of rounded cells. In all peritoneal biopsies, the mesothelium expressed cytokeratin 8/18, vimentin, and the mesothelioma cell antigen but not E-cadherin. In touch preparations, expression of the putative fibroblast antigen ranged from negative to weakly positive. HPMC from non-EOC cases grew slowly in vitro except when exposed to L-cysteine (L-cys 30 micrograms/mL) during the initial 24 hours of culture. Conversely, cells from EOC sources grew more rapidly, especially when exposed to both epidermal growth factor (EGF 10 ng/mL) and hydrocortisone (HC 400 ng/mL). HPMC coexpressed cytokeratin 8/18 and vimentin in vitro, but the expression of the putative fibroblast antigen increased during primary culture, whereas that of the mesothelioma cell antigen decreased in successive passages. Furthermore, in FACS, cultured HPMC did not express CD14, CD16, or CD34. CONCLUSION: In peritoneal biopsies from non-EOC and EOC patients, HPMCs showed different morphology but similar immunostaining characteristics, whereas cultured cells from different sources were similar in both morphology and phenotype. L-cysteine enhanced the growth of non-EOC but not of EOC-derived HPMCs, which had a maximal response to EGF and HC. The growth advantage of HPMCs from EOC in vitro suggests these cells are in a primed or activated state.
The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus.
Acquired immune deficiency syndrome (AIDS) is characterized by opportunistic infections and by 'opportunistic neoplasms' (for example, Kaposi's sarcoma). Persistent generalized lymphadenopathy (PGL) is epidemiologically associated with AIDS, especially in male homosexuals. A subset of T lymphocytes positive for the CD4 antigen (also termed T4 antigen), is depleted in AIDS and PGL patients. A retrovirus found in T-cell cultures from these patients is strongly implicated in the aetiology of AIDS because of the high frequency of isolation and the prevalence of specific antibodies in the patients. Here we have detected cell-surface receptors for the AIDS retrovirus (human T-cell leukaemia virus-III (HTLV-III) and lymphadenopathy-associated virus-1 (LAV-1) isolates) by testing the susceptibility of cells to infection with pseudotypes of vesicular stomatitis virus bearing retroviral envelope antigens, and by the formation of multinucleated syncytia on mixing virus-producing cells with receptor-bearing cells. Receptors were present only on cells expressing CD4 antigen; among 155 monoclonal antibodies tested, each of the 14 anti-CD4 antibodies inhibited formation of syncytia and blocked pseudotypes. Productive infection of CD4+ cells with HTLV-III or LAV-1 markedly reduced cell-surface expression of CD4. In contrast, receptors for HTLV-I and HTLV-II were not restricted to CD4+ cells, were not blocked by anti-CD4 antibodies; cells productively infected with HTLV-I and HTLV-II expressed surface CD4. Hence, we conclude that the CD4 antigen is an essential and specific component of the receptor for the causative agent of AIDS.
Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients.
Human T-lymphotropic virus type III (LAV, HTLV-III) is aetiologically linked to acquired immune deficiency syndrome (AIDS) and persistent general lymphadenopathy (PGL). Specific radioimmunoassays (RIA), enzyme-linked assays, immunofluorescence assays (IFA) and immunoblotting techniques are being used widely to detect serum antibodies to HTLV-III in infected patients and in those at risk of infection. However, these assays do not functionally identify those antibodies that neutralize the infectivity of the virus. We have used three methods of titrating serum neutralizing factors: inhibition of syncytium induction, neutralization of envelope pseudotypes of vesicular stomatitis virus (VSV) and reduction of infectivity of HTLV-III for a cell line permissive to virus replication. We report here that sera from subjects in various disease categories possess only low-level neutralizing activity, even when antibodies to viral membrane antigens are present in high titre. Envelope pseudotypes prepared from four HTLV-III isolates made in three different countries are equally sensitive to neutralization by positive sera, including sera from patients yielding two of the virus isolates.
Variable and conserved neutralization antigens of human immunodeficiency virus.
Human immunodeficiency virus type 1 (HIV-1, HTLV-III/LAV), the retrovirus responsible for acquired immune deficiency syndrome (AIDS), shows a high degree of genetic polymorphism, particularly in the env gene. We have examined sera from rabbits and guinea pigs immunized with gp130, a recombinant env glycoprotein, and sera from HIV-1-infected subjects, to test their capacity to neutralize a panel of genetically divergent HIV-1 isolates. The sera raised against recombinant antigen specifically neutralized the virus strain from which the env gene was cloned (HTLV-IIIB), but not an independent isolate (HTLV-IIIRF). One rabbit serum tested on seven isolates cross-neutralized two at lower titres. In contrast, human sera from Britain and Uganda, chosen for ability to neutralize HTLV-IIIRF, cross-neutralized six other HIV-1 isolates. When serum and isolate were derived from the same subject, the serum was in some cases effective at slightly lower concentrations (higher titres). Human complement did not affect neutralization titres. These findings indicate that genetically diverse HIV-1 isolates carry both variable and widely conserved antigenic epitopes for neutralizing antibodies. The identification of shared epitopes may help the development of protective vaccines.