摘要:

ObjectiveOur long-term objective is to determine the consequences of HIV-1 expression in the mammalian fetus using the mouse as a model system. This study describes HIV gene expression in micro-injected and electroporated embryos during the pre-implantation period.DesignProcedures were adopted to create a non-infectious HIV system to assay HIV long terminal repeat (LTR) activation in a non-human mammal.MethodsTwo constructs (RSV promoter-HIVtatgene; HIV LTR-lacZ gene) were co-micro-injected (10 μg/ml each) into pronuclei of fertilized eggs or one nucleus of the two-cell stage and expression assessed after 2–5 days. The techniques of electroporation and micro-injection were compared for their ability to deliver the constructs expressed subsequently.ResultsWe found that HIV-1 expression, as monitored by β-galactosidase production, can occur as early as the eight-cell to blastocyst stage. The intensity of HIV expression varied from high to low; the proportion of the embryo expressing HIV varied from half to only two cells. The material was too limited to allow a determination of integration.ConclusionsThe expression rate of the HIV-LTR was low, averaging slightly over 1%. The data demonstrate that the HIV-LTR can be activated in early mammalian development, even before implantation. This information is valuable to those studying HIV-transgenic mice, to those interested in factors governing HIV expression, and to those concerned about pathologies accompanying developmental expression of HIV.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTat, an essential regulatory protein of HIV, acts as a growth factor for Kaposi's sarcoma (KS)-derived cells in culture. We tested the hypothesis that HIV-negative epidemic KS patients who are also at high risk for HIV disease might have been infected with a defective HIV-1 virus that retained the ability to express Tat.MethodsWe evaluated the presence of Tat sequences in KS tissue and peripheral blood mononuclear cells (PBMC) of HIV-1-negative individuals with epidemic KS who had risk factors for HIV infection by polymerase chain reaction using specific primers for the Tat region of HIV-1.ResultsNo evidence for the presence of Tat-1 sequences or for Tat-expressing defective HIV-1 virus was found.ConclusionThese results suggest that HIV-1 Tat does not play a role in the initiation of KS in HIV-1-negative individuals. Tat might play an indirect role in epidemic KS in HIV-infected patients.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectivePrimarily to determine whether an intestinal microsporidian recently identified in AIDS patients disseminates from the bowel to infect other organs.DesignDisseminated microsporidiosis has been reported in immunocompromised humans, but never due toEnterocytozoon bieneusi, the most common species in AIDS patients and one that evidently infects only enterocytes. In animals, dissemination follows ingestion ofEncephalitozoon cuniculispores, apparently via macrophages, and pathology occurs in, for example, kidneys and brain. A second, un-namedEncephalitozoon-like intestinal microsporidia has been identified in five AIDS patients with chronic diarrhea; because it infects lamina propria macrophages, it was logical to investigate its dissemination.MethodsLight and transmission electron microscopy were used to study urine sediment from four out of five patients with biopsy-documented small intestinal infection due to the second intestinal microsporidian. The gall bladder from one patient and autopsy specimens from anE. bieneusi-infected patient were similarly studied.ResultsSystemic dissemination was documented by detecting abundant spores, both free and within renal tubular and transitional cells, in the urine of two patients. Many of the lamina propria macrophages in these two patients' intestinal biopsies contained microsporidia, while those of the two negative patients either contained onlyMycobacterium aviumcomplex or only occasional parasites. The gall bladder was co-infected with this microspordian and with cytomegalovirus. At autopsy, the patient with documented enteritis due toE. bieneusi2 years before death had disseminated microsporidiosis, not ofE. bieneusi, but apparently of the second intestinal species. The microsporidian had caused severe tubulointerstitial nephritis. Parasites were also observed in non-parenchymal cells of the liver and bronchial epithelium.ConclusionA newly describedEncephalitozoon-like intestinal microsporidian, which causes chronic diarrhea in AIDS patients, can disseminate and cause renal pathology.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveHuman T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are closely related human retroviruses. HTLV-I has been implicated in a chronic progressive myelopathy, known as tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). We sought to determine whether autoantibodies to brain antigens were present in the cerebrospinal fluid (CSF) of a patient with chronic progressive spastic myelopathy with evidence of both HIV-1 infection and HTLV-I/II seropositivity.DesignA 54-year-old bisexual man with clinical features of HAM/TSP of over 20 years' duration was followed.MethodsWe applied discriminatory DNA amplification (polymerase chain reaction) to distinguish HTLV-I from HTLV-II and to verify co-infection with HIV-1. The patient's CSF was used to screen a human brain cDNA expression library to identify antibodies directed against brain antigens. Autoreactive bacteriophage clones were isolated and sequenced.ResultsThe patient was found to be co-infected with both HIV-1 and HTLV-II, but not with HTLV-I. HTLV-II proviral levels in the peripheral blood remained relatively constant, despite therapy with zidovudine. Prominent oligoclonal banding of immunoglobulins was present in the patient's CSF. A single repeatedly reactive cDNA clone was identified, by screening with CSF antibody, sequenced, and found to be the human homologue of the rat insulinoma gene,rig.ConclusionsHTLV-II infection may predispose to development of a HAM/TSP-like illness. Autoimmune mechanisms, such as autoantibody formation, may play a role in pathogenesis.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo evaluate the correlation between clinical and autopsy findings in 250 AIDS patients.MethodsClinical and autopsy diagnoses of AIDS-defining diseases in 250 AIDS patients who died in Milan between May 1984 and February 1991 were compared.ResultsPneumocystis carinii (PCP) and oesophageal candidiasis were the most frequent clinical diagnoses, while cytomegalovirus (CMV) infection was observed in almost half of the autopsies. Forty-seven per cent of the diseases found at autopsy had not been diagnosed during life; CMV infection, mycoses, HIV-specific brain lesions, cerebral lymphomas and progressive multifocal leukoencephalopathy (PML) had a higher rate of non-diagnosis in life. CMV visceral infection accounted for the majority of the diseases not recognized in life. In contrast, clinically diagnosed PCP, oesophageal candidiasis and, to a lesser degree, brain toxoplasmosis were often not found at autopsy, possibly indicating a significant rate of recovery and prevention of relapse. Finally, bacterial pneumonia and sepsis, although not AIDS indicator diseases, were observed in approximately one-third of the autopsies.ConclusionConsiderable differences in the frequency and type of the AIDS-defining diseases diagnosed during life and atpost mortemwere found.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo describe the clinical manifestations of tuberculous meningitis in HIV-positive patients with acellular cerebrospinal fluid (CSF).DesignRetrospective analysis of case reports.MethodsFour HIV-positive patients with acellular CSF and tuberculous meningitis are reported.ResultsClinical presentation did not indicate meningeal infection in three of the four cases, and CSF tests were unusual in all cases. Two patients were diagnosed only after death.ConclusionsAcellular CSF may obstruct the diagnosis of tuberculous meningitis in AIDS patients.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo compare the haematological toxicity and efficacy of oral dapsone and nebulized pentamidine asPneumocystis cariniipneumonia (PCP) prophylaxis in HIV-infected patients receiving zidovudine.DesignRandomized, prospective.SettingInfectious diseases hospital with participants drawn from both inpatient and outpatient departments.PatientsThose eligible were starting treatment with zidovudine, needed PCP prophylaxis (CD4+ count < 200 x 106/l or < 20% total lymphocyte count or previous episode of PCP), and had a normal glucose-6-phosphate dehydrogenase screen. Of the 98 patients enrolled, 96 returned for follow-up.InterventionsFifty patients received dapsone (100 mg orally twice weekly) and 46 pentamidine (400 mg nebulized monthly). Follow-up was for a median of 18 months.Main outcome measuresThe development of PCP, transfusion requirements, monthly complete blood cell counts, serious adverse reactions and death were recorded.ResultsNine (18%) dapsone and eight (17%) pentamidine recipients developed PCP. There was no significant difference in number of patients transfused (12 dapsone and nine pentamidine recipients) or transfusion-free survival. At exit from the study, mean haemoglobin (11.7 versus 12.4 g/dl), white blood cell (3.9 versus 3.7 x 109/l) and platelet (195 versus 184 x 109/l) counts did not differ for the dapsone and pentamidine arms, respectively. There was no significant difference in the occurrence of serious adverse reactions (six in the dapsone and eight in the pentamidine arm).ConclusionsDapsone can be recommended in preference to pentamidine as PCP prophylaxis on the basis of equivalent efficacy, absence of excessive haematological toxicity, low cost and ease of administration.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma.DesignA retrospective case notes review.SettingThe departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK.PatientsAll patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy.InterventionsTreatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5–5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated.Outcome measuresResponse, toxicity and survival.ResultsOverall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 106(20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9 months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P= 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon.ConclusionsTreatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectiveTo determine the prevalence of HIV-1 and syphilis antibodies in a population of pregnant women in Nairobi, Kenya, between 1989 and 1991.MethodsAs part of an ongoing prospective study on the effect of HIV-1 infection and sexually transmitted diseases, 4883 pregnant women were screened for HIV-1 and syphilis antibodies in one health-centre in Nairobi.ResultsHIV-1 seroprevalence increased from 6.5 to 13.0% (PP= 0.002), while there was no change in gonococcal infection rates. The most rapid increase in HIV-1 prevalence was observed in women aged less than 25 years. There was no evidence of demographic fluctuations in the population during this time, or of changes in sexual behaviour, except that fewer women enrolled in 1991 reported having more than one sex partner, compared with women enrolled in 1989 (39.1 versus 20.0%;P= 0.0001). HIV-1-seropositive women were more likely to be seroreactive for syphilis than HIV-1-seronegative mothers (7.7 versus 3.2%; odds ratio = 2.5; 95% confidence interval, 1.7–3.8;PConclusionThese data confirm an association between HIV-1 and syphilis infection, and indicate that both are spreading rapidly among women in Nairobi outside high-risk groups. Increased efforts to control both infections are urgently required.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ObjectivesTo study the epidemiological trends, clinical patterns, evolution and prognosis of HIV infection in women.DesignCohort study of 1816 HIV-infected patients.ResultsUp to 1 January 1991, 483 (26.6%) of the patients reported to the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine surveillance system were women. The male-to-female ratio has decreased progressively (3.4:1 in 1985; 2.7:1 in 1990) over time. Fifty per cent of HIV-infected women are or have been intravenous drug users (IVDU). The proportion of heterosexually acquired HIV infection increased from 11.6 to 34.6% over the last 5 years; 46.9% of the women infected through heterosexual intercourse reported sexual contacts with male IVDU. Excluding Kaposi's sarcoma, no significant difference was observed between men and women in the overall distribution of AIDS-defining events. The observed trend of a slower progression to AIDS in women, compared with men, disappeared when controlling for prognostic variables. However, female sex significantly enhanced survival after AIDS diagnosis in multivariate analysis (relative risk, 2.7; 95% confidence interval, 1.1–6.2).ConclusionEarly diagnosis of HIV infection in female patients and prevention of HIV infection among women is now a priority for public health interventions, both in industrialized and in developing countries.

ISSN:0269-9370    

出版商:OVID    

年代:1992

数据来源: OVID