Pediatric morbidity in a hospital of Kampala, Uganda from 1985 to 1990.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
O Müller
Publications and source records attributed to O Müller.
Knowledge, attitudes and behaviour among HIV-positive and HIV-negative clients of a confidential HIV counselling and testing centre in Thailand.
OBJECTIVE: To describe the clients, operation and impact of an Asian public HIV counselling and testing centre. DESIGN AND SETTING: Analysis of samples from clients attending the Thai Red Cross Anonymous Clinic (TRC-AC) in Bangkok, Thailand in 1993. SUBJECTS: HIV-positive and HIV-negative consecutive clients (250 of each). MAIN OUTCOME MEASURES: HIV seroprevalence rates, knowledge, attitudes and behaviour. RESULTS: Overall HIV-1 prevalence was 16%; 13% in men and 24% in women. Reasons for requesting an HIV test were high-risk behaviour (21%), feeling unwell (20%), checking a previous HIV test result (18%), a planned marriage or new relationship (10%), and planning a baby (5%). Heterosexual risk behaviour was reported by 85% of clients, while in each case only 1% reported male homosexual or intravenous drug use risk behaviour. Factors associated with HIV infection on univariate analysis included a history of sexually transmitted disease, not using condoms, a low level of education and salary, and being female. Knowledge about HIV transmission risks and AIDS prevention measures was good, and most clients expressed a caring attitude towards people with HIV and AIDS. A former negative HIV test result was associated with higher levels of condom use, and most clients expressed the intention to reduce their HIV risk behaviour in response to a positive or negative HIV test result (more so if positive). CONCLUSIONS: Our study demonstrates the demand for and the feasibility of confidential HIV counseling and testing services in Thailand and illustrates the value of these services in achieving behaviour changes. Such services should be considered as an additional approach for reducing HIV transmission in Asia, especially in areas with high HIV seroprevalence rates.
Adult↗
Association of the APC gene product with beta-catenin.
Mutations in the human APC gene are linked to familial adenomatous polyposis and to the progression of sporadic colorectal and gastric tumors. To gain insight into APC function, APC-associated proteins were identified by immunoprecipitation experiments. Antibodies to APC precipitated a 95-kilodalton protein that was purified and identified by sequencing as beta-catenin, a protein that binds to the cell adhesion molecule E-cadherin. An antibody specific to beta-catenin also recognized the 95-kilodalton protein in the immunoprecipitates. These results suggest that APC is involved in cell adhesion.
Adenomatous Polyposis Coli Protein↗
Voluntary HIV counselling and testing in developing countries.
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Acquired Immunodeficiency Syndrome↗
Mitogenic signal transduction in T lymphocytes in microgravity.
The activation by concanavalin A Con A of human peripheral blood lymphocytes (PBLs) in the presence of monocytes as accessory cells was investigated in cultures exposed to microgravity conditions in Spacelab. Activation of T cells was measured as incorporation of [3H]thymidine into DNA, secretion of interleukin-2 (IL-2), and interferon-gamma, and expression of IL-2 receptors. Whereas, as discovered in earlier experiments, the activation of resuspended T cells is strongly inhibited, activation of cells attached to microcarrier beads is more than doubled in microgravity. The results suggest that the depression of the activation in resuspended cells may be attributed to a malfunction of monocytes acting as accessory cells. In fact, although the ultrastructure of resuspended monocytes is not altered in microgravity, the secretion of IL-1 is strongly inhibited. Our data suggest that (1) IL-2 is produced independently of IL-1, (2) IL-1 production is triggered only when monocytes (and lymphocytes?) adhere to microcarriers, (3) the expression of IL-2 receptors depends on IL-1, and (4) provided sufficient IL-1 is available, activation is enhanced in microgravity. Finally, cultures of resuspended PBLs and monocytes in microgravity constitute a complete and natural system in which monocytes are not operational. This may be useful for studies of the role of accessory cells and cell-cell interactions in T lymphocyte activation.
Aerospace Medicine↗
Culture of hybridoma and Friend leukemia virus transformed cells in microgravity. Spacelab IML-1 mission.
The behaviour of two mammalian cell lines was investigated in Biorack during the 1st Spacelab international microgravity laboratory flight (IML-1) in the ESA facility Biorack. The parameters determined were cell proliferation, biosynthesis of specific cell products, consumption of glucose, glutamine and production of ammonia and lactate respectively. Murine Friend leukemia virus-transformed cells (Friend cells) were induced to differentiate and express hemoglobin (Hg) genes upon induction with dimethylsulfoxide (DMSO). No change was observed in all metabolic parameters including the production of Hg and the number of Hg-positive cells. Electron microscopy analysis showed no difference in morphology, mean cell volume and mitotic index between the different cell samples. Murine hybridoma cells revealed an increase (+ 30-40%) of cell proliferation rate in microgravity, whereas the metabolic parameters, production of monoclonal antibodies included, were lower in the 0 g than in the 1 g controls. The results clearly show that not all mammalian cells undergo dramatic changes in microgravity and that the effects reported on human T lymphocytes represent a unique case.
Animals↗
Clinical efficacy of dirithromycin in pharyngitis and tonsillitis.
A total of 193 patients with streptococcal pharyngitis/tonsillitis received 500 mg dirithromycin once daily and 196 patients 250 mg erythromycin four times daily for ten days in a double-blind, parallel-group multicentre study. In the dirithromycin treatment group, 97 (50.3%) patients completed the study and were evaluated for efficacy analysis, and 99/196 (50.5%) erythromycin-treated were evaluated for efficacy of treatment. Favourable clinical responses to treatment (cure or improvement of symptoms) at the post-therapy visit (three to five days after therapy completion) occurred in 89 (91.7%) dirithromycin- and 93 (93.9%) erythromycin-treated patients. Bacteriological response was favourable (pathogen eliminated in 81 (83.5%) dirithromycin- and 87 (87.9%) erythromycin-treated patients. At late post-therapy (three to five weeks after treatment) 82/89 (92.1%) dirithromycin- and 90/93 (96.8%) erythromycin-treated patients had a favourable clinical response. Bacteriological response at late post-therapy was favourable in 77 (86.5%) dirithromycin- and 85 (94.4%) erythromycin-treated patients. No deaths occurred during or after treatment, and the serious events experienced by three dirithromycin- and one erythromycin-treated patients were unrelated to treatment. Five patients taking dirithromycin and seven taking erythromycin discontinued treatment prematurely, mainly due to gastrointestinal disturbances. Adverse events that occurred in 2% or more of patients in each treatment group were mainly gastrointestinal (diarrhoea, abdominal pain, nausea and vomiting); headache and rash were also reported. No significant differences in clinical laboratory data were detected that were considered to be drug-related.
Adolescent↗
Comparison of azithromycin versus clarithromycin in the treatment of patients with upper respiratory tract infections.
The efficacy and safety of azithromycin and clarithromycin were compared in an open multicentre study involving 380 adult patients with acute otitis media, acute sinusitis, or acute streptococcal pharyngitis or tonsillitis. Patients were assigned randomly to receive azithromycin as a single dose of 500 mg daily for three days, or clarithromycin 250 mg bid for ten days. Overall clinical efficacy was found to be similar in each treatment group at day 10-14, with a satisfactory outcome (cured or improved) in 95% of azithromycin and 96% of clarithromycin patients. Bacteriological efficacy was also similar, with eradication of the pathogen in 94% and 95% of isolates, respectively, in the azithromycin and clarithromycin groups. In otitis media, a satisfactory clinical response was seen in 97% of patients in each treatment group. Azithromycin therapy resulted in a clinical response rate of 93% in sinusitis patients, with bacteriological eradication in 93% of patients. Two patients (who were cured clinically) had persistent pathogens. Similarly, clarithromycin achieved clinical response and bacteriological eradication in 95% and 92% of sinusitis patients, respectively. Pathogens persisted in two patients with clinical cure, and in one case of clinical failure. In pharyngitis or tonsillitis, Streptococcus pyogenes was eradicated successfully in 95% of patients in both groups, and the clinical success rates were 96% and 97% for azithromycin and clarithromycin, respectively. No case of clinical failure was associated with persistence of S. pyogenes infection. At the follow-up assessment of this diagnosis group, reinfection had occurred in three (8%) azithromycin patients and one (3%) clarithromycin patient, and all but one patient remained asymptomatic. Both drugs were well-tolerated, with 8.4% of patients on azithromycin and 7.4% on clarithromycin reporting adverse events, mainly gastrointestinal. It was concluded that a three-day course of azithromycin was as effective and well-tolerated as a ten-day course of clarithromycin in adults with acute upper respiratory tract infections.
Acute Disease↗
[Multiple drug dependence].
This study includes all inpatients of the years 1977-1988 treated for multiple drug abuse, in a psychiatric department of a general hospital in Berlin. The descriptive assessment of combined drug abuse in the last half year before admission for withdrawal treatment was the research object. 1176 persons with multiple drug abuse were admitted. The mean-value of age was 36.8 years, the duration of addictive behaviour 9.2 years and, they had 1.9 withdrawal treatments as inpatients before their admission here. On an average they took 2.91 substances simultaneously, predominantly alcohol and benzodiazepines. The third rank is occupied by combinations of analgesics, and the fourth one by heroin. Some preferred combinations with characteristic variables of their users are evaluated.
Adolescent↗
Activation of microcarrier-attached lymphocytes in microgravity.
A technology has been developed to achieve optimal attachment of adhesion-independent lymphocytes to microcarrier beads. The activation of T-lymphocytes by concanavalin A was tested under microgravity conditions in an experiment carried out in space during the first Spacelab Life Science Mission. Activation, measured as the synthesis of deoxyribonucleic acid (DNA) and the production of interferon-gamma, more than doubled in attached lymphocytes in microgravity. The depression of the activation discovered in previous space experiments is due to an impairment not of the lymphocyte but of the macrophage function. The system described here may be useful for radiobiological investigations on the effect of high-energy particles and for testing the efficiency of the immune system in humans during the long-duration space flight planned in the future. The biotechnological significance of the increased lymphokine production in space remains to be assessed.
Biotechnology↗
Molecular cloning and nucleic acid binding properties of the GAP-associated tyrosine phosphoprotein p62.
p62 is a tyrosine phosphoprotein that associates with p21ras GTPase-activating protein (GAP). Purification and cDNA cloning of p62 reveal extensive sequence similarity to a putative hnRNP protein, GRP33. Recombinant human p62 purified from insect Sf9 cells binds to DNA and to mRNA and, like many proteins involved in mRNA processing, recombinant p62 is modified by dimethylation on multiple arginine residues. p62 also binds tightly to p21ras GAP in vitro: this binding depends on phosphorylation of p62 on tyrosine residues and occurs through SH2 regions of GAP. These data suggest that p120-GAP and p62 play a role in some aspect of mRNA processing or utilization and that this role may be regulated by tyrosine phosphorylation, and indirectly, by p21ras.
3T3 Cells↗
Role of mutations at codon 61 of the c-Ha-ras gene during diethylnitrosamine-induced hepatocarcinogenesis in C3H/He mice.
Liver tumors of certain strains of mice frequently contain mutations at codon 61 of the c-Ha-ras gene. In our study, we investigated the significance of these mutations in the carcinogenic process. Male C3H/He mice received a single injection of diethylnitrosamine (DEN) on day 15 after birth, and groups of animals were killed at various time intervals between 11 and 52 wk after treatment. At the earlier time points (11-29 wk), we analyzed microdissected tissue from precancerous glucose-6-phosphatase-deficient liver lesions larger than approximately 200 microns in diameter, for the presence and pattern of c-Ha-ras codon 61 mutations. In parallel, the growth characteristics of these liver lesions were studied by pulse labeling with [3H]thymidine and by determining the size distribution of the lesions. At the later time points (42-52 wk after DEN treatment), liver tumors were dissected and also analyzed for the presence of c-Ha-ras mutations. We found mutations to be already present in some of the enzyme-altered liver lesions at weeks 11-29, suggesting that the mutations occurred early in the carcinogenic process. Whereas about 10% of the precancerous focal liver lesions showed mutations in the c-Ha-ras gene, the mutation frequency was increased to about 50% in the later-appearing hepatocellular adenomas and carcinomas, suggesting that c-Ha-ras codon 61 mutations may provide a selective advantage to the mutated cell clones.
Animals↗
Absence of mutations in the functional parts of the p120-GAP gene in carcinogen-induced mouse liver tumors.
The GTPase activating proteins (GAP) stimulate the intrinsic GTPase activity of ras-p21 thus converting the protein into its inactive form. We have now analyzed carcinogen-induced mouse liver tumors for the possible occurrence of mutational changes in one of the two known GAP genes, namely p120-GAP. RNA from a total of 21 tumors was reverse transcribed by use of GAP-specific primers, amplified by PCR and sequenced. All known functional domains of p120-GAP were included into the analysis. None of the liver tumors analyzed was found to be mutated within these regions of the gene. Moreover, Southern blot analysis of the gene did not reveal any structural changes. However, at five positions we discovered deviations from the published mouse fibroblast sequence, including two mouse strain-specific sequence polymorphisms.
Animals↗
HIV prevalence, attitudes and behaviour in clients of a confidential HIV testing and counselling centre in Uganda.
OBJECTIVE: To describe clients, operation and impact of an African public HIV testing and counselling centre. DESIGN AND SETTING: Analysis of samples from clients attending the AIDS Information Centre (AIC) in Kampala, Uganda in early 1991. SUBJECTS: HIV-1-positive and HIV-negative consecutive clients (250 of each), 86 consecutive couples, and 200 consecutive clients who were HIV-negative in 1990 and were attending for their repeat test. MAIN OUTCOME MEASURES: HIV seroprevalence rates, attitudes, behaviour and behaviour change. RESULTS: HIV-1 prevalence was 28% overall, 24% in men and 35% in women. Reasons for taking the HIV test were a planned marriage or a new relationship (27%; 84% in couples), to plan for the future (35%), distrust of sexual partner (14%) and illness or disease/death (not HIV-specific) of partner (20%). The majority of the reported intentions in response to a positive or a negative HIV test result were positive, demonstrating the ability to cope with this information. Of repeat clients, two (1%) had become HIV-1-positive. The majority of repeat clients reported one sexual partner only (67%) or sexual abstinence (25%). Compared with pre-test information from AIC clients attending for the first time, repeat clients reported casual sexual contacts less often (6 versus 25%) and, of those, the majority used condoms. CONCLUSIONS: Our study demonstrates the demand for and the feasibility of confidential HIV testing and counseling services in Uganda, and illustrates the value of these services in achieving behaviour changes. Such services should be considered an additional approach for the reduction of HIV transmission in Africa, especially in areas with high HIV seroprevalence rates.
Acquired Immunodeficiency Syndrome↗
Application of blood transfusion guidelines in a major hospital of Kinshasa, Zaire.
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Adult↗
Differences in GTPase-activating protein activity between liver tumors and normal liver tissue in mice.
The intrinsic GTPase activity of the cellular protein p21ras is strongly increased by two cytosolic proteins, the GTPase-activating protein (GAP) produced by the neurofibromatosis type 1 gene (NF1-GAP) and a GAP of 120 kDa molecular mass (p120-GAP). The GAP-mediated stimulation of p21ras GTPase activity was measured in cytosol obtained from carcinogen-induced liver tumors and normal liver tissues of mice of two strains, namely C3H/He and C57BL/6J. For this purpose, cytosolic extracts were incubated with recombinant human p21ras complexed to [gamma-32P]GTP and the time-dependent decrease in p21ras bound radioactivity was measured. Liver cytosolic extracts mediated an increase in the GTPase activity of wild-type p21ras. There were great differences between tumor and normal tissues in the maximal velocity (Vmax) and in the apparent Michaelis constant (KM) of the p21ras GTPase reaction. Both Vmax and apparent KM were decreased in the liver tumors. Cytosolic extracts isolated from liver tumors that harbored point mutations in codon 61 of the c-H-ras gene did not differ in their activity from extracts obtained from non-mutated liver tumors. Since both GAP proteins are important cellular regulators of the ras signaling pathway and probably also effectors of p21ras, the observed differences in GAP activity may be of relevance for the tumorigenic process in mouse liver.
Animals↗
HIV-1 disease in a Kampala Hospital 1985-89.
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Acquired Immunodeficiency Syndrome↗
Detection of genomic alterations in carcinogen-induced mouse liver tumors by DNA fingerprint analysis.
DNA fingerprint analysis was used to study structural abnormalities in the genome of mouse liver tumor cells. Liver tumors were induced in three strains of mice, namely C57BL/6J, C3H/He and B6C3F1, by a single injection of 20 micrograms/g body wt. diethylnitrosamine on day 15 after birth. DNA from liver tumors was digested with Hinfl restriction enzyme and hybridized on Southern blots with wild-type bacteriophage M13 DNA as probe. The resulting fingerprints of tumor DNA were compared with those of DNA from normal liver tissue. Genomic aberrations were detected in two out of 68 tumors analyzed, one stemming from a C57BL/6J and the other from a C3H/He mouse.
Animals↗