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Biomedical subjects

G J Bhat

Publications and source records attributed to G J Bhat.

At least 37 records · Page 2Linked to original sources
PubMed1995

Measles infection in hospitalized children in Lusaka, Zambia.

A 2-year hospital-based survey of measles infections were carried out at the University Teaching Hospital (UTH) in Lusaka, Zambia from January 1992 to December 1993. During this period, a total of 1066 children with a clinical diagnosis of measles were admitted to the paediatric isolation ward at UTH. Measles cases were seen throughout both 1992 and 1993. However, there was a peak from September to December, 1992. The number of cases decreased with age, and 370 (34.7%) were under 1 year old. It is noteworthy that 203 (19.0%) were less than the 9 months of age which is the recommended time for measles vaccination in Zambia. The overall case fatality rate was 12.6%, and was higher in children aged 0-3 years (14.3%) than in those aged 4 years and above (6.7%). Measles vaccination status could be checked from the child's immunization card for 343 measles cases over 9 months of age, 118 (34.4%) of these having previously received measles vaccine. Vaccinated children had a significantly lower case fatality rate (6.4%) than the unvaccinated group (17.0%). This suggests that while measles vaccine cannot prevent infection, it can reduce the severity of infection.

Adolescent↗
PubMed1995

The effect of routine hospital care on the health of hypothermic newborn infants in Zambia.

A prospective cohort study was carried out at the University Teaching Hospital, Lusaka, Zambia, to investigate the prevalence of neonatal hypothermia, type of infant care and incidence of mortality. Two-hundred-and-sixty-one infants, aged 0-7 days, admitted to the pediatric unit during the 'warm' season were recruited to the study. Forty-four per cent of the infants were hypothermic (< 36 degrees C) on admission, and admission hypothermia correlated to admission weight and home delivery in the youngest age group (0-24 hours). Exclusively breastfed infants (age group 1-7 days) were less likely to be hypothermic at admission. 'Hypothermia' was not recorded as an admission diagnosis and no special attention was given to those infants in terms of clinical management. Mean time to reach a body temperature above 35.9 degrees C did not differ between infants kept in a cot and in an incubator. Total numbers of death was 82 (31 per cent) and the mortality was higher in infants who were hypothermic at admission compared to those who were not. This study demonstrates that a change of existing care routines is needed.

Cohort Studies↗
PubMed1994

Angiotensin II stimulates sis-inducing factor-like DNA binding activity. Evidence that the AT1A receptor activates transcription factor-Stat91 and/or a related protein.

Recent studies on cytokine and growth factor stimulated signal transduction have defined a direct pathway (Stat91) linking cell surface receptors to target genes in the nucleus. The Stat91 pathway regulated c-fos gene transcription involves activation by tyrosine phosphorylation of the DNA binding factor SIF (sis-inducing factor) in the cytoplasm, its nuclear translocation, and interaction with the regulatory element SIE (sis-inducing element). SIF is a complex of proteins containing members of the STAT family of transcription factors. We determined whether angiotensin II (AII), which acts as a growth factor in many cell types, could activate the Stat91 pathway. We used neonatal rat cardiac fibroblasts expressing G-protein linked AII receptors and CHO-K1 cells expressing stably transfected angiotensin type 1A (AT1A) receptors to address this question. Angiotensin II induced SIF-like activity in both cell types, with initial induction at 15-30 min, maximal around 2-3 h, and undetectable at 6 h. Cytoplasmic and nuclear fractions from cells exposed to AII contained DNA binding activity to SIE. The SIF activity was insensitive to protein synthesis inhibitors and sensitive to the tyrosine kinase inhibitor genistein. Stat91 or a related protein was identified as a component of the AII-induced SIF complex and increased levels of this tyrosine-phosphorylated protein were found in nuclear extracts of cells treated with AII. This is the first evidence that a seven transmembrane, G-protein-coupled receptor, namely AT1A, activates the Stat91-nuclear signaling pathway.

Angiotensin II↗
PubMed1993

HIV, BCG and TB in children: a case control study in Lusaka, Zambia.

Even before the onset of the HIV epidemic, studies reported large variations in the protective effect of BCG against TB. The current HIV/AIDS epidemic has increased the incidence of tuberculosis in many countries in sub-Saharan Africa. Thus, local estimates of the effectiveness of BCG are needed which take prevalence of HIV into account for planning strategies for vaccination and TB control programmes. A case control study was conducted in Lusaka, Zambia. The study included 116 TB cases and 154 hospital controls. Eighty-eight per cent of controls had BCG scars compared to 77 per cent of the cases. BCG was not associated with TB in HIV positive children (OR 1.0, 95 per cent CI 0.2, 4.6). However, there was 59 per cent protective effect (OR 0.41, 95 per cent CI 0.18, 0.92) in HIV negative children. The results also suggest an eight times higher risk of TB in HIV positive children.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Transcript-specific developmental regulation of polyadenylation in Trypanosoma brucei mitochondria.

Transcripts from many mitochondrial genes in kinetoplastids are heterogeneous in size, often occurring as 2 distinct size classes, but this cannot be accounted for by RNA editing alone. Analyses of transcripts from 6 mitochondrial genes of Trypanosoma brucei indicates that the size variation is due to poly(A) tail length. A larger fraction of CYb, COI and COII transcripts have longer poly(A) tails in procyclic than in bloodstream forms. These transcripts are also more abundant in the procyclic forms. In contrast, a more substantial fraction of CR1 transcripts have longer poly(A) tails in bloodstream than in procyclic forms and these transcripts tend to be more abundant in bloodstream forms. Both ND4 and MURF1 transcripts show a similar size distribution of poly(A) tail lengths in these life cycle states although both transcripts are more abundant in bloodstream forms. Furthermore, genes with edited transcripts tend to have longer poly(A) tails than unedited transcripts. Transcript abundance is not strictly correlated with longer poly(A) tails. Thus, poly(A) length variation appears to be developmentally regulated in a transcript-specific fashion in T. brucei. This regulation of polyadenylation may influence mitochondrial gene expression as polyadenylation can regulate cytoplasmic gene expression in eukaryotes.

Animals↗
PubMed1991

Cycles of progressive realignment of gRNA with mRNA in RNA editing.

We characterized numerous partially edited NADH dehydrogenase 7 and ATPase 6 cDNAs. Most of these have a stretch of incompletely edited sequence at the junction of mature and unedited sequences. The characteristics of the junctions suggest editing of sites multiple times and that editing within each junction does not proceed precisely 3' to 5'. Analyses of gRNAs and corresponding junction sequences predict a series of progressively more stable, but incompletely base-paired, interactions in the junction region. The predicted interactions suggest that the gRNA is progressively realigned with the mRNA being edited. We suggest that gRNA interactions with the mRNA result in regions of lower thermodynamic stability that are selected for editing, thus driving toward the most stable structure, the complete gRNA/mRNA duplex.

Adenosine Triphosphatases↗
PubMed1991

The two ATPase 6 mRNAs of Leishmania tarentolae differ at their 3' ends.

We have determined the complete nucleotide sequence of ATPase 6 mRNA from Leishmania tarentolae. RNA editing occurs only in the 5' one-third of the mRNA and is the most extensive observed to date in this species. We have identified a potential gRNA sequence, encoded in a minicircle, for a portion of the edited sequence. The predicted amino acid sequence is about 85% homologous to that predicted from the more extensively edited Trypanosoma brucei ATPase 6 mRNA. The edited L. tarentolae mRNA exists as two distinct size classes which differ in the size of their 3' ends. Although variation in the length of the 3' untranslated region cannot be excluded, the size difference is probably to be due to variation in the length of the poly(A) tail.

Adenosine Triphosphatases↗
PubMed1990

The MURF3 gene of T. brucei contains multiple domains of extensive editing and is homologous to a subunit of NADH dehydrogenase.

Mitochondrial MURF3 transcripts of T. brucei are extensively edited by the addition and deletion of uridines. The editing creates potential initiation and termination codons and a continuous open reading frame. The predicted amino acid sequence has homology to a subunit of NADH dehydrogenase (ND7). ND7 is independently edited in two distinct domains, suggesting two editing initiation sites. Editing in the two domains is differentially regulated: the 5' domain is edited in both bloodstream and procyclic forms but the 3' domain is completely edited only in the bloodstream form. Two potential guide RNA (gRNA) coding sequences were identified in the same minicircle. One is complementary to edited sequence in the 5' domain, the other to edited sequence in the 3' domain.

Amino Acid Sequence↗
PubMed1990

An extensively edited mitochondrial transcript in kinetoplastids encodes a protein homologous to ATPase subunit 6.

The mitochondrial MURF4 gene of T. brucei has pronounced G versus C strand bias and heterogeneously sized transcripts, characteristic of genes encoding extensively edited transcripts. We find that MURF4 transcripts of T. brucei are extensively edited throughout by the addition and deletion of numerous uridines, creating potential initiation and termination codons and a continuous open reading frame. A potential guide RNA sequence occurs in a minicircle between inverted repeats. The 5' region of L. tarentolae MURF4 transcripts is also extensively edited, with a created initiation codon. The predicted MURF4 amino acid sequences have homology to those of mitochondrial ATP-ase subunit 6 genes from a variety of organisms. In addition, their hydropathic profiles are quite similar to those of other species. We therefore conclude that MURF4 encodes ATPase subunit 6 genes.

Adenosine Triphosphatases↗
PubMed1990

Syphilis intervention in pregnancy: Zambian demonstration project.

Despite availability of simpler serologic tests for syphilis and near cure with penicillin, unacceptably high prevalence of infectious maternal syphilis exist in many developing countries, including Zambia. It is the foremost risk factor for mid-trimester abortions, stillbirths, prematurity and morbidity and mortality among infants born with congenital syphilis in Zambia. An intervention project was conducted in Lusaka aimed at demonstrating the effectiveness of new health education methods and prenatal screening for syphilis in reducing the adverse outcomes during pregnancy. During pre-intervention phase, approximately 150 consecutive pregnant women from each of the three study and the three control centres were recruited when they presented in labour at the University Teaching Hospital. The intervention phase lasted for one year at the three study centres during which new methods of health education were introduced to improve early attendances during pregnancy. Also, on-site syphilis screening was performed twice during pregnancy and seroreactive women, and in many cases their sexual partners, were treated by the existing prenatal clinic staff. During the post-intervention phase the steps of pre-intervention phase were repeated to evaluate the impact of intervention. Overall, 8.0% of women were confirmed seroreactive for syphilis; there was no difference between the study and the control centres (p greater than 0.05). Fifty seven percent (132/230) of syphilitic pregnancies ended with an adverse outcome, that is, abortion (RR 5.0), stillbirth (RR 3.6), prematurity (RR 2.6) and low birth weight (RR 7.8). The overall risk of adverse outcomes due to syphilis was 8.29 (95% confidence interval 6.53, 10.53). The new methods of health education were effective and the percentage of women who had their first prenatal visit under 16 weeks of gestation improved from 9.4 to 42.5. Although screening and treatment during intervention was suboptimal, the adverse outcomes attributable to syphilis were reduced to 28.3%; this is almost a two-third reduction when compared with 72.4% of adverse outcomes at control centres (p < less than 0.001). The intervention is culturally and politically acceptable in Zambia. The cost of each prenatal screening is US$0.60 and of averting each adverse outcome US$12. In countries with high rates of syphilis, there is an urgent need for STD control and Maternal and Child Health (MCH) programmes to pool their resources together to revitalise the prenatal care.

Adult↗
PubMed1989

Perinatal transmission of HIV-I in Zambia.

OBJECTIVE--To determine the occurrence of vertical transmission of HIV-I from women positive for the virus and the prognosis for their babies. DESIGN--Women presenting in labour were tested for HIV-I. Their newborn babies were also tested. Women positive for the virus were followed up with their babies for two years. SETTING--Teaching hospital in Lusaka, Zambia. SUBJECTS--1954 Women, of whom 227 were seropositive. Of 205 babies, 192 were positive for HIV-I. After birth 109 seropositive mothers and their babies and 40 seronegative mothers and their babies were available for follow up. MAIN OUTCOME MEASURES--Serological examination of mothers and their babies by western blotting. Birth weight and subsequent survival of babies. Women and babies were tested over two years for signs of seroconversion and symptoms of infection with HIV, AIDS related complex, and AIDS. RESULTS--Of the 109 babies born to seropositive mothers and available for follow up, 18 died before 8 months, 14 with clinical AIDS. Of the 91 remaining, 23 were seropositive at 8 months. By 24 months 23 of 86 surviving babies were seropositive, and a further five infected babies had died, four were terminally ill, 17 had AIDS related complex, and two had no symptoms. The overall rate of perinatal transmission was 42 out of 109 (39%). The overall mortality of infected children at 2 years was 19 out of 42 (44%). Before the age of 1 year infected children had pneumonia and recurrent coughs, thereafter symptoms included failure to thrive, recurrent diarrhoea and fever, pneumonia, candidiasis, and lymphodenopathy. All babies had received live attenuated vaccines before 8 months with no adverse affects. CONCLUSIONS--Vertical transmission from infected mothers to their babies is high in Zambia and prognosis is poor for the babies. Perinatal transmission and paediatric AIDS must be reduced, possibly by screening young women and counselling those positive for HIV-I against future pregnancy.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Anthropometric parameters of Zambian infants at birth.

Mean, standard deviations, and percentile values for weight, length, head, chest, and mid-arm circumferences were calculated by measuring 2353 'normal' singleton babies born at University Teaching Hospital (UTH), Lusaka, Zambia. The mean values were as follows: birth weight 3.08 +/- 0.40 kg; crown-heel length 48.57 +/- 2.53 cm; head circumference 34.55 +/- 1.57 cm; chest circumference 32.14 +/- 1.92 cm; and mid-arm circumference 10.68 +/- 0.96 cm. Physical measurements increased with increase in gestational age up to 42 weeks and male babies were larger than their female counterparts.

Anthropometry↗
PubMed1988

Heme is a positive regulator of cytochrome P-450 gene transcription.

Inhibitors of heme biosynthesis such as CoCl2, 3-amino-1,2,4-triazole, and thioacetamide block the 3-methylcholanthrene-mediated induction of cytochrome P-450 (c + d) messenger RNAs and their transcription in rat liver. This effect is specific, since the messenger RNA levels for albumin and glutathione transferase (Ya + Yc) and their transcription are not significantly influenced under conditions of heme depletion. Exogenous administration of heme at very low doses (50 micrograms/100 g body wt) is able to completely counteract the effects of the heme biosynthetic inhibitors on cytochrome P-450 (c + d) messenger RNA levels and their transcription. This constitutes a direct proof for the role of heme as a positive regulator of cytochrome P-450 gene transcription.

Amitrole↗
PubMed1987

Regulation of cytochrome P-450 messenger RNA and apoprotein levels by heme.

2-Allylisopropylacetamide, a porphyrinogen which decreases the microsomal and cytosolic heme pools, is a phenobarbitone-like inducer of cytochrome P-450(b + e) messenger RNAs in rat liver. The porphyrinogen, however, does not affect the nuclear heme pool and enhances the transcription of cytochrome P-450(b + e) messenger RNAs strikingly. Inhibitors of heme biosynthesis, such as CoCl2 and 3-amino-1,2,4-triazole, which decrease the total heme levels including that of the nuclear heme pool, block the 2-allylisopropylacetamide- or phenobarbitone-mediated increase in the transcription of cytochrome P-450(b + e) messenger RNAs. Administration of exogenous heme at a very low concentration (25 micrograms/100 g) is able to counteract the inhibitory effects of the heme biosynthetic inhibitors. Addition of heme in vitro to heme-depleted nuclei leads to a significant increase in the transcription rates for cytochrome P-450(b + e) messenger RNAs. 2-Allylisopropylacetamide, unlike phenobarbitone, fails to increase the levels of cytochrome P-450b protein at 12 h after the drug administration, although there is a striking increase in the messenger RNA levels. Under conditions of 2-allylisopropylacetamide treatment, the cytochrome P-450 messenger RNA is translated, but the newly synthesized apoprotein undergoes rapid degradation. It is concluded that heme is a positive modulator of cytochrome P-450 gene transcription and is also required to stabilize the freshly synthesized apoprotein.

Allylisopropylacetamide↗
PubMed1987

Differential effects of cycloheximide on rat liver cytochrome P-450 gene transcription in the whole animal and hepatoma cell culture.

The induction of cytochrome P-450 (c+d) messenger RNAs in rat liver by 3-methyl cholanthrene follows a biphasic pattern. Administration of cycloheximide blocks the induction of cytochrome P-450 (c+d) messenger RNAs by 3-methylcholanthrene as well as cytochrome P-450 (b+e) messenger RNAs by Phenobarbitone. Transcription of these messenger RNAs in isolated nuclei is also blocked by cycloheximide administration. Thus cycloheximide not only fails to mimic the superinduction effects reported in hepatoma cell cultures, but actually blocks the specific transcription process. Exogenous hemin, while counteracting the effects of CoCl2 (heme biosynthetic inhibitor) on cytochrome (c+d) messenger RNA induction by the hydrocarbon, fails to counteract the effects of cycloheximide. It is suggested that a positive labile transcription factor is involved in the regulation of cytochrome P-450 gene expression in vivo.

Animals↗