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Biomedical subjects

C A Hart

Publications and source records attributed to C A Hart.

At least 163 records · Page 9Linked to original sources
PubMed1999

Rotavirus G and P types in children with acute diarrhea in Blantyre, Malawi, from 1997 to 1998: predominance of novel P[6]G8 strains.

One hundred rotavirus strains detected in children with acute diarrhea in Blantyre, Malawi, between July 1997 and January 1998 were characterized for G (VP7) and P (VP4) types by using multiplex, heminested, reverse transcription-polymerase chain reaction. A novel P[6]G8 rotavirus strain was identified in 42% of the specimens. The remaining strains comprised P[8]G3 (20%), P[6]G3 (10%), P[4]G8 (9%), P[6]G9 (3%), P[8]G4 (2%), P[6]G4 (2%), and P[4]G3 (1%). Rotavirus strains with mixed G or P types were identified in 2% of the specimens. Nine percent of the strains were nontypeable with the primers used. The P[6] genotype was identified in 57% of strains overall. This first description of serotype G8 rotavirus as a predominant strain has important implications for vaccine development in Africa. The finding of novel P/G combinations (P[6]G8 and P[4]G8) highlights the extraordinary diversity of rotaviruses in some countries.

Acute Disease↗
PubMed1998

Effect of ribavirin on zidovudine efficacy and toxicity in vitro: a concentration-dependent interaction.

Zidovudine (ZDV) is converted to its active triphosphate (ZDVTP) by intracellular kinases. The intermediate ZDV monophosphate (ZDVMP) is believed to play a major role in ZDV toxicity. Manipulation of ZDV phosphorylation is a possible therapeutic strategy for altering the risk-benefit ratio. Here we investigate whether combining RBV with ZDV is able to modulate efficacy and toxicity of ZDV. We have measured the intracellular activation of ZDV (0.3 microM) in the absence and presence of ribavirin (RBV; 2 and 20 microM) in Molt 4 and U937 cells. MTT cytotoxicity of ZDV (10-1000 microM) was also measured with and without RBV (2 microM) in Molt 4 and U937 cells. Measurement of endogenous deoxythymidine triphosphate (dTTP) allowed investigation of the dTTP/ZDVTP ratio. The antiviral efficacy of ZDV in combination with RBV (2 microM) was assessed by HIV p24 antigen measurements. In the presence of RBV (2 and 20 microM) a decrease in total ZDV phosphates was observed, owing mainly to an effect primarily on ZDVMP rather than the active ZDVTP. RBV also increased endogenous dTTP pools in both cell types, resulting in an increase in the dTTP/ZDVTP ratio. ZDV alone significantly reduced p24 antigen production, with an IC50 of 0.34 microM. Addition of RBV increased the IC50 approximately fivefold (1.52 microM). However, at higher concentrations of ZDV (10 and 100 microM) the antagonistic effect of RBV (2 microM) on ZDV was lost. The RBV-mediated decrease in ZDVMP may explain the reduction in ZDV toxicity when combined with RBV (2 microM). Cytotoxicity of ZDV was reduced in the presence of RBV (2 microM) at all concentrations in both cell lines, probably owing to saturation of ZDVTP formation. The interaction of ZDV and RBV is concentration dependent.

Anti-HIV Agents↗
PubMed1998

Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival.

Human neutrophils possess a very short half-life because they constitutively undergo apoptosis. Cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), and other agents can rescue neutrophils from apoptosis but the molecular mechanisms involved in this rescue are undefined. Here, we show by Western blotting that human neutrophils do not express Bcl-2 or Bcl-X but constitutively express Bax. However, cellular levels of these proteins are unaffected by agents which either accelerate or delay neutrophil apoptosis. In contrast, neutrophils express the antiapoptotic protein Mcl-1 and levels of this protein correlate with neutrophil survival. Thus, cellular levels of Mcl-1 decline as neutrophils undergo apoptosis and are enhanced by agents (eg, GM-CSF, interleukin-1beta, sodium butyrate, and lipopolysaccharide) that promote neutrophil survival. Neutrophils only possess few, small mitochondria, and much of the Mcl-1 protein seems to be located in nuclear fractions. These observations provide the first evidence implicating a Bcl-2 family member in the regulation of neutrophil survival. Moreover, this work also provides a potential mechanism whereby cytokine-regulated gene expression regulates the functional lifespan of neutrophils and hence their ability to function for extended time periods during acute inflammation.

Apoptosis↗
PubMed1998

Prevalence and transmission of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in Ugandan children and adolescents.

We studied the seroprevalence and transmission of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), among 215 Ugandan children, adolescents and young adults. We measured antibodies to a latent nuclear antigen (LANA) and a lytic cycle protein encoded by open reading frame (orf) 65. Infection with KSHV/HHV8 occurred during early childhood and reached adult levels (approx. 50%) before the age of puberty. In children younger than 12 years of age, antibodies to LANA and the orf65 protein were independently associated with hepatitis B infection (p < 0.005). KSHV/HHV8 infection was not associated with antibodies to hepatitis A virus and hepatitis C virus, nor with the quality of the water supply, household size, previous blood transfusions, number of boy/girl friends or marital status. Antibodies to the orf65 protein, but not LANA, were weakly associated with a history of i.v. injections. Our results show that, in contrast to its sexual mode of transmission among homo/bisexual men and sexually transmitted diseases clinic attendees of Northern Europe and the US, transmission of KSHV in Uganda occurs largely before puberty. Among Ugandan children, KSHV transmission follows a horizontal pattern similar to other herpesviruses, in particular the related gamma herpesvirus, Epstein-Barr virus. Transmission of KSHV may be facilitated by living conditions that also promote infection with hepatitis B virus.

Adolescent↗
PubMed1998

Synchronous oral carcinomas: independent or common clonal origin?

Second primary tumors in patients with head and neck cancer have a detrimental impact on long-term survival; at least 15% of patients develop additional tumors. Originally, it was hypothesized that multiple tumors developed independently after widespread epithelial exposure to carcinogens (the field cancerization theory), but recent molecular studies now support the alternative theory of a common clonal origin. If multiple tumors originate from the same clone, early genetic alterations in these cells should be common to all of the tumors. We have compared the pattern of allelic imbalance in paired tumors from five male patients with two synchronous oral squamous cell carcinomas and in peripheral dysplasia using microsatellite markers on chromosomes 3p, 9p, and 17p. Discordance, usually through loss of alternate alleles at the same microsatellite loci, was detected in two patients. The remaining three patients had identical alterations in their tumors. The changes identified occurred early in tumorigenesis, because, with only one exception, these were also present in the associated dysplasia. Thus, we provide evidence that synchronous oral squamous cell carcinomas are of independent origin in some patients but may be of common clonal origin in others.

Alleles↗
PubMed1998

Severe hypophosphatemia in children with kwashiorkor is associated with increased mortality.

Severe hypophosphatemia, serum phosphate concentration <0.32 mmol/L (<1.0 mg/dL), occurred in 8 of 68 (12%) of children with kwashiorkor within 48 hours of admission; 5 of 8 (63%) of these children died, compared with 13 of 60 (22%) children without severe hypophosphatemia (P <.02). Dermatosis and dehydration were significantly correlated with severe hypophosphatemia, but these clinical signs could not reliably predict fatal cases. Severe hypophosphatemia seems to be common and life-threatening in children with kwashiorkor in Malawi.

Child, Preschool↗
PubMed1998

Hepatitis G virus infection in drug users in Liverpool.

OBJECTIVES: To establish the prevalence of hepatitis G (HGV) in drug users in Liverpool; to explore the risk factors for, and the effects of, HGV infection. METHODS: Serum samples from 129 drug users who had attended the Infectious Diseases Unit at Fazakerley Hospital, Liverpool, between January 1995 and June 1996 were examined for HGV RNA using PCR, HGV RNA results were collated with demographic data, information on drug-use behaviour, hepatitis B (HBV) and C (HCV) serology, and the results of serum bilirubin and aspartate amino-transferase (AST) measurements. RESULTS: Overall, 37 (29%) of patients were HGV RNA positive, 89 (69%) were negative, and equivocal results were obtained in three (2%) cases. Direct sequencing of PCR products of the 5' non-translated region for 13 patients showed that these were generally more closely related to the HGV than the GB virus C (GBV-C) sequence. HGV co-infection with HCV and HBV was common: of HGV-positive patients, 28 (76%) and 16 (44%) had antibodies to HCV (anti-HCV) and hepatitis B core protein (anti-HBc), respectively. Increasing duration of injecting drug use was associated with a decreasing seroprevalence of HGV RNA, dropping from 39% for 0-4 years of injecting to 14% for > 12 years injecting. Serum bilirubin and AST values were frequently elevated, but statistical analysis showed no differences between HGV-positive and HGV-negative patient groups. CONCLUSIONS: HGV infection is common in drug users in Liverpool, but HGV RNA prevalence falls with increasing duration of injecting drug use, probably as a result of viral clearance and the development of protective immunity. HGV infection does not appear to be a significant cause of hepatic dysfunction in Liverpool drug users.

Adult↗
PubMed1998

Seroprevalence of hepatitis B and C and HIV in Malawian pregnant women.

OBJECTIVES: to describe the seroprevalence of hepatitis B (HBV) and C (HCV) infection in HIV-positive and HIV-negative pregnant women from rural Malawi. METHODS: descriptive study using serum samples collected between 1993-1995 in the Shire valley in rural Malawi. Fifty HIV-positive and 100 HIV-negative samples were selected randomly from 153 HIV-positive and 443 HIV-negative women delivering in the hospital. RESULTS: evidence of HBV and HCV infection was found in 71.7 and 16.5% of women, respectively. Chronic carriage of HBV (HBsAg positive) is high (13%) and in agreement with prevalences reported from highly endemic areas. Exposure to HBV and HCV probably occurred well before adulthood as the prevalence of anti-HBc antibody was high in young mothers <20 years of age (22/27; 81%). CONCLUSION: HBV and HCV infections are highly endemic in rural Malawi. There was no statistical evidence to suggest that HIV positivity was associated with an increased prevalence of HBV or HCV markers. Infection with HBV or HCV was not statistically associated.

Adult↗
PubMed1998

The use of pulsed-field gel electrophoresis to examine the epidemiology of Bordetella bronchiseptica isolated from cats and other species.

A collection (164) of isolates of Bordetella bronchiseptica made predominantly from cats (132) but also from dogs (15), pigs (12) and other species was examined by pulsed field gel electrophoresis following macrorestriction digestion with XbaI. Each isolate was analysed twice and the patterns were entirely reproducible. The isolates fell into 17 different strains (> 3 bands different) and within strains there were numerous subtypes. Feline isolates fell into 12 of the 17 strains. In general, cats housed together had similar or identical strains and subtypes of B. bronchiseptica. There was no difference in the PFGE patterns of isolates made from carrier cats and those from cats with respiratory disease. Isolates from pigs and dogs were in general similar to the feline isolates and there was no great evidence for species specificity. The PFGE pattern of feline and canine isolates were more related to whether the animals were housed together rather than whether they came from dogs or cats.

Animals↗
PubMed1998

Immunogenicity of Haemophilus influenzae-diphtheria CRM197 protein conjugate vaccine (HbOC) in Libyan infants.

The immunogenicity of the HbOC, a Haemophilus influenzae type b conjugate vaccine, was evaluated in a randomized clinical trial of Arab children resident in Tripoli. The HbOC vaccine was given as part of a three-dose series at 2, 3 and 4 months of age together with hepatitis B, OPV and DPT to 90 children. Anti-H. influenzae antibody levels were compared with 81 infants receiving hepatitis B, OPV and DPT but not the HbOC vaccine. The immunogenicity and safety of HbOC was as high as that observed in industrialised countries. There were no major complications, and fever and temporary local discomfort were observed in fewer than approximately 2% of the infants. Infants receiving the HbOC vaccine had an increase in Hib antibodies with only one dose. Geometric mean anti-Hib antibody levels were 0.41, 1.36 and 2.91 mg/ml after one, two and three doses. After two doses, all children had antibody levels above 0.20 mg/ml and the lowest antibody concentration was 0.80 mg/ml. Antibody levels in our children are similar to those observed in Europe and the USA and it is thus likely that HbOC will provide good clinical protection in this population. As most of the children develop antibody titres above or near 1 mg/ml, it is likely that they are protected even with two doses of the vaccine. The anti-Hib antibody levels observed are similar to those in studies from Europe where hepatitis B vaccine is not routinely given.

Antibodies, Bacterial↗
PubMed1998

Clinical predictors of hypoxaemia in children with pneumonia.

A prospective study to determine which clinical factors identified children with acute lower respiratory infection who were hypoxaemic and at risk of death was done over a 9-month period on children under 5 years of age admitted to a district hospital in rural Zambia. Of 158 children studied, 55 (35%) were found to be hypoxaemic and 23 (14.6%) died. For the subgroup of children under 1 year of age, a respiratory rate of > 70 was the only significant predictor of hypoxaemia (p < 0.001, sensitivity 63%, specificity 89%). In older children, only the presence of crepitations/bronchial breathing was predictive (p = 0.018, sensitivity 75%, specificity 57%). The likelihood of death was increased in those children with low oxygen saturation (p = 0.021) and poor nutrition (p = 0.007). It is concluded that, on the basis of raised respiratory rate, the WHO guidelines are likely to identify children under 1 year of age who are hypoxaemic. However, it may be necessary to include auscultatory findings in the guidelines to recognize hypoxaemia in older children in order to ensure that they receive appropriate treatment with oxygen. This study demonstrates that hypoxaemia and malnutrition are risk factors for death.

Acute Disease↗
PubMed1998

Granulocytic ehrlichiosis: an emerging or rediscovered tick-borne disease?

The Ehrlichieae are gram-negative obligately intracellular bacterial pathogens. They can be divided into at least three genogroups on the basis of 16S rRNA gene sequences, but are also classified by target cell specificity. A group of granulocytic ehrlichiae primarily infect neutrophils and fall into genogroup II. The granulocytic ehrlichiae are subdivided by their target hosts, i.e., Ehrlichia phagocytophila in cattle and sheep, E. equi in horses, and the agents of human (HGE) and llama (LGE) granulocytic ehrlichioses. However, these subdivisions may give a false impression, as all these species are closely related both antigenically and on the basis of 16S rRNA operon sequence. In addition, cross-species transmission can occur naturally or by experimental infection. The vectors for these granulocytic ehrlichiae are hard-bodied ixodid ticks, and the reservoir hosts are probably wild rodents, deer and sheep. In each host, this illness presents as a febrile disease which can be followed by immunosuppression leading to secondary infections.

Animals↗
PubMed1998

Flagellin gene variation between clinical and environmental isolates of Burkholderia pseudomallei contrasts with the invariance among clinical isolates.

The flagellin gene sequence from a clinical isolate of Burkholderia pseudomallei was used to design oligonucleotide primers for PCR/RFLP analysis of flagellin gene variation among clinical and environmental isolates of B. pseudomallei. Genes from four clinical and six environmental isolates were amplified and compared by RFLP. The clinical isolates were indistinguishable, but variation was detected among some of the environmental isolates. Sequence analysis of flagellin gene amplified products demonstrated high levels of conservation amongst the flagellin genes of clinical isolates (>99% similarity), compared to the variation observed between the clinical isolates and one of the environmental isolates (<90% similarity). Genomic comparisons with pulsed-field gel electrophoresis (PFGE) revealed differences between the relationships inferred by flagellin genotyping and PFGE, suggesting that a combination of molecular methods may be useful for the subtyping of B. pseudomallei strains.

Bacterial Outer Membrane Proteins↗