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Biomedical subjects

J Embree

Publications and source records attributed to J Embree.

16 recordsLinked to original sources

High resolution sequence-based DPB1 typing identified two novel DPB1 alleles, DPB1*9401 and DPB1*9501, from a Kenyan population.

Two novel DPB1 alleles, DPB1*9401 and DPB1*9501, were identified from a Kenyan population during sequence-based HLA-DPB1 typing. Molecular cloning and sequencing of multiple clones confirmed that one of the new DPB1 alleles is identical to DPB1*0402 at exon 2 except for a single nucleotide substitution (CGG -->TGG), changing codon 70 from Arg to Trp. The new allele has been named DPB1*9401. This is the first report of polymorphism at codon 70 of HLA-DPB1 alleles. New codon combinations have been identified in another novel DPB1 allele named DPB1*9501. The extensive diversity at DPB1 locus of this East African population is being revealed by high resolution sequence-based DPB1 typing.

Amino Acid Sequence↗

HLA-A and HLA-B in Kenya, Africa: allele frequencies and identification of HLA-B*1567 and HLA-B*4426.

HLA-A and HLA-B alleles of a population from Kenya, Africa were examined by sequencing exon 2 and exon 3 DNA and typing using a Taxonomy-based Sequence-analysis (TBSA) method. Extensive diversities were observed at both HLA-A and HLA-B loci in this population. Forty-one HLA-A alleles were identified from 159 unrelated individuals. The most frequently observed alleles were A*6802 (11.64%), A*02011/09 (9.75%), A*7401/02 (9.43%), A*3001 (7.86%), A*3002 (7.23%) and A*3601 (6.6%). Forty-nine HLA-B alleles were identified in 161 unrelated individuals, including two novel alleles, B*1567 and B*4426. The most frequently observed HLA-B alleles were B*5301 (9.01%), B*5801 (8.38%), B*4201 (7.76%), B*1503 (7.14%), B*1801 (6.21%), and B*5802 (5.90%). The most frequently observed HLA-A-B haplotypes were A*3601-B*5301 (3.55%) and A*3001-B*4201 (3.19%), followed by A*7401/02-B*5801 (2.84%), A*7401/02-B*5802 (2.84%) and A*02011/09-B*1503 (2.13%). Linkage disequilibrium and chi2 analysis showed the association of these HLA-A-B haplotypes at the antigen level to be significant. The frequencies of HLA-A and HLA-B alleles from the Kenyan population were compared with that of a population from Cameroon. The difference in allele and haplotype frequency distributions partly reflected the different ethnic composition of these two African populations.

Adult↗

Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected children in Nairobi.

BACKGROUND: Reference lymphocyte subset values for African children are lacking. This study documents these values as well as their alterations associated with perinatal and postnatal HIV-1 transmission and with protection from HIV-1 infection. METHODS: Lymphocyte subsets were determined for HIV-1-seronegative nonpregnant women and their children (controls) and for uninfected, perinatally infected and postnatally infected children born to HIV-1-seropositive mothers in Nairobi, Kenya. The mean, median and 5th and 95th percentile values for CD4+ and CD8+ lymphocyte counts and percentages were determined and compared at the age ranges birth to 3 months, 4 months to 1 year, yearly from 1 to 5 years and from 6 to 10 years of age. RESULTS: Among control children counts differed from published values of other populations. In all age ranges, whereas the absolute values were significantly higher than adult values, the percentages were significantly lower. Children perinatally infected with HIV-1 had clearly distinguishable differences in lymphocyte subset percentages by 3 months of age, when the median CD4+ percentage was 27.9% (5th to 95th percentile, 25.7 to 30.1%) for infected vs. 35.9% (33.3 to 38.7%) for uninfected and 39.9% (37.8 to 42.2%) for control children, P < 0.001; whereas the median CD8+ percentage was 37.0% (33.1 to 41.0%) for infected vs. 27.5% (24.2 to 30.8%) for uninfected and 27.5% (24.2 to 30.8%) for control children, P = 0.001. Differences between uninfected and control children disappeared after 1 year of age. CONCLUSIONS: Normal lymphocyte subset values among African children differ from those in other populations. Significant differences are detectable by 3 months of age in CD4+ and CD8+ lymphocyte percentages among perinatally infected infants, which may be useful as an adjunct in diagnosis. Transient differences observed among HIV-1-exposed but uninfected infants could reflect a successful immune response to HIV-1 challenge.

CD4 Lymphocyte Count↗

Mother-child class I HLA concordance increases perinatal human immunodeficiency virus type 1 transmission.

Major histocompatibility complex (MHC) gene products are expressed on human immunodeficiency virus (HIV)-infected cells and incorporated into the lipid envelope of HIV virions. Macaques immunized with human MHC gene products are protected from simian immunodeficiency virus challenge when the virus is grown in cells expressing the same MHC alleles. To relate these findings to mother-to-child transmission of HIV-1, investigations of whether sharing HLA between mother and infant influenced the risk of transmission of HIV-1 to the child were carried out. Class I HLA concordance was independently associated with a stepwise increase in the risk of perinatal HIV-1 transmission for each additional concordant allele (odds ratio, 2.63; 95% confidence interval, 1.36-5.07; P = .003). Thus, discordant HLA may provide infants with a means of protection against HIV-1 as a result of allogeneic infant anti-maternal MHC immune responses.

Adult↗

Comparison of the declines in CD4 counts in HIV-1-seropositive female sex workers and women from the general population in Nairobi, Kenya.

Studies from Kenya have reported rapid clinical disease progression among HIV-infected professional sex workers. The reasons for this rapid decline are unknown. To better understand factors influencing the course of disease, HIV-1 disease progression was explored in terms of declines in CD4 counts. Two samples from Nairobi, Kenya, were studied, one from a cohort of female sex workers and another, as a comparison group, from mothers enrolled in an HIV-1 vertical-transmission study. A Markov model was used to analyze transitions between HIV-1 disease stages as defined by CD4 counts. It appears that sex workers experience a rapid decline in CD4 counts, consistent with earlier findings of rapid clinical disease progression among individuals in this group. The rate of decline in CD4 counts among the mothers appears to be lower. It is speculated that either intensive exposure to sexually transmitted pathogens or infection with several strains of HIV-1 may account for the rapid disease progression among female sex workers.

Adult↗

Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2.

We describe an infant with three unusual features of perinatally acquired herpes simplex virus type 2 encephalitis: onset of illness at 34 days of age, absolute cerebrospinal fluid neutrophilia, and systemic viral dissemination after central nervous system disease. To provide early, effective antiviral therapy, clinicians should be aware of atypical presentations of serious herpes simplex virus infections.

Encephalitis↗

Development of oligonucleotide primers and probes against structural and regulatory genes of human immunodeficiency virus type 1 (HIV-1) and their use for amplification of HIV-1 provirus by using polymerase chain reaction.

The polymerase chain reaction is a powerful technique for amplifying a few copies of double-stranded genetic material to millions of copies in a few hours. The sensitivity and specificity of the polymerase chain reaction technique depend to some extent on the nucleotide sequences of the oligonucleotide primer pair used in the amplification. We report new oligonucleotide primers and probes which can be used for the amplification and detection of human immunodeficiency virus type 1 provirus sequences of not only structural but also regulatory genes. These primers are very sensitive and specific and can be used for the detection of African and North American strains of human immunodeficiency virus type 1.

Adult↗

Short-course antibiotic therapy for urinary tract infections in children. A methodological review of the literature.

We performed a methodological review of 14 published clinical trials of short-course (less than or equal to 4 days) vs conventional (seven to ten days) antibiotic therapy for urinary tract infection in children. Four reviewers independently assessed each study, without knowledge of authorship, according to 35 criteria, 14 of which were considered critical for this type of study. Reviewer ratings were summed so that any study could receive a potential score of 140 for all criteria and 56 for the critical criteria. Only one study met more than 75% of all the criteria, whereas four studies met 75% of critical criteria. Two studies found short-course antibiotic therapy significantly less effective than conventional therapy. The remaining 12 had insufficient sample size to warrant the conclusion that the two therapies were equivalent. We conclude that there is insufficient evidence to warrant the use of short-course antibiotic therapy for urinary tract infection in children and that a much larger study, with attention to some of the details described, is warranted.

Anti-Bacterial Agents↗

Mycoplasma hominis in maternal and fetal infections.

Although prevalence of M. hominis colonization during pregnancy varies from 12-50%, its role in infections of the mother and newborn infants is unclear. Definite correlations exist with chorioamnionitis and amniotic fluid infections, but as it is rarely isolated alone during these infections, its pathogenic role is uncertain. Its association with septic abortion is similarly questioned. Prevalence and antibody titers to M. hominis increase with increasing parity. Transient bacteremia occurs in approximately 2.5% of normal deliveries. M. hominis does have a significant role in postpartum fever. Women harboring the organism during labor with low predelivery antibody titers are at risk. Approximately 30% of exposed infants are colonized (4% of all infants) but there are only a few reports of neonatal meningitis, pneumonia, or skin abscesses due to M. hominis. Most recover without specific therapy. The role of antimicrobial therapy of M. hominis in pregnancy and the neonatal period is unclear. Further studies of these issues should simultaneously consider all potential genital tract pathogens.

Abortion, Spontaneous↗

Comparison of nasopharyngeal aspirate and nasopharyngeal swab specimens for respiratory syncytial virus diagnosis by cell culture, indirect immunofluorescence assay, and enzyme-linked immunosorbent assay.

Paired nasopharyngeal aspirate (NPA) and nasopharyngeal swab (NPS) specimens obtained from each of 32 hospitalized infants with X-ray-confirmed pneumonia (91%) or bronchiolitis were tested for respiratory syncytial virus (RSV) infection by virus culture, the indirect immunofluorescent-antibody (IFA) technique, enzyme-linked immunosorbent assay (ELISA; Ortho Diagnostic Systems, Inc.), and spot hybridization with a human genomic probe to quantitate cellular DNA. RSV was isolated in cell cultures from 72% (23 of 32) of patients by using NPA specimens compared with 47% (15 of 32) by using NPS specimens. With tissue culture positivity as the reference test, the sensitivities of the ELISA on NPA and NPS specimens were found to be 69% (16 of 23) and 61% (14 of 23), respectively, with a specificity and a positive predictive value from both sites of 100%. The sensitivities of the IFA technique compared with the cell culture on NPA and NPS specimens were 61% (14 of 23) and 52% (12 of 23) with specificities of 89 and 78% and positive predictive values of 96 and 92%, respectively. Despite the recovery of significantly more cells (as shown by detection of more cellular DNA by using NPA specimens), virus was detected by the IFA technique or ELISA at similar frequencies in paired specimens. However, virus was recovered more often from NPA than NPS specimens by cell culture, and ELISA optical density readings and the number of RSV-positive fluorescing cells were greater for NPA specimens. NPA specimen collection was less traumatic for the patient, was an easier procedure for the physician to perform, and provided a superior laboratory specimen for RSV diagnosis than the NPS technique.

Animals↗

Right-sided juxtaposition of the atrial appendages in an anencephalic.

A case of the uncommon right-sided juxtaposition of the atrial appendages is presented--to our knowledge the 17th instance reported so far. The interest of this case resides in the fact that there were no associated major cardiac anomalies, and that it occurred in an anencephalic female. It is the second reported case of this association. Both cases had in common the presence of ventricular D-looping, normal relationships of the great arteries and only minor cardiac defects. The absence of major cardiac anomalies, in contrast to the more common left-sided juxtaposition, and the association with anencephaly which has not yet been reported in the left-sided variant of juxtaposition, are features which have to be emphasised.

Anencephaly↗

Nonspecific vaginitis among women attending a sexually transmitted diseases clinic.

We studied 33 women who presented to the sexually transmitted disease clinic at Boston City Hospital (Boston, Massachusetts); most of the women attended the clinic for management of uncomplicated anogenital gonococcal infection. A clinical diagnosis of nonspecific vaginitis was based on the finding of three or more of the following: homogeneous vaginal discharge, vaginal pH of greater than 4.5, abnormal odor on the addition of 10% KOH to vaginal secretions, and the presence of "clue cells." This diagnosis was assigned to 21 (64%) of the 33 women; it was confirmed by use of gas-liquid chromatographic analysis of vaginal secretions (succinate:lactate ratio of greater than 0.4 or detection of priopionate or butyrate) in 20 of the 21 women. About two-thirds of the women with nonspecific vaginitis were symptom-free. We conclude that nonspecific vaginitis is exceedingly common among women attending an inner-city clinic for sexually transmitted diseases and that most of the infected women are asymptomatic.

Adult↗