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Biomedical subjects

H Williams

Publications and source records attributed to H Williams.

At least 127 records · Page 7Linked to original sources

Genetic and physical mapping of 2q35 in the region of the NRAMP and IL8R genes: identification of a polymorphic repeat in exon 2 of NRAMP.

Recent interest has focused on the region of conserved synteny between mouse chromosome 1 and human 2q33-q37, particularly over the region encoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate Nramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluster. In this paper, identification of a restriction fragment length polymorphism in the IL8RB gene in 35 pedigrees previously typed for markers in the 2q33-q37 interval provided evidence (lod scores > 3) for linkage between IL8RB and the 2q34-q35 markers FN1, TNP1, VIL1, and DES. Physical mapping, using yeast artificial chromosomes isolated with VIL1, confirmed that IL8RA, IL8RB, and the IL8RB pseudogene map within the NRAMP-VIL1 interval, with the physical distance (155 kb) from 5' LSH to 3' VIL1 representing approximately 3-fold that observed in the mouse. Partial sequencing of NRAMP confirmed the presence of the N-terminal proline/serine-rich putative SH3 binding domain in exon 2 of the human gene. Further analysis of Brazilian leprosy and visceral leishmaniasis pedigrees identified a rare second allele varying in a 9-nucleotide repeat motif of the exon 2 sequence but segregating independently of the disease phenotype.

Animals↗

Inhibition of calcineurin by a novel FK-506-binding protein.

FK-506, a potent immunosuppressive drug, acts during the commitment phase of T-lymphocyte activation to block a subset of calcium-associated events necessary for transcription of certain early lymphokine genes. The drug binds to an abundant, cytosolic 11.8-kDa protein termed the FK-506-binding protein (FKBP12). The FKBP12.FK-506 complex inhibits calcineurin, a calcium-dependent phosphatase that is a component of the signal transduction pathway leading to early lymphokine gene transcription. FKBP12 is one member of a growing gene family. Prior to this report, all other FKBP family members had been irrelevant to the mechanism of action of FK-506 because no other FKBP.FK-506 complexes were able to bind and inhibit calcineurin. Here, we report the purification and characterization of a novel FK-506-binding protein, FKBP12.6. Having 85% amino acid sequence identity to FKBP12, FKBP12.6 is, among the FKBPs, most closely related to FKBP12. When complexed with FK-506, FKBP12.6 binds to and inhibits calcineurin, making it only the second FKBP discovered thus far to do so. The ability to inhibit calcineurin establishes the potential relevance of FKBP12.6 to the immunosuppressive or toxic side effects of FK-506.

Amino Acid Isomerases↗

Genetic regulation of leishmanial and mycobacterial infections: the Lsh/Ity/Bcg gene story continues.

A common basis to genetic regulation of leishmanial and mycobacterial infections is provided by the action of the murine Lsh/Ity/Bcg gene in controlling the priming/activation of macrophages for antimicrobial activity. This relies on the TNF-alpha-dependent sustained expression of the inducible nitric oxide synthase (iNOS) gene responsible for the generation of large amounts of toxic nitric oxide (NO). The Lsh/Ity/Bcg gene has many pleiotropic effects, including differential expression of the early response gene KC following stimulation of macrophages with bacterial lipopolysaccharide (LPS) and mycobacterial lipoarabinomannan (LAM). The major signal transduction pathway involved in KC induction requires the generation of low levels of NO via constitutive nitric oxide synthase (cNOS) activity, leading to activation of guanylate cyclase and the cGMP-dependent kinase pathway. NO therefore appears to provide a common link between the early influence of Lsh in regulating the expression of genes which mediate many pleiotropic effects, and the later production of NO as the final effector mechanism for kill. The recently cloned candidate for Lsh/Ity/Bcg, designated Nramp for Natural resistance associated macrophage protein, encodes a polytopic integral membrane protein that has structural features common to prokaryotic and eukaryotic transporters and includes a conserved binding-protein-dependent transport motif which may be involved in interaction with peripheral ATP-binding subunits. The N-terminal sequence also carries a proline/serine rich putative SH3 binding domain, consistent with a role for tyrosine kinases in regulating Nramp function. (ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

The incidence of histological chorioamnionitis in IVF/GIFT preterm births.

A retrospective case control study was designed to investigate the role of subclinical infection as a risk factor for the high rate of preterm deliveries in IVF/GIFT pregnancies. The cases and the controls were identified from the records of consecutive livebirths of < 35 weeks' gestational age (GA), at King George V Hospital from 1987-1993. Fifty one singleton and 58 twin IVF/GIFT preterm births were matched for GA, year of birth, plurality, maternal age, parity, preclampsia and antepartum haemorrhage. As a marker of subclinical infection, the incidence of histological chorioamnionitis (HCA) in the 2 groups (as defined by the standardized, semiquantitative method of Benirschke) was compared. The matched variables did not differ significantly between the IVF/GIFT group and the control group. No significant difference in the incidence of HCA was detected between IVF/GIFT and control groups for singletons or twins. Overall 24% of IVF/GIFT and 30% of controls showed evidence of HCA, odds ratio (95% confidence intervals), 0.72 (0.40-1.31). This study showed no evidence that the incidence of HCA, is significantly increased in IVF/GIFT preterm births compared with other matched, preterm births. Therefore, we conclude that subclinical infection/inflammation cannot explain the 4-fold increase in preterm births in the IVF/GIFT population.

Adult↗

Do follow-up home visits by military nurses of chronically ill medical patients reduce readmissions?

The study included patients admitted three times or more. Patients were 45 years of age or older and lived within 25 miles of the hospital. Patients were randomly assigned to a control group and those that received home visits. Patients were visited by the RN within 7 days after discharge. Each patient had nine visits over the next 3 months. Seventy-five patients participated in this study. The average age of the sample was 66.12 +/- 16 years. There was an equal number of men and women in the two groups. The nurses made 130 home visits. During these visits, 38 interventions were accomplished. These interventions allowed the patients to remain at home. Prior to this study, the incidence of readmission for these patients was notable. This study showed that home visits with appropriate interventions by military staff nurses reduces the incidence of rehospitalization.

Aged↗

A model for long-term intracochlear administration of pharmacologic agents.

A technique is described that provides a method to study the effects of intracochlear pharmacologic agents on the degenerating auditory nerve. The model involves implanting a guinea pig with an osmotic minipump that allows slow perfusion of the cochlea over a period of hours to days with up to two water soluble substances. Neomycin and horseradish peroxidase, whose histopathologic effects on the cochlea are well known, are used in the present study to validate the efficacy of the system.

Animals↗

Oral and dental complications in dieting disorders.

This study investigated the oral status and dental complications in patients with both anorexia and bulimia nervosa. Results revealed that prolonged periods of dietary restraint in anorexic patients did not result in changes to bacteria associated in dental caries. Furthermore, patients did not have lower decay rates or salivary flow but did have more acidic saliva. Moreover, both groups of patients revealed changes indicative of gingivitis and gingival recession but not necessarily of periodontitis when compared to control subjects.

Adolescent↗

Temporal patterning of song production: participation of nucleus uvaeformis of the thalamus.

Birdsong is a learned vocal behavior used in intraspecific communication. The motor pathway serving learned vocalizations includes the forebrain nuclei NIf, HVC, and RA; RA projects to midbrain and brain stem areas that control the temporal and acoustic features of song. Nucleus Uvaeformis of the thalamus (Uva) sends input to two of these forebrain nuclei (NIf and HVC) but has not been thought to be important for song production. We used three experimental approaches to reexamine Uva's function in adult male zebra finches. (1) Electrical stimulation applied to Uva activated HVC and the vocal motor pathway, including tracheosyringeal motor neurons that innervate the bird's vocal organ. (2) Bilateral lesions of Uva including the dorso-medial portion of the nucleus affected the normal temporal organization of song. (3) Chronic multiunit recordings from Uva during normal song and calls show bursts of premotor activity that lead the onset of some song components, and also larger bursts that mark the end of complete song motifs. These results implicate Uva in the production of learned vocalizations, and further suggest that Uva contributes more to the temporal structure than to the acoustic characteristics of song.

Animals↗

Escherichia coli leader peptidase: production of an active form lacking a requirement for detergent and development of peptide substrates.

The report by Zimmermann et al. (J. Biol. Chem. 257, 1982, 6529-6536) that the active site of Escherichia coli leader peptidase (LPase) is located in the periplasm led us to explore the possibility that soluble, active short forms of LPase could be produced. Detergent-free delta 2-75 mutant protein (LPase-sf) lacking the two N-terminal transmembrane spanning and the cytoplasmic domains was produced in high yield. The mass of the protein determined by electrospray ionization mass spectrometry was 27,952 amu. The increase of 42 amu over that predicted by the expected amino acid sequence indicates that the N-terminus of LPase-sf is acetylated. This is consistent with the inability to obtain an N-terminal sequence. LPase-sf lacks the site of autolysis present in LPase, thus circumventing problems associated with enzyme autocatalytic instability. LPase-sf and wild type LPase displayed comparable activity versus two peptide substrates. The peptides, based upon the cleavage sites of procoat and the precursor of maltose binding protein, were processed at the expected sites. In addition, the activity of both LPase's was not inhibited by classical inhibitors of the four classes of proteases. LPase-sf displayed similar activity in the presence and absence of detergent. Wild type LPase displayed specificity for alanine in the P1 subsite of the peptide WSASALX*KI and did not hydrolyze peptides with glycine, valine, or serine in that position. The availability of a detergent-free active form of LPase should facilitate mechanistic and structural studies.

Amino Acid Sequence↗

M.D.M.A. ("Ecstasy"); a case of possible drug-induced psychosis.

3, 4, Methylenedioxymetamphetamine (M.D.M.A., Ecstasy) is a modified amphetamine with stimulant and hallucinogenic properties. Ecstasy has been increasingly abused in Dublin in recent years. It is commonly perceived by users as a safe drug. We report a case of prolonged psychosis following brief recreational use of Ecstasy.

3,4-Methylenedioxyamphetamine↗

Nosocomial spread of Staphylococcus aureus showing intermediate resistance to methicillin.

A nosocomial outbreak of infection and colonization involving six patients and caused by a strain of Staphylococcus aureus showing intermediate resistance to methicillin (MIC = 4-8 mg l-1) is described. The outbreak was associated with skin-carriage of the epidemic strain by a nurse suffering from severe eczema. The reduced susceptibility of the outbreak strain to methicillin was associated with beta-lactamase production. Elimination or inhibition of beta-lactamase activity produced a two-fold decrease in methicillin MIC. There was no evidence for the presence of either penicillin-binding protein 2a or the corresponding mec gene, which mediate resistance in fully methicillin-resistant strains.

Carrier State↗

Synteny mapping in the horse using horse-mouse heterohybridomas.

In a study of 35 horse-mouse heterohybridoma cell lines, synteny in the horse was found between LDHB, PEPB and IGF1 and between NP, MPI and IDH2. A synteny between ADA and PEPC was also indicated. The loci for horse immunoglobulin light chain (IgL) genes and for LDHA were independent.

Adenosine Deaminase↗

Psychopathology in primary care patients: a four year study in rural and urban settings in Zimbabwe.

It has been argued that prevalence rates for psychopathology in Africa are stable over time and setting. There are, however, few longitudinal studies, and these conclusions are mainly based upon point prevalence studies. It has also been observed that African patients present with somatic symptoms, a feature argued to impede detection. Furthermore, it has been argued that such multiple somatic symptoms (three or more) are diagnostic of psychopathology. The present study examined these questions in the context of a longitudinal design. Prescriptive screenings of both rural and urban primary care patients were undertaken, and repeated the following year. The measures indicate that there is no significant difference in the rates in urban and rural settings, nor any difference in the rates over time. There were few differences between cases and non-cases in demographic characteristics, but there were differences in the clinical characteristics of the two groups. Cases tended to present with more symptoms than non-cases, thus corroborating earlier findings. In addition, the symptoms of cases tended to implicate more physiological systems than non-cases.

Adolescent↗

Human immunodeficiency virus infection among patients in a gynecology emergency department.

OBJECTIVE: To determine the extent of human immunodeficiency virus (HIV) infection risk factors and the relationship to the clinical diagnosis in women seen in a busy inner-city gynecology emergency department. METHODS: We performed a cross-sectional survey by offering routine voluntary HIV-1 antibody screening and obtaining HIV risk behavior profiles in 1033 (35%) of 2952 women seeking care in our gynecology emergency department during a 5-week period. RESULTS: The HIV seroprevalence was 2%. Six (35%) of the infected women reported a history of intravenous drug use, five (29%) reported a history of crack cocaine use, and five (29%) reported no risk factors for infection. Seropositive women were more likely than were seronegative women to have clinical symptoms consistent with pelvic inflammatory disease (18 versus 3%; P < .01). CONCLUSION: These data suggest that women attending the gynecology emergency room in our hospital are at substantial risk for HIV infection.

Acquired Immunodeficiency Syndrome↗

Are viral warts seen more commonly in children with eczema?

BACKGROUND AND DESIGN: We sought to test the hypothesis that warts are seen more commonly in individuals with eczema by analyzing skin examination data from a national birth cohort study of 9263 British children born between March 3 and 9, 1958. RESULTS: Warts were seen less frequently in those with visible eczema at ages 11 and 16 years (relative risk, 0.60; 95% confidence intervals, 0.37 to 0.95; P = .03). This inverse association persisted after adjustment for potential confounders and was consistent within each age and sex group for children with a history of eczema who did not have visible eczema at the time of examination and for children with asthma/wheezy bronchitis regardless of eczema status. Visible acne or psoriasis was not associated with a decreased prevalence of warts. CONCLUSIONS: These findings contradict previous suggestions of an increased risk of viral warts in atopic eczema and raise new questions regarding the role of cell-mediated immunity in atopic subjects.

Acne Vulgaris↗