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H Howard

Publications and source records attributed to H Howard.

14 recordsLinked to original sources
PubMed1998

Restriction map of a YAC and cosmid contig encompassing the oculopharyngeal muscular dystrophy candidate region on chromosome 14q11.2-q13.

As part of our effort to clone positionally the oculopharyngeal muscular dystrophy (OPMD) gene, we constructed a YAC contig, a cosmid contig, and an EcoRI restriction map of the OPMD candidate region. The YAC contig spans more than 2 Mb and encompasses the loci D14S283 and D14S990 and the cardiac alpha and beta myosin heavy chain genes (MYH6 and MYH7). A 700-kb cosmid contig containing the D14S990 and the myosin genes and a long-range restriction map covering the region between D14S990 and the MYH6 and MYH7 gene cluster were established. A detailed EcoRI restriction map of the cosmid contig was determined, and five putative CpG islands were identified. Based on these data, the four loci were mapped within an approximately 600-kb region with the following centromere to telomere order: D14S283, D14S990, MYH6, and MYH7. The YAC and cosmid contigs will facilitate the identification of genes lying within the OPMD candidate interval.

Chromosome Walking↗
PubMed1998

Consequences for fetus and neonate of maternal red cell allo-immunisation.

AIMS: To study the distribution of clinically important red cell antibodies in pregnancy, and the associated fetal and neonatal morbidity and mortality. METHODS: The case notes of women with clinically important red cell antibodies identified in their serum during pregnancy were reviewed. RESULTS: During a 12 month period 22,264 women were referred for antenatal screening. Clinically important red cell antibodies were detected in 244 (1%). Of these, 100 were anti-D and 144 were non-RhD antibodies. There were three intrauterine deaths, three fetuses required intrauterine transfusion, 10 neonates were transfused, 27 others had phototherapy, and 27 with a positive direct antiglobulin test received no treatment. Early fetal losses occurred in the presence of both high and low levels of anti-D. CONCLUSIONS: Anti-D remains the most common clinically important antibody in pregnancy, and accounts for the greatest fetal and neonatal morbidity and mortality. Of the other antibodies detected, anti-c was associated with most neonatal morbidity. The production of many of the non-D antibodies detected could be avoided by the use of selected red cells when transfusing pre-menopausal women.

Blood Group Antigens↗
PubMed1997

Metabolism and excretion of the novel antipsychotic drug ziprasidone in rats after oral administration of a mixture of 14C- and 3H-labeled ziprasidone.

The metabolism and excretion of ziprasidone (5-[2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-yl]ethyl]-6-++ +chloroindolin-2-one hydrochloride hydrate) were studied in Long Evans rats after oral administration of a single dose of a mixture of 14C- and 3H-labeled ziprasidone. The radioactive dose was quantitatively recovered over 7 days in both male and female rats. The percentage of the dose excreted in urine, bile, and feces of rats was 21.6, 19.2, and 55.6%, respectively. The total excretion in urine and bile suggested that at least 41% of the drug was absorbed. Absorption of ziprasidone was rapid, and the mean plasma concentrations of the unchanged drug and metabolites were slightly higher in the female rats than in the males. The maximal plasma concentrations for ziprasidone and metabolites were reached at 1 hr in both male and female rats. Based on AUC (0-12 hr) values, approximately 59 and 52% of the circulating radioactivity (average of 14C and 3H) was attributable to metabolites in male and female rats, respectively. Ziprasidone was extensively metabolized in rats, and only a small amount of ziprasidone was excreted as unchanged drug. Twelve metabolites were identified by ion spray LC/MS, using a combination of parent ion and product ion scanning techniques. The structures of eight metabolites were unambiguously confirmed by coelution on HPLC with synthetic standards, and four additional metabolites were partially identified. There was a gender-related difference in the excretion of urinary metabolites in Long Evans rats. The major route of metabolism in male rats involved N-dealkylation. In female rats the major metabolites were due to oxidation at the benzisothiazole ring. Based on the structures of these metabolites, four major and two minor routes of metabolism of ziprasidone were identified. The major routes included 1) N-dealkylation of the ethyl side chain attached to the piperazinyl nitrogen, 2) oxidation at the sulfur, resulting in the formation of sulfoxide and sulfone, 3) oxidation on the benzisothiazole moiety (other than sulfur), and 4) hydration of the C==N bond and subsequent oxidation at the sulfur of the benzisothiazole moiety. The minor routes involved N-oxidation on the piperazine ring and hydrolysis of the oxindole moiety.

Administration, Oral↗
PubMed1988

Pathogenicity of rotavirus in rabbits.

The role of rotavirus in diarrheal disease of rabbits was investigated, and a model for human rotavirus infection was established. Orogastric inoculation of 8- and 12-week-old New Zealand White rabbits with a rabbit strain of rotavirus (L:ALA:84) resulted in fecal shedding of virus for 6 to 8 days from 2 to 5 days after inoculation. Most rabbits exhibited diarrhea, coincident with the onset of viral shedding, which persisted for 2 to 4 days. Diarrhea was characterized by soft or fluid stools and fecal staining of the perineum. Inoculation of 3-week-old rabbits resulted in a briefer period of viral shedding and diarrhea of a milder nature. Histopathologic examination during the period of viral shedding revealed a mild, nonsuppurative enteritis. Inoculated rabbits exhibited antibodies in serum to rotavirus by enzyme-linked immunosorbent assay. Sham-inoculated or uninoculated rabbits maintained in the same cage or the same room with inoculated rabbits acquired rotavirus infection. The mild diarrheal disease which resulted with a rotavirus isolate from severe field cases suggests that cofactors were involved.

Animals↗
PubMed1987

Epidemiology and etiology of diarrhea in colony-born Macaca nemestrina.

The epidemiology of diarrhea in colony-born M. nemestrina was studied in 205 neonates and infants in an Infant Primate Research Laboratory (IPRL), and in 248 neonates, juveniles and adolescents up to 4 years of age at a separate breeding and holding facility (Primate Field Station, PFS). Computerized medical records of individual animals over a 5-year period were analyzed to determine the incidence of diarrhea; age, duration and number of episodes; mortality and etiology. The incidence of diarrhea at the IPRL was highest in infants at less than 1 month of age (18.6 cases per 1000 animal days) and at 1-6 months olds (2.0 cases per 1000 animals days). Many infants had multiple episodes. All episodes were less than 10 days in duration. Mortality was low. At the PFS, the highest incidence occurred in infants at 6-12 months of age (1.36 cases per 1000 animal days). Multiple episodes were less common. Duration was variable. The infectious agents diagnosed at both facilities were Shigella, Campylobacter and Cryptosporidium. No pathogens were identified in many episodes. Shigella was more common at PFS than at the IPRL. Chronic diarrhea occurred in approximately 10% of animals at PFS. Intestinal amyloidosis and retroperitoneal fibromatosis were found in 13 animals with chronic diarrhea. Further studies are needed to determine the pathogenesis of chronic diarrhea, the etiologic significance of Campylobacter, and the causes of diarrhea when no pathogens are isolated.

Animals↗
PubMed1986

Comparison of a slow-release trimethoprim with co-trimoxazole: efficacy and selection of resistance in the Enterobacteriaceae.

One hundred and fifty one patients with symptoms of urinary tract infection were treated randomly in a double blind study with a slow release form of trimethoprim or with co-trimoxazole. Similar cure rates were seen. There was no difference between the proportions of patients in the two groups who acquired trimethoprim-resistant Enterobacteriaceae. Further clinical trials with slow release trimethoprim should be performed.

Adult↗