Search PubMed⌕ Search

Biomedical subjects

D Wilson

Publications and source records attributed to D Wilson.

At least 325 records · Page 18Linked to original sources

Genetic dissection of autoimmune type I diabetes in the BB rat.

The BB rat is among the best models of insulin-dependent diabetes mellitus--with onset and pathogenesis closely resembling the human disease. One unusual feature is a severe T-cell lymphopenia, which appears to be inherited as a recessive trait controlled by a single gene, Lyp. Based on genetic analysis of several crosses, we show that development of diabetes involves at least three genes: Lyp, which is tightly linked to the neuropeptide Y (Npy) gene on chromosome 4, a gene linked to the major histocompatibility complex (MHC) on chromosome 20, and a third unmapped gene for which the Fischer rat strain carries an allele conferring resistance.

Animals↗

Anterior cervical discectomy and fusion. A comparison of techniques in an animal model.

An animal model for three-level anterior cervical discectomy and fusion was established in the goat. Twenty-one goats underwent surgery, with seven goats in each of three experimental groups. In Group I, all seven goats underwent three-level anterior cervical discectomy without fusion. In Group II, each of the seven goats had a three-level discectomy with autogenous bone performed according to the Smith-Robinson technique. In Group III, fresh-frozen allograft bone was used for each of the three-level discectomy and fusion. Each goat was then killed after 12 weeks. Analysis consisted of radiographic review, fluorochrome labeling, biomechanical rigidity and flexion and extension, axial compressive load, and torsion. Histologic analysis was also performed for evidence of fusion and vertebral body histomorphometric analysis. The analysis of results showed that radiographic union was judged to have occurred in 0 of 21 Group I disc spaces, 10 of 21 Group II disc spaces, and 8 of 21 Group III disc spaces. Histologic fusion was judged to have occurred in 0 of 21 Group I goats, 10 of 21 Group II goats, and 0 of 21 Group III goats. The histologic fusion rate was significantly higher in Group II than either Group I or Group III. Biomechanically, the spines that had autogenous bone grafting (Group II) were significantly stiffer in compressive axial load and in extension. Both Group II and Group III were stiffer in flexion than Group I. An evaluation of the peri-endplate vascularity showed that the vascularity measured 10.4% in Group I, 16.7% in Group II, and 8.5% in Group III.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recurrent neuroleptic malignant syndrome in a man with mild mental handicap.

A case of recurrent neuroleptic malignant syndrome (NMS) occurring in a 29-year-old man with mild mental handicap and a superadded psychotic disorder is described. The case illustrates a number of unusual features such as recurrent episodes and resolution with administration of intravenous Procyclidine. The possibility of NMS occurring in people with mental handicap, who have a high level of neuroleptic drug prescription, must be borne in mind.

Adult↗

The short-term psychological health of alcoholic and non-alcoholic liver transplant recipients.

In response to limited resources and overwhelming clinical need, we previously developed an approach to alcoholic patient selection for liver transplant based on factors reported to predict short- and long-term sobriety in prospective studies of alcoholics. The present study reports follow-up data comparing alcohol dependent (n = 22, DSM-3-R criteria) and non-dependent (n = 39) subjects followed from 6 months to 3 years post-transplant. Nine percent of the alcoholics had returned to symptomatic drinking with 14% reporting some exposure to ethyl alcohol. Nearly half (46%) of the non-alcoholic group reported occasional social alcohol use. The alcoholic patients were less likely to be in their first marriage and more likely to be asked about alcohol use at follow-up clinic visits. In most other respects the two groups resembled each other more often than they differed. The alcoholic group reported continued high rates of prognostic factors associated with long-term abstinence although the content of these shifted noticeably between pre- and postoperative assessment. Members of both groups reported high frequencies of medication side effects, of missed doses of medications, and of depressive symptoms. Most felt the transplant had improved their lives but had brought on significant financial burden. There were no differences in subjective appraisals of either psychological or physical health between the two groups. These follow-up data suggest that carefully selected alcohol dependent patients will do as well as non-dependent patients after liver transplant.

Adaptation, Psychological↗

Hearing loss--an underestimated public health problem.

Estimates of hearing loss in Australia, collected over the last decade and a half, have reported a prevalence rate ranging from 0.1 to 7 per cent. This survey of a random sample of South Australians provides, depending upon definition, two estimates of 15 and 19 per cent. These data suggest that hearing loss has been underestimated as a public health problem. The need for an epidemiological study which measures actual hearing impairment, which can be used to develop an appropriate public health response, is discussed.

Adolescent↗

Characterization of a cryptic gene pair from Neisseria gonorrhoeae that is common to pathogenic Neisseria species.

A pair of genes, each of which produces in Escherichia coli a 20-kDa, periplasmically localized protein that cross-reacts with anti-rpoN monoclonal antibody, was isolated from Neisseria gonorrhoeae. Homologs of the two genes were detected in pathogenic Neisseria species but not in commensal species. These genes are designated cnp1 and cnp2 (cryptic neisserial protein).

Amino Acid Sequence↗

The local side effects of transdermally absorbed nicotine.

Percutaneous nicotine administration induces predominant sudorific and rubiform responses in the skin which may be accompanied by subtle piloerection, hyperalgesia and pruritus (although these signs are not overtly manifest). These dermal responses are complex and mechanisms have been proposed for the direct nicotine-stimulation of sweat glands, piloerection and vasoconstriction. These reactions are accompanied by secondary activation and release of vasodilator peptides which produce a predominating vasodilator tone following topical administration, this response masking the direct axon reflex-mediated vasoconstriction.

Administration, Cutaneous↗

Transfer and metabolism of retinol by the perfused human placenta.

The transfer and metabolism of retinol by human placenta was investigated using an in vitro perfusion system with independent maternal and fetal circulations. 3H-retinol bound to albumin added to the maternal perfusate was rapidly taken up and concentrated by the placenta to levels 16.5 +/- 5.28 times the maternal perfusate. Approximately 8% of the retinol retained in the placenta was esterified. No metabolites were detected in the perfusates. Perfusion of placenta with retinol bound to retinol-binding protein (RBP) reduced the placental concentration to 4.4 +/- 1.72 times the maternal concentration and eliminated evidence of metabolism. The transfer rate of RBP:3H-retinol was less than that of albumin:14C-retinol when measured concurrently in three experiments (clearances 0.11 versus 0.75 mL/min, 0.21 versus 1.7 mL/min, and 0.29 versus 0.48 mL/min, respectively). Transfer of the radioactive retinol was more rapid than 125I-RBP or albumin, indicating that retinol was transferred independently of the proteins. The transfer index of retinol (clearance retinol:clearance L-glucose) was 0.73 +/- 0.085 compared to 2.1 +/- 0.36 for thiamin and 3.4 +/- 0.95 for riboflavin, both water-soluble vitamins with active transport systems. The retinol transferred to the fetal perfusate is not bound to RBP, as demonstrated by gel filtration chromatography and chromatography on a transthyretin affinity column, despite the availability of RBP in the cord serum added to the perfusate. The endogenous retinol in the cord serum is bound to RBP.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport, Active↗

Psychometric properties of the revised UCLA Loneliness Scale and two short-form measures of loneliness in Zimbabwe.

The cross-cultural reliability in Zimbabwe of the Revised University of California at Los Angeles (UCLA) Loneliness Scale and two short forms of the Revised UCLA Loneliness Scale were investigated. Subjects comprised a sample of 1,354 adolescents and another sample of 754 adults. The reliability of the Revised UCLA Loneliness Scale was acceptable. The internal consistency of an eight-item short form of the Revised UCLA Loneliness Scale was adequate, but the reliability of a four-item short form was low. Factor analysis of the Revised UCLA Loneliness Scale, which yielded two factors similar to those reported in North America by Zakahi and Duran (1982) supported the construct validity of the Revised UCLA Loneliness Scale in Zimbabwe. The Revised UCLA Loneliness Scale and the eight-item short form were highly correlated, but this association was spuriously elevated by the fact the eight-item short form is part of the full scale. Factor analysis of the eight-item short form suggested that this scale does not consistently reflect the factor structure of the full scale. We concluded that the Revised UCLA Loneliness Scale possesses acceptable reliability and factorial validity in Zimbabwe and that the eight-item version is superior to the four-item form of the Revised UCLA Loneliness Scale as a short loneliness measure. However, additional refinements may be needed to further improve the eight-item short version.

Adolescent↗

Molecular genetic study of the frequency of monosomy 22q11 in DiGeorge syndrome.

It is well established that DiGeorge syndrome (DGS) may be associated with monosomy of 22q11-pter. More recently, DNA probes have been used to detect hemizygosity for this region in patients with no visible karyotypic abnormality. However, DGS has also been described in cases where the cytogenetic abnormality does not involve 22q11; for instance, four cases of 10p- have been reported. In this study we have prospectively analyzed patients, by using DNA markers from 22q11, to assess the frequency of 22q11 rearrangements in DGS. Twenty-one of 22 cases had demonstrable hemizygosity for 22q11. Cytogenetic analysis had identified interstitial deletion in 6 of 16 cases tested; in 6 other cases no karyotype was available. When these results are combined with those from our previous studies, 33 of 35 DGS patients had chromosome 22q11 deletions detectable by DNA probes.

Chromosome Deletion↗

Workplace smoking restrictions, occupational status, and reduced cigarette consumption.

Reductions in workday cigarette consumption among indoor workers subject to different levels of smoking restriction were examined using representative population data for both blue-collar and white-collar workers. Regardless of whether workplace smoking bans were total or applied only to the usual work station, reported workday cigarette consumption was reduced by approximately five cigarettes per day compared with leisure-day consumption. This was in contrast to there being no difference between workday and leisure-day consumption among those who had no ban on smoking at their usual work station. This pattern of findings applied to all occupational-status groups, after controlling for sex and number of cigarettes smoked on a leisure day. These results are discussed with reference to potential public-health benefits and to implications for reduced retail sales of cigarettes.

Adult↗

Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity.

The human epithelial mucin which is the product of the MUC1 gene is expressed by many carcinomas, including those of breast, ovary, colon, and lung. The core protein is aberrantly glycosylated in the tumors resulting in the exposure or appearance of novel epitopes. To examine the possibility of using the MUC1 gene and its products in active immunization against breast and other carcinomas, we have developed a syngeneic mouse model, by transfecting the gene into the mouse mammary epithelial tumor cell 410.4. An 8.3-kilobase EcoRI fragment of the gene was transfected using the expression vector pEMSV scribe alpha 2. Transcripts of the correct size, initiating from the transcriptional start site seen in human cells, were observed in the transfectants. The mucin was expressed in the cytoplasm and in the membrane, and the glycosylation pattern appeared to be similar to that seen in human tumor cells, since the core protein epitopes recognized by antibodies HMFG-1, HMFG-2, and SM-3 were exposed. The 410.4 transfectants expressing the human mucin showed a reduction in tumor incidence at low inocula and a delay in tumor growth at higher inocula. Pretreatment with 10(4) transfected cells could inhibit the development of tumors from a subsequent inoculum of 10(6) transfectants, but had no effect on the tumor development of the untransfected 410.4 cells. Our results suggest that the human mucin expressed by the 410.4 cells may mobilize an immune response which inhibits tumor development. They also indicate that the mouse model will be useful for evaluation of efficacy of immunogens based on the MUC1 gene and its product.

Animals↗

Comparison of protein synthesis inhibition kinetics and cell killing induced by immunotoxins.

Immunotoxins comprised of a monoclonal antibody covalently coupled to recombinant ricin A chain or to a binding-defective form of diphtheria toxin were compared with respect to their rates of protein synthesis inhibition and efficiencies of killing target cells. Protein synthesis inhibition rates were established by measuring the incorporation of L-[14C]leucine in toxin-treated cells relative to untreated cells at several times after exposure of cells to an immunotoxin. Cell killing was assessed by a limiting dilution assay which measures the number of cells surviving toxin treatment relative to untreated cells. At equivalent protein concentrations, the diphtheria toxin immunotoxin inhibited protein synthesis significantly more rapidly than the ricin A immunotoxin but, contrary to previous predictions, achieved a significantly lower cell kill. Thus, the kinetics of protein synthesis inactivation do not necessarily correlate with killing efficiencies. Possible explanations for these results are that the effect of the diphtheria toxin immunotoxin on protein synthesis is partially reversible or that the diphtheria toxin immunotoxin enters the cytosol at a faster rate than the ricin A immunotoxin but also is degraded at a faster rate.

Antibodies, Monoclonal↗

Diabetes segregates as a single locus in crosses between inbred BB rats prone or resistant to diabetes.

Diabetes-prone (DP) BB rats spontaneously develop insulin-dependent diabetes resembling type 1 diabetes mellitus in man. They also exhibit lifelong T cell deficiency. The segregation of both diabetes and lymphopenia was studied in crosses between this inbred line of rats and the related but nondiabetic and nonlymphopenic inbred diabetes-resistant (DR) BB rat line. Diabetes segregated as a single, autosomal recessive trait and was always accompanied by lymphopenia. Among the limited number of differences in the genomic DNA sequences of the two lines, DP and DR BB, one may account for the development of diabetes and lymphopenia in the DP BB rats. It may be possible to screen the genomic DNA for such differences to detect a marker for the phenotypes.

Aging↗