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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 487 records · Page 27Linked to original sources

Recruitment strategies for black women at risk for noninsulin-dependent diabetes mellitus into exercise protocols: a qualitative assessment.

The literature is devoid of any specific data describing exercise therapy in blacks at risk for diabetes. The increasing and striking prevalence of obesity and diabetes among several indigenous populations demonstrates the unfortunate interplay between genetic predisposition and a "modern" sedentary lifestyle. Any successful intervention to reduce the risk of acquiring or attenuating the severity of diabetes must focus on behavioral, cultural, psychosocial, and social factors that are amenable to change. Thus, the objective of this study is to present qualitative data that can be useful in the recruitment of blacks into exercise protocols that could prove to be beneficial in preventing diabetes. Focus groups were conducted on 57 black women residing in Washington, DC, Columbia, Maryland, and Hartford, Connecticut. Barriers to exercising included lack of child care, lack of transportation, neighborhood constraints, and family. Incentives that would increase black women's ability to participate in an exercise protocols include transportation, child care, and an exercise environment that includes blacks.

Adult↗

Taking the problem oriented medical record forward.

The problem oriented medical record (POMR) has proved to be very successful in providing a structure that helps doctors record their notes about patients, and view those notes subsequently in a manner that quickly gives them a good understanding of that patients history. This approach has been validated by the American Institute of Medicine. With the increased use of computer systems that implement the POMR by doctors, the limitations of this structure have become apparent, and there is clearly scope for developing the model further to improve the quality of the data recorded, and adding meaning to it. This paper describes some of the limitations of the POMR, and discusses a number of areas in which it may be extended. Crucially, this is done in a manner which is both implementable, and usable. The extensions explored include some types of entity including encounters, episodes and subproblems; and an alternative view-the Timeline. The terminology used for the extensions is clarified. Mechanisms by which these extensions have been implemented are described. Ways in which systems can manage these extensions automatically are suggested. Such implementations are constrained by the need not to allow the demands of the computer to intrude into the patient encounter. They are also constrained by the requirements for reporting by professional and governmental institutions, and by what is pragmatically feasible in software and hardware.

Computer Systems↗

Linkage, association and mutational analysis of the dopamine D3 receptor gene in schizophrenia.

This study follows the observation of an association between homozygosity of an Mscl polymorphism in exon 1 and schizophrenia, which gives rise to a glycine to serine substitution and may alter the functional properties of the receptor. Alternatively the polymorphism may not itself be of functional significance but may be in linkage disequilibrium with another genetic variant in the coding or regulatory regions. To examine the second possibility we have screened all six exons of DRD3 by single-stranded conformational polymorphism analysis (SSCP) in 36 cases and 36 controls. Our findings suggest that the gene is highly conserved since we found no other mutations which alter protein structure. However we did detect a 5-bp deletion in the 3' intronic sequence flanking exon 5 which occurred in 7-8% of subjects within both case and control samples. A single bp substitution (g to a) in exon 3, which does not alter an amino acid was found in one affected individual. In addition we carried out a linkage study of 24 families multiply affected with schizophrenia and a non-parametric linkage study of 90 affected sibling pairs. These studies give no support for either major or moderate gene effects on schizophrenia susceptibility. Finally we have extended our association sample and observe a non-significant excess of homozygotes for the Mscl polymorphism in the sample overall (chi 2 = 2.09, 1 d.f., P = 0.15). The excess of homozygotes is specific to males (chi 2 = 4.617, 1 d.f., P = 0.032) and not females (chi 2 = 0.243, 1 d.f., NS). When these data are added to our previous published data a highly significant excess of homozygotes is observed in males (chi 2 = 13.766, 1 d.f., P = 0.00021) but not females (chi 2 = 0.606, 1 d.f., NS). In conclusion the accumulated data suggest strongly that genetic variation at the DRD3 locus increases susceptibility of schizophrenia, at least in males. At present the Mscl polymorphism in exon 1 of the gene remains a candidate for bringing about functional change in the receptor but this has not been formally tested. Other coding region polymorphisms have not been detected but it remains possible that variation within the promoter may alter receptor function.

Base Sequence↗

Evidence for positional differentiation of prestalk cells and for a morphogenetic gradient in Dictyostelium.

We present evidence that Dictyostelium slug tip cells, the pstA cells, may arise by positional differentiation, but at a site remote from that which they will eventually occupy. When first detectable, the pstA cells form a peripheral ring surrounding the other prestalk cell subtype, the pstO cells, but subsequently move above the pstO cells to form the tip. Because pstA cell differentiation requires a 10-fold higher concentration of differentiation-inducing factor, the stalk cell inducer, the initial patterning seems likely to reflect the existence of a morphogenetic gradient. The subsequent redistribution of the two cell types is explicable by their different rates of chemotaxis to cyclic AMP. These results help reconcile the two apparently opposing views of pattern formation in Dictyostelium, that there is positional differentiation and that pattern formation occurs by cell sorting.

Animals↗

Peptidyl alpha-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl alpha-ketobenzoxazoles.

A series of peptidyl alpha-ketobenzoxazoles were synthesized and evaluated for their in vitro and in vivo inhibition of human neutrophil elastase (HNE). These compounds inhibit HNE by forming both a covalent bond between the ketone carbonyl carbon atom and the hydroxyl group of Ser-195 and a hydrogen bond between the benzoxazole nitrogen atom and His-57. Appending to the parent benzoxazole ring a variety of substituents which spanned a range of physicochemical properties had only a modest effect on in vitro potency (Ki = 3-0.4 nM). This apparent lack of a significant effect is believed to result from the fact that any increased ketone carbonyl activation by the ring substituent is counter balanced by a corresponding decrease in the hydrogen-bonding ability of the benzoxazole nitrogen atom. In contrast to the results in vitro, maximizing in vivo activity was critically dependent upon the choice of the benzoxazole ring substituent. Several substituted peptidyl alpha-ketobenzoxazoles effectively inhibited HNE-induced lung injury when administered intratracheally 24 h prior to the enzyme.

Amino Acid Sequence↗

Metacarpal fracture associated with lymphosarcoma-induced osteolysis in a horse.

A 19-year-old Appaloosa gelding was reluctant to move. Radiography revealed diffuse, permeative lysis of the cortex and subchondral bone of the phalanges, third metacarpal bones, proximal sesamoid bones, radius, carpal bones, tibia, mandible, and nasal bones of the skull. A comminuted fracture of the distal aspect of the left third metacarpal bone was identified on a lateral to medial radiographic view of the left metacarpophalangeal joint. Histologic examination of the first phalanx, third metacarpal bone, and sternum revealed multifocal infiltrates of nodular lymphosarcoma in cortical and subchondral bone. Osteoclastic cavities were apparent in bone trabeculae contiguous with nodular foci of lymphosarcoma. Osteoclastic osteolysis was not evident at bone surfaces that were not directly adjacent to neoplastic cells. Although lymphosarcoma is the most frequent malignant neoplasia encountered in horses, diffuse neoplastic infiltration of cortical and subchondral bone of the appendicular and axial skeleton represents an unusual presentation of lymphosarcoma.

Animals↗

GPs in principle but not in practice: a study of vocationally trained doctors not currently working as principals.

OBJECTIVES: To identify doctors who are vocationally trained but not currently practising as principals in general practice; their reasons for not practising as principals; and whether the prospect of a re-entry course would appear to this group. DESIGN: Postal questionnaire survey based on semistructured interviews. SUBJECTS: Doctors who had been vocationally trained but were not currently practising as principals: 351 possible subjects identified by a process of "networking." SETTING: Trent Regional Health Authority. RESULTS: 166 of the doctors who replied fitted the criteria (100 women; 66 men). The out of hours commitment was ranked as the most important factor for not practising as a principal--95 women and 50 men rated it important--followed by difficulty in combining work with family commitments--84 women, 31 men. 82 respondents (49%) said they would be interested in a re-entry course if one were available. CONCLUSIONS: There is a pool of vocationally trained doctors in Trent region who are not practising as principals in general practice. More flexible working patterns and the availability of a re-entry course could make the post of principal in general practice a more attractive proposition to these doctors.

Adult↗

Tay-Sachs disease in persons of French-Canadian heritage in northern New England.

This study sought to determine whether persons of French-Canadian heritage in northern New England are at high risk for the lethal infantile form of Tay-Sachs disease. In order to accomplish this, death records and laboratory diagnostic records were surveyed to ascertain Tay-Sachs deaths in a cohort of 372,000 live births between 1977-1986. The proportion of the total population with French-Canadian or Jewish heritage was determined from census and birth records, and the ethnic background of Tay-Sachs cases was determined from the corresponding birth records. In 1,860 births, both parents were of Ashkenazi Jewish heritage. One of those children was diagnosed with Tay-Sachs disease. In 41,000 births, both parents were of French-Canadian heritage, and in an additional 93,000 births, one parent was of French-Canadian heritage. No cases of Tay-Sachs disease were identified in the offspring of those individuals. Approximately 14 cases (95% confidence interval 8-20) would be expected, if the gene frequency approximated that reported for individuals of Ashkenazi Jewish heritage. Based on the results of this study, routine testing for Tay-Sachs disease heterozygosity is not indicated for persons of French-Canadian heritage in northern New England. This conclusion may not necessarily be valid for persons of French-Canadian heritage residing in other states. Further studies of Tay-Sachs disease mutations and prevalence among persons of French-Canadian heritage will be important to determine possible regional variations in gene frequencies.

Child↗

Cloning, sequencing and bacterial expression of human glycine tRNA synthetase.

The human glycine tRNA synthetase gene (GlyRS) has been cloned and sequenced. The 2462 bp cDNA for this gene contains a large open reading frame (ORF) encoding 685 amino acids with predicted M(r) = 77,507 Da. The protein sequence has approximately 60% identity with B. mori GlyRS and 45% identity with S. cerevisiae GlyRS and contains motifs 2 and 3 characteristic of Class II tRNA synthetases. A second ORF encoding 47 amino acids is found upstream of the large ORF. Translation of this ORF may precede the expression of GlyRS as a possible regulatory mechanism. The enzyme was expressed in E. coli as a fusion protein with a 13 kDa biotinylated tag with an apparent M(r) = 90 kDa. The fusion protein was immunoprecipitated from crude bacterial extract with human EJ serum, which contains autoantibodies directed against GlyRS, and with rabbit polyclonal serum raised against a synthetic peptide derived from the predicted amino acid sequence of human GlyRS. Bacterial extract containing the fusion protein catalyses the aminoacylation of bovine tRNA with [14C]-gly at 10-fold increased level above normal bacterial extract and confirms that the cDNA encodes human GlyRS.

Acylation↗