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Biomedical subjects

M Watkins

Publications and source records attributed to M Watkins.

At least 37 records · Page 2Linked to original sources

The contryphans, a D-tryptophan-containing family of Conus peptides: interconversion between conformers.

We previously characterized contryphan-R, a D-tryptophan-containing octapeptide from the venom of Conus radiatus. In this study, we present evidence that the contryphan family of peptides is widely distributed in venoms of the fish-hunting cone snails. We purified, synthesized and characterized contryphan-Sm from Conus stercusmuscarum venom, and obtained molecular evidence for the existence of a third peptide, contryphan-P from Conus purpurascens venom ducts. The sequences of these three contryphans showed identity in seven of eight amino acids and a conserved pattern of post-translational modification. We also demonstrate that contryphan-Sm equilibrates between two distinct conformational states.

Amino Acid Sequence↗

A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom.

A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).

Amino Acid Sequence↗

Bromocontryphan: post-translational bromination of tryptophan.

We demonstrate that post-translational bromination of a tryptophan residue occurs in the biologically active octapeptide bromocontryphan, purified and characterized from Conus radiatus venom. Clones encoding bromocontryphan were identified from a cDNA library made from C. radiatus venom ducts. The mRNA sequence obtained predicts a prepropeptide which has the mature peptide sequence at the C-terminal end, with the L-6-bromotryptophan residue encoded by UGG, the Trp codon. These data provide the first direct evidence for post-translational bromination of a polypeptide which is translated through the normal cellular machinery. In addition to bromination, the peptide, which induces a "stiff tail" syndrome in mice, has several other modifications as shown by the sequence [Formula: See Text] in which Hyp = hydroxyproline. Asterisks indicate post-translational modifications (left to right): proteolytic cleavage at the N-terminus; hydroxylation of Pro3; epimerization of Trp4; bromination of Trp7, and C-terminal amidation. Bromocontryphan appears to have the highest density of post-translational modifications known among gene-encoded polypeptides. The overall result is a molecule which closely resembles marine natural products produced through specialized biosynthetic pathways comprising many enzyme-catalyzed steps.

Amino Acid Sequence↗

Evaluation of a new night nursing service for elderly people suffering from dementia.

A new night hospital nursing service was developed for older people with dementia. A case study approach to evaluation was adopted using a structure-process-outcome quality assurance cycle. The effects and attendance of patients are reported and discussed. Discussion relating to care provision for the future is presented. The effects on carers of patients' attendance are briefly discussed.

Activities of Daily Living↗

Youths and communities: toward comprehensive strategies for youth development.

Society's conventional response to problems of young people--such as teenage pregnancy, school dropout, substance abuse, juvenile delinquency, and violence--is to target a specific problem and develop intervention or prevention programs for individuals who manifest the problem or are at high risk of it. Research shows that overlapping risk and protective factors affect the occurrence of all of these problems and that prevention strategies aimed at enhancing youths' development, reducing communities' specific risks, and strengthening protective factors are likely to be more successful than programs addressing the problem behaviors themselves. Among such strategies deserving wider consideration are "comprehensive community initiatives" that create collaborative partnerships among public officials, service providers, primary institutions, and citizens to promote the well-being of children, youths, and families.

Adolescent↗

Treatment of liver injuries at level I and level II centers in a multi-institutional metropolitan trauma system. The Midwest Trauma Society Liver Trauma Study Group.

OBJECTIVE: The development of trauma systems and trauma centers has had a major impact on the fate of the critically injured patient. However, some have suggested that care may be compromised if too many trauma centers are designated for a given area. As of 1987, the state of Missouri had designated six adult trauma centers, two Level I and four Level II, for the metropolitan Kansas City, Mo, area, serving a population of approximately 1 million people. To determine whether care was comparable between the Level I and II centers, we conducted a concurrent evaluation of the fate of patients with a sentinel injury, hepatic trauma, over a 6-year period (1987-1992) who were treated at these six trauma centers. METHODS: All patients during the 6-year study period who suffered liver trauma and who survived long enough to be evaluated by computerized tomography or celiotomy were entered into the study. Patients with central nervous system trauma were excluded from analysis. Information concerning mechanism of injury, RTS, Injury Severity Score (ISS), presence of shock, liver injury scoring, mode of treatment, mortality, and length of stay were recorded on abstract forms for analysis. Care was evaluated by mortality, time to the operating room (OR), and intensive care unit (ICU) and hospital length of stay. RESULTS: Over the 6-year period 300 patients with non-central nervous system liver trauma were seen. Level I centers cared for 195 patients and Level II centers cared for 105. There was no difference in mean ISS or ISS > 25 between Level I and II centers. Fifty-five (28%) patients arrived in shock at Level I centers and 24 (23%) at Level II centers. Forty-eight patients (16%) died. Thirty-two (16%) died at Level I centers, and 16 (15%) died at Level II centers. Twenty of 55 patients (36%) in shock died at Level I centers, and 11 of 24 (46%) died at Level II centers (p = 0.428). Forty-three patients (22%) had liver scaling scores of IV-VI at Level I centers, and 10 (10%) had similar scores at Level II centers (p < 0.01). With liver scores IV-VI, 22 of 43 (51%) died at Level I centers and 10 of 14 (71%) died at Level II centers (p = 0.184). There was no difference in mean time or in delays beyond 1 hour to the OR for those patients in shock between Level I and II centers. There was a longer ICU stay at Level II centers (5.0 +/- 8.3 vs. 2.8 +/- 8.4 days, p = 0.04). This difference was confined to penetrating injuries. There was no difference in hospital length of stay. CONCLUSIONS: In a metropolitan trauma system, when Level I and II centers were compared for their ability to care for victims of hepatic trauma, there was no discernible difference in care rendered with respect to severity of injury, mortality, delays to the OR, or hospital length of stay. It was observed that more severe liver injuries were seen at Level I centers, but this did not seem to significantly affect care at Level II centers. There was a longer ICU stay observed at Level II centers owing to penetrating injuries, possibly because there were fewer penetrating injuries treated at these facilities. Although the bulk of patients were seen at Level I centers, care throughout the system was equivalent.

Adult↗

Molecular cloning of the human ryudocan promoter.

The promoter region of human ryudocan was isolated from a human lambda dash genomic library and cloned into pBluescript. The 5'flanking region contained a classical TATA box and GC rich regions that are commonly found in constitutively expressed genes. Two fusion gene constructs, one of 898 bp and the other of 480 bp of the 5' flanking DNA coupled to the luciferase gene, were transiently expressed in a mouse endothelioma cell line and in human umbilical endothelial cell cultures. Both constructs were capable of driving luciferase expression; the 898 bp construct produced greater levels of luciferase activity than the 480 bp construct in both cell types examined. Analysis of the sequence revealed the presence of several potential sites for nuclear transcription factor binding; the relevance of these sites is presently unknown.

Base Sequence↗

Improvement in cost recovery at an urban level I trauma center.

With escalating health care costs and health reimbursement reorganization, the greatest danger to trauma centers will remain expensive uncompensated care. This is caused primarily by costs incurred in treating complex, life-threatening injuries and to the large population of trauma patients with no, or inadequate, means of compensation. In 1986 and 1987, this urban level I trauma center experienced an operating loss totaling $2,335,200. To attempt to reverse this expense, annual tracking of the trauma service's financial performance was begun in 1989. In addition, changes were made. Early multidisciplinary baseline assessment of each admission was instituted for financial profiling and discharge planning. Attempts were made on admission to identify health and vehicular insurance information. Processing for Medicaid and Medicare reimbursement was begun as soon as possible, and coding for diagnoses was checked by medical records personnel and the trauma nurse coordinator. If appropriate, Missouri Crime Victims Compensation was sought. Base on costs incurred in providing trauma services, as required by the state of Missouri and the American College of Surgeons, a trauma response charge was developed and instituted. Over a 5-year period, 1989 to 1993, financial audits were conducted. The cost recovery ratio (CRR) (collections/cost) was utilized as the measure of financial success. The CRR improved from 0.74 in 1989 to 0.93 in 1993, and in 2 years, 1991 and 1992, was 1.03 and 0.99. Over this period, the acuity of injury, as measured by the Injury Severity Score, remained essentially the same, but length of hospital stay decreased from 10.0 to 8.7 days. The CRR was greatest for private insurance.(ABSTRACT TRUNCATED AT 250 WORDS)

Financial Audit↗

Early profound jaundice following blunt hepatic trauma: resolution after lobectomy--case report.

The patient presented herein was seen and evaluated following a motor vehicle crash. Although hemodynamically stable, he was found to have a liver injury and orthopedic trauma. Following admission he developed rapidly deepening jaundice. Radiographic studies demonstrated biliary pooling in the left lobe without antegrade obstruction. After a left hepatic lobectomy steady improvement in his hyperbilirubinemia was seen. Despite our inability to identify a communication anatomically in the resected specimen, one explanation considered was a traumatic fistulization between a biliary radical and an hepatic vein.

Accidents, Traffic↗

A radiation hybrid map of the BRCA1 region of chromosome 17q12-q21.

The chromosomal region 17q12-q21 contains a gene (BRCA1) conferring susceptibility to early-onset familial breast and ovarian cancer. An 8000-rad radiation-reduced hybrid (RH) panel was constructed to provide a resource for long-range mapping of this region. A large fraction of the hybrids (approximately 90%) retained detectable human chromosome 17 sequences. The complete panel of 76 hybrids was scored for the presence or absence of 22 markers from this chromosomal region, including 14 cloned genes, seven microsatellite repeats, and one anonymous DNA segment. Statistical analysis of the marker retention data employing multipoint methods provided both comprehensive and framework maps of this chromosomal region, including distance estimates between adjacent markers. The comprehensive RH map includes 17 loci and spans 179 cRays(8000). Likelihood ratios of at least 1000:1 support the 10-locus framework order: cen-D17S250-ERBB2-(THRA1, TOP2A)-D17S855-PPY-D17S190-MTBT1-GP3A++ +-BTR-D17S588-tel. The order obtained from RH mapping, when used in conjunction with other methods, will be useful in linkage analysis of breast cancer families and will facilitate the development of a physical map of this region.

Base Sequence↗

Isolation and characterization of somatic cell hybrids with breakpoints spanning 17q22-->q24.

Somatic cell hybrid mapping panels have previously been constructed to assist in the regional assignment of anonymous DNA probes and cloned genes to human chromosome 17. While a substantial number of hybrids are available that subdivide the short arm of this chromosome and the proximal portion of its long arm into specific regions, relatively few exist with breakpoints in the distal portion of the long arm. To increase the resolution of this region, four additional human x rodent somatic cell hybrids have been constructed that include breakpoints spanning the region 17q22-->q24. Hybrid clones carrying the long-arm derivative of chromosome 17 were initially identified by fluorescence in situ hybridization. Hybrids were subsequently screened using the polymerase chain reaction with primer sets representing DNA markers previously mapped to chromosome 17. These hybrids expand the existing somatic cell hybrid panel for the distal portion of the long arm of chromosome 17.

Animals↗