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Biomedical subjects

D Harrison

Publications and source records attributed to D Harrison.

At least 73 records · Page 4Linked to original sources
PubMed1996

Acceptability and feasibility of a community approach to asthma management: the Neighborhood Asthma Coalition (NAC).

Understanding of asthma and co-management between patient and physician improves outcome. Feasibility of programs to achieve these goals in underserved settings is not documented. We used the Precede-Proceed model to document (a) community acceptance of a program to engage peer support of asthma management and care; (b) program revision to emphasize greater attention to availability of care and promotional events as channels for education; (c) engagement of intended audiences in planning and implementation; (d) participation of parents in program activities; and (e) peer-based education/support to reach parents, including socially isolated parents whose children experience heightened morbidity.

Adult↗
PubMed1996

Unilobar intrahepatic lithiasis 22 years after cholecystectomy.

Complaints of right upper quadrant pain, jaundice, and fever in the postcholecystectomy patient provide the physician with a challenging diagnosis. This case concerns a patient with intrahepatic lithiasis and fibrotic atrophy of the right lobe 22 years after open cholecystectomy.

Bile Ducts, Intrahepatic↗
PubMed1995

Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants and tape stripping.

p21WAF1/CIP1 is a nucleoprotein that was initially characterized by its ability to be regulated transcriptionally by p53 and by its ability to mediate growth arrest by binding to cyclin-dependent kinases. Although p21WAF1/CIP1 is thought to mediate the effects of p53 in causing growth arrest, p21WAF1/CIP1 is also regulated in a p53-independent manner, e.g., during terminal differentiation of some cell lines. Growth factors including epidermal growth factor also induce p21WAF1/CIP1 through p53-independent pathways. Because the epidermal growth factor signaling pathway is abnormal in psoriatic epidermis, we studied p21WAF1/CIP1 expression, using in situ hybridization and immunohistochemistry, in psoriasis. Both p21WAF1/CIP1 mRNA and protein were significantly elevated in untreated psoriatic plaques compared with uninvolved psoriatic skin (p < 0.0001), with the up-regulation of p21WAF1/CIP1 being predominantly suprabasal. This increase was accompanied by a small increase in p53 protein expression of uncertain significance. Furthermore, p21WAF1/CIP1 expression was induced in skin after sellotape stripping and by the application of agents, such as dithranol, that are capable of inducing hyperproliferation. The pattern of p21WAF1/CIP1 expression observed is consistent with a role in induction and maintenance of differentiation. Our experiments, however, cannot determine whether the abnormalities of p21WAF1/CIP1 epidermal expression in psoriasis and after insult are independent of changes in p53 expression.

Anthralin↗
PubMed1995

G-protein mutations in human pituitary adrenocorticotrophic hormone-secreting adenomas.

Activating mutations of Gs alpha (gsp) and Gi2 alpha (gip) have been described in various endocrine neoplastic conditions. The objective of this study was to assess the prevalence of gsp and gip mutations in human adrenocorticotrophin hormone-secreting pituitary adenomas. Adrenocorticotrophin hormone production and secretion by pituitary corticotroph cells is under stimulatory control by corticotrophin-releasing factor, acting via the production of cyclic AMP. Interference with this regulatory pathway as a result of G-protein dysfunction could lead to disordered corticotroph cell function and growth. We have studied 32 corticotroph adenomas for the presence of gsp and gip mutations using site-directed oligonucleotide hybridization of polymerase chain reaction-amplified DNA. G-protein gene mutations were identified in three (9%) tumours: gsp mutations were demonstrated in two tumours at codon 227, and a gip mutation was identified in one tumour at codon 179. We did not observe a correlation between tumour phenotype and the presence of G-protein gene mutations. We conclude that G-protein gene mutations are an uncommon abnormality in corticotroph adenomas.

Adenoma↗
PubMed1995

Repair of a massive ventral hernia in a morbidly obese patient.

Aggressive perioperative management, with progressive preoperative pneumoperitoneum, is a worthy method of repairing massive ventral hernias with associated loss of domain in morbidly obese patients. The authors present a case and its successful outcome.

Adult↗
PubMed1994

Expression, crystallization and preliminary crystallographic analysis of human carbonyl reductase.

The cDNA of human placental carbonyl reductase (EC 1.1.1.184), a member of the short-chain dehydrogenase family of enzymes, was introduced into the plasmid vector pET-11a and the enzyme overexpressed in Escherichia coli. Recombinant carbonyl reductase was purified to homogeneity, characterized physically and kinetically, and crystallized for X-ray diffraction study. The recombinant protein was indistinguishable from human tissue carbonyl reductase (CR8.5 form) on the basis of partial sequence analysis, substrate specificity, susceptibility to inhibitors and immunochemical analysis. Similar to the tissue enzyme which which occurs in multiple molecular forms thought to arise from autocatalytic modification by 2-oxocarboxylic acids, a second form of the recombinant enzyme was generated under bacterial growth conditions producing high pyruvate concentrations. Purified recombinant protein, which corresponds to the smallest, most basic tissue form (CR8.5), was crystallized against 20% polyethyleneglycol 6000 in 25 mM 2-(N-morpholino)ethanesulfonic acid buffer (Mes) at pH 6.0 using the hanging drop method. Crystals of human carbonyl reductase diffract to better than 3.0 A, and the diffraction symmetry is consistent with a crystal that belongs to the tetragonal space group P4(1)(3)2(1)2 with unit cell dimensions of a = b = 55 A, c = 175 A, alpha = beta = gamma = 90.0. The asymmetric unit contains one molecule of 30.2 kDa.

Alcohol Oxidoreductases↗
PubMed1994

Penetrance and expressivity of the chromosome 9p melanoma susceptibility locus (MLM).

A susceptibility locus for familial melanoma has been localized to the short arm of chromosome 9. Penetrance of melanoma was estimated by calculating the Kaplan-Meier function and fitting a log normal hazard function in 124 gene carriers in three 9p-linked kindreds. The penetrance of the gene for melanoma was estimated to be 53% by age 80. Additionally, nevus counts, skin type, and sun exposure histories were gathered for 119 individuals in two kindreds. Gene carriers were found to have higher nevus counts and nevus densities than non-gene carriers. Among gene carriers, individuals with melanoma were found to have more sun exposure within each skin type than gene carriers without melanoma. These analyses suggest that the 9p melanoma susceptibility is related to total number of nevi and that it interacts with other genetic and environmental factors to produce melanoma.

Adult↗
PubMed1994

Destruction of Xenopus cyclins A and B2, but not B1, requires binding to p34cdc2.

The specific and rapid destruction of cyclins A and B during mitosis is their most remarkable property. A short peptide motif of approximately 10 amino acids near the N-terminus, known as the destruction box, is absolutely required for programmed proteolysis. In this paper we show that although the destruction box is necessary for the degradation of cyclin A, it is not sufficient. Mutant versions of cyclin A that cannot form complexes with p34cdc2 are stable, which we interpret to mean that this cyclin must bind to p34cdc2 in order to undergo programmed proteolysis. Thus, N-terminal fragments of cyclin A containing little more than the destruction box and its surroundings are indestructible. p34cdc2 binding also appears to be required for the destruction of cyclin B2. In contrast, cyclin B1 does not require p34cdc2 binding for specific proteolysis. The systems for the proteolysis of cyclins A, B1 and B2 thus appear to show important differences in the way they recognize their substrates.

Amino Acid Sequence↗
PubMed1994

Trends in alcoholism among male doctors in Scotland.

Alcohol abuse within the medical profession has long been an issue of concern. Recently, the General Medical Council reported that half of the doctors reported for health difficulties liable to affect professional competence were found to have an alcohol problem. This paper examines how rates of alcoholism among male doctors in Scotland have changed over the last three decades. Admission and discharge rates for doctors to psychiatric inpatient beds with diagnoses of alcoholism are compared with non-medical professions, for the years 1963-87. The results, assessed in the light of changing Standardized Mortality Rates for liver cirrhosis for the medical profession, suggest that doctors as a group remain at a higher risk of alcoholism compared to other professionals, but that this increased risk appears to be largely accounted for by a cohort of heavy-drinking doctors over the age of 45 years.

Adult↗
PubMed1994

Oncoprotein immunoreactivity in human pituitary tumours.

OBJECTIVE AND DESIGN: The immediate early gene locus AP-1, incorporating the cellular oncogenes c-fos and c-jun (and their oncoprotein products Fos and Jun respectively) play a key role in regulating cell growth and differentiation. The myc-gene is also known to promote cell growth. In order to investigate the possible role of these oncogenes in human pituitary adenomas, Fos, Jun and Myc oncoprotein immunoreactivities were assessed in surgically resected pituitary adenomas in relation to in-vivo characteristics (hormone secretion, size and invasiveness) and an in-vitro index of cell proliferation (Ki-67 immunoreactivity). Thirty-three human pituitary adenomas and 16 normal pituitary glands were examined. MEASUREMENTS: Oncoprotein immunoreactivity was recorded as present (+) or absent (-), and Ki-67 labelling indices were scored quantitatively. Tumour size was scored from CT scan appearances and radiographic evidence of bone erosion was noted. RESULTS: Oncoprotein immunoreactivity was present in a total of 32/33 cases. Myc immunoreactivity was restricted to the only ACTH-secreting tumour in the series (1/33). Ki-67 immunoreactivity was present in 24/32 cases and labelling indices varied from 0.1 to 3.2%. CONCLUSIONS: Oncoprotein immunoreactivity did not correlate with hormonal profile, bone erosion or the size of the proliferating compartment estimated by Ki-67 labelling indices. Although oncoprotein expression is common in human pituitary adenomas, its significance remains to be elucidated.

Adenoma↗
PubMed1994

Anabolic effects of recombinant insulin-like growth factor-I in cachectic patients with the acquired immunodeficiency syndrome.

The loss of lean body mass accompanying acquired immunodeficiency syndrome (AIDS)-associated cachexia is refractory to current modes of therapy. GH and insulin-like growth factor-I (IGF-I) stimulate protein accretion, but resistance to GH action has been reported in malnutrition and infection. We hypothesized that GH resistance occurs in AIDS-associated cachexia, but that treatment with IGF-I would be anabolic. A single injection of GH produced a smaller increase in circulating IGF-I in 21 patients with AIDS compared to that in 23 age-matched controls (141 +/- 15 vs. 194 +/- 15 micrograms/L; P < 0.02), indicating partial GH resistance. Ten subjects received either low or high dose iv recombinant IGF-I 12 h daily for 10 days. Cumulative nitrogen retention was positive for both dosage groups (low dose, 15.42 +/- 6.37 g; high dose, 3.62 +/- 4.15 g), but a significant increase in daily nitrogen retention occurred only in the low dose group on days 2, 4, 5, 6, and 7. Nitrogen balance and protein turnover (estimated by [13C]leucine and [15N] glycine kinetics) during the final 3 days of treatment were unchanged compared to baseline values, confirming the transient nature of the anabolic response. Repeated administration of IGF-I decreased IGF-binding protein-3 levels, producing lower intrainfusion levels of IGF-I and limiting its therapeutic efficacy. The basal metabolic rate increased with high dose IGF-I and may have contributed to the lack of anabolic effect. We conclude that partial GH resistance occurs in AIDS-associated cachexia. Treatment with low dose recombinant IGF-I produces significant, but transient, nitrogen retention. Alternate routes of IGF-I administration or coadministration with GH may prevent attenuation of IGF-I action.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Unit-based shared governance can work!

The Nurse Executive Council at a 540-bed community teaching health center planned and implemented Shared Governance in a 10-bed Medical Intensive Care Unit (MICU). Paid time was provided for nurses to take part in one of four councils. After a pilot year resulting in satisfaction with job autonomy and input into decision-making, staff reaffirmed their commitment to shared governance as a permanent "way of life" in the MICU. During the second year, patient care assistants and unit clerks were integrated into the Councils and staff began serving as consultants to other units and institutions.

Decision Making, Organizational↗
PubMed1993

Insights into interfacial activation from an open structure of Candida rugosa lipase.

The structure of the Candida rugosa lipase determined at 2.06-A resolution reveals a conformation with a solvent-accessible active site. Comparison with the crystal structure of the homologous lipase from Geotrichum candidum, in which the active site is covered by surface loops and is inaccessible from the solvent, shows that the largest structural differences occur in the vicinity of the active site. Three loops in this region differ significantly in conformation, and the interfacial activation of these lipases is likely to be associated with conformational rearrangements of these loops. The "open" structure provides a new image of the substrate binding region and active site access, which is different from that inferred from the structure of the "closed" form of the G. candidum lipase.

Amino Acid Sequence↗