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Biomedical subjects

K Harris

Publications and source records attributed to K Harris.

At least 55 records · Page 3Linked to original sources
PubMed1998

Outcome after ileoanal anastomosis in pediatric patients with ulcerative colitis.

BACKGROUND: To review the outcome after restorative proctocolectomy among children and adolescents with ulcerative colitis at a pediatric inflammatory bowel disease center. METHODS: The records of all patients with ulcerative colitis undergoing colectomy and ileoanal anastomosis at The Hospital for Sick Children, Toronto, Canada, were reviewed. Questionnaires concerning functional results were sent to patients with restored transanal defecation. RESULTS: Seventy three patients (mean age, 13.2 years; range, 2.6-18.8 years) underwent ileoanal anastomosis (19 straight ileoanal anastomosis, 41 J pouch, 13 S pouch) between January 1980 and June 1995 and were observed 5.8+/-3.3 years. The ileoanal anastomosis is nonfunctional in 19 (26%) patients. Excision rates according to type of restorative procedure were J pouch, 7% (3 of 41); S pouch, 32% (4 of 13); and straight ileoanal anastomosis, 32% (6 of 19). Failure was usually attributable to intractable diarrhea among patients with straight ileoanal anastomosis but was caused by anastomotic leak or pelvic-perianal sepsis among patients with pouch procedures. Failure rates did not vary with age at ileoanal anastomosis. Among patients retaining ileoanal continuity, continence problems reported in the questionnaire were frequent and tended to be more extreme among younger patients. Overall, 90% of respondents reported satisfaction with the functional outcome of the restorative operation. CONCLUSIONS: The success rate of the ileoanal anastomosis/J-pouch procedure is comparable to that in adult series. The ileoanal anastomosis/J-pouch procedure is the operation of choice for children and adolescents who want ileoanal continuity restored after colectomy for ulcerative colitis.

Adolescent↗
PubMed1997

An automated MALDI mass spectrometry approach for optimizing cyclosporin extraction and quantitation.

A combinatorial extraction method and an automated matrix-assisted laser desorption/ionization (MALDI) mass spectrometry procedure were used to improve the clinical analysis of the immunosuppressant drug cyclosporin A. Cyclosporin extracts from whole blood were analyzed by MALDI and electrospray ionization (ESI) mass spectrometry, allowing for their identification and quantification. Due to limitations associated with the current multistep cyclosporin extraction procedure from whole blood, a combinatorial approach was devised to optimize this extraction. Optimization was performed by generating an array of solvent systems to be used for extraction from blood, and an automated analysis was carried out on a MALDI mass spectrometer to identify successful extractions. The first generation of experiments revealed four binary solvent systems to be effective for cyclosporin extraction (hexane/EtOH, ACN/H2O, ACN/MeOH, and hexane/CHCl3). A new array based on these solvent systems was generated, and a second iteration of these experiments was then performed. In the second generation of experiments, hexane/CHCl3 (70:30) was found to provide the most effective single-step extraction of these solvent systems for cyclosporin and its metabolites. The limits of detection were determined to be 15 ng/mL in whole blood for ESI/MS and MALDI-MS and could also be used for identifying major drug metabolites. In addition to applying this combinatorial approach to extraction procedures, this experimental design could easily be extended to examine other approaches, such as optimizing chemical reactions and screening inhibitors in enzymatic reactions.

Cyclosporine↗
PubMed1997

A transcultural pattern of drug use: qat (khat) in the UK.

BACKGROUND: This study investigates patterns of qat use among 207 Somalis living in London. METHOD: Subjects were recruited using privileged access interviewing. Somalian interviewers were recruited who shared the same culture as the subjects. Data were collected by means of a structured interview. RESULTS: One hundred and sixty-two subjects (78%) had used qat. The majority (76%) used more qat than in Somalia. Some users reported moderate dependence; a minority reported severe problems. Adverse psychological effects included sleep problems, anxiety and depression. Medical problems associated with qat use were rare. CONCLUSIONS: Qat users who continue to use this drug when it is transplanted from a traditional context may experience difficulties. Qat use can also be seen as playing a positive role in supporting the cultural identity of the Somalian community. Severe problems were rarely reported. Qat consumption should be considered when addressing health-related topics with patients from those communities in which qat use is common.

Adolescent↗
PubMed1996

Cloning of a potential cytochrome P450 from the archaeon Sulfolobus solfataricus.

Abstract A gene, CYP119, for a potential cytochrome P450 has been isolated and sequenced from the extreme acidothermophilic archaeon Sulfolobus solfataricus. The gene predicts a polypeptide of 368 amino acids containing the consensus heme-binding sequence Phe-Gly-Xaa-Gly-Xaa-His-Xaa-Cys-Xaa-Gly- Xaa3-Ala-Arg-Xaa-Glu. It most closely resembles the cytochrome P450s found in the bacterium Bacillus subtilis, with which it shares 129 identical amino acid residues (35%). This first sequence of a potential archaeal cytochrome P450 represents an important step in tracing the complex evolutionary history of this biologically important enzyme family.

Amino Acid Sequence↗
PubMed1996

Faking the MMPI-2: utility of the Subtle-Obvious scales.

We explored the effect of different subject response sets on the profile configuration of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and the utility of traditional validity, Back F, and Subtle-Obvious scales in detecting response set. College students were administered the MMPI-2 under one of three response sets; faking good, faking bad, or standard report. Results revealed significant differences across the three response set groups on all clinical, content, validity, obvious, and two of the five subtle scales in the expected direction. Additionally, respondents in the faking conditions produced consistent T-score patterns and significant O-S differences on the Subtle-Obvious scales. Examination of these subtle-obvious patterns may offer clinicians valuable information regarding profile validity beyond that offered by the traditional validity and Back F scales.

Adolescent↗
PubMed1996

A computational model of cholinergic disruption of septohippocampal activity in classical eyeblink conditioning.

A previous neurocomputational model of corticohippocampal interaction (Gluck & Myers, 1993) can provide a framework for examining the behavioral effects of septohippocampal modulation during classical conditioning. The model assumes that the hippocampal region is necessary for forming new stimulus representations during learning, but not for the formation of simple associations. This paper considers how septohippocampal interaction could affect this function. The septal nuclei provide several modulatory inputs to the hippocampus, including a cholinergic input which Hasselmo (1995) has suggested may function to regulate hippocampal dynamics on a continuum between two states: a storage state in which incoming information is encoded as an intermediate-term memory and a recall state when this information is reactivated. In this theory, anticholinergic drugs such as scopolamine should disrupt learning by selectively reducing the hippocampus's ability to store new information. An approximation of Hasselmo's idea can be implemented in the corticohippocampal model by a simple manipulation of hippocampal learning rate; this manipulation is formally equivalent to adjusting the amount of time the hippocampus spends in learning and recall states. With this manipulation, the model successfully accounts for the effects of scopolamine in retarding classical conditioning in humans (Solomon, Groccia-Ellison, Flynn, Mirak, Edwards, Dunehew, & Stanton, 1993) and animals (Solomon, Soloman, van der Schaaf, & Perry, 1983). The model further predicts that although cholinergic agonists (such as Tacrine) may improve learning in subjects with artificially depressed brain acetylcholine levels, there may be limited memory improvement in normal subjects from such cholinergic therapy. This is consistent with the general finding of a U-shaped dose response curve for cholinergic drugs in normal subjects: low to moderate doses may improve learning, but higher doses are ineffective or even degrade learning (e.g., Ennaceur & Meliani, 1992; Dumery, Derer, & Blozovski, 1988; etc.).

Animals↗
PubMed1996

The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients--a randomised prospective study.

The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P = 0.0223) and 4-year (P = 0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P < 0.01). Group B also experienced fewer rejection episodes than groups A and C (P < 0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.

Administration, Oral↗
PubMed1996

Inhibition of basal transcription by poliovirus: a virus- encoded protease (3Cpro) inhibits formation of TBP-TATA box complex in vitro.

Host cell RNA polymerase II (pol II)-mediated transcription is inhibited by poliovirus infection. We demonstrate here that both TATA- and initiator-mediated basal transcription is inhibited in extracts prepared from poliovirus-infected HeLa cells. This inhibition can be reproduced by incubation of uninfected HeLa cell extracts with purified, recombinant poliovirus protease, 3Cpro. Transient-transfection assays demonstrate that 3Cpro, in the absence of other viral proteins, is able to inhibit cellular pol II-mediated transcription in vivo. Three lines of evidence suggest that inactivation of TATA-binding protein (TBP) is the major cause of inhibition of basal transcription by poliovirus. First, RNA pol II transcription in poliovirus-infected cell extract is fully restored by bacterially expressed TBP. Second, addition of purified TBP restores transcription in heat-treated nuclear extracts from mock- and virus-infected cells to identical levels. Finally, using a gel mobility shift assay, we demonstrate that incubation of TBP with the viral protease (3Cpro) inhibits its ability to bind TATA sequence in vitro. These results suggest that inhibition of pol II transcription in mammalian cells infected with poliovirus is, at least in part, due to the inability of modified TBP to bind pol II promoter sequences.

3C Viral Proteases↗
PubMed1996

UVB therapy decreases the adhesive interaction between peripheral blood mononuclear cells and dermal microvascular endothelium, and regulates the differential expression of CD54, VCAM-1, and E-selectin in psoriatic plaques.

A dermal lymphocytic infiltrate is a characteristic feature of psoriasis, and may be involved in the pathogenesis of the disease. We have previously shown that specialized dermal microvascular endothelial cells (DMEC) in psoriatic lesions promote the selective adherence of the CD4 CD45Ro helper T-cell subset. In this study, we examined the adhesive interaction between peripheral blood mononuclear cells and psoriatic DMEC in patients treated with ultraviolet B light (UVB), and correlated the results with the expression and function of endothelial adhesion molecules on DMEC. Seven psoriatic patients were exposed to one MED of UVB daily for 14 days, and the binding properties of their peripheral blood mononuclear cells (PBMC), and tissue specimens taken from their lesions on days 0, 2, 3, 6, 8, 11 and 14 of UVB treatment, were studied. The ability of psoriatic PBMC to adhere to non-irradiated control or UVB-treated psoriatic plaques was reduced by 70% after treatment with 2-3 MED, and complete inhibition was obtained after 8-11 MED. In contrast, exposure of psoriatic plaques to 2-3 MED had no effect on the capacity of DMEC to support normal PBMC binding, which was only reduced after 8-11 MED. In addition, psoriatic plaques which were shielded from direct UVB exposure also showed decreased PBMC binding, suggesting a systemic effect of UVB treatment. Immunoperoxidase staining revealed that CD54 (ICAM-1) and E-selectin were strongly expressed on dermal vessels in untreated psoriatic plaques. Treatment of patients with 6-8 MED significantly decreased CD54 and E-selectin expression. In contrast, VCAM-1 expression on untreated plaques was weaker than that of CD54 and E-selectin, but was markedly induced following UVB treatment. In functional blocking studies, preincubation of tissue from untreated psoriatic plaques with anti-E-selectin antibody, but not antibodies against CD54 and VCAM-1, significantly inhibited the ability to bind normal PBMC. These observations suggest that UVB treatment interferes with the adhesive properties of both psoriatic PBMC and endothelial cells, and differentially regulates the expression of endothelial adhesion molecules. The study also provided direct evidence for the involvement of E-selectin in the adhesion of circulating lymphocytes to psoriatic endothelial cells.

Adult↗
PubMed1996

Association between eye dominance and training for rifle marksmanship: a pilot study.

BACKGROUND: This pilot study was performed to determine the effect, if any, exerted by crossed dominance (contralateral hand and eye dominance) on the ability of novice riflemen to learn how to accurately shoot a rifle. METHODS: Sighting dominance was used to determine the dominant eye. Hand dominance was determined by the arm used to shoulder the rifle in the shooting position. Subjects were 308 military recruits at the Fort Benning Army Base in Columbus, Georgia, who had undergone basic training in rifle marksmanship. Qualification scores obtained at the base rifle range were used to measure the subjects' ability to learn marksmanship skills. RESULTS: The subjects with right-hand/right-eye and left-hand/left-eye (uncrossed) dominance had qualification scores that were significantly higher (p = .009) than the subjects with right hand/left-eye and left-hand/right-eye (crossed) dominance. A significantly higher percentage of subjects with uncrossed dominance achieved rifle qualification (86.1 percent) than subjects with crossed dominance (56.5 percent) (p = .000). CONCLUSIONS: The learning of rifle marksmanship is influenced by eye dominance. Individuals who shoot right handed and are left-eye dominant or who shoot left handed and are right-eye dominant do not learn marksmanship skills as readily as individuals who have matched eye and hand dominance. Since crossed hand and eye dominance can be easily determined, it should be possible to identify cross dominant individuals and provide them with special training so that they can perform at a higher level of skill.

Firearms↗