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Biomedical subjects

K Harris

Publications and source records attributed to K Harris.

At least 37 records · Page 2Linked to original sources

Measuring the self-esteem of adolescents with mental health problems: theory meets practice.

Occupational therapists frequently address the self-esteem of young clients despite little empirical evidence that the clients have low self-esteem to begin with, and that occupational therapy intervention is effective in addressing self-esteem. This article examines the self-esteem of 39 adolescents with mental health problems referred to a pre-vocational programme in an effort to compare clinical practice with empirical findings. The Self-Perception Profile for Adolescents and the Importance Rating Scale for Adolescents are employed to compare the self-esteem of the adolescents with mental health problems with the normative sample, prior to (n = 39) and upon completion of the pre-vocational programme (n = 14). Results indicate no difference between the two groups' self-esteem and no change in self-esteem scores following participation in the pre-vocational programme. Global self-esteem is significantly correlated with physical appearance and behavioural conduct (n = 39). Competence-importance discrepancy scores are significantly related to global self-esteem (n = 14). This finding supports the theory that it is the domain of self-concept which is low and important to the adolescent which will influence his/her self-esteem. These results are consistent with previous studies. Possible explanations for the discrepancy between clinical perceptions and objective findings are discussed. Implications for practice are presented.

Adolescent↗

Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function.

BACKGROUND: Contrast MRI enhancement patterns in several pathophysiologies resulting from ischemic myocardial injury are controversial or have not been investigated. We compared contrast enhancement in acute infarction (AI), after severe but reversible ischemic injury (RII), and in chronic infarction. METHODS AND RESULTS: In dogs, a large coronary artery was occluded to study AI and/or chronic infarction (n = 18), and a second coronary artery was chronically instrumented with a reversible hydraulic occluder and Doppler flowmeter to study RII (n = 8). At 3 days after surgery, cine MRI revealed reduced wall thickening in AI (5+/-6% versus 33+/-6% in normal, P<0.001). In RII, wall thickening before, during, and after inflation of the occluder for 15 minutes was 35+/-5%, 1+/-8%, and 21+/-10% and Doppler flow was 19.8+/-5.3, 0.2+/-0.5, and 56.3+/-17.7 (peak hyperemia) cm/s, respectively, confirming occlusion, transient ischemia, and reperfusion. Gd-DTPA-enhanced MR images acquired 30 minutes after contrast revealed hyperenhancement of AI (294+/-96% of normal, P<0.001) but not of RII (98+/-6% of normal, P = NS). Eight weeks later, the chronically infarcted region again hyperenhanced (253+/-54% of normal, n = 8, P<0.001). High-resolution (0.5 x 0.5 x 0.5 mm) ex vivo MRI demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis with and without reperfusion at 1 day (R = 0.99, P<0.001) and 3 days (R = 0.99, P<0.001) and collagenous scar at 8 weeks (R = 0.97, P<0.001). CONCLUSIONS: In the pathophysiologies investigated, contrast MRI distinguishes between reversible and irreversible ischemic injury independent of wall motion and infarct age.

Animals↗

Caspase inhibition reduces myocyte cell death induced by myocardial ischemia and reperfusion in vivo.

Myocardial ischemia and reperfusion lead to myocyte cell death, at least in part, by an apoptotic mechanism. Caspases are a conserved family of proteases that play an essential role in the execution of apoptosis; however, their potential contribution to ischemic myocardial cell death is largely unknown. To examine their role in this process, we subjected rabbits to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Immunoblot analyses revealed that caspases-2, -3 and -7 were proteolytically activated during myocardial ischemia and reperfusion in vivo. In addition, the well-characterized caspase substrate poly(ADP-ribose) polymerase (PARP) was selectively cleaved into its signature apoptotic fragment in ischemic/reperfused myocardium. Systemic administration of the broad-spectrum caspase inhibitor acetyl-Tyr-Val-Ala-Asp chloromethylketone (YVAD-cmk, 4.8 mg/kg) partially blocked caspase activation and dramatically reduced the percentage of terminal dUTP deoyxynucleotidyl-transferase nick end-labeling (TUNEL)-positive myocyte nuclei in the infarct region (3.9+/-0.8%v 13.0+/-2.2% in control animals, P=0.012). Moreover, YVAD-cmk reduced myocardial infarct size by approximately 31% (31.1+/-3.3%v 45.3+/-4.9% in control animals, P=0.032). These results indicate that caspases are critical mediators of myocardial injury induced by ischemia and reperfusion in vivo, and they suggest that caspase inhibition may be therapeutically beneficial in myocardial infarction.

Amino Acid Chloromethyl Ketones↗

Analysis of primary structural determinants that distinguish the centromere-specific function of histone variant Cse4p from histone H3.

Cse4p is a variant of histone H3 that has an essential role in chromosome segregation and centromere chromatin structure in budding yeast. Cse4p has a unique 135-amino-acid N terminus and a C-terminal histone-fold domain that is more than 60% identical to histone H3 and the mammalian centromere protein CENP-A. Cse4p and CENP-A have biochemical properties similar to H3 and probably replace H3 in centromere-specific nucleosomes in yeasts and mammals, respectively. In order to identify regions of Cse4p that distinguish it from H3 and confer centromere function, a systematic site-directed mutational analysis was performed. Nested deletions of the Cse4p N terminus showed that this region of the protein contains at least one essential domain. The C-terminal histone-fold domain of Cse4p was analyzed by changing Cse4p amino acids that differ between Cse4p and H3 to the analogous H3 residues. Extensive substitution of contiguous Cse4p residues with H3 counterparts resulted in cell lethality. However, all large lethal substitution alleles could be subdivided into smaller viable alleles, many of which caused elevated rates of mitotic chromosome loss. The results indicate that residues critical for wild-type Cse4p function and high-fidelity chromosome transmission are distributed across the entire histone-fold domain. Our findings are discussed in the context of the known structure of H3 within the nucleosome and compared with previous results reported for CENP-A.

Amino Acid Sequence↗

The plans in unplanned pregnancy: secondary gain and the partnership.

A total of 128 North London women were interviewed using a semi-structured interview technique. Life-events, difficulties, variables relating to the quality of their sexual partnerships, self-esteem and the secondary gain inherent in becoming pregnant were examined. Results indicated that women with unplanned pregnancies were significantly more likely to have been in a situation of potential secondary gain from a pregnancy than were women with planned pregnancies and women who were not pregnant. Measurements of the women's partnerships were also linked to the intentionality of pregnancy. The implications of these results are discussed.

Adult↗

Report of the first case of invasive fungal sinusitis caused by Scopulariopsis acremonium: review of scopulariopsis infections.

Scopulariopsis acremonium is a species of saprophytic fungus not previously reported to cause invasive disease in humans, although invasive infections from other species of Scopulariopsis have been reported and are reviewed. Deep infection with this fungus is associated with a high mortality rate. Invasive fungal sinusitis, in general, is a potentially fatal disease that typically affects immunocompromised patients, such as those receiving intensive chemotherapy or undergoing bone marrow transplantation. We report a case of invasive fungal sinusitis caused by Scopulariopsis acremonium in a patient with leukemia, who was successfully treated with amphotericin B, itraconazole, endoscopic sinus surgery, and granulocyte colony-stimulating factor.

Antineoplastic Agents↗

Aspects of oligonucleotide and peptide sequencing with MALDI and electrospray mass spectrometry.

Biopolymer sequencing with mass spectrometry has become increasingly important and accessible with the development of matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI). Here we examine the use of sequential digestion for the rapid identification of proteolytic fragments, in turn highlighting the general utility of enzymatic MALDI ladder sequencing and ESI tandem mass spectrometry. Analyses were performed on oligonucleotides ranging in size from 2 to 50 residues, on peptides ranging in size from 7 to 44 residues and on viral coat proteins. MALDI ladder sequencing using exonuclease digestion generated a uniform distribution of ions and provided complete sequence information on the oligonucleotides 2-30 nucleic acid residues long. Only partial sequence information was obtained on the longer oligonucleotides. C-terminal peptide ladder sequencing typically provided information from 4 to 7 amino acids into the peptide. Sequential digestion, or endoprotease followed by exoprotease exposure, was also successfully applied to a trypsin digest of viral proteins. Analysis of ladder sequenced peptides by LCMS generated less information than in the MALDI-MS analysis and ESI-MS2 normally provided partial sequence information on both the small oligonucleotides and peptides. In general, MALDI ladder sequencing offered information on a broader mass range of biopolymers than ESI-MS2 and was relatively straightforward to interpret, especially for oligonucleotides.

Base Sequence↗

Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore components.

CP1 (encoded by CEP1) is a Saccharomyces cerevisiae chromatin protein that binds a DNA element conserved in centromeres and in the 5'-flanking DNA of methionine biosynthetic (MET) genes. Strains lacking CP1 are defective in chromosome segregation and MET gene transcription, leading to the hypothesis that CP1 plays a general role in assembling higher order chromatin structures at genomic sites where it is bound. A screen for mutations synthetically lethal with a cep1 null allele yielded five recessive csl (cep1 synthetic lethal) mutations, each defining a unique complementation group. Four of the five mutations synergistically increased the loss rate of marker chromosomes carrying a centromere lacking the CP1 binding site, suggesting that the cep1 synthetic lethality was due to chromosome segregation defects. Three of these four CSL genes were subsequently found to be known or imputed kinetochore genes: CEP3, NDC10, and CSE4. The fourth, CSL4, corresponded to ORF YNL232w on chromosome XIV, and was found to be essential. A human cDNA was identified that encoded a protein homologous to Csl4 and that complemented the csl4-1 mutation. The results are consistent with the view that the major cellular role of CP1 is to safeguard the biochemical integrity of the kinetochore.

Amino Acid Sequence↗

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↗

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↗

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↗

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↗