Search PubMed⌕ Search

Biomedical subjects

K Harris

Publications and source records attributed to K Harris.

At least 37 records · Page 2Linked to original sources
PubMed2001

Thoracic lymphatic pumping and the efficacy of influenza vaccination in healthy young and elderly populations.

The authors investigated whether thoracic lymphatic pumping (TLP) after FluShield vaccination enhanced the production of anti-influenza immunoglobulins in elderly individuals, who are at particular risk for influenza. Osteopathic students and non-TLP-treated elderly subjects served as controls. Serum antibody titers were quantified with enzyme-linked immunosorbent assay, and hemagglutination inhibition assay, both of which generated comparable results. While approximately 70% of the younger controls had increased anti-influenza immunoglobulin production on vaccination, only 30% to 35% of the aged population had increased antibody production. There was no significant enhancement in anti-influenza immunoglobulin production in the TLP-treated subjects. The authors' findings suggest that TLP in conjunction with influenza vaccination does not enhance immunization against influenza in otherwise healthy and active populations. However, such techniques may be of value when applied in conjunction with vaccination to nonambulatory patients or on actual influenza exposure of at-risk individuals.

Adult↗
PubMed2000

Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins.

Cholesterol lowering involving different therapies improves the clinical outcome of patients. To define the underlying pathomechanism, we studied whether treatment with statins was associated with changes in blood thrombogenicity, endothelial dysfunction and soluble adhesion molecule levels. Fifty hypercholesterolemic patients were treated with pravastatin (40 mg/day, n=24) or simvastatin (20 mg/day, n=26). Lipid profile and blood thrombogenicity were assessed in all patients before and after 3 months of cholesterol reducing therapy. Blood thrombogenicity was assessed as thrombus formation, perfusing non-anticoagulated blood directly from the patients' vein through the Badimon perfusion chamber (shear rate 1690/s). Endothelial-dependent vasomotor response was tested by laser-Doppler flowmeter. Soluble adhesion molecule level were measured by ELISA. Total and LDL cholesterol were reduced in the two treatment groups by statin therapy. Statin therapy was associated with a significant reduction in blood thrombogenicity and endothelium-dependent vasoresponse. No differences were observed between simvastatin or pravastatin treatment. Lipid lowering by statins had no effect on plasma levels of fibrinogen, sL-selectin, sP-selectin and sICAM-1 antigen. Cholesterol lowering by both statins reduced the increased blood reactivity and endothelial dysfunction present under hypercholesterolemia. The multiple effects of lipid lowering therapy by statins may explain the benefits observed in recent epidemiological trials.

Anticholesteremic Agents↗
PubMed2000

An agenda for research into uterine artery embolization: results of an expert panel conference.

PURPOSE: To develop a research agenda for uterine artery embolization (UAE) for the treatment of symptomatic leiomyomata. MATERIALS AND METHODS: An expert panel was convened to examine data and develop a consensus for UAE research. Panelists reviewed data from articles about UAE and data on hysterectomy and myomectomy, which were abstracted into evidence tables. A modified Delphi process was used to rate the importance of measuring specific outcomes and a nominal group process was used to develop ideas for study designs. RESULTS: Panelists agreed that UAE studies would have to examine certain key measures. Outcomes identified as either "important to measure" or "essential to measure" were death, reoperation, operative injury, menorrhagia, premature menopause, recurrence of myomata, and satisfaction. The panel proposed four areas for research: randomized trial, prospective registry, disease-specific quality-of-life instrument, and cost analysis. CONCLUSIONS: Symptomatic uterine leiomyomata are a major health concern for women. New techniques that promise to provide symptom relief deserve careful consideration. Traditionally, surgical procedures have been poorly studied until after they have been widely used. If the process described in this article can guide the acquisition of knowledge in this field, it may serve as a model for evaluating other new technologies before they become widely adopted.

Costs and Cost Analysis↗
PubMed2000

Hepatitis C virus-associated oral lichen planus: no influence from hepatitis G virus co-infection.

There is a variable geographic distribution in the prevalence of hepatitis C virus (HCV)-related oral lichen planus (OLP), which appears unrelated to either HCV genotype or HCV epidemiology. The present study investigated whether hepatitis G virus (HGV) co-infection may be a feature of patients with HCV-related OLP, which might explain these phenomena. HGV co-infection was detected in 6 of 39 Italian patients with HCV-related OLP, but the presence of HGV did not influence the clinical presentation of OLP. It is concluded that HGV co-infection is unlikely to influence the clinical detection of HCV-related OLP.

Adult↗
PubMed2000

A T-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo.

Human interleukin 2 (IL-2; Proleukin) is an approved therapeutic for advanced-stage metastatic cancer; however, its use is restricted because of severe systemic toxicity. Its function as a central mediator of T-cell activation may contribute to its efficacy for cancer therapy. However, activation of natural killer (NK) cells by therapeutically administered IL-2 may mediate toxicity. Here we have used targeted mutagenesis of human IL-2 to generate a mutein with approximately 3,000-fold in vitro selectivity for T cells over NK cells relative to wild-type IL-2. We compared the variant, termed BAY 50-4798, with human IL-2 (Proleukin) in a therapeutic dosing regimen in chimpanzees, and found that although the T-cell mobilization and activation properties of BAY 50-4798 were comparable to human IL-2, BAY 50-4798 was better tolerated in the chimpanzee. BAY 50-4798 was also shown to inhibit metastasis in a mouse tumor model. These results indicate that BAY 50-4798 may exhibit a greater therapeutic index than IL-2 in humans in the treatment of cancer and AIDS.

Animals↗
PubMed2000

Giant cell tumor of the infratemporal fossa.

Giant cell tumors are an uncommon neoplasm; most are found in the long bones, formed by endochondral ossification. This article presents a case of giant cell tumor of the infratemporal fossa, which by radiographic and clinical examination appears to have originated in the squamous portion of the temporal bone.

Case Reports↗
PubMed2000

The N terminus of the centromere H3-like protein Cse4p performs an essential function distinct from that of the histone fold domain.

Cse4p is an evolutionarily conserved histone H3-like protein that is thought to replace H3 in a specialized nucleosome at the yeast (Saccharomyces cerevisiae) centromere. All known yeast, worm, fly, and human centromere H3-like proteins have highly conserved C-terminal histone fold domains (HFD) but very different N termini. We have carried out a comprehensive and systematic mutagenesis of the Cse4p N terminus to analyze its function. Surprisingly, only a 33-amino-acid domain within the 130-amino-acid-long N terminus is required for Cse4p N-terminal function. The spacing of the essential N-terminal domain (END) relative to the HFD can be changed significantly without an apparent effect on Cse4p function. The END appears to be important for interactions between Cse4p and known kinetochore components, including the Ctf19p/Mcm21p/Okp1p complex. Genetic and biochemical evidence shows that Cse4p proteins interact with each other in vivo and that nonfunctional cse4 END and HFD mutant proteins can form functional mixed complexes. These results support different roles for the Cse4p N terminus and the HFD in centromere function and are consistent with the proposed Cse4p nucleosome model. The structure-function characteristics of the Cse4p N terminus are relevant to understanding how other H3-like proteins, such as the human homolog CENP-A, function in kinetochore assembly and chromosome segregation.

Alanine↗
PubMed2000

Effect of recombinant SP-C surfactant in a porcine lavage model of acute lung injury.

Synthetic surfactants allow examination of the effects of specific components of natural surfactant. To determine whether surfactant containing apoprotein C, dipalmitoyl-phosphatidylcholine, phosphatidylglycerol, and palmitic acid restores gas-exchanging function in acute lung injury (ALI), we administered such surfactant (in doses of 50 or 100 mg/kg and in volumes from 1 to 6 ml/kg) or phospholipid (PL) alone, by intratracheal instillation, to pigs with ALI induced by massive saline lavage. Animals ventilated with 100% O(2) and receiving 1, 2, 4, or 6 ml/kg of 50 mg/kg recombinant surfactant apoprotein C (rSP-C) surfactant or 2 ml/kg of 50 mg/kg PL (control) had mean arterial PO(2) values, 4 h after treatment, of 230, 332, 130, 142, or 86 Torr, respectively. Animals receiving 1, 2, or 4 ml/kg of 100 mg/kg rSP-C surfactant or 2 ml/kg of 100 mg/kg PL (control) had mean arterial PO(2) values of 197, 214, 148, or 88 Torr, respectively. Surfactant PL distribution was homogeneous. Hyaline membrane formation was reduced in treated animals. Thus, in this model of ALI, rSP-C with PL has the capacity to improve gas exchange and possibly modify lung injury.

Animals↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗