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Biomedical subjects

K Clark

Publications and source records attributed to K Clark.

At least 127 records · Page 7Linked to original sources
PubMed1995

The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains.

Characterization of the polycystic kidney disease 1 (PKD1) gene has been complicated by genomic rearrangements on chromosome 16. We have used an exon linking strategy, taking RNA from a cell line containing PKD1 but not the duplicate loci, to clone a cDNA contig of the entire transcript. The transcript consists of 14,148 bp (including a correction to the previously described C terminus), distributed among 46 exons spanning 52 kb. The predicted PKD1 protein, polycystin, is a glycoprotein with multiple transmembrane domains and a cytoplasmic C-tail. The N-terminal extracellular region of over 2,500 aa contains leucine-rich repeats, a C-type lectin, 16 immunoglobulin-like repeats and four type III fibronectin-related domains. Our results indicate that polycystin is an integral membrane protein involved in cell-cell/matrix interactions.

Amino Acid Sequence↗
PubMed1995

The efficacy of prophylactic ondansetron, droperidol, perphenazine, and metoclopramide in the prevention of nausea and vomiting after major gynecologic surgery.

The prophylactic antiemetic efficacy of intravenous (i.v.) ondansetron, droperidol, perphenazine, and metoclopramide was evaluated in a prospective, double-blind study of 360 ASA physical status I-III patients undergoing total abdominal hysterectomy (TAH). Subjects were randomized to receive i.v., one of ondansetron 4 mg, droperidol 1.25 mg, perphenazine 5 mg, metoclopramide 10 mg, or placebo prior to induction of anesthesia. Hypotension immediately after administration of metoclopramide was observed in two patients and four patients given ondansetron developed profound systolic hypotension at induction of anesthesia. Twenty-two percent of patients receiving droperidol became sedated. Postoperatively, patients developing severe nausea, retching, or vomiting, defined as severe emetic sequelae (SES), were deemed to have failed antiemetic prophylaxis and received antiemetic rescue. A significantly larger number of patients who received i.v. ondansetron (63%), droperidol (76%), and perphenazine (70%) were free of SES when compared to placebo (43%); P < 0.05. Metoclopramide was ineffective. Although ondansetron, droperidol, and perphenazine were effective in providing antiemetic prophylaxis, only i.v. perphenazine was free of side effects. Hence, we conclude that perphenazine is the best choice for antiemetic prophylaxis after TAH.

Akathisia, Drug-Induced↗
PubMed1994

Potential use of buccal smears for rapid diagnosis of autosomal trisomy or chromosomal sex in newborn infants using DNA probes.

Buccal smears from 3 women and 1 man were probed with alpha satellite DNA probes for chromosomes 8, 18, X, and Y. Buccal smears were also collected from an adolescent phenotypic female with uterine agenesis, as well as from newborn infants with suspected trisomy 18 and trisomy 21. The clinical cases were confirmed with conventional cytogenetic studies of peripheral lymphocytes. Overall probe efficiency at detecting expected chromosome number in interphase cells was found to be 71% +/- 6.8%. Higher than expected n-1 signal numbers may be due to karyopyknotic intermediate epithelial cells present in all collected samples. Overall probe efficiency was found to be consistent using alpha satellite and cosmid probes, both of which accurately reflected the modal copy number of the target chromosomes. False trisomy was less than 1%. This study suggests DNA probes can be used in buccal smears for rapid diagnosis of trisomies and chromosomal sex in newborns, but because of high rates of false hypoploid signals, probed buccal smear specimens may not be accurate at diagnosing mosaicism.

Adult↗
PubMed1994

Structural characterization of the copper site in galactose oxidase using X-ray absorption spectroscopy.

X-ray absorption spectroscopy has been used to characterize the local structural environment of the Cu ion in the reductively inactivated, oxidatively activated, and active+substrate oxidation state derivatives of galactose oxidase. In all three cases, the local environment of the Cu is best modeled by a single shell of low-Z (N or O) scatterers. This is generally consistent with the structure determined crystallographically, although the EXAFS bond lengths are slightly, but significantly, shorter than those found crystallographically. The best-fit average bond lengths are 1.97, 1.95, and 1.98 A for inactive, active, and active+substrate, respectively. The CuII ion in the active and inactive derivatives has an apparent coordination number of 4, consistent with the equatorial ligation seen crystallographically. The CuI ion in the reduced+substrate derivative appears to have either a lower coordination number or a significantly more distorted local environment. The observed CuI-(N/O) bond length favors a model where the Cu become 3-coordinate in the substrate-reduced complex.

Copper↗
PubMed1994

Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules.

Reagents that inhibit the ubiquitin-proteasome proteolytic pathway in cells have not been available. Peptide aldehydes that inhibit major peptidase activities of the 20S and 26S proteasomes are shown to reduce the degradation of protein and ubiquitinated protein substrates by 26S particles. Unlike inhibitors of lysosomal proteolysis, these compounds inhibit the degradation of not only abnormal and short-lived polypeptides but also long-lived proteins in intact cells. We used these agents to test the importance of the proteasome in antigen presentation. When ovalbumin is introduced into the cytosol of lymphoblasts, these inhibitors block the presentation on MHC class I molecules of an ovalbumin-derived peptide by preventing its proteolytic generation. By preventing peptide production from cell proteins, these inhibitors block the assembly of class I molecules. Therefore, the proteasome catalyzes the degradation of the vast majority of cell proteins and generates most peptides presented on MHC class I molecules.

Amino Acid Sequence↗
PubMed1994

Implicit and explicit memory in patients with Parkinson's disease with and without dementia.

OBJECTIVE: To study explicit and implicit memory processes in patients with Parkinson's disease. DESIGN: Case-control design. All subjects were given a neuropsychological test battery, and the test scores were compared among the groups. SETTING: Government-funded research facility. All subjects were examined as outpatients. PATIENTS: We tested nondemented (n = 13) and demented (n = 5) patients with Parkinson's disease and normal controls (n = 12) matched for age, gender, and educational level. MAIN OUTCOME MEASURES: Memory for verbal and pictorial stimuli under both explicit and implicit retrieval conditions. RESULTS: Both nondemented and demented patients with Parkinson's disease exhibited impairment on tests of explicit memory. Their impairment could be graded based on the level of effort required by the task: impaired free recall in nondemented patients and impaired free recall, cued recall, and recognition in demented patients. By contrast, neither group showed evidence of impairment on automatic (modality monitoring and word frequency estimation) or implicit (word and picture fragment identification) memory tasks. Correlation analyses did not support any association between the effortful memory deficits and neurologic variables, mood, or performance on executive function tests. CONCLUSIONS: Memory deficits in patients with Parkinson's disease primarily involve the conscious, effortful strategic aspects of searching long-term memory.

Aged↗
PubMed1994

Pharmacological evaluation of the cholinergic system in progressive supranuclear palsy.

Severe cholinergic loss occurs in the brains of patients with progressive supranuclear palsy. To evaluate the functional implications of this neuronal deficit, dose-response curves were obtained in patients with progressive supranuclear palsy and normal control subjects undergoing intravenous cholinergic blockade (scopolamine) and stimulation (physostigmine). Physostigmine had no significant neurobehavioral effects at any dose in patients with progressive supranuclear palsy. Scopolamine, at low and medium doses, significantly impaired memory performance of both groups, but worsened the gait of only the patients. High-dose scopolamine, which could not be tolerated by the patients, resulted in gait deterioration among control subjects. Thus, patients with progressive supranuclear palsy have increased sensitivity to cholinergic blockade compared to control subjects. Since loss of cholinergic neurons appears to contribute to the pathogenesis of certain cognitive and motor deficits found in progressive supranuclear palsy, the use of oral anticholinergics should ordinarily be avoided in this disorder. On the other hand, physostigmine at clinically tolerated dose levels seems to be therapeutically ineffective.

Aged↗
PubMed1994

A radiation hybrid map of 506 STS markers spanning human chromosome 11.

We present a high resolution radiation hybrid map of human chromosome 11 using 506 sequence tagged sites (STSs) scored on a panel of 86 radiation hybrids. The 506 STSs fall into 299 unique positions (average resolution of about 480 kilobases (kb)) that span the whole chromosome. A subset of 260 STSs (143 positions) form a framework map that has a resolution of approximately 1 megabase between adjacent positions and is ordered with odds of at least 1,000:1. The centromere was clearly defined with pericentric markers unambiguously assigned to the short or long arm. The map contains most genes (125) and expressed sequence tags (26) currently assigned to chromosome 11 and more than half of the STSs are polymorphic microsatellite loci. These markers and the map can be used for high resolution physical and genetic mapping.

Animals↗
PubMed1994

A personality profile of patients diagnosed with post-polio syndrome.

Post-polio syndrome (PPS) refers to the late development of new neuromuscular symptoms in previously stable poliomyelitis patients. Whether psychological disturbance plays a role in the manifestation of symptoms in these patients is unclear. We examined 22 patients fulfilling the clinical criteria for PPS with the Minnesota Multiphasic Personality Inventory-II (MMPI-II), Beck Depression Inventory, Spielberger State-Trait Anxiety Scales, Chapman and Chapman Psychosis-Proneness Scales, Fatigue Scales, a neurobehavioral rating scale, and Cognitive Symptoms Self-Report Scales. The overwhelming majority of scale scores were within normal limits, and there was no indication that psychopathologic symptoms were associated with the development or severity of new muscle weakness in PPS patients. Women with PPS had significantly more somatic complaints, but were less socially isolated than men with PPS. This study confirms that the development or severity of new muscle weakness in carefully diagnosed PPS patients is not due to, or influenced by, underlying psychopathology.

Adult↗
PubMed1994

Play behavior and communication between deaf and hard of hearing children and their hearing peers in an integrated preschool.

Sixty preschoolers (30 deaf and hard of hearing, 30 hearing) were observed in their integrated school during "centers" and outdoor play. Half the children experienced auditory communication and half total communication modes of communication. All children had known their classmates for six months to three years. It was found that all children preferred to play and communicate with same-hearing status children, however 63% of all children communicated with children of other-hearing status. Amounts of social play and communication differed somewhat between the two communication environments, and context of interaction was related to the behavior and communication of children who were deaf and hard of hearing. Implications are discussed for the education of young children who are deaf and hard of hearing--specifically that educational and social benefits accrue to those who are integrated throughout the school day (across context) and have access to hearing classmates and classmates who are deaf and hard of hearing.

Child, Preschool↗
PubMed1994

University of Alberta norms of relative meaning frequency for 566 homographs.

For many models of lexical ambiguity resolution, relative frequency of the different meanings of homographs (words with more than one meaning) is crucial. Although several homograph association norms have been published in the past, none has involved a large number of subjects responding to a large number of homographs, and most homograph norming studies are now at least a decade old. In Experiment 1, associations to 566 homographs were collected from an average of 192 subjects per homograph. Frequency of occurrence for the three most common meanings is reported, along with the corresponding associates, and a measure of the overall ambiguity of each homograph. Homographs whose meanings differed in part of speech were more ambiguous overall than homographs whose different meanings belonged to a single grammatical class. Homographs whose pronunciation depended on meaning (heterophones) were no more ambiguous than nonheterophones, and word frequency was unrelated to overall ambiguity. Estimates of homograph balance across different norming studies were compared, and homographs with two meanings of approximately equal relative meaning frequency (balanced homographs) and homographs with one clearly dominant meaning (polarized homographs) were identified. In Experiment 2, reliability of meaning categorizations was measured for a subset of the homographs in the first experiment. Meaning categorizations were shown to be highly reliable across raters.

Humans↗
PubMed1994

Thymic peptides increase glutathione level and glutathione disulfide reductase activity in vascular endothelial cells.

The glutathione redox cycle plays an important role in antioxidant and detoxification mechanisms. We recently reported that a calf thymic peptide (TP) protected vascular endothelial cells from oxidant injury induced by hydrogen peroxide. Using electrophoresis and amino acid sequencing analysis, we have now shown that TP consists of two peptides. The fast-moving peptide has 9 amino acid residues at the NH2 terminal and accounts for 92% of total quantity, while the other peptide has 18 amino acid residues at the NH2 terminal and amounts to 8%. The present study investigated the effect of TP on glutathione redox cycle. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were incubated with TP (12.5-100 micrograms/mL) for 24-48 h. TP caused a dose-dependent increase in glutathione (GSH) level and glutathione disulfide reductase activity but no significant change in GSH peroxidase activity. Exposure of PAEC to an organic oxidant t-butyl hydroperoxide (tBHP) resulted in decreased GSH level, increased lipid peroxidation, and elevated leakage of intracellular lactate dehydrogenase. Preincubation of PAEC with TP prevented these changes induced by tBHP. The data suggest that the antioxidant effect of TP may be due, at least in part, to its modulation of the GSH redox cycle in vascular endothelial cells. TP may thus be considered a new antioxidant with novel activities in addition to being an immune regulator.

Amino Acid Sequence↗
PubMed1994

Guiding patients and their families through peripheral stem cell transplantation with the help of a teaching booklet.

PURPOSE/OBJECTIVE: To present a booklet designed to educate patients and their families about peripheral blood stem cell transplantation (PBSC). DATA SYNTHESIS: The booklet describes the procedure, self-care, preliminary chemotherapy regimens, necessary follow-up tests, and appropriate resources. CONCLUSIONS: Preliminary evaluation indicates the booklet has been well-received and appreciated by patients and nursing staff alike. IMPLICATIONS FOR NURSING PRACTICE: The booklet supplements basic patient education in regard to PBSC, anticipates patient questions, and provides patients and families with a take-home, written resource.

Aftercare↗
PubMed1994

Nutritional guidance to soccer players for training and competition.

Strategies for a nutrition education as applied to individual soccer players provide a key to guiding them towards appropriate food selection. Scientific investigations have associated energy requirements, composition of the diet and carbohydrate intake with muscle glycogen storage, and adequacy of fluids with optimal athletic performance. In general, soccer players appear to consume adequate energy but low carbohydrate diets. The training diet should be comprised of 55-65% carbohydrate, 12-15% protein and less than 30% fat. The goal of the training diet is to provide adequate energy for weight maintenance, and 7-10 g of carbohydrate per kg body weight for maximizing glycogen storage. Nutritional needs for competition include eating prior to and after matches. Consumption of carbohydrate-rich foods for energy needs and glycogen resynthesis are key behaviours soccer players need to focus on daily. Qualified dietitians should be on hand to provide personal nutrition counselling, carbohydrate resource lists and education on food labels as simple and quick nutrition education strategies to guide soccer players, their parents, coaches and trainers towards improved food selections.

Dietary Carbohydrates↗
PubMed1993

Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages.

Antigens in extracellular fluids can be processed and presented with major histocompatibility complex (MHC) class I molecules by a subset of antigen presenting cells (APCs). Chicken egg ovalbumin (Ova) linked to beads was presented with MHC class I molecules by these cells up to 10(4)-fold more efficiently than soluble Ova. This enhanced presentation was observed with covalently or noncovalently linked Ova and with beads of different compositions. A key parameter in the activity of these conjugates was the size of the beads. The APC that is responsible for this form of presentation is a macrophage. These cells internalize the antigen constructs through phagocytosis, since cytochalasin B inhibited presentation. Processing of the antigen and association with MHC class I molecules appears to occur intracellularly as presentation was observed under conditions where there was no detectable release of peptides into the extracellular fluids. When injected in vivo in C57BL/6 mice, Ova-beads, but not soluble Ova, primed CD4- CD8+ cytotoxic T lymphocytes (CTLs). Similar results were obtained in BALB/c mice immunized with beta-galactosidase-beads. The implications of these findings for development of nonliving vaccines that stimulate CTL immunity are discussed.

Animals↗
PubMed1993

Procedural learning in Parkinson's disease and cerebellar degeneration.

We compared procedural learning, translation of procedural knowledge into declarative knowledge, and use of declarative knowledge in age-matched normal volunteers (n = 30), patients with Parkinson's disease (n = 20), and patients with cerebellar degeneration (n = 15) by using a serial reaction time task. Patients with Parkinson's disease achieved procedural knowledge and used declarative knowledge of the task to improve performance, but they required a larger number of repetitions of the task to translate procedural knowledge into declarative knowledge. Patients with cerebellar degeneration did not show performance improvement due to procedural learning, failed to achieve declarative knowledge, and showed limited use of declarative knowledge of the task to improve their performance. Both basal ganglia and cerebellum are involved in procedural learning, but their roles are different. The normal influence of the basal ganglia on the prefrontal cortex may be required for timely access of information to and from the working memory buffer, while the cerebellum may index and order events in the time domain and be therefore essential for any cognitive functions involving sequences.

Adult↗
PubMed1993

Acute chest syndrome in sickle cell anaemia.

A patient suffering from sickle cell anaemia who presented with the acute chest syndrome is described. The syndrome is reported to be one of the commonest causes of death in adults suffering from sickle cell disease. As it is difficult at presentation to distinguish the syndrome from infection, it is usual to give treatment appropriate for both. Early exchange transfusion is thought to limit further damage from sickling and offers the best hope of recovery.

Acute Disease↗