Search PubMed⌕ Search

Biomedical subjects

K Robinson

Publications and source records attributed to K Robinson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Homocysteinemia and vascular disease in end-stage renal disease.

Homocysteine is an intermediate amino acid formed during the metabolism of methionine, a sulfur-containing essential amino acid, and cleared by the kidneys. The two major acquired causes of increased homocysteine values are chronic renal failure and absolute or relative deficiencies of folate, vitamin B12 or vitamin B6, three vitamins involved in the normal metabolism of methionine. We studied 176 patients (97 men and 79 women with mean age 56.3 +/- 14.8 years) with end-stage renal disease on peritoneal or hemodialysis. Homocysteine concentrations averaged 26.6 +/- 1.5 mumol/liter in patients with renal failure as compared to 10.1 +/- 1.7 mumol/liter in normals. Abnormal values exceeded the 95th percentile for normal controls in 149 patients, giving an overall prevalence of homocysteinemia of 85%. There was preservation of the negative correlation between homocysteine and folate (r = -0.48), suggesting responsiveness in spite of impairment. Increased homocysteine concentrations were associated with an increased odds ration for atherosclerotic and thrombotic complications independent of other traditional risk factors and the length of time on dialysis. The odds ratio for vascular events with homocysteine levels was 2.9 (CI 1.4 to 5.8) for the upper two quintiles of homocysteine values compared to the lower three quintiles adjusted for age, gender, hypertension, diabetes, hypercholesterolemia, smoking and time on dialysis. These data indicate that plasma homocysteine values represent an independent risk factor for vascular events in patients on peritoneal and hemodialysis. The mechanism by which high homocysteine concentrations might cause vascular damage in patients with renal failure remains unclear.

Arteriosclerosis↗
PubMed1995

Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease.

BACKGROUND: High plasma homocysteine is associated with premature coronary artery disease in men, but the threshold concentration defining this risk and its importance in women and the elderly are unknown. Furthermore, although low B vitamin status increases homocysteine, the link between these vitamins and coronary disease is unclear. METHODS AND RESULTS: We compared 304 patients with coronary disease with 231 control subjects. Risk factors and concentrations of plasma homocysteine, folate, vitamin B12, and pyridoxal 5'-phosphate were documented. A homocysteine concentration of 14 mumol/L conferred an odds ratio of coronary disease of 4.8 (P < .001), and 5-mumol/L increments across the range of homocysteine conferred an odds ratio of 2.4 (P < .001). Odds ratios of 3.5 in women and of 2.9 in those 65 years or older were seen (P < .05). Homocysteine correlated negatively with all vitamins. Low pyridoxal 5'-phosphate (< 20 nmol/L) was seen in 10% of patients but in only 2% of control subjects (P < .01), yielding an odds ratio of coronary disease adjusted for all risk factors, including high homocysteine, of 4.3 (P < .05). CONCLUSIONS: Within the range currently considered to be normal, the risk for coronary disease rises with increasing plasma homocysteine regardless of age and sex, with no threshold effect. In addition to a link with homocysteine, low pyridoxal-5'-phosphate confers an independent risk for coronary artery disease.

Age Factors↗
PubMed1995

Targeted deletion of 5'HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus.

The beta-globin locus control region (LCR) is a complex regulatory element that is essential for the appropriate red cell-specific expression of all cis-linked beta-globin genes. Of the five hypersensitive sites that define the LCR, only 5'HS2 has been shown to augment gene expression in vitro in both transient and stable assays, as well as in transgenic mice. Thus, 5'HS2 has been assumed to be an important element for the function of the LCR in vivo. We have utilized homologous recombination in murine embryonic stem (ES) cells and phenotypic analysis in derived mice to investigate the function of 5'HS2 in its normal chromosomal position in the murine beta-globin locus. Replacement of 5'HS2 with a selectable marker gene (delta HS2 + neo) causes a 2-5-fold reduction in expression of all of the genes in the locus, and a more pronounced effect (10-12-fold) on the most 5' embryonic globin gene, Ey, when expression of this gene is first detectable during embryogenesis. The mutation produces no alterations in the developmental timing of expression of the globin genes. When homozygous, the deletion/replacement mutation is lethal in utero, with the embryos dying during the stage of yolk sac and early fetal liver erythropoiesis. To distinguish phenotypic effects resulting from the deletion of 5'HS2 from those attributable to insertion of the selectable marker, the selectable marker was removed by expressing the FLP site-specific recombinase in ES cells harboring the homologous recombination event. Mice derived from these ES cells (delta HS2 delta neo) demonstrated nearly full expression of all the beta-like globin genes on the mutated chromosome. These results indicate that although 5'HS2 demonstrates significant regulatory activities in a variety of assays, deletion of this element from the endogenous beta-globin locus has no significant effect on the timing or extent of expression of the locus. In addition, this result emphasizes that when using homologous recombination to analyze complex regulatory elements in vivo, the inserted selectable marker must be removed to avoid influencing the phenotype of the mutation.

Animals↗
PubMed1995

Crystallization and preliminary X-ray analysis of maize ZBP14 protein, a member of a new family of zinc-binding proteins.

A preliminary X-ray crystallographic study of a novel zinc-binding protein from maize is presented. Native and several heavy-atom derivative sets of data have been collected on synchrotron sources, to a resolution of 2.1 A. The space group was found to be orthorhombic, P2(1)2(1)2(1), with unit-cell dimensions of a = 92.64, b = 129.45 and c = 196.31 A.

Journal Article↗
PubMed1995

Expression and characterization of maize ZBP14, a member of a new family of zinc-binding proteins.

A maize gene (Mz2-12), with a deduced amino acid sequence similar to that of a protein kinase C (PKC) inhibitor from bovine brain, has been expressed in Escherichia coli and the protein (ZBP14) purified to homogeneity. The bovine protein was originally identified by Walsh's group and named PKC inhibitor-1 (PKCI-1). The recombinant maize protein (ZBP14) shares characteristics of bovine PKCI-1: it has similar secondary structure, is dimeric, and has a similar affinity for zinc. However, the maize ZBP14 had very little activity as an inhibitor of mammalian brain PKC, thus precluding zinc sequestration as the mechanism of inhibition. The biological role for the maize protein in plant kinase regulation is therefore unclear. In the presence of both maize ZBP14 and 14-3-3 protein (which inhibits PKC in the absence of diacylglycerol), the effects on PKC appeared to be synergistic.

Animals↗
PubMed1995

Occult and frequent transmission of atherosclerotic coronary disease with cardiac transplantation. Insights from intravascular ultrasound.

BACKGROUND: Transplant coronary artery disease is a major cause of morbidity and mortality after cardiac transplantation. However, limited data exist regarding the potential contribution of coronary atherosclerosis in the donor heart to cardiac-allograft vasculopathy. METHODS AND RESULTS: We performed quantitative coronary angiography and intravascular ultrasound imaging in 50 of 62 consecutive heart-transplant recipients (40 men, 10 women, mean age, 53 +/- 9 years) 4.6 +/- 2.6 weeks after transplantation. The donor population consisted of 30 men and 20 women (mean age, 32 +/- 12 years). Ultrasound imaging visualized all three coronary arteries in 22 patients, two coronary arteries in 23, and one coronary artery in 5. Ultrasound imaging detected coronary atherosclerosis (intimal thickness > or = 0.5 mm) in 28 patients (56%). However, the angiography was abnormal in only 13 patients (26%). The sensitivity and specificity of coronary angiography were 43% and 95%, respectively. With ultrasound, the average atherosclerotic plaque thickness was 1.3 +/- 0.6 mm and the cross-sectional area narrowing was 34 +/- 16%. Atherosclerotic involvement frequently was focal (85%), eccentric (mean eccentricity index, 87 +/- 8), and near arterial bifurcations. Donors of the transplant recipients with coronary atherosclerosis were older than those without atherosclerosis (37 +/- 12 versus 25 +/- 10 years, P = .001). Maximal intimal thickness correlated with donor age (r = .54, P = .0001). Multivariate analysis demonstrated that donor age (P = .0001), male sex of donor (P = .0006), and recipient age (P = .03) were independent predictors of atherosclerosis. CONCLUSIONS: Coronary atherosclerosis is frequently but inadvertently transmitted by means of cardiac transplantation from the donor to the recipient. Long-term outcomes of donor-transmitted coronary artery disease will require further evaluation.

Adult↗
PubMed1995

Ototoxicity of topical ticarcillin and clavulanic acid in the chinchilla.

BACKGROUND: Currently available topical otic preparations contain a variety of antibiotics and other ingredients that are potentially damaging to the middle and inner ear. There is therefore a need to identify agents that are safe as well as effective for topical otologic use. In pursuit of that goal, we used an animal model to evaluate the ototoxic potential of the broad-spectrum, penicillin derivative ticarcillin--both alone and combined with clavulanic acid (a beta-lactamase inhibitor). METHODS: Twenty chinchillas served as subjects. Ten of the animals were given a single middle ear application of ticarcillin; the remaining 10 animals received ticarcillin disodium plus clavulanate potassium (Timentin). Five animals from each of the two groups were killed after 1 week to assess short-term effects and the other five animals in each group were kept for 4 weeks before their temporal bones were removed for histologic study. RESULTS: Significant toxic effects, involving both the middle and inner ear, were observed in all experimental groups. Alterations of the middle ear at 1 week included inflammation, hemorrhage, and effusions. Middle ear cholesteatomas were observed at 4 weeks. Inner ear changes seen at 1 and 4 weeks included hair cell loss, supporting cell degeneration, and strial damage. CONCLUSION: The study results indicate that ticarcillin should not be considered for further evaluation as a possible antibiotic for use in ototopical preparations.

Administration, Topical↗
PubMed1995

Oral and parenteral vaccination against Trichinella spiralis infections in high- and low-responder mice.

Vaccination by different routes and with different adjuvants is known to influence profiles of immune responses and may be used to overcome genetically determined low-responsiveness to infection. A mouse model of infection with the intestinal nematode Trichinella spiralis was used to investigate the effect of mode of vaccination upon immune responsiveness and worm expulsion phenotype in high- (NIH) and low- (C57 BL/10) responder strains of mice. Muscle larval homogenate antigen was given subcutaneously in Freund's complete adjuvant (FCA) to induce a systemic immune response or with cholera toxin (CT) orally to stimulate mucosal immunity. Both approaches significantly protected NIH mice. Vaccination with FCA was correlated with elevated serum IgG after infection, whereas oral CT-vaccination resulted in increased levels of intestinal IgA. Neither type of vaccination successfully protected the low-responder C57 BL/10 strain and there were no effects on the low antibody levels that infection induced in this strain.

Administration, Oral↗
PubMed1995

Immune response profiles in vaccinated and non-vaccinated high- and low-responder mice during infection with the intestinal nematode Trichinella spiralis.

NIH and C57 BL/10 (B10) mice show genetically determined differences in their response to Trichinella spiralis infection. This study examines the influence of these on parameters of the immune response to infection after vaccination using muscle-larval excretory-secretory antigen in Freund's complete adjuvant. Serum antibody levels were greatly elevated when mice of both strains were vaccinated prior to infection; however, NIH produced significantly higher-level antibody responses than B10. Vaccination accelerated and increased the capacity of mesenteric lymph node T-cells to proliferate in vitro in response to specific antigen stimulation in both mouse strains but, in general, the stimulation indices of NIH cells were higher than those of the B10. The capacity of mesenteric lymph node cells (MLNC) and spleen cells (SC) to produce IL-5 and gamma IFN was measured after specific in vitro stimulation and early gamma IFN secretion was noted in the supernatants of NIH MLNC and SC, but not in B10 SC. Concentrations of IL-5 rose steadily over the first 10-14 days after infection in cell cultures from both strains. Prior vaccination of these animals appeared to enhance cytokine levels. It is postulated that the efficacy of vaccination in NIH mice is a consequence of their genetically determined capacity to produce early and high-level responses to the antigens of T. spiralis and to express these in intestinal effector mechanisms.

Animals↗
PubMed1995

Isolates of Trichuris muris vary in their ability to elicit protective immune responses to infection in mice.

Much of what is currently known of the host-parasite interaction between mice and the parasitic nematode Trichuris muris has come from experiments using a single parasite isolate (E/N). This isolate has been compared with 2 others which, on morphological criteria, belong to the same species. In 3 inbred strains of mouse that show distinct, genetically determined response phenotypes, there was a consistent pattern in terms of parasite survival time regardless of host strain, E/K worms being expelled early, E/N expelled later and S worms very late or not at all. High-responder CBA mice expelled E/K and E/N worms earlier than low-responder C57 B1/10 mice. B10.BR mice were permissive to S isolate infection, mounted a very late response to E/N worms but expelled E/K worms effectively by day 25. The differential response of mice to these isolates provides an experimental system for identifying the basis of variation in this host-parasite relationship.

Adaptation, Physiological↗
PubMed1995

Is otoscopy reliable? A structured teaching method to improve otoscopic accuracy in trainees.

Otoscopy is an important skill for primary care physicians and otologists. Until now, training has been by repeated exposure to patients with ear disease. Structured instruction in how to assess an ear has not previously been reported. Not-diseased ears and those with varying types of chronic (suppurative) otitis media were chosen to be photographed as this is an important condition to be able to diagnose and in which pneumatic otoscopy has no role. Two sets of 30 slides of equal difficulty were shown to 10 trainees, one before and one after structured teaching. The overall error rate fell from 44 to 21% (P < 0.001). Most importantly, the error rate in assessing ear activity fell from 35 to 17% (P < 0.05). In conclusion, a structured approach to otoscopy has been shown to improve the diagnostic ability of trainess tested with photographs of ears with chronic otitis media. Such a teaching approach is likely to be equally beneficial to other otological conditions and to live otoscopy.

Diagnostic Errors↗
PubMed1995

Immunity to Trichinella spiralis transferred by serum from vaccinated mice not protected by immunization.

Serum antibody responses to infection with the intestinal helminth Trichinella spiralis in mice remain at low levels for the first ten to 12 days, slowly increasing to high titres around day 20. It is thought that antibody, therefore, has a limited role in the primary immune response raised against this infection and this is confirmed by the inability of primary infection serum to transfer immunity adoptively. High-responder NIH and low-responder B10 mice were vaccinated with T.spiralis antigen in Freund's complete adjuvant prior to challenge. This procedure conferred significant protection on NIH mice but not B10. Sera from these mice were transferred into recipients before and during challenge infection. Significant levels of protection were obtained in both strains with both homologous and heterologous sera, even though vaccination itself had not resulted in protection of the B10 donor mice. These data indicate that the B10 strain is potentially capable of making a protective immune response against the intestinal phase of T.spiralis.

Animals↗
PubMed1995

Generation of rubella virus-neutralising antibodies by vaccination with synthetic peptides.

Four short peptides from rubella virus proteins E1 and E2, predicted to contain B cell epitopes, were used to vaccinate BALB/c mice. Sera from peptide-vaccinated animals reacted with viral antigens in ELISA and three of the four induced virus-neutralising antibody (nAb) responses. Peptide PY4, in contrast to the others, induced IgG2a responses upon vaccination and stimulated spleen cells in vitro produced IFN gamma in the absence of IL-5. It was reasoned that vaccination with PY4 caused Th1 subset activation, the appropriate type of response for anti-viral immunity and hence the efficient neutralising antibody response. Presentation of peptide for vaccination proved to be as important as the sequence. Similar profiles of IgG1 and IgG2a were detected in the sera of mice vaccinated with PY4 in Freund's complete adjuvant or alum; however nAb responses were not found when alum was used.

Alum Compounds↗
PubMed1995

Changes in intensity discrimination following monaural long-term use of a hearing aid.

Previous work has shown that a normally aided ear tested without the hearing aid is better able to identify speech-in-noise than the unaided ear at high sound levels, while performance for the unaided ear is superior at lower sound levels [S. Gatehouse, J. Acoust. Soc. Am. 86, 2103-6 (1989); J. Acoust. Soc. Am. 92, 1258-68 (1992)]. This effect was further explored using intensity discrimination for complex stimuli. Stimuli were half-octave bandpass-filtered tone complexes centered at 0.25 and 3 kHz. Four bilateral, symmetric hearing-impaired listeners with mean HL of 24 dB at 0.25 kHz, and 58 dB at 3 kHz were tested. Intensity discrimination was performed across the dynamic range of the listeners. At sound-pressure levels greater than 85 dB, the normally aided ear tested without the aid was more sensitive to changes in intensity than the unaided ear, whereas at lower levels, the converse occurred. This pattern was observed only for the 3-kHz center frequency, and not for the 0.25-kHz center frequency. Insertion gain measurements using the aids at normal volume showed an average of 20 dB gain at 3 kHz, and -2 dB gain at 0.25 kHz. The changes in intensity discrimination in the normally aided ear are consistent with the frequency-gain characteristics of the hearing aid, and suggest that a change in intensity coding occurred.

Adolescent↗
PubMed1995

Efficacy of oral vaccination against the murine intestinal parasite Trichuris muris is dependent upon host genetics.

Oral vaccinations with Trichuris muris adult worm homogenate antigen with cholera toxin as the adjuvant were successful in both high-responder BALB/c and low-responder C57BL/10 mice, resulting in high levels of protection against subsequent infection, but were ineffective in the low-responder B10.BR mice. Subcutaneous vaccination with antigen in Freund's complete adjuvant resulted in protection of all of these strains but was most effective in high-responder BALB/c and least effective in B10.BR mice. Oral vaccination resulted in a T. muris-specific intestinal immunoglobulin A response only in the two protected strains. High levels of serum immunoglobulin G1 antibody were induced by Freund's complete adjuvant vaccination in all cases. A relationship between vaccine efficacy, expulsion phenotype, and induced T-helper subset-associated cytokines (interleukin-5 and gamma interferon) was noted. It was concluded that effective vaccination against T. muris requires the induction of Th2 responses and that this can be achieved by both oral and parenteral administration of antigens.

Administration, Oral↗
PubMed1995

National perspective of acute coronary care in the Republic of Ireland.

OBJECTIVE: To assess the use of acute coronary care facilities in the Republic of Ireland with regard to case mix, patient characteristics, mortality and factors associated with mortality, time intervals to admission, utilisation of thrombolysis, and risk factor profiles. DESIGN: A 1 week prospective census of all hospitals admitting acute coronary cases. These comprised 23 coronary care units (CCU) and 17 combined coronary care/intensive care units (CCU/ICU). Data were collected by standardised methods on each new patient "upon whom a cardiac monitor was placed". RESULTS: Acute coronary heart disease was confirmed in 185 (44.9%) of 412 patients. Of these 109 (26.4%) had a confirmed myocardial infarction and 76 (18.4%) unstable angina. Women were significantly older than men in all groups. Of those with proven acute coronary heart disease, 42.6% were current smokers, 23.1% were aware of having a raised cholesterol concentration, and 42.3% gave a history of prior hypertension. Only 44% were transported by ambulance. Median delay time from the onset of symptoms to admission was 6 h in Dublin and 4 h elsewhere. 34.9% of patients with a confirmed myocardial infarction received thrombolysis. Mortality of patients with myocardial infarction CCU/ICU at 7 days was 10.9 %. CONCLUSIONS: There is potential for considerable improvement in the management of coronary heart disease in the Republic of Ireland through a reduction in delay times to admission to hospital, increased use of thrombolytic treatment, and intensification of advice on primary and secondary risk factors.

Adult↗