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Biomedical subjects

K Peters

Publications and source records attributed to K Peters.

At least 163 records · Page 9Linked to original sources
PubMed1998

Neighborhood social context and racial differences in women's heart disease mortality.

Compared to white women, black women experience similar rates of heart disease morbidity, but higher rates of heart disease mortality. This puzzling relationship may be due to several factors working at varied levels to affect each race. For example, the high heart disease mortality rate may be due to individual health or socioeconomic risk factors or to social structural factors. We conduct a multi-level analysis to address these issues, using data from a newly released data file that links the National Health Interview Survey with death certificate information from the National Death Index, and with additional community level data from the 1990 Census STF-3A files. We are primarily interested in the effects of female-headship rates in the census tracts on coronary heart disease mortality (CHD) among black and white women. We find that women who live in communities with high concentrations of female-headed families are more likely to die of heart disease, net of other characteristics. For younger women, the effect appears to be routed primarily through poverty whereas for older women the effect of female-headship rates remains, net of other census tract characteristics. This study, then, highlights the importance of examining the effect of neighborhoods and their social content on mortality.

Adolescent↗
PubMed1997

Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth.

Tie2 is a novel receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium. Disruption of Tie2 function in transgenic mice resulted in embryonic lethality secondary to characteristic vascular defects; similar defects occurred after disruption of the Tie2 ligand. These findings indicate that the Tie2/Tie2 ligand pathway plays important roles during development of the embryonic vasculature. To determine whether the Tie2 pathway was involved in pathologic angiogenesis in adult tissues, a soluble form of the extracellular domain of murine Tie2 (ExTek.6His) was developed and used as a Tie2 inhibitor. After a single application of the ExTek.6His protein into a rat cutaneous window chamber, growth of a mammary tumor inside the chamber was reduced by > 75% (P < 0.005), and tumor vascular length density was reduced by 40% when compared with control-treated tumors (P < 0.01). In the rat cornea, ExTek.6His blocked angiogenesis stimulated by tumor cell conditioned media. ExTek.6His protein did not affect the viability of cultured tumor cells, indicating that the antitumor effect of ExTek.6His was due to the inhibition of tumor angiogenesis. These data demonstrate a role for the Tie2 pathway in pathologic angiogenesis, suggesting that targeting this pathway may yield effective antiangiogenic agents for treatment of cancer and other angiogenic diseases.

Animals↗
PubMed1997

Predictors of response to exercise training in severe chronic congestive heart failure.

We prospectively assessed whether baseline central hemodynamics and exercise capacity can predict improvement of VO2 at ventilatory threshold (VT) after exercise training in patients with severe chronic congestive heart failure. Eighteen patients (mean +/- SEM; age 52 +/- 2 years), half of them listed for transplant, underwent 3 weeks of exercise training (interval cycle and treadmill walking; 5 x/week) and 3 weeks of activity restriction in a random-order crossover trial. Baseline data were not significantly different for groups with exercise training first and activity restriction first: cardiac index at rest (2.1 +/- 0.1 L/m2/min), maximum cardiac index (3.1 +/- 0.2 L/m2/min) (Fick), and echocardiographic ejection fraction (21 +/- 1%). The same was true for cardiopulmonary exercise data (cycle ergometry; up 12.5 W/min): VO2 at VT (9.3 +/- 0.4 ml/kg/min), maximum VO2 (12.2 +/- 0.7 ml/kg/min), VT in percentage of predicted maximum VO2 (31 +/- 2%), heart rate at VT (95 +/- 4 beats/min), and decrease of dead space-to-tidal volume ratio from rest to VT (33 +/- 1 --> 29 +/- 1). Improvement of VO2 at VT after training (2.2 +/- 0.4 ml/kg/min; p <0.001) was not related to baseline central hemodynamics (r = <0.10 for each), but was greater in patients with a lower baseline VO2 at VT (r = -0.65; p <0.01), peak VO2 (r = -0.66; p <0.01), VT in percentage of predicted maximum VO2 (r = -0.74; p <0.001), heart rate at VT (r = -0.63; p <0.01), and smaller decrease of dead space-to-tidal volume ratio from rest to VT (r = 0.65; p <0.01). Ejection fraction after exercise training (24 +/- 2%) and activity restriction (23 +/- 2%) did not differ significantly compared with baseline, and patient status (heart failure and cardiac rhythm) remained stable. Three parameters accounted for 84% of the variance of improvement in VO2 at VT: VO2 at VT in percent predicted maximum VO2, decrease of dead space-to-tidal volume ratio, and heart rate at VT. The findings suggest that there was a greater increase in VO2 at VT after exercise training in patients with greater peripheral deconditioning at baseline. The improvement was unrelated to central hemodynamics. Clinically stable patients with severe chronic congestive heart failure, potential heart transplant candidates, and those awaiting transplantation may benefit from involvement in a short-term exercise training program.

Exercise↗
PubMed1997

Human cornea and sclera studied by atomic force microscopy.

The purpose of this study was to investigate the ultrastructure of the extracellular matrix of human cornea and sclera by using the atomic force microscope (AFM). Specimens of human cornea (n=16) and sclera (n=10) were obtained from a cornea bank or from enucleated eyes (n=1; clinical and histopathological diagnosis: choroidal melanoma) and fixed in Karnovsky solution. The AFM resolved individual collagen fibrils in corneal and scleral tissue. Scleral collagen fibrils had a diameter ranging from 118.3 to 1268.0 nm and showed clear banding with a mean axial D-periodicity of 77.02 nm. The mean gap depth between the two overlaps was larger in the sclera than in the cornea. The diameter of corneal collagen fibrils ranged from 48.0 to 113.0 nm. In contrast to the sclera, the corneal collagen fibrils did not exhibit clear banding as their surface pattern. Closely attached fibrils with a beaded to globular structure were predominant in the cornea. The mean axial D-periodicity of the corneal collagen fibrils was 68.50 nm. In both tissues, the AFM resolved structures resembling cross-bridges between adjacent fibrils. The corneal collagen fibrils showed fibrillar properties that were different from those of the sclera, and that therefore might be essential for the spatial organization responsible for the optical quality of the cornea.

Cornea↗
PubMed1997

Short-term reproducibility of cardiopulmonary measurements during exercise testing in patients with severe chronic heart failure.

Eleven men with severe chronic heart failure (peak cardiac index 4.0 +/- 0.2 L/m2/min), six on a heart transplantation waiting list, were prospectively assessed. To determine reproducibility of cardiopulmonary and hemodynamic variables for clinical purposes during ramp bicycle ergometry, the patients underwent two ramp bicycle ergometer tests (3 minutes unloaded, work rate increments of 12.5 W/min) with a 1-week interval between tests. Oxygen uptake (VO2) carbon dioxide production (VCO2), and ventilation were measured breath by breath, and calculations were performed to determine gas exchange ratio, oxygen pulse, ventilatory equivalents of oxygen and carbon dioxide, and end-tidal partial pressure for oxygen and carbon dioxide. Additionally, heart rate, blood pressure, and lactate levels were assessed. Measurements were performed at submaximum work rate levels of 25 W, 50 W, and 75 W at ventilatory threshold and at peak work rate. At all measurement points, the coefficient of variation for cardiopulmonary variables was between 1.4% and 7.1% for submaximum work rate levels, between 1.2% and 4.4% at ventilatory threshold, and between 2.4% and 7.1% at peak work rate. For heart rate, blood pressure, and lactate levels, coefficient of variation was between 2.7% and 5.7% for submaximum work rate levels, between 1.4% and 6.1% at ventilatory threshold, and between 1.2% and 5.5% at peak work rate. The data suggest high reproducibility for duplicate measurements of cardiopulmonary and hemodynamic variables during ramp bicycle ergometry in patients with severe chronic heart failure. The results may be used to determine whether any variable in a single patient is significantly different from that obtained in a previous exercise test or if the change is within experimental error.

Anaerobic Threshold↗
PubMed1997

Relative validity of clinical techniques for measuring the body composition of persons with amyotrophic lateral sclerosis.

Tracking body composition is necessary to understand how amyotrophic lateral sclerosis (ALS) is affecting a patient's morphology and to provide a basis for appropriate nutritional advice throughout disease progression. Dual X-ray absorptiometry (DEXA) has been shown to reliably detect body composition changes in persons with ALS. However, this procedure is expensive and available primarily for research. The purpose of this study was to determine the relative validity of two common clinical techniques, anthropometry and bioelectrical impedance analysis (BIA), for measuring the body composition of persons with ALS. Twenty-three persons with ALS volunteered for the study; seven with primarily bulbar symptoms, five with primarily arm weakness, five with primarily leg weakness, and six with significant weakness in all extremities. On a single day subjects underwent body composition analysis by the three techniques, with DEXA serving as the criterion method. Anthropometry and BIA results were converted to lean and fat mass using eight prediction equations commonly cited in the literature. Anthropometry measures were also converted to estimates of muscle mass using two additional equations. Both BIA and anthropometry tended to overestimate lean mass and underestimate fat mass compared to DEXA. However, the BIA prediction equations had smaller mean differences, larger correlations, and smaller standard errors of estimate than the anthropometry equations. The Lukaski et al. BIA equation (Lukaski, H.C., Bolonchuk, W.W., Hall, C.B., Siders, W.A., 1986. Validation of tetrapolar bioelectrical impedance method to assess human body composition. J. Appl. Physiol. 60, 1327-1332) most closely matched the values derived by DEXA and is probably the best method for measuring the lean and fat mass of persons with ALS, as long as they maintain adequate hydration levels. The Heymsfield et al. equation (Heymsfield, S.B., McManus, C., Smith, J., Stevens, V., Nixon, D.W., 1982. Anthropometric measurement of muscle mass: revised equations for calculating bone-free arm muscle area. Am. J. Clin. Nutr. 36, 680-690) for estimating muscle mass may also be a useful clinical tool for this population. Further longitudinal studies are needed to determine whether the equations that correlated best with DEXA at a single point in time are also sensitive enough to detect changes in body composition over a period of time.

Absorptiometry, Photon↗
PubMed1997

Betulinic acid: isolation from Triphyophyllum peltatum and Ancistrocladus heyneanus, antimalarial activity, and crystal structure of the benzyl ester.

The known lupane-type triterpene betulinic acid (3) was isolated for the first time from Triphyophyllum peltatum and Ancistrocladus heyneanus. It was found to exhibit moderate to good in vitro antimalarial activity against asexual erythrocytic stages of the human malaria parasite Plasmodium falciparum. A first X-ray structure analysis succeeded after conversion into its benzyl ester 4.

Animals↗
PubMed1997

The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation.

The zebrafish cloche mutation affects both the endothelial and hematopoietic lineages at a very early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W., Zon, L. I. and Fishman, M. C. (1995). Development 121, 3141-3150). The most striking vascular phenotype is the absence of endocardial cells from the heart. Microscopic examination of mutant embryos reveals the presence of endothelial-like cells in the lower trunk and tail regions while head vessels appear to be missing, indicating a molecular diversification of the endothelial lineage. Cell transplantation experiments show that cloche acts cell-autonomously within the endothelial lineage. To analyze further the role of cloche in regulating endothelial cell differentiation, we have examined the expression of flk-1 and tie, two receptor tyrosine kinase genes expressed early and sequentially in the endothelial lineage. In wild-type fish, flk-1-positive cells are found throughout the embryo and differentiate to form the nascent vasculature. In cloche mutants, flk-1-positive cells are found only in the lower trunk and tail regions, and this expression is delayed as compared to wild-type. Unlike the flk-1-positive cells in wild-type embryos, those in cloche mutants do not go on to express tie, suggesting that their differentiation is halted at an early stage. We also find that the cloche mutation is not linked to flk-1. These data indicate that cloche affects the differentiation of all endothelial cells and that it acts at a very early stage, either by directly regulating flk-1 expression or by controlling the differentiation of cells that normally develop to express flk-1. cloche mutants also have a blood deficit and their hematopoietic tissues show no expression of the hematopoietic transcription factor genes GATA-1 or GATA-2 at early stages. Because the appearance of distinct levels of flk-1 expression is delayed in cloche mutants, we examined GATA-1 expression at late embryonic stages and found some blood cell differentiation that appears to be limited to the region lined by the flk-1-expressing cells. The spatial restriction of blood in the ventroposterior-most region of cloche mutant embryos may be indicative of a ventral source of signal(s) controlling hematopoietic differentiation. In addition, the restricted colocalization of blood and endothelium in cloche mutants suggests that important interactions occur between these two lineages during normal development.

Amino Acid Sequence↗
PubMed1997

Introduction of a proline residue into position 31 of the loop of the dimeric 4-alpha-helical protein ROP causes a drastic destabilization.

The exchange of an alanine with a proline residue in position 31 of the loop region of the dimeric 4-alpha-helical-bundle protein ROP causes a reduction in the alpha-helix content of 7% and a reduction in stability of about 40% compared to the wild type parameters. The Gibbs energy of unfolding by denaturants extrapolated linearly to zero denaturant concentration, delta G0D (buffer, 25 degrees C), has been determined to be 43 kJ (mol dimer)-1. The corresponding ROPwt value is 72 kJ (mol dimer)-1 (Steif et al., 1993). The extrapolated delta G0D values obtained from urea and GdmHCI un- and refolding studies are identical within error limits. Deconvolution of the stability values into enthalpy and entropy terms resulted in the following parameters. At T1/2 = 43 degrees C (Cprotein = 0.05 mg.ml-1) the ROP A31P mutant is characterized by delta Hv.H.0 = 272 kJ (mol dimer)-1, delta Cp = 7.2 kJ (mol dimer)-1 K-1, delta S0 = 762 J (mol dimer)-1 K-1. These parameters are only approximately 50% as large as the corresponding values of ROPwt. We assume that the significant reduction in stability reflects the absence of at least one hydrogen bond as well as deformation of the protein structure. This interpretation is supported by the reduction in the change in heat capacity observed for the A31P mutant relative to ROPwt, by the increased aggregation tendency of the mutant and by the reduced specific CD absorption at 222 nm. All results support the view that in the case of ROP protein the loop region plays a significant role in the maintenance of native structure and conformational stability.

Alanine↗
PubMed1997

Fine mapping of the nail-patella syndrome locus at 9q34.

Nail-patella syndrome (NPS), or onychoosteodysplasia, is an autosomal dominant, pleiotropic disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns, and nephropathy. Previous studies have demonstrated linkage of the nail-patella locus to the ABO and adenylate kinase loci on human chromosome 9q34. As a first step toward isolating the NPS gene, we present linkage analysis with 13 polymorphic markers in five families with a total of 69 affected persons. Two-point linkage analysis with the program MLINK showed tight linkage of NPS and the anonymous markers D9S112 (LOD = 27.0; theta = .00) and D9S315 (LOD = 22.0; theta = .00). Informative recombination events place the NPS locus within a 1-2-cM interval between D9S60 and the adenylate kinase gene (AK1).

Chromosome Mapping↗
PubMed1997

The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the treatment of interstitial cystitis: a double-blind, prospective, placebo controlled trial.

PURPOSE: Interstitial cystitis is a debilitating bladder disease of unknown etiology with no cure. A recent report suggested that bacillus Calmette-Guerin (BCG) may be effective in the treatment of interstitial cystitis. A randomized, prospective, double-blind, placebo controlled trial to evaluate the safety and efficacy of intravesical BCG in treating interstitial cystitis was done. MATERIALS AND METHODS: Patients meeting the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis received 6 weekly instillations of Tice strain BCG or placebo. Periodic questionnaires, voiding diaries and cystometrograms were obtained. A total of 30 evaluable subjects was enrolled in the study with a mean followup of 8 months (range 6 to 13). Based on an exit questionnaire a responder was defined as one who rated the interstitial cystitis symptoms as moderately improved or better. RESULTS: A 60% BCG response rate was noted, compared to a 27% placebo response rate. Minimum voided volume and quality of life improved in the BCG group compared to placebo. Adverse events were similar in each group, mostly irritative in nature, and no significant systemic events were noted. CONCLUSIONS: Intravesical Tice strain BCG appears to be safe and efficacious in the treatment of interstitial cystitis. Additional studies must be performed to confirm the results of this pilot study.

Adjuvants, Immunologic↗
PubMed1997

[Mivacurium--a new muscle relaxant compared with atracurium and vecuronium].

This study investigates the effects of mivacurium (3 times ED95) on neuromuscular block, intubation conditions and general safety in comparison with equipotent doses of atracurium and vecuronium. Following Ethical Care Committee approval and informed consent, 90 ASA I+II patients aged 18 to 65 were studied undergoing elective ENT surgery. Anaesthesia was induced with 1.5 mg/kg propofol and 0.2 mg/kg alfentanil and maintained through continuous infusion of propofol (8 to 10 mg . kg-1 . h-1) and nitrous oxide in oxygen. After achieving stable anaesthesia, the patients received bolus injections of mivacurium (0.20 mg/kg, n = 30), atracurium (0.69 mg/kg, n = 30) or vecuronium (0.14 mg/kg, n = 30) for endotracheal intubation. Intubation was attempted 120 s after drug application and the intubation conditions were assessed. Relaxation was recorded using peripheral nerve stimulation (Train of four). During the observation period, signs of histamine release, respiratory difficulty, cardiovascular events or other adverse signs were monitored. Onset of relaxation was longer for mivacurium (2.3 +/- 1.3 min) compared with atracurium (1.4 +/- 0.7 min) or vecuronium (1.3 +/- 0.3 min). Intubation conditions 120 s after drug application were good or very good in only 67% of cases given mivacurium compared with 90% given atracurium and 100% given vecuronium. The recovery time (DUR 25) was shorter in the mivacurium group (19.5 +/- 7.9 min) compared with atracurium (54.7 +/- 6.6 min) and vecuronium (44.3 +/- 8.6 min). Heart rate and blood pressure were similar in all groups. Facial flushing and mild bronchospasms as signs of histamine release resulted more often in the mivacurium (20%) and atracurium groups (23%) than in the vecuronium group (3%). In contrast to atracurium and vecuronium, recovery from mivacurium-induced neuromuscular blockade is rapid. However, the onset time after 3 times ED95 was significantly longer for mivacurium than for atracurium or vecuronium.

Adult↗
PubMed1997

Villous cytotrophoblast proliferating potential in complete and partial hydatidiform mole: diagnostic value of silver-stained nucleolar organizer region (AgNOR)-associated proteins.

Aside from their typical morphologic features, complete (CHM) and partial hydatidiform mole (PHM) are characterized by variable trophoblastic proliferation and/or atypia. CHM and PHM usually present little diagnostic difficulty. However, some may be extremely difficult to distinguish by morphologic features alone. Therefore, we investigated the diagnostic value of silver-stained nucleolar organizer region (AgNOR)-associated proteins in cytotrophblasts as compared to cytogenetic features of nine CHM, nine PHM and six non-molar spontaneous embryonic abortions (controls), as well as of two suspected CHM and two histologically suspected PHM. Tissue sections were submitted to autoclave pretreatment and to silver colloid solution. The proliferating potential of cytotrophoblasts was determined by the analysis of mean number and mean area of AgNORs per nucleus using a PC-based image analysis system. Mean values of AgNOR parameters were significantly different from each other (p < 0.001). Each of the four cases of tentative diagnosis could be assigned to the corresponding group of examined trophoblastic lesions. The evaluation of AgNORs in cytotrophoblasts contributes to a reliable discrimination of CHM and PHM; this fairly simple and economical method could serve as an useful addition to conventional methods of diagnosis in gestational trophoblastic disease.

Cell Division↗
PubMed1996

Structure of a ternary complex of proteinase K, mercury, and a substrate-analogue hexa-peptide at 2.2 A resolution.

The crystal structure of a ternary complex of proteinase K, Hg(II) and a hexapeptide N-Ac-Pro-Ala-Pro-Phe-Pro-Ala-NH2 has been determined at 2.2 A resolution and refined to an R factor of 0.172 for 12,910 reflections. The mercury atom occupies two alternate sites, each of which was assigned an occupancy of 0.45. These two sites are bridged by Cys-73 S gamma which forms covalent bonds to both. Both mercury sites form regular polyhedrons involving atoms from residues Asp-39, His-69, Cys-73, His-72, Met-225, and Wat-324. The complex formation with mercury seems to disturb the stereochemistry of the residues of the catalytic triad Asp-39, His-69, and Ser-224 appreciably, thus reducing the enzymatic activity of proteinase K to 15%. The electron density in the difference Fourier map shows that the hexapeptide occupies the S1 subsite predominantly and the standard recognition site constituted by Ser-132 to Gly-136 and Gly-100 to Tyr-104 segments is virtually empty. The hexapeptide is held firmly through a series of hydrogen bonds involving protein atoms and water molecules. As a result of complex formation, Asp-39, His-69, Met-225, Ile-220, Ser-219, Thr-223, and Ser-224 residues move appreciably to accommodate the mercury atoms and the hexapeptide. The largest movement is observed for Met-225 which is involved in multiple interactions with both mercury and the hexapeptide. The activity results indicate an inhibition rate of 95%, as a result of the combined effect of mercury and hexapeptide.

Amides↗