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Biomedical subjects

K Peters

Publications and source records attributed to K Peters.

At least 181 records · Page 10Linked to original sources
PubMed1996

Strategy to design peptide inhibitors: structure of a complex of proteinase K with a designed octapeptide inhibitor N-Ac-Pro-Ala-Pro-Phe-DAla-Ala-Ala-Ala-NH2 at 2.5 A resolution.

The crystal structure of a complex formed by the interaction between proteinase K and a designed octapeptide amide, N-Ac-Pro-Ala-Pro-Phe-DAla-Ala-Ala-Ala-NH2, has been determined at 2.5 A resolution and refined to an R-factor of 16.7% for 7,430 reflections in the resolution range of 8.0-2.50 A. The inhibitor forms a stable complex through a series of hydrogen bonds and hydrophobic interactions with the protein atoms and water molecules. The inhibitor is hydrolyzed between Phe4I and DAla5I (I indicates the inhibitor). The two fragments are separated by a distance of 3.2 A between the carbonyl carbon of Phe4I and the main-chain nitrogen of DAla5I. The N-terminal tetrapeptide occupies subsites S1-S5 (S5 for acetyl group), whereas the C-terminal part fits into S1'-S5' region (S5' for amide group). It is the first time that such an extended electron density for a designed synthetic peptide inhibitor has been observed in the prime region of an enzyme of the subtilisin family. In fact, the inhibitor fills the recognition site completely. There is only a slight rearrangement of the protein residues to accommodate the inhibitor. Superposition of the present octapeptide inhibitor on the hexapeptide inhibitor studied previously shows an overall homology of the two inhibitors, although the individual atoms are displaced significantly. It suggests the existence of a recognition site with flexible dimensions. Kinetic studies indicate an inhibition rate of 100% by this specifically designed peptide inhibitor.

Amides↗
PubMed1996

Thermitase - kinetic differentiation to the subtilisins.

In the last 12 years more than 80 peptidyl substrates and substrate analogous inhibitors were synthesized in our group and used to characterize thermitase, a serine proteinase of the subtilisin family produced by Thermoactinomyces vulgaris. The kinetic parameters of hydrolysis and inhibition reactions, respectively, with thermitase were determined and compared with those found with related enzymes. Conclusions with respect to the extent of the active site of thermitase and to the specificity of the different subsites could be drawn.

Binding Sites↗
PubMed1996

Detection of abnormal aortic elastic properties in asymptomatic patients with Marfan syndrome by combined transoesophageal echocardiography and acoustic quantification.

OBJECTIVE: To evaluate the potential value of transoesophageal echocardiography combined with automated border detection and acoustic quantification for the assessment of elastic properties of the thoracic aorta in patients with Marfan syndrome. SUBJECTS: 16 patients with Marfan syndrome and 12 age matched normal controls. METHODS: Transoesophageal echocardiography was performed in all subjects. Minimum and maximum diameters of the descending thoracic aorta were obtained from M mode images and acoustic quantification was used for the on-line evaluation of cross sectional aortic area and peak positive area changes over time. Compliance, distensibility, and stiffness index were calculated using M mode data and non-invasively measured blood pressure and were compared with the indices derived from acoustic quantification. RESULTS: Aortic dimensions normalised for body surface area were not statistically different between patients and normal controls, but there were significant differences for all elasticity indices except compliance. Marfan patients had a lower distensibility [4.2 (SD 1.8) v 5.8 (2.1) cm2/dyn, P < 0.05] and a higher stiffness index [9.7 (3.0) v 7.1 (1.8), P < 0.05]. The dynamic indices derived from the acoustic quantification were significantly smaller in Marfan patients [peak positive area change: 5.1 (1.0) v 7.7 (1.7) cm2/s; P < 0.001; and normalised peak positive area change: 2.5 (1.2) v 4.0 (0.8) cm2/s respectively, P < 0.001] and were suitable to discriminate between normal and abnormal elastic properties. CONCLUSIONS: In Marfan syndrome elastic properties of the descending aorta are significantly different from normal controls, even in the absence of vessel dilatation. In addition to established static indices, indices derived from acoustic quantification reflect dynamic changes of the cross sectional area for the evaluation of regional vessel mechanics. The on-line assessment of peak positive area change allows differentiation from normal individuals and may be more accurate than standard M mode measurements.

Adult↗
PubMed1996

Desferrioxamine in chronic progressive multiple sclerosis: a pilot study.

Chronic progressive Multiple Sclerosis is refractory to many conventional treatments. We performed a pilot study testing desferroxamine (DFO) as a candidate in the treatment of chronic progressive Multiple Sclerosis. DFO was given daily by 8 h subcutaneous infusions at a dose of 2 grams daily for 7 days, followed by 1 gram daily for 7 days. Eighteen of 19 individuals completed the full dose of 21 grams. One patient was unable to complete the course due to nausea. No acute deterioration of neurological status was seen during the administration of DFO. No worsening of vision or hearing was noted except that the one patient who was unable to tolerate the medication had a transient reduction in hearing. All patients had a local redness at the injection site. None of the patients had any sudden worsening during or shortly after the treatment. This pilot study suggests that DFO is relatively well tolerated by Multiple Sclerosis patients when given in a short course of therapy.

Adult↗
PubMed1996

Predicting subjective disability in chronic pain patients.

Subjective disability is considered as the variable that reflects the impact of chronic pain on a patient's life. This study examines the questions of which syndrome or patient characteristics determine subjective disability and whether there are differences between samples of patients with chronic headaches and low back pain. Direct pain variables and depression, pain coping strategies, and pain-related self-statements (including catastrophizing) are introduced into multivariate regression analyses as potential predictors of disability using a sample of 151 pain patients. Disability is not predicted by pain severity in patients with headaches or back pain. Psychological variables, especially coping strategies, are far more influential. Coping explains more variance in disability in the headache sample than in the chronic law hack pain group, whereas depression is more relevant for the degree of disability in the back pain sample. In this study, we present a critical analysis of possible interpretations of our results. We point to an overlap of concepts underlying some of the variables used: this overlap also considerably invalidates conclusions drawn from a multitude of studies done in this field, including the one presented. We strongly argue for a conceptual clarification, and consequently for the revision of assessment instruments, before further empirical work in this area is done.

Journal Article↗
PubMed1996

How much extra does "adequate" peritoneal dialysis cost?

Our objective was to investigate the extra cost associated with implementing an adequacy program in peritoneal dialysis (PD) and to evaluate the cost effectiveness of a variety of PD prescriptions. This was a cross-sectional study of all 37 patients attending the PD clinic at a university teaching hospital. Extra costs incurred on dialysate, tubing, and cyclers as a consequence of implementing an adequacy program in PD were measured. Costs per unit KT/V for a variety of PD prescriptions were also calculated. Thirteen patients (35%) required an alteration in prescription for adequacy reasons. The average extra costs incurred for all patients was Cdn. $2,323 per annum, which represents a 16% increase per patient. The most cost-effective prescriptions were high volume continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) with two daytime dwells. The least cost-effective prescriptions were day dry APD and high volume APD with only one daytime dwell. Significant extra expense is incurred when an adequacy program is implemented in PD. This is mainly due to the requirement to put more patients on APD. An alternative pricing policy for PD is suggested.

Adolescent↗
PubMed1996

Tissue transglutaminase expression in human breast cancer.

Tissue transglutaminase (tTG) is postulated to play a role in apoptosis, cell adhesion, metastasis, and extracellular matrix (ECM) assembly. In this study, the distribution and expression of tissue transglutaminase was investigated in normal human mammary tissue and in intraductal and invasive human breast cancer by immunohistochemistry and in situ hybridization. Frozen and formalin-fixed paraffin-embedded sections of normal, intraductal, and invasive human breast carcinoma were examined with an avidin-biotin complex immunoperoxidase method for tTG antigen and by in situ hybridization to determine the cell types expressing tTG mRNA. The expression of tTG in normal and malignant mammary epithelium in culture was evaluated by quantitative immunoblot analysis. Low-level expression of tTG was found in normal tissues with the antigen located in the ECM surrounding the ducts and in the endothelium. In intraductal cancer, there was a marked increased expression of the tTG antigen, and the increased staining was found in the ECM and was also localized in a distinct pattern at the boundary between the in situ tumor cells and the normal tissue. Further immunohistochemical analysis revealed that the cells in this boundary also stained for the endothelial cell markers CD31, CD34, and von Willebrand factor. In invasive tumors, the tTG antigen was no longer localized to the normal tissue/tumor boundary but dispersed around the tumor cells. In situ hybridization studies revealed three distinct compartments of tTG synthesis: (a) tumor cells, (b) endothelial cells, and (c) stromal cells. In addition, normal and malignant epithelial cells in culture expressed variable amounts of tTG, and the expression of tTG in these epithelial cells was at least 17-fold less than endothelial cells. The up-regulation of tTG in intraductal and invasive human breast cancer and its localization to the ECM and neovasculature suggest that tTG may regulate tumor growth and metastasis.

Breast Neoplasms↗
PubMed1995

The bli-4 locus of Caenorhabditis elegans encodes structurally distinct kex2/subtilisin-like endoproteases essential for early development and adult morphology.

Many secreted proteins are excised from inactive proproteins by cleavage at pairs of basic residues. Recent studies have identified several serine endoproteases that catalyze this cleavage in the secretory pathways of yeast and metazoans. These enzymes belong to the kex2/subtilisin-like family of proprotein convertases. In this paper we describe the molecular characterization of the bli-4 gene from Caenorhabditis elegans, which was shown previously by genetic analysis of lethal mutants to be essential for the normal development of this organism. Sequencing of cDNA and genomic clones has revealed that bli-4 encodes gene products related to the kex2/subtilisin-like family of proprotein convertases. Analysis of bli-4 cDNAs has predicted four protein products, which we have designated blisterases A, B, C, and D. These protein products share a common amino terminus, but differ at the carboxyl termini, and are most likely produced from alternatively spliced transcripts. We have determined the molecular lesions for three bli-4 alleles (h199, h1010, and q508) that result in developmental arrest during late embryogenesis. In each case, the molecular lesions are within exons common to all of the BLI-4 isoforms. The original defining allele of bli-4, e937, is completely viable yet exhibits blistering of the adult cuticle. Molecular analysis of this allele revealed a deletion that removes exon 13, which is unique to blisterase A. No RNA transcript corresponding to exon 13 is detectable in the blistered mutants. These findings suggest that blisterase A is required for the normal function of the adult cuticle.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Cytogenetic findings in regressing skin lesions of lymphomatoid papulosis.

In this report, we present the cytogenetic findings in an adult female patient with lymphomatoid papulosis (LyP) type A, a cutaneous lymphoproliferative disorder with possible progression to lymphoma. Karyotyping of the CD30+ atypical lymphoid cells revealed numerical and structural aberrations. Trisomy 7, a common finding in hematologic disorders such as adult T-cell leukemia and non-Hodgkin lymphomas, was detected. Additionally, a breakpoint was found at 10q24 in the region of the TCL3 oncogene. These results contrast with cells of a young female patient (age 3) with a type A LyP, which showed a normal karyotype as well as cells of a male adult with type B LyP. None of the cases showed the t(2;5)p(23;q35) common in CD30+ anaplastic large cell lymphomas, which can closely resemble LyP. Our findings are discussed in the context of the literature concerning the histology, immunophenotyping, and cytogenetics of LyP. Together the results suggest different steps in the development of LyP and distinct forms of this one disease.

Adult↗
PubMed1995

Bench evaluation: three face-shield CPR barrier devices.

UNLABELLED: Due to the fear of disease transmission, the practice of mouth-to-mouth (M-M) rescue breathing is rarely performed; to address this concern, many types of CPR barrier devices have been developed. These include bag-valve-mask devices, mouth-to-mask devices, and face shields (FS). The purpose of this study was to measure the volumes delivered during mouth-to-face shield (M-FS) breathing, to measure the back pressure and calculate the resistance to flow through their 1-way valves, and to test for backward leak of gas through the valves. METHODS: Three FS brands were evaluated: Kiss of Life (KOL), MicroSHIELD (Micro) and Res-Cue Key (RCK). Volume delivered during M-M and M-FS breathing was evaluated by 10 rescuers who used the devices while performing rescue breathing on a CPR mannequin. Back pressure was measured and resistance calculated by directing airflow through the 1-way valves. Backward leak was evaluated by measuring the O2 concentration at the rescuer side of the valve while 100% O2 was directed toward the patient side of the valve. Differences among the brands were evaluated using analysis of variance. RESULTS: The mean (SD) values for volumes in L were: M-M 1.00 (0.25), Micro 0.77 (0.20), RCK 0.64 (0.10), and KOL 0.24 (0.11). Mean values for back pressure in cm H2O at 50 L/min were Micro 16.7 (1.29), KOL 7.22 (0.13), and RCK 2.15 (0.16). Significant backward leak only occurred with RCK. CONCLUSION: Not one of the FSs tested met all of the requirements suggested by the American Heart Association and by the International Standards Organization.

Analysis of Variance↗
PubMed1995

[Initial clinical experiences with TIPS (transjugular intrahepatic portasystemic stent-shunt)].

15 patients with predominantly alcoholtoxic liver cirrhosis (mean age 50 years; 8 men and 7 women) were treated by the technically successful implantation of a transjugular portosystemic stent-shunt (TIPS) within a period of 1 year. The indications for TIPS implantation were the following: gastroesophageal bleedings in 12 cases (10 patients with recurrent variceal bleeding including 2 emergency cases with severe bleeding resistant to conventional therapy and 2 patients with exclusively gastral bleeding due to severe hypertensive gastropathy) and ascites resistant to conventional therapy in 3 cases. Portovenous pressure could be effectively reduced by mean of 37%. Within a mean observation period of 8 months 13 patients including the emergency cases remained without recurrent bleeding. Duplexsonography showed patent stents. 1 patient suffered from an early recurrent bleeding due to occlusion of the stent-shunt. The estimation of liver function according to the Child-Pugh-classification showed only minor changes. Before TIPS 9 patients were in class A, 4 in B, 2 in C; after TIPS 8 patients in A, 5 in B and 2 in C. Ascites resolved completely. Following TIPS all patients appeared to abstain from alcohol. After TIPS 5 from 14 surviving patients (36%) developed clinically manifest encephalopathy within the first 4-8 weeks (2 patients with previous episodes of encephalopathy, 2 other patients after withdrawal of lactulose). By enhanced conservative treatment (lactulose, paromomycine and protein restriction) encephalopathy could be overcome. 8 from 11 surviving patients investigated displayed characteristic MRI changes with an increased signal intensity in the basal ganglia (T1 weighted images). According to our preliminary results TIPS represents a new successful interventional regimen for the treatment of portal hypertension in selected cases.

Adult↗
PubMed1994

Targeted expression of a dominant negative FGF receptor blocks branching morphogenesis and epithelial differentiation of the mouse lung.

Mouse lung development begins when two lung buds sprout from the epithelium of the embryonic gut. Patterning of the airways is then accomplished by the outgrowth and repetitive branching of the two lung buds, a process called branching morphogenesis. One of the four fibroblast growth factor (FGF) receptor genes, FGFR2, is expressed in the epithelium of a number of embryonic organs including the lung buds. To block the function of FGFR2 during branching morphogenesis of the lung without affecting its function in other embryonic tissues, the human surfactant protein C promoter was used to target expression of a dominant negative FGFR2 exclusively to lung bud epithelium in transgenic mice. Newborn mice expressing the transgene were completely normal except that instead of normally developed lungs they had two undifferentiated epithelial tubes that extended from the bifurcation of the trachea down to the diaphragm, a defect that resulted in perinatal death. Thus, the dominant negative FGF receptor completely blocked airway branching and epithelial differentiation, without prohibiting outgrowth, establishing a specific role for FGFs in branching morphogenesis of the mammalian lung.

Animals↗
PubMed1994

Spatial displacement limits for cyclopean (stereoscopic) apparent-motion perception.

The range of spatial displacements over which cyclopean (stereoscopic) apparent motion is perceived was investigated. The cyclopean stimuli were created from retinal disparity embedded in dynamic random-dot stereograms. In one experiment, the displacement range for crossed-disparity cyclopean motion was compared with that for luminance-domain motion. The results showed that cyclopean motion was perceived over spatial displacements that were about two to three times larger than the displacements over which luminance motion was perceived. In a second experiment, the displacement range for crossed-disparity cyclopean motion was compared with that for uncrossed-disparity cyclopean motion. The results revealed that the displacement range was restricted (motion quality was poor) for uncrossed motion relative to crossed motion. It is inferred that cyclopean motion from crossed disparity is represented at a coarse spatial scale, relative to luminance motion, and that cyclopean motion from uncrossed disparity is suppressed due to occlusion cues present when uncrossed stimuli are seen behind a textured background.

Female↗
PubMed1994

[Chromosomal in situ hybridization and interphase cytogenetics in single cell and tissue section preparations: new methods in tumor diagnosis and clinical cytogenetics].

To overcome the shortcomings encountered in classical cytogenetics, a variety of in situ hybridization techniques have been developed enabling metaphase and interphase cytogenetics on routinely processed tissues and cells. These techniques comprise the detection of numerical chromosome aberrations, the delineation or "painting" of whole chromosomes or certain chromosome regions and the visualization of structural chromosome rearrangements in interphase nuclei. Some of these new methods can reliably be applied also on paraffin-embedded tissues, among them the comparative genomic in situ hybridization (CGH) technique suitable for providing a survey of over- or underrepresented genetic material on the chromosomal level even if only tumour DNA is available.

Chromosome Aberrations↗
PubMed1994

[Severe mechanical hemolysis after incomplete ductus arteriosus closure: implantation of a second Rashkind occluder].

A 72 year-old female patient with a persistent ductus arteriosus suffered from a severe mechanical hemolysis after incomplete PDA closure with a Rashkind occluder. The residual shunt was closed with a second occluder 2 days later. Hemolysis was stopped immediately; complete closure of the duct was confirmed by color Doppler 6 weeks and 6 months later.

Acute Kidney Injury↗