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Biomedical subjects

J Peters

Publications and source records attributed to J Peters.

At least 289 records · Page 16Linked to original sources
PubMed1996

Role of the circulating renin-angiotensin system in the pathogenesis of hypertension in transgenic rats. TGR(mREN2)27.

Transgenic rats, termed TGR(mREN2)27, which carry the mouse ren2d renin gene, develop fulminant hypertension. To evaluate the role of the circulating renin-angiotensin system (RAS) in hypertension of TGR(mREN2)27, we determined plasma levels of its components and their regulation by ether-stress. Plasma prorenin was elevated in prehypertensive and in adult heterozygous TGR(mREN2)27 (fourtyfold), when compared with Sprague Dawley (SD) controls, whereas plasma renin concentration (PRC) and angiotensin II were not in SD rats ether anesthesia increased PRC at day (11 a.m.; fivefold), but not at night (11 p.m.). Ether had no effect on PRC in TGR(mREN2)27. In contrast, ether increased plasma corticosterone levels at day and night in both strains to a similar degree. Our data indicate that plasma active renin is not a pathogenetic factor for hypertension in TGR(mREN2)27 and suggest a primary role of circulating prorenin. The lack of stimulation of PRC by ether in TGR(mREN2)27 probably reflects predominant extrarenal origin of renin.

Animals↗
PubMed1996

Anoxia in vitro does not induce neuronal swelling or death.

To improve the understanding of neuronal cell swelling in cerebral ischemia, cell volume regulation, viability, intracellular electrolytes, and lactate production of Neuro-2A neuroblastoma cells were studied using an in vitro model. The volume regulatory capacity of Neuro-2A cells was assessed after incubation in hypo- and hypertonic media. Anoxia was studied alone and together with inhibition of glycolysis by iodoacetate. Reducing the tonicity of the incubation medium to 250, 200, or 150 mosm/l caused immediate swelling followed by a regulatory volume decrease within 20 min, which, however, was not complete. The final cell volume after regulation depended on the tonicity of the medium and remained above control. There was no regulatory volume increase after cell shrinking in hypertonic media. Despite the severe anisotonic incubation, viability decreased only slightly without reaching statistical significance. In contrast to in vivo conditions, anoxia for 90 min with or without iodoacetate for additional inhibition of anaerobic energy metabolism neither caused neuronal cell swelling nor a decrease of viability. Reoxygenation after the anoxic period also did not induce volume and viability changes. Intracellular K+ of Neuro-2A cells was markedly decreased, while Na+ increased in a 1:1 ratio during complete energy failure by anoxia plus iodoacetate. A similar effect, occurring however somewhat delayed, was seen when the Neuro-2A suspension was exposed to iodoacetate alone. Anoxia without inhibition of glycolysis had no effect on intracellular ion concentrations, but lactate production was nearly six times higher than normal. In vitro, with a large extracellular volume and sufficient glucose supply, the energetic demands of Neuro-2A cells to maintain stable transmembraneous ion gradients during anoxia are obviously met by anaerobic glycolysis. The current results confirm that neuronal cells are able to adequately regulate cell volume in response to hyposmotic stress. On the other hand, maintenance of a normal cell size during complete energy deprivation suggests strongly that energy failure per se does not suffice to induce neuronal swelling. Cell swelling in cerebral ischemia in vivo thus appears a secondary phenomenon due to mediator mechanisms such as tissue acidosis or elevated extracellular glutamate levels.

Aerobiosis↗
PubMed1996

Ventricular laceration and cardiac tamponade during laparoscopic Nissen fundoplication.

Laparoscopic fundoplication is now accepted as an excellent alternative to long term medical therapy for select patients with gastroesophageal reflux disease. Morbidity is uncommon and usually not life threatening. The procedure requires retraction of the left lateral segment of the liver, which has emerged as one of the most troubling technical aspects. This case report represents an uncommon, albeit dramatic, complication involving traumatic injury to the right ventricle thought secondary to trauma from a non-disposable, fan shaped, liver retractor.

Aged↗
PubMed1995

Adaptation of Spodoptera exigua larvae to plant proteinase inhibitors by induction of gut proteinase activity insensitive to inhibition.

Tobacco plants were transformed with a cDNA clone of chymotrypsin/trypsin-specific potato proteinase inhibitor II (PI2) under the control of a constitutive promoter. Although considerable levels of transgene expression could be demonstrated, the growth of Spodoptera exigua larvae fed with detached leaves of PI2-expressing plants was not affected. Analysis of the composition of tryptic gut activity demonstrated that only 18% of the proteinase activity of insects reared on these transgenic plants was sensitive to inhibition by PI2, whereas 78% was sensitive in insects reared on control plants. Larvae had compensated for this loss of tryptic activity by a 2.5-fold induction of new activity that was insensitive to inhibition by PI2. PI2-insensitive proteolytic activity was also induced in response to endogenous proteinase inhibitors of tobacco; therefore, induction of such proteinase activity may represent the mechanism by which insects that feed on plants overcome plant proteinase inhibitor defense.

Adaptation, Physiological↗
PubMed1995

Residence times of the buried water molecules in bovine pancreatic trypsin inhibitor and its G36S mutant.

The three-dimensional structure of the bovine pancreatic trypsin inhibitor (BPTI) contains 4 internal water molecules, denoted W111, W112, W113, and W122, the latter being replaced by a seryl side chain in the BPTI(G36S) analogue. To investigate the effect of the exchange between these explicit water sites and the bulk solvent, we have measured water 17O and 2H nuclear magnetic relaxation in solutions of BPTI and the G36S mutant over the Larmor frequency range 2.6-49 MHz. A comparison of the data from the two nuclei shows unequivocally that the isolated buried water molecule, W122, of BPTI contributes only to 2H, but not to 17O relaxation, while the other 3 waters contribute fully to the relaxation of both nuclei. This demonstrates that the residence time of W122 is in the range 10-200 microseconds, while the residence times of W111-W113 are in the range 15 ns-1 microseconds. The slower exchange of W122 indicates that the functionally active region of BPTI, near the Cys14-Cys38 disulfide bond, is less flexible than the central region of BPTI, where the other 3 buried waters are located.

Amino Acid Sequence↗
PubMed1995

Glycated haemoglobin and metabolic control of diabetes mellitus: external versus locally established clinical targets for primary care.

OBJECTIVES: To examine current targets for glycated haemoglobin as a marker for metabolic control in diabetes mellitus in relation to datasets from several areas, and to consider whether target setting could be improved. DESIGN: Data collected from enhanced care records of general practices for a representative community based sample of people with diabetes. SETTING AND SUBJECTS: 3022 people with diabetes on the lists of 37 general practices (total list size 222,550) in South Glamorgan in 1992; samples of glycated haemoglobin had been processed at two laboratories with different methodologies and reference ranges. MAIN OUTCOME MEASURES: Last glycated haemoglobin level measured in subjects for 1992 and published data from other studies considered in relation to existing goals and standards for the metabolic control of diabetes. RESULTS: An ascertainment rate for people with diabetes of 1.36% was obtained. The rate of data capture for haemoglobin A1 was 75.7%, and the mean level for study samples was 10.5% at one laboratory and 10.0% at the other (similar values to those of comparable studies). These mean levels of haemoglobin A1 in representative populations of people with diabetes are poor or very poor according to published standards, including those of the British Diabetic Association. These findings are set in the context of the psychology of goal setting and performance in complex clinical situations. CONCLUSION: Targets for clinical care that are set in the absence of normative data and local feasibility assessments should be treated with caution. Targets are more likely to enhance health care if target setters recognise the importance of psychological aspects of goal setting and motivation.

Biomarkers↗
PubMed1995

The thermosome of Thermoplasma acidophilum and its relationship to the eukaryotic chaperonin TRiC.

A high molecular-mass protein complex from the archaebacterium Thermoplasma acidophilum, referred to here as the 'thermosome', is built from two subunits (M(r) 58 and 60). The thermosome has been purified to homogeneity. The molecular mass of the native complex was determined to be 1061 +/- 30 Da by scanning transmission electron microscopy. It shows a weak ATPase activity and is able to bind denatured polypeptides. Averages obtained from electron micrographs of negatively stained molecules in the end-on and side-on orientations, respectively, were compared with those of the t-complex polypeptide 1 ring complex (TRiC), isolated from bovine testes. Both molecules consist of two stacked pseudo eightfold symmetric rings which build up a cylindrical particle with a large cavity in the center. Sequence alignments of peptides generated from both subunits of the thermosome and different subunits of TRiC reveal a high partial similarity to each other and to the archaebacterial chaperonin thermophilic factor 55 from Sulfolobus shibatae as well as to eukaryotic TCP1 proteins. These striking structural similarities confirm the proposition that all these molecules belong to a single protein family which is structurally and functionally related to the GroEL class of molecular chaperones.

Adenosine Triphosphatases↗
PubMed1995

Tetrabrachion: a filamentous archaebacterial surface protein assembly of unusual structure and extreme stability.

The surface (S-) layer of the hyperthermophilic archaebacterium Staphylothermus marinus was isolated, dissected into separate domains by chemical and proteolytic methods, and analyzed by spectroscopic, electron microscopic and biochemical techniques. The S-layer is formed by a poorly ordered meshwork of branched, filiform morphological subunits resembling dandelion seed-heads. A morphological subunit (christened by us tetrabrachion) consists of a 70 nm long, almost perfectly straight stalk ending in four straight arms of 24 nm length that provide lateral connectivity by end-to-end contacts. At 32 nm from the branching point, tetrabrachion carries two globular particles of 10 nm diameter that have both tryptic and chymotryptic protease activity. Tetrabrachion is built by a tetramer of M(r) 92,000 polypeptides that form a parallel, four-stranded alpha-helical rod and separate at one end into four strands. These strands interact in a 1:1 stoichiometry with polypeptides of M(r) 85,000 to form the arms. The arms are composed entirely of beta-sheets. All S-layer components contain bound carbohydrates (glucose, mannose, and glucosamine) at a ratio of 38 g/100 g protein for the complete tetrabrachion-protease complex. The unique structure of tetrabrachion is reflected in an extreme thermal stability in the presence of strong denaturants (1% (w/v) SDS of 6M guanidine): the arms, which are stabilized by intramolecular disulphide bridges, melt around 115 degrees C under non-reducing conditions, whereas the stalk sustains heating up to about 130 degrees C. Complete denaturation of the stalk domain requires treatment with 70% (v/v) sulfuric acid or with fuming trifluoromethanesulfonic acid. The globular protease can be heated to 90 degrees C in 6M guanidine and to 120 degrees C in 1% SDS and represents one of the most stable proteases characterized to date.

Archaea↗
PubMed1995

The tight skin 2 mouse. An animal model of scleroderma displaying cutaneous fibrosis and mononuclear cell infiltration.

OBJECTIVE: To describe the histopathologic and biochemical characteristics of skin from the Tsk2/+ mouse, a mutation with phenotypic features resembling those of systemic sclerosis (SSc), and to report the initial genetic mapping of the Tsk2 locus. METHODS: Histologic examination was performed and collagen content and type I collagen messenger RNA (mRNA) levels were determined in skin biopsy specimens from Tsk2/+ mice and normal mice. An intersubspecific backcross was conducted as a first step toward identifying the position of the Tsk2 locus on mouse chromosome 1. RESULTS: Histologic examination of Tsk2/+ mouse skin revealed marked accumulation of collagen and infiltration with mononuclear cells in the dermis and adipose tissue. Biochemical studies of Tsk2/+ mouse skin showed increased collagen content and elevated steady-state levels of alpha 1 (I) procollagen mRNA. Tsk2 was mapped to a 15.3-centimorgan interval on mouse chromosome 1. CONCLUSION: Tsk2 is a novel mutation which displays histopathologic and biochemical abnormalities similar to those present in the skin of patients with SSc, including increased collagen content and expression of type I collagen genes. This mutation has been mapped to a 15.3-cM region on mouse chromosome 1. Further study of this novel mutation will allow the identification of previously undescribed mechanisms involved in the regulation of normal and pathologic collagen gene expression.

Animals↗
PubMed1995

Individual assessment of visual perception by surgeons observing the same laparoscopic organs with various imaging systems.

Laparoscopic surgery necessitates that operations be performed via a television screen; therefore, image quality is crucial in determining the final outcome. Electronic imaging systems are constantly undergoing revisions and incorporating new ideas. Recently, we have been confronted with a variety of systems, and we, as operators, have no idea what the differences are between the old and the newer systems. As clinicians, we have no electronic yardstick available to compare the options presented or to check the specifications. This study examines critical aspects of image perception. General surgeons, gynecologists, operating-room nurses, as well as allied health personnel all experienced in laparoscopic surgery participated as test subjects. A blinded study was performed in which various camera systems (single chip, three-chip, digitized and nondigitized) were displayed in random fashion. Porcine abdominal areas were displayed using the various imaging units. Participants graded image perception based on the following characteristics: sharpness, color, contrast, and depth of field. The audience were blinded to the types, brand, and number of cameras utilized. A significant preference was shown for digitized systems (P < 0.0001). Also, digitized single-chip cameras scored higher than three-chip cameras (P < 0.05). We propose thorough testing by surgeons and nursing personnel before deciding what type of equipment to purchase.

Allied Health Personnel↗
PubMed1995

An intraluminal surgical approach to the management of gastric bezoars.

Trichobezoars are difficult to remove endoscopically, often cause nausea and vomiting, and can result in small-bowel obstruction. A patient with a trichobezoar presented to our clinic with symptoms of partial small-bowel obstruction. Multiple attempts at flexible endoscopic removal were unsuccessful. Two large-diameter percutaneous gastrostomies with an inflatable balloon and distal foam-rubber stent to assure intragastric positioning were introduced under general anesthesia. Visualization was provided by a 0 degree panavision laparoscope placed through one of the gastrostomies. The bezoar was removed through the second gastrostomy using standard laparoscopic instruments. The patient made an uneventful recovery. This is the first reported case of percutaneous removal of a trichobezoar. We conclude large-diameter gastrostomies may serve as a port of access for numerous other intraluminal procedures.

Bezoars↗
PubMed1995

Sequence characterization of ENU-induced mutants of glucose phosphate isomerase in mouse.

Four of five mutations producing GPI1 null lethal phenotypes in the homozygous state, which were previously identified from the offspring of male mice, spermatogonially treated with N-ethyl N-nitrosourea (ENU), have been characterized at the nucleotide level by reverse transcription of RNA from heterozygotes for mutant and wild-type alleles and cycle sequencing with cDNA-derived primers. In three of the mutations studied, a single nucleotide substitution, altering the predicted amino acid on translation, was observed in the mutant allele. In Gpi1-sam1H amino acid residue 277, TCA Ser (wild type), is altered to CCA Pro, and in Gpi1-sbm3H and Gpi1-sbm4H amino acid residue 510 Asp GAC (wild type) is altered to GGC Gly. These ENU-induced mutations occur at A-T base pairs in agreement with the current view of the mechanism of action for this mutagen. These changes also occur at residues implicated as being important in the catalytic functioning of the enzyme, from crystallographic studies, and may explain the loss of enzyme function. The fourth identified mutation, Gpi1-sbm2H, is a deletion of amino acid residues Arg134 to Leu162 inclusive, which may arise from incorrect splicing of mRNA; a fifth mutation has remained undetermined.

Animals↗
PubMed1995

Sequence characterization of alleles Gpi1-Sa and Gpi1-Sb at the glucose phosphate isomerase structural locus.

The sequences of alleles Gpi1-sa and Gpi1-sb at the glucose phosphate isomerase structural locus have been determined from cDNA of the mouse inbred strains 101/H Gpi1-sa and C3H/HeH Gpi1-sb by RT PCR and direct sequencing of the amplified products. Four individual nucleotide differences were observed between the two alleles. The difference at amino acid residue 94, (Gpi1-sa GAT Asp, Gpi1-sb AAT Asn) may account for the differing electrophoretic migration, isoelectric point, and thermostability of the two alleles. Two of the other observed differences in the coding region (amino acid residue 12 Leu, Gpi1-sa CTC, Gpi1-sb CTG and amino acid residue 17 Arg, Gpi1-sa CGC, Gpi1-sb CGT) are silent and do not affect the predicted amino acid residues on translation. The fourth observed difference is located within the 3' noncoding sequences of the cDNA. The change at amino acid residue 94 is associated with the presence of a Hinf1 restriction site in Gpi1-sb, which is absent in Gpi1-sa, and may be a useful method for determining this marker.

Alleles↗
PubMed1995

Clearance and metabolism of arachidonic acid by C6 glioma cells and astrocytes.

Effects of increased levels of arachidonic acid (AA) were analyzed in vitro by employment of C6 glioma cells and astrocytes from primary culture. The cells were suspended in a physiological medium added with arachidonic acid (AA) in a concentration range from 0.01 to 0.5 mM. The concentration profiles of the fatty acid and AA-metabolites were subsequently followed for 90 min. AA was measured by gas chromatography, whereas the AA-metabolites PGF2 alpha and LTB4 by radioimmunoassay (RIA). Following administration of AA at 0.05 or 0.1 mM the medium was completely cleared from the fatty acid within 10 to 15 min. However, when 0.5 mM were added, AA concentrations of 0.36 +/- 0.055 mM were found at 20 min, while 0.275 +/- 0.045 mM at 90 min. Addition of AA (0.1 mM) to cell-free medium was also associated with a steady decline of its concentration, although the decrease was markedly delayed as compared to the clearance in the presence of glial cells. AA was subjected to dose-dependent metabolisation in the cell suspension as demonstrated by the production of PGF2 alpha and LTB4. Following addition of 0.01 or 0.5 mM, concentrations of PGF2 alpha increased to a 1.9- or 4.9-fold level within 10 min, whereas those of LTB4 rose to a 1.3- or 33.7-fold level. This was attenuated or completely blocked, respectively, by the cyclo- and lipoxygenase inhibitor BW 755C. Formation of both metabolites from AA was also observed when studying astrocytes from primary culture. The current findings demonstrate an impressive efficacy of C6 glioma cells and astrocytes to clear arachidonic acid from the suspension medium and to convert the lipid compound into prostaglandins and leukotrienes. Uptake and metabolisation of AA by the glial elements may play an important role in vivo, for example in cerebral ischemia.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗