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Biomedical subjects

T Peters

Publications and source records attributed to T Peters.

At least 19 recordsLinked to original sources
PubMed2000

Hagfish (Myxine glutinosa) red cell membrane exhibits no bicarbonate permeability as detected by (18)O exchange.

The bicarbonate permeability of the plasma membrane of intact hagfish (Myxine glutinosa) red blood cells and the intracellular carbonic anhydrase activity of these cells were determined by applying the (18)O exchange reaction using a special mass spectrometric technique. When the macromolecular carbonic anhydrase inhibitor Prontosil-Dextran was used to suppress any extracellular carbonic anhydrase activity, the mean intracellular acceleration of the CO(2) hydration/HCO(3)(-) dehydration reaction over the uncatalyzed reaction (referred to as intracellular carbonic anhydrase activity A(i)) was 21 320+/-3000 at 10 degrees C (mean +/- s.d., N=9). The mean bicarbonate permeability of the red blood cell membrane (P(HCO3)-) was indistinguishable from zero. It can be concluded that CO(2) transport within hagfish blood does not follow the classical scheme of CO(2) transport in vertebrate blood. It is suggested that the combination of considerable intraerythrocytic carbonic anhydrase activity and low P(HCO3)- may serve to enhance O(2) delivery to the tissue in the exceptionally hypoxia-tolerant hagfish.

Animals↗
PubMed1999

NMR experiments reveal distinct antibody-bound conformations of a synthetic disaccharide representing a general structural element of bacterial lipopolysaccharide epitopes.

The recognition reactions between a synthetic disaccharide alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl and two monoclonal antibodies (mAbs) were studied by NMR, yielding two distinct bound conformations of the carbohydrate ligand. One mAb, S23-24, recognizes the disaccharides alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl and alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl with similar affinities, whereas mAb S25-2 binds to the disaccharide alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl with an approximately 10-fold higher affinity than to the disaccharide alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl. Compared to S25-2, S23-24 binds to alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl with an approximately 50-fold increased affinity. We used NMR experiments that are based on the transferred NOE effect, specifically, trNOESY, trROESY, QUIET-trNOESY, and MINSY experiments, to show that the (2-->8)-specific mAb, S25-2, stabilizes a conformation of the alpha-(2-->4)-linked disaccharide that is not highly populated in solution. S23-24 recognizes two conformations of alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl, one that is highly populated in aqueous solution and another conformation that is similar to the one bound by S25-2. This is the first example where it is experimentally shown that a carbohydrate ligand may adopt different bioactive conformations upon interaction with mAbs with different fine specificities. Our NMR studies indicate that a careful examination of spin diffusion is critical for the analysis of bioactive conformations of carbohydrate ligands.

Antibodies, Bacterial↗
PubMed1999

Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation.

The Fused toes (Ft) mouse mutation was created by insertional mutagenesis, resulting in the deletion of several hundred kb of genomic sequences of mouse Chromosome (Chr) 8. Mice heterozygous for the Ft mutation are characterized by partial syndactyly of forelimbs and massive thymic hyperplasia indicating that programmed cell death is affected. Homozygous Ft/Ft embryos die at midgestation and show severe malformations of craniofacial structures. Furthermore, establishment of left-right asymmetry is random. Here we report on the positional cloning of a novel gene by exon trap analysis of a genomic clone encoding wild-type sequences corresponding to parts of the deletion in Ft mutants. RT-PCR experiments demonstrated that the newly identified gene, Fatso (Fto), is expressed throughout embryonic development. Wide expression was also found in tissues of adult mice. We show that expression of Fto is completely absent in mouse embryonic fibroblasts homozygous for the Ft mutation. In addition, we isolated the full-length cDNA which encodes a putative 58-kDa protein showing no similarities to known proteins or protein motifs. The expression data of Fto define it as a candidate gene involved in processes such as programmed cell death, craniofacial development, and establishment of left-right asymmetry.

Amino Acid Sequence↗
PubMed1999

Screening for hypercholesterolaemia in 10,000 neonates in a multi-ethnic population.

UNLABELLED: An immunoassay was developed for the detection of hypercholesterolaemia in dried blood spots collected from 6-day-old neonates. Blood spot samples (9,673) were subjected to immunoturbidimetric assay to determine the levels of apolipoprotein B (apoB), an index of plasma low density lipoprotein, and of apolipoprotein A-1 (apoA-1), an index of plasma high density lipoprotein. Infants with raised apoB or a reduced apoA-1/apoB ratio were recalled, retested and, if appropriate, referred to the Vascular Risk Clinic at King's College Hospital for medical management. A total of 189 were recalled for further testing; of whom 82 (45%) attended the recall clinic. A group of 16 families (24 individuals) had abnormal lipid profiles; of these, 7 families (14 individuals) had lipid profiles consistent with inherited hypercholesterolaemia. CONCLUSION: Neonatal screening for hypercholesterolaemia using blood spot apolipoprotein measurements is feasible but ethnic variations in disease prevalence must be considered in the design of a screening programme.

Adult↗
PubMed1999

Effects of AL 107, a novel semisynthetic cardiac glycoside, on the cardiovascular system in anaesthetized beagle dogs with pentobarbital-induced cardiac insufficiency.

The inotropic efficacy, arrhythmogenicity and cardiohaemodynamic properties of AL 107 (3-alpha-methyl-digitoxigenin glucoside, CAS 62190-59-4), a novel cardiac glycoside, were studied in anaesthetized dogs with pentobarbital-induced acute cardiac insufficiency. Three groups of dogs received AL 107, ouabain or verhicle. The cardiac glycosides were infused intravenously in eight increasing dose levels which where given cumulatively. Slope of left ventricular pressure rise (LVdp/dtmax) increased in the AL 107- and ouabain-treated groups. At the end of the 6th dose level ouabain caused a significantly higher LVdp/dtmax (137 +/- 15% of the baseline value taken before induction of insufficiency) than AL 107 (94 +/- 9%). Further increase of the dose resulted in a reduction of LVdp/dtmax in ouabain-treated dogs, whereas AL 107 continuously increased LVdp/dtmax up to the highest dose infused, where 130 +/- 16% of the baseline value was reached. In ouabain-treated dogs, ECG abnormalities accompanied the decrease of LVdp/dtmax whereas ECG-changes did not interfere with the development of left ventricular contractility in AL 107-treated dogs. The 6th dose of ouabain provoked a maximal increase of cardiac output (CO) (up to 107 +/- 8% of baseline values) and stroke volume (SV) (up to 122 +/- 6% of baseline values) which decreased upon further dose elevation. In the dose-range studied AL-107 induced a continuous increase of both parameters which, however, hardly reached the baseline values. ECG abnormalities occurred in both substance-treated groups and showed quantitative but not qualitative differences. The ECG showed rapid recovery after cessation of AL 107 infusion but did not normalize during a postinfusional recovery period of 1 h after treatment with ouabain. In conclusion, AL 107 increased cardiac performance in an acute canine model of cardiac insufficiency. It was slightly less active than ouabain. However, the ECG disorders were more moderate in AL 107--than in ouabain-treated dogs, a difference which was most pronounced with respect to reversibility in the postinfusional period.

Anesthesia↗
PubMed1999

Contraction parameters, myosin composition and metabolic enzymes of the skeletal muscles of the etruscan shrew Suncus etruscus and of the common European white-toothed shrew Crocidura russula (Insectivora: soricidae).

In the Etruscan shrew, the isometric twitch contraction times of extensor digitorum longus (EDL) and soleus muscles are shorter than in any other mammal, allowing these muscles to contract at outstandingly high contraction frequencies. This species has the highest mass-specific metabolic rate of all mammals and requires fast skeletal muscles not only for locomotion but also for effective heat production and for an extremely high ventilation rate. No differences could be detected in the fibre type pattern, the myosin heavy and light chain composition, or in the activity of the metabolic enzymes lactate dehydrogenase and citrate synthase of the two limb muscles, the EDL and the soleus, which in larger mammalian species exhibit distinct differences in contractile proteins and metabolic enzymes. All properties determined in EDL and soleus muscles of Suncus etruscus, as well as in the larger Crocidura russula, are typical for fast-oxidative fibres, and the same holds for several other skeletal muscles including the diaphragm muscle of S. etruscus. Nevertheless, the EDL and soleus muscles showed different mechanical properties in the two shrew species. Relaxation times and, in C. russula, time to peak force are shorter in the EDL than in the soleus muscle. This is in accordance with the time course of the Ca(2+) transients in these muscles. Such a result could be due to different parvalbumin concentrations, to a different volume fraction of the sarcoplasmic reticulum in the two muscles or to different Ca(2+)-ATPase activities. Alternatively, the lower content of cytosolic creatine kinase (CK) in the soleus compared with the EDL muscle could indicate that the observed difference in contraction times between these shrew muscles is due to the CK-controlled activity of their sarcoplasmic reticulum Ca(2+)-ATPase.

Animals↗
PubMed1999

A prospective, randomized study comparing the results of open discectomy with those of video-assisted arthroscopic microdiscectomy.

BACKGROUND: The usefulness of video-assisted arthroscopic microdiscectomy for the treatment of a herniated lumbar disc has been studied previously. In the current prospective, randomized study, the results of this procedure were compared with those of conventional open laminotomy and discectomy. METHODS: Sixty patients who had objective evidence of a single intracanalicular herniation of a lumbar disc caudad to the first lumbar vertebra were randomized into two groups consisting of thirty patients each; Group 1 was managed with open laminotomy and discectomy, and Group 2 was managed with video-assisted arthroscopic microdiscectomy. None of the patients had had a previous operation on the low back, and all had failed to respond to nonoperative measures. Analysis of the outcomes of both procedures was based on the patient's self-evaluation before and after the operation, the preoperative and postoperative clinical findings, and the patient's ability to return to a functional status. The patients were followed for nineteen to forty-two months postoperatively. RESULTS: On the basis of the patient's preoperative and postoperative self-evaluation, the findings on physical examination, and the patient's ability to return to work or to normal activity, twenty-eight patients (93 percent) in Group 1 and twenty-nine patients (97 percent) in Group 2 were considered to have had a satisfactory outcome. The mean duration of postoperative disability before the patients were able to return to work was considerably longer in Group 1 than in Group 2 (forty-nine compared with twenty-seven days). The patients in Group 1 used narcotics for a longer duration postoperatively. No neurovascular complications or infections were encountered in either group. CONCLUSIONS: Although the rate of satisfactory outcomes was approximately the same in both groups, the patients who had had an arthroscopic microdiscectomy had a shorter duration of postoperative disability and used narcotics for a shorter period. These findings suggest that arthroscopic microdiscectomy may be useful for the operative treatment of specific symptoms, including radiculopathy, that are caused by lumbar disc herniation, provided that patients are properly selected--that is, they must have a herniated disc at a single level as confirmed on imaging studies, have failed to respond to nonoperative management, have no evidence of spinal stenosis, and have a herniation not exceeding one-half of the anteroposterior diameter of the spinal canal. Moreover, the surgeon must be familiar with this technique and must have received training in its use.

Adolescent↗
PubMed1999

Anxiety among women with mild dyskaryosis: a randomized trial of an educational intervention.

BACKGROUND: Women with mild dyskaryosis are currently managed by six-month cytological surveillance. While there is good evidence that women suffer psychological distress on receipt of an abnormal test, and that this is amenable to educational intervention, it remains uncertain whether this distress is prolonged and, if so, how it should best be managed. AIM: To investigate whether a structured educational intervention containing a risk communication package impacts upon psychological sequelae associated with this surveillance. METHOD: A pragmatic cluster-randomized controlled trial during 14 months in 1995 and 1996, based in general practices in Avon and South Glamorgan, that compared the intervention with standard care. Follow-up was by postal questionnaire at six weeks and four months after the screening laboratory had reported the test result. The intervention was an invitation to attend the general practice to consult with a practice nurse trained to deliver the package. The main outcome measures were Spielberger state-anxiety, SF-36 Mental Health dimension, four condition-specific questions regarding concerns about gynaecological health and timing of the repeat smear test, and attendance for the repeat test. RESULTS: Of 514 eligible women, 270 were recruited, of whom 240 returned the six-week questionnaire and 181 returned the four-month questionnaire. On all but one outcome measure, the differences between the groups were not statistically significant. At six-week follow-up, the proportion who preferred the repeat test to be sooner than six months was statistically significantly higher among controls (74% versus 53%; 95% CI = 9% to 33%). At the four-month follow-up, the difference was 7% (95% CI = -7% to 21%). CONCLUSION: There appear to be high levels of anxiety during surveillance for mild dyskaryosis that were not reduced by the intervention. Given that a personally delivered educational intervention designed to reduce anxiety could be viewed as the best available practice, it is of concern that women in the intervention group demonstrated sustained anxiety over a four-month period. The research agenda therefore seems to return to the fundamental question of whether surveillance should be the management of choice.

Adult↗
PubMed1998

A clinical and virological study of hepatitis C virus-related cryoglobulinemia in Germany.

BACKGROUND/AIMS: Several reports, especially from Southern Europe, have demonstrated a close association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia. In this study we have analyzed the significance of HCV-related cryoglobulinemia in Germany. METHODS: Sera from 79 patients with cryoglobulinemia of type I (n=21), II (n=28) or III (n=30) were investigated for HCV markers. Furthermore, 132 consecutive patients with chronic hepatitis C were studied for the presence of cryoglobulins. Genotypes of HCV were determined according to Simmonds, and HCV-RNA concentrations were measured in patients with and without cryoglobulinemia. RESULTS: In 79 patients with cryoglobulinemia we found anti-HCV antibodies in 17 (22%) and HCV-RNA in 11 patients (14%). HCV antibodies were more frequent in essential (44%) compared to secondary mixed cryoglobulinemia (15%). In 132 patients with chronic HCV infection cryoglobulins were detected in 37 patients (28%), in 21 of them at low levels. Clinical symptoms due to cryoglobulinemia were observed in eight of the 37 patients, severe vasculitis in three patients with high cryocrit-levels and cryoprecipitation at room temperature. HCV genotype 1 and subtype 1b were most prevalent, both in patients with and without cryoglobulinemia, and mean HCV-RNA levels were not different between the two groups. Comparison of HCV-RNA levels in cryoprecipitates, supernatant and native serum suggests binding of HCV-RNA to the cryoprecipitate with different affinity in individual patients. CONCLUSIONS: The lower prevalence of HCV-related cryoglobulinemia in our study compared with data from Italy and France suggests a south-north gradient in the prevalence of HCV-associated cryoglobulinemia in Europe.

Adult↗
PubMed1998

Natural defenses and autoprotection: naturotherapy, an old concept of healing in a new perspective.

Recent molecular-biological and molecular-genetic research has shown that important cellular-based autoprotective mechanisms are mediated by heat-shock proteins (HSPs) or stress-response proteins, also called 'chaperones'. This can happen because cells react to extracellular stimuli by activating signal transduction pathways which result in activating the genetic program. Molecular biologists and cardiologists are tempted to evaluate these phenomena in respect to their potential meaning for a better understanding of the complex notions of health and disease. When molecular geneticists or cardiologists talk about autoprotective or natural defense mechanisms, and physicians talk about salutogenesis, they all mean something very specific. The phenomenon seen here belongs to the body's own defense mechanisms which make it capable of reacting to harmful influences and allow it to stabilize a structure and/or function of the body for a certain period. Here we see a connecting link to the historically grounded term self-healing forces, which has challenged medical doctors in the different historical periods of medical science. They tried to explain these effects based on the current model of the organism. Their understanding of this phenomenon played a role in defining the concept of health and disease. Thus, it seems very fitting to look back into history, since the phenomena discussed here as well as the insights into autoprotective mechanisms will continue to influence medical understanding of health and disease.

Animals↗
PubMed1998

Mechanisms of autoprotection and the role of stress-proteins in natural defenses, autoprotection, and salutogenesis.

We hypothesize that in all physiotherapeutically oriented procedures of naturotherapy -- such as helio-, climate-, thalasso- or hydrotherapy or certain forms of physical exercise -- the transient expression of stress-proteins (heat-shock proteins, HSPs) is an important element of salutogenesis. These therapeutical procedures all cause a transitory 'disturbance' by an unspecific stressor that leads to functional responses. These functional responses can be trained and thus increase the forces and the capacity for resistance of the organism. The autoprotective mechanisms which we want to deal with in more detail are based on the functions of the heat-shock proteins (HSPs, stress-response proteins, 'chaperones') and represent archaic autoprotective responses. In addition, more complex mechanisms of autoprotection seem to have evolved that may play a role in the natural defenses against disease and which show a hierarchy of various genomically conserved strategies with different time-constants and time windows. This becomes apparent by studying autoprotective responses of the cardiovascular system of warm-blooded animals under ischemic stress. Recent extensive experimental protocols and clinical observations in elucidating the molecular basis of cardiac ischemia show that powerful autoprotective mechanisms are involved in the phenomena of 'hibernation', 'stunning', and 'ischemic preconditioning'. The system of the heat-shock proteins may therefore be regarded as a basic model for the principle of autoprotection and salutogenesis.

Animals↗
PubMed1998

Conformational analysis of a Chlamydia-specific disaccharide alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl in aqueous solution and bound to a monoclonal antibody: observation of intermolecular transfer NOEs.

The disaccharide alpha-Kdo-(2-->8)-alpha-Kdo (Kdo: 3-deoxy-D-manno-oct-2-ulosonic acid) represents a genus-specific epitope of the lipopolysaccharide of the obligate intracellular human pathogen Chlamydia. The conformation of the synthetically derived disaccharide alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl was studied in aqueous solution, and complexed to a monoclonal antibody S25-2. Various NMR experiments based on the detection of NOEs (or transfer NOEs) and ROEs (or transfer ROEs) were performed. A major problem was the extensive overlap of almost all 1H NMR signals of alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl. To overcome this difficulty, HMQC-NOESY and HMQC-trNOESY experiments were employed. Spin diffusion effects were identified using trROESY experiments, QUIET-trNOESY experiments and MINSY experiments. It was found that protein protons contribute to the observed spin diffusion effects. At 800 MHz, intermolecular trNOEs were observed between ligand protons and aromatic protons in the antibody binding site. From NMR experiments and Metropolis Monte Carlo simulations, it was concluded that alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl in aqueous solution exists as a complex conformational mixture. Upon binding to the monoclonal antibody S25-2, only a limited range of conformations is available to alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl. These possible bound conformations were derived from a distance geometry analysis using transfer NOEs as experimental constraints. It is clear that a conformation is selected which lies within a part of the conformational space that is highly populated in solution. This conformational space also includes the conformation found in the crystal structure. Our results provide a basis for modeling studies of the antibody-disaccharide complex.

Antibodies, Monoclonal↗