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Biomedical subjects

J W Peters

Publications and source records attributed to J W Peters.

At least 19 recordsLinked to original sources

[How to manage a rectal lesion in horses in clinical practice].

The most feared complication after a rectal examination of horses and ponies is to cause a tear of all the layers in the intraperitoneal part of the rectum. The description of the anatomy is an attempt to explain that the rectal tear is mostly located in the dorsal or dorsolateral part of the rectum. This article describes a relatively simple suture technique for the rectal tear by using the needle of Deschamp which is modified by Professor B. Huskamp. Furthermore there is a description of this method as treatment of two horses in practice circumstances. The issue whether causing a rectal tear should be regarded as a case of malpractice is discussed. Advises as prevention of rectal tears are given.

Animals

Redox-dependent structural changes in the nitrogenase P-cluster.

The structure of the nitrogenase MoFe-protein from Azotobacter vinelandii has been refined to 2.0 A resolution in two oxidation states. EPR studies on the crystals indicate that the structures correspond to the spectroscopically assigned oxidized (P(OX)/M(OX)) and the native or dithionite-reduced (P(N)/M(N)) forms of the enzyme. Both MoFe-protein structures are essentially identical, with the exception of the P-cluster. The MoFe-protein P-cluster in each state is found to contain eight Fe and seven S atoms. Interconversion between the two redox states involves movement of two Fe atoms and an exchange of protein coordination for ligands supplied by a central S atom. In the oxidized P(OX) state, the cluster is coordinated by the protein through six cysteine ligands, Ser-beta188 O gamma, and the backbone amide of Cys-alpha88. In the native P(N) state, Ser-beta188 O gamma and the amide N of Cys-alpha88 no longer coordinate the cluster due to movement of their coordinated Fe atoms toward the central sulfur. Consequently, this central sulfur adopts a distorted octahedral environment with six surrounding Fe atoms. A previously described model of the P-cluster containing 8Fe-8S likely reflects the inappropriate modeling of a single structure to a mixture of these two P-cluster redox states. These observed redox-mediated structural changes of the P-cluster suggest a role for this cluster in coupling electron transfer and proton transfer in nitrogenase.

Aspergillus

Involvement of the P cluster in intramolecular electron transfer within the nitrogenase MoFe protein.

Nitrogenase is the catalytic component of biological nitrogen fixation, and it is comprised of two component proteins called the Fe protein and MoFe protein. The Fe protein contains a single Fe4S4 cluster, and the MoFe protein contains two metallocluster types called the P cluster (Fe8S8) and FeMo-cofactor (Fe7S9Mo-homocitrate). During turnover, electrons are delivered one at a time from the Fe protein to the MoFe protein in a reaction coupled to component-protein association-dissociation and MgATP hydrolysis. Under conditions of optimum activity, the rate of component-protein dissociation is rate-limiting. The Fe protein's Fe4S4 cluster is the redox entity responsible for intermolecular electron delivery to the MoFe protein, and FeMo-cofactor provides the substrate reduction site. In contrast, the role of the P cluster in catalysis is not well understood although it is believed to be involved in accumulating electrons delivered from the Fe protein and brokering their intramolecular delivery to the substrate reduction site. A nitrogenase component-protein docking model, which is based on the crystallographic structures of the component proteins and which pairs the 2-fold symmetric surface of the Fe protein with the exposed surface of the MoFe protein's pseudosymmetric alpha beta interface, is now available. During component-protein interaction, this model places the P cluster between the Fe protein's Fe4S4 cluster and FeMo-cofactor, which implies that the P cluster is involved in mediating intramolecular electron transfer between the clusters. In the present study, evidence supporting this idea was obtained by demonstrating that it is possible to alter the rate of substrate reduction by perturbing the polypeptide environment between the P cluster and FeMo-cofactor without necessarily disrupting the metallocluster polypeptide environments or altering component-protein interaction.

Amino Acid Sequence

Nitrogenase structure and function: a biochemical-genetic perspective.

Biological nitrogen fixation is catalyzed by nitrogenase, an enzyme composed of two component proteins called the Fe protein and the MoFe protein. During catalysis, electrons are delivered one at a time from the Fe protein to the MoFe protein in a process involving component-protein association and dissociation and hydrolysis of at least two MgATP for each electron transfer. The Fe protein contains the sites for MgATP binding and hydrolysis, whereas the site for substrate binding and reduction is located on the MoFe protein. Among the important aspects of nitrogenase enzymology discussed here are (a) the structures of the metal centers that participate in electron transfer, (b) the organization of the metalloclusters within the polypeptides and their contributions to substrate binding and electron transfer, (c) the nature of the dynamic interactions between the two component proteins that lead to nucleotide hydrolysis and intermolecular electron transfer, (d) the mechanism by which the multiple electrons necessary for substrate reduction are distributed within the MoFe protein, (e) the nature of the intramolecular electron path within the MoFe protein, and (f) where and how substrate and various inhibitors become bound to the substrate-reduction site. This chapter summarizes biochemical-genetic strategies used to address these questions and discussed them in the context of the recently proposed three-dimensional models for both the Fe protein and MoFe protein from Azotobacter vinelandii.

Metalloproteins

Identification of a nitrogenase protein-protein interaction site defined by residues 59 through 67 within the Azotobacter vinelandii Fe protein.

During nitrogenase catalysis the Fe protein and the MoFe protein associate and dissociate in a MgATP-dependent process involving electron transfer from the Fe protein to the MoFe protein. A docking model, based primarily on the crystal structures of the separate components from Azotobacter vinelandii, was previously proposed in which the 2-fold symmetric surface of the homodimeric Fe protein interacts with the exposed surface of a MoFe protein pseudosymmetric alpha beta-unit interface. In this model, a loop, which is included within residues 59 through 67 of the Fe protein primary sequence, is likely to interact with the MoFe protein during component protein docking. In the present study, evidence supporting the component protein docking model was obtained by construction of an A. vinelandii strain that produces a hybrid Fe protein for which residues 59 through 67 have been replaced by the corresponding residues from the Fe protein of Clostridium pasteurianum. Biochemical analyses of the hybrid Fe protein revealed the following features when compared with the unaltered Fe protein. First, the hybrid Fe protein exhibited half the maximum specific activity of the normal Fe protein and was insensitive to inhibition by low levels of NaCl. Second, the hybrid Fe protein activity was hypersensitive to a molar excess of MoFe protein, which also resulted in the uncoupling of MgATP hydrolysis from substrate reduction. Third, stopped-flow spectrophotometry experiments showed that during catalysis the hybrid Fe protein dissociates from the MoFe protein at only half the normal rate of Fe protein-MoFe protein dissociation. Thus, the salient feature of the hybrid Fe protein is that it appears to form a relatively tighter complex with the MoFe protein. This property is in line with previous biochemical reconstitution experiments where it was shown that a heterologous mixture of Fe protein from C. pasteurianum and MoFe protein from A. vinelandii form a tight, inactive complex and supports the proposal that a region defined by residues 59 through 67 within the Fe protein is involved in component protein interaction.

Adenosine Triphosphate

[Simultaneous measumrement of the renal excretion of 131I-hippuran and 99mTc-MAG3].

This study describes methods of measuring simultaneously the renal excretion of two radiopharmaceuticals and of evaluating their different kinetics. For quantification of the dynamic contributions of scattered radiation in a double-radionuclide study a high-resolution pure germanium detector was used. The geometry of the arrangement was a semi-shielded whole-body counter according to E. Oberhausen. An intra-individual comparison of the renal elimination of 99mTc-MAG3 and 131I-Hippuran shows a systemic difference between both tracers depending on the time after injection, its average being around 11% between the 10th and 20th min. The inter-individual comparison shows deviations from the mean between -29 and +20%.

Adult

High-dose-rate intraluminal brachytherapy in the treatment of endobronchial malignancy. Work in progress.

Remote afterloading high-dose-rate brachytherapy (RAHDRB) was used endobronchially for the management of malignant airway obstruction in 82 patients, 72 of whom had primary disease in the lung. Treatment was palliative (n = 58) or definitive (n = 24). The extent of airway compromise was determined at bronchoscopy and with symptoms of hemoptysis, dyspnea, or cough or with radiographic evidence of atelectasis. RAHDRB doses were 1,000-4,700 cGy in one to five fractions. External beam radiation was used in previously unirradiated patients. A substantial reduction ,N airway disease and an improvement in symptoms were seen in 82% of patients. Obstruction scores showed an overall 74% improvement. Complications occurred in only 10 patients (two of whom died). Median survival was short (palliative group, 5 months; definitive group, 12 months); however, symptoms remained palliated in 62 patients (76%) until death or the last follow-up examination. RAHDRB is effective and can be applied with equal success in all patients with malignant airway obstruction, even those whose disease has recurred after external beam irradiation.

Aged

Demonstration of carbon-carbon bond cleavage of acetyl coenzyme A by using isotopic exchange catalyzed by the CO dehydrogenase complex from acetate-grown Methanosarcina thermophila.

The purified nickel-containing CO dehydrogenase complex isolated from methanogenic Methanosarcina thermophila grown on acetate is able to catalyze the exchange of [1-14C] acetyl-coenzyme A (CoA) (carbonyl group) with 12CO as well as the exchange of [3'-32P]CoA with acetyl-CoA. Kinetic parameters for the carbonyl exchange have been determined: Km (acetyl-CoA) = 200 microM, Vmax = 15 min-1. CoA is a potent inhibitor of this exchange (Ki = 25 microM) and is formed under the assay conditions because of a slow but detectable acetyl-CoA hydrolase activity of the enzyme. Kinetic parameters for both exchanges are compared with those previously determined for the acetyl-CoA synthase/CO dehydrogenase from the acetogenic Clostridium thermoaceticum. Collectively, these results provide evidence for the postulated role of CO dehydrogenase as the key enzyme for acetyl-CoA degradation in acetotrophic bacteria.

Acetates

Chronic lateral ankle instability.

Chronic lateral ankle instability may be present in as many as 10% to 30% of people suffering from acute lateral ankle ligament injuries. Ankle instability has been referred to as either functional instability or mechanical instability. Management options consist of either nonoperative or operative treatment, with the majority of the literature emphasizing operative management for chronic instability. Long-term studies assessing the different types of available operative repairs have now been published. This review article discusses chronic lateral ankle ligament instability from a functional, anatomical point of view. The indications for treatment, nonoperative and operative treatment, as well as the biomechanical information available regarding these methods of treatment are considered. The major emphasis of this review is discussion and analysis of the many different surgical treatment options. Following this review, we presently recommend anatomical repair to the bone of both the anterior talofibular ligament and the calcaneofibular ligament, together with imbrication of the ligaments. In patients with hypermobility, long-standing instability, or arthritis, reconstruction using the Chrisman-Snook technique is recommended.

Ankle Joint

Proximal femurectomy for decubitus ulceration in the spinal cord injury patient.

The results of proximal femoral resections in nine patients were analyzed after an average four year follow-up, together with a retrospective analysis of the patients. The indication for surgery was decubitus ulceration that had failed to respond to multiple previous treatments. The decubitus ulcers were associated with septic arthritis, osteomyelitis, hip dislocation and ankylosis. All patients achieved short term healing with 50% achieving long term healing. The incidence of subsequent surgery for decubitus ulcers decreased significantly. No patient suffered a deterioration in function.

Adult

[Determination of cerebral blood flow using an 81Rb/81mKr generator system].

A method is being developed which not only measures cerebral blood flow as a static quantity but also its changes with time. For that purpose a semiconductor device ascertains the proportion of intracerebral 81 Rb and 81mKr activities. By opening the hemato-encephalic barrier in animal experiments a sufficient concentration of intracerebral 81 Rb could be attained and the modified blood circulation after step-wise ligature of all brain arteries brought into relation to the corresponding Rb/Kr quotient. Over the range from undisturbed to completely interrupted cerebral blood flow this quotient varied up to 25% of its initial value.

Animals

Biofeedback and hypnosis in weaning from mechanical ventilators.

Weaning patients from mechanical ventilation can be hindered by both physical and psychologic factors. Biofeedback has been used successfully as an adjunct in difficult weaning problems. We have used a combination of hypnosis and biofeedback to wean a patient with neurologic disease who previously failed weaning by standard procedures. A 30-year-old woman with respiratory failure secondary to multiple sclerosis with transverse myelitis was given eight sessions of biofeedback over 12 days in which the movements of her chest wall, as monitored by magnetometers, were displayed on an oscilloscope. The patient was praised for targeted respiratory rate, amplitude, and rhythm. These sessions included hypnosis in which the patient was given suggestions of well-being and that she could breathe as she had five years earlier. In this manner the patient was successfully weaned. Respiratory biofeedback and hypnosis appear to be useful adjuncts in weaning patients from ventilators.

Adult

Atypical Pneumocystis carinii pneumonia: the potential hazards of empiric treatment.

Pneumocystis carinii pneumonia occurred in two patients with unusual clinical findings. In one case, P carinii infection was diagnosed for the first time in a patient with Crohn's disease. Due to the lack of typical features in both cases an empiric trial of antimicrobial therapy could have delayed diagnosis and initiation of specific treatment for P carinii. Contrariwise, without histologic confirmation, specific therapy for P carinii pneumonia might have been mistakenly discontinued in the second patient. Empiric therapy with trimethoprim-sulfamethoxazole may cause rapid disappearance of P carinii cysts from pulmonary tissues and cause subsequent biopsies to be falsely negative in patients who fail to respond to treatment.

Adult

[Delayed parturition in sheep by clenbuterol (author's transl)].

The effect of treatment with clenbuterol on lambing during the period from 9 p.m. to 5 a.m. was studied in a field trial in sheep, which was continued for twenty-two days. The date of tupping was not known. The sheep were divided into an experimental and a control group, each numbering 106 animals. Animals of the experimental group were assessed every day at approximately 7.30 p.m., using a system of scoring for the development of udders and vulvae, and were treated with oral administration of 200 micrograms of clenbuterol when the findings suggested that parturition would occur that night. Seventy-nine animals of the experimental group lambed. twelve of them lambing during the night (two of these had been treated in the evening before lambing); of the group of controls, seventy-two lambed, twenty-three doing so during the night (difference significant: P greater than 0.05). The difference in the number of lambings during the night between treated and untreated animals was highly significant (P less than 0.001). Side-effects of clenbuterol were not recorded. The amount of clenbuterol used in the group of controls was: 3.49 tablets/lambing sheep, 5.03 tablets/treated sheep and 5.02 tables/treated and lambing sheep. This high consumption rate is attributed to the fact that the date of tupping was not known as well as to the defectiveness of the criteria on which the decision to treat or not to treat was based.

Administration, Oral