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Biomedical subjects

C Klein

Publications and source records attributed to C Klein.

At least 343 records · Page 19Linked to original sources

Fatigue and recovery contractile properties of young and elderly men.

The 24 h recovery pattern of contractile properties of the triceps surae muscle, following a period of muscle fatigue, was compared in physically active young (25 years, n = 10) and elderly (66 years, n = 7) men. The fatigue test protocol consisted of 10 min of intermittent submaximal 20 Hz tetani. The maximal twitch (Pt) and tetanic force at 3 frequencies (10, 20 and 50 Hz) were determined at baseline and at 15 min, 1, 4 and 24 h after fatiguing the muscle. Maximal voluntary contraction (MVC) and vertical jump (MVJ) were also assessed. The loss of force during the fatigue test was not significantly different between the young (18 +/- 13%) and elderly (22 +/- 15%). Both groups showed similar and significant reductions of Pt (15%), tetanic force (10 to 35%) and rate of force development (dp/dt) (20%) 15 min and 1 h into recovery. The loss of force was greater at the lower stimulation frequencies of 10 and 20 Hz. Time-to-peak tension was unchanged from baseline during recovery in either group. The average rate of relaxation of twitch force (-dPt/dt) was decreased (p less than 0.05) and half-relaxation time significantly increased at 15 min and 1 h in the elderly but not the young. The findings indicate that after fatiguing contractions, elderly muscle demonstrates a slower return to resting levels of the rate and time course of twitch relaxation compared to the young.

Adult↗

Age does not alter human vascular and nonvascular beta 2-adrenergic responses to isoproterenol.

beta-Adrenoceptor-mediated functions appear to diminish with aging, but the exact scope of these changes is unknown, because most studies have been limited to beta 1-adrenergic cardiac phenomena. To evaluate both a vascular and a nonvascular beta 2-adrenergic response in the aged, we have studied 12 healthy elderly and 12 healthy young subjects infused with increasing doses of isoproterenol and compared the change in peripheral vascular resistance, measured by venous occlusion plethysmography, and insulin release. In both groups vascular resistance fell and insulin concentrations increased. These changes were equivalent in both groups, and we therefore infer no significant decline in either of these beta 2-adrenergic functions in the elderly.

Adult↗

[Value of conventional x-ray diagnosis and computerized tomography in the detection of Hill-Sachs defects and bony Bankart lesions in recurrent shoulder dislocations].

Forty patients with anterior dislocation of the shoulder were examined in order to demonstrate Hill-Sachs defects and bony Bankart lesions. All patients had conventional radiographs of the shoulder in two planes, special views according to Hermodsson and Bernageau and CT. The examinations were evaluated by three observers. CT was regarded as the gold standard. Sensitivity for demonstrating Hill-Sachs defects for the standard views was 45% and for the Hermodsson views was 76%. For demonstrating Bankart lesions, standard views had a sensitivity of 37% and the Bernageau view 64%. Computed tomography was markedly superior to the standard and the special views, both for demonstrating the lesions and the agreement between various observers.

Female↗

Evidence that a glycolipid tail anchors antigen 117 to the plasma membrane of Dictyostelium discoideum cells.

We describe the biochemical features of the putative cell cohesion molecule antigen 117, indicating that it is anchored to the plasma membrane by a glycolipid tail. Antigen 117 can be radiolabeled with [3H]myristate, [3H]palmitate, and [14C]ethanolamine. The fatty acid label is removed by periodate oxidation and nitrous acid deamination, indicating that the fatty acid is attached to the protein by a structure containing carbohydrate and an unsubstituted glucosamine. As cells develop aggregation competence, the antigen is released from the cell surface in a soluble form that can still be radiolabeled with [14C]ethanolamine but not with [3H]myristate or [3H]palmitate. The molecular weight of the released antigen is similar to that found in the plasma membrane, but it preferentially partitions in Triton X-114 as a hydrophilic, as opposed to a hydrophobic, protein. Plasma membranes contain the enzyme activity responsible for the release of the antigen in a soluble form.

Antigens, Surface↗

An unusual protein kinase phosphorylates the chemotactic receptor of Dictyostelium discoideum.

We report the cAMP-dependent phosphorylation of the chemotactic receptor of Dictyostelium discoideum in partially purified plasma membranes. The protein kinase responsible for receptor phosphorylation is associated with this fraction and preferentially phosphorylates the ligand-occupied form of the receptor. 8-Azido[32P]cAMP labeling of the cell surface has shown that the cAMP receptor exists in two forms. A 45-kDa protein is predominant on unstimulated cells. cAMP stimulation results in an increased receptor phosphorylation such that the receptor migrates on NaDodSO4/PAGE as a 47-kDa protein. Phosphorylation of the chemotactic receptor is not detected in membrane preparations unless cAMP is added to the incubation mixture. Only under those conditions is the phosphorylated 47-kDa form observed. The requirement for cAMP reflects the fact that the kinase involved preferentially uses the ligand-occupied receptor as a substrate. In vitro phosphorylation of the receptor does not involve tyrosine residues. The enzyme does not appear to be a cAMP- or cGMP-dependent protein kinase nor is it sensitive to guanine nucleotides, Ca2+/calmodulin, Ca2+/phospholipid, or EGTA. Similarities with the beta-adrenergic receptor protein kinase are discussed.

Cyclic AMP↗

Inhibition of N-linked glycosylation in Dictyostelium discoideum: effects of aggregate formation.

The aggregation program of Dictyostelium discoideum is extremely sensitive to the effects of tunicamycin when the drug is added to cells during the first few hours of starvation. Inhibition of development is observed with concentrations as low as 0.5 micrograms/ml, which cause only a 25%-30% inhibition of general N-linked glycosylation. However, 0.5 micrograms/ml tunicamycin can result in the total inhibition of N-linked glycosylation of specific, developmentally regulated, proteins, as exemplified by the glycoprotein 117 antigen. If added after the first hours of starvation, tunicamycin cannot inhibit aggregation even when present at 10 micrograms/ml, which maximally inhibits N-linked glycosylation. cAMP pulses can override the inhibitory effects of tunicamycin on cell aggregation. The data support the hypothesis that there is an early developmental pathway that is dependent on the N-linked glycosylation of one, or a small set of developmentally regulated proteins and that this pathway may involve the biogenesis of the chemotactic signalling system. In addition, the data raise questions as to the role of N-linked oligosaccharides in cell cohesion.

Cell Aggregation↗

Immunophotometric quantification of extravascular immunoglobulin deposits in the synovial membrane of patients with osteoarthritis and rheumatoid arthritis.

The amount of extravascular immunoglobulin deposits in the synovial membrane of patients with osteoarthritis and rheumatoid arthritis was studied in comparison with that of patients suffering from non-joint diseases. Immunoglobulin deposits were immunostained using the three-layer immunoperoxidase method. The staining results were quantified with the help of a microscope photometer connected with a scanning stage. Several experiments involving artificial test substrates, diseases with allegedly increased extravascular deposits or diseases not exhibiting extravascular deposits of immunoglobulins are used to validate the described microspectrophotometrical approach for measuring extravascular immunoglobulin deposits. The scanning photometry demonstrates significantly higher amount of extravascular immunoglobulin deposits in rheumatoid arthritis as compared with osteoarthritis and non-joint diseases.

Arthritis, Rheumatoid↗

Pertussis and cholera toxin ADP-ribosylation in Dictyostelium discoideum membranes.

We report a 39 kDa substrate for cholera and pertussis toxins is present in D. discoideum membranes. This protein did not co-migrate with alpha subunits of either Gs (45 kDa and 52 kDa) or Gi (41 kDa) from control mammalian cells. The presence of GTP or its non-hydrolyzable analogs enhanced the ADP-ribosylation in response to cholera toxin, but did not significantly alter ADP-ribosylation by pertussis toxin. Divalent cations inhibited the ADP-ribosylation by both toxins. The possible association of this novel G-protein with D. discoideum adenylate cyclase may underlie some of the unique regulatory features of this enzyme. Alternatively, this G-protein may regulate one of several other cellular responses mediated by the cAMP receptor.

Adenosine Diphosphate Ribose↗

Characterization of antigen 117. A developmentally regulated cell surface glycoprotein of Dictyostelium discoideum.

Antigen 117 is involved in the process of intercellular cohesion in Dictyostelium discoideum (Brodie, C., Klein, C., and Swierkosz, J. Cell 32, 1115-1123 (1983]. The antigen was shown to arise from a 62,000-64,000-dalton precursor. The mature antigen consists of two forms of molecular weights, 69,000 and 72,000. These forms are glycosylated, phosphorylated, acylated, and sulfated. Developmental changes in the cellular and cell surface levels of the antigen reflect changes in its rate of synthesis. All aggregating cells express antigen 117 on their surfaces. Antigen 117 then disappears from the surface of all cells when tip formation occurs. The antigen is re-expressed briefly again on cells undergoing culmination.

Antibodies, Monoclonal↗

Population pharmacokinetics of phenytoin in South African black patients.

In the routine care of 37 patients at the epilepsy outpatient clinic of Baragwanath Hospital, Johannesburg, 100 steady-state serum phenytoin concentrations were measured. Total and free phenytoin as well as albumin serum concentrations were determined. Computer analysed data were fitted to the Michaelis-Menten model for steady-state serum concentrations. As a function of the Michaelis-Menten constant (P less than 0.1) total serum phenytoin concentration provided a significantly better fit than free phenytoin combined with albumin serum concentrations. The Vm and Km of 6.5 mg/kg/d and 13.6 mumol/l respectively, determined by using total serum concentration, could be to estimate phenytoin dosage requirements in a hospital population.

Adolescent↗

Ammonium sulfate modifies adenylate cyclase and the chemotactic receptor of Dictyostelium discoideum. Evidence for a G protein effect.

(NH4)2SO4 was found to activate adenylate cyclase in Dictyostelium discoideum membranes. The effect of (NH4)2SO4 on the enzyme was observed after pretreatment of membranes but could not be observed if the salt was added to the assay mixture. Activation was seen when membranes were pretreated with 0.16 M (NH4)2SO4 and was maximal at 0.6-1.0 M. The maximal activation of the enzyme was observed within 3 min of pretreatment and was not readily reversible. The effect was specific for the NH+4 ion since pretreatment of membranes with other NH+4 salts could activate the enzyme, whereas pretreatment with NaCl or KCl could not. Pretreatment of plasma membranes with (NH4)2SO4 eliminated the sensitivity of the enzyme to the inhibitory effect of guanine nucleotides. (NH4)2SO4 pretreatment also significantly attenuated the inhibition by guanine nucleotides of cAMP binding to its plasma membrane receptor. The effect of (NH4)2SO4 on GTP inhibition of cAMP binding to its receptor was even more dramatic when the salt was present in the binding assay. (NH4)2SO4 also increased the ADP-ribosylation by cholera toxin of a 39,000-Da membrane protein. The data support the hypothesis that (NH4)2SO4-induced changes in adenylate cyclase and the cAMP receptor are due to an alteration of a putative G protein.

Adenylyl Cyclases↗

Toxoplasma gondii encephalitis in an immunocompetent adult. A case report.

A healthy young adult with no evidence of immunosuppression presented with a diffuse encephalopathy considered to be due to Toxoplasma gondii. A marked eosinophilia as well as an anamnestic reaction to a previous parasitic infestation was present. The clinical picture and abnormalities on computed tomography were in keeping with the diagnosis, which was supported by serological tests. Treatment with pyrimethamine and sulphadiazine was effective and there were negligible sequelae.

Adult↗

Regulation of Dictyostelium discoideum adenylate cyclase by manganese and adenosine analogs.

Adenylate cyclase is the critical enzyme in the chemotactic signal relay mechanism of the slime mold amoeba, Dictyostelium discoideum. However, few studies examining the regulation of this enzyme have been performed in vitro due to the instability of enzyme activity in crude lysates. For studies presented in this communication, a membrane preparation has been isolated that exhibits a high specific activity adenylate cyclase that is stable during storage at -70 degrees C and under assay conditions at 27 degrees C. The enzyme was activated by micromolar concentrations of MnCl2. GTP and its non-hydrolyzable analog, guanosine 5'-(beta, gamma-imino)triphosphate, inhibited the enzyme non-competitively in the presence of either Mg2+ or Mn2+. However, this inhibition was more pronounced in the presence of Mn2+. Since guanylate cyclase activity in the D. discoideum membranes was less than 10% of the adenylate cyclase activity, there could not be a significant contribution by guanylate cyclase toward the production of cyclic AMP. Experiments indicate that D. discoideum adenylate cyclase was also regulated by adenosine analogs. The enzyme was inhibited by 2',5'-dideoxyadenosine and 2'-deoxyadenosine and inhibition was augmented by the presence of Mn2+. However, the inhibition was not entirely consistent with that which would be expected for the P-site of eukaryotic systems because some purine-modified adenosine analogs also inhibited the enzyme. Guanine nucleotides had no effect on the inhibition by either purine-modified or ribose-modified adenosine analogs. The binding of cyclic AMP to its receptor on the D. discoideum membranes was not affected by either MnCl2 or adenosine analogs.

Adenosine↗

Therapeutic drug level monitoring in the management of epilepsy.

A selected group of poorly controlled epileptic patients had their drug plasma concentrations measured. Of those on a single drug, 33% were noncompliant, 33% had drug concentrations in the subtherapeutic or toxic ranges and 34% had levels in the therapeutic range, 86% of which were in the low therapeutic range. In only 9% of the group on multiple drugs were both drug levels in the therapeutic range. Twenty-two per cent of patients were non-compliant for both drugs. Patients were followed up over 12 months with drug level monitoring and dosage adjustments; 49% were seizure-free and 36% had a reduction in seizure frequency of at least 50% over an 8-month period. All but 3.9% were put on a single-drug regimen, and 15.6%, which matched well with the number of non-compliant patients, had no change in seizure frequency. Therapeutic drug level monitoring is a most useful aid in rationalising drug therapy and improving seizure control.

Adolescent↗

Rebound hypertension after discontinuation of transdermal clonidine therapy.

Three (and possibly all four) elderly hypertensive patients who were followed sequentially after discontinuation of transdermal clonidine monotherapy manifested a rapid rise in blood pressure to levels above control (pre- and post-therapy) readings. No signs of an "overshoot" in plasma norepinephrine levels or symptoms of beta-adrenergic overactivity were seen. Such rebound hypertension suggests hypersensitivity to alpha-adrenergic receptor stimulation and could pose a heretofore unreported potential hazard to elderly or otherwise compromised patients who discontinue transdermal clonidine therapy.

Administration, Cutaneous↗

The balance between vascular alpha- and beta-adrenoceptors is not changed in the elderly.

It has been suggested that beta-adrenoceptor-mediated functions are diminished with aging and that these responses are reduced to a greater extent than are alpha-adrenoceptor-mediated responses. The resulting imbalance in the elderly may produce an increased vascular resistance from the unopposed alpha-adrenoceptor stimulation in the peripheral vasculature. To evaluate this hypothesis, we studied 12 healthy elderly and 12 healthy young subjects during a graded infusion of epinephrine and compared blood pressure response, vascular resistance, and calf blood flow as determined by venous occlusion plethysmography. In both groups, heart rate increased, blood flow to the leg increased, and vascular resistance fell in response to epinephrine infusion, but in the elderly the systolic blood pressure failed to rise as it did in the young subjects. From these data we conclude that the overall vascular response to epinephrine does not change with age and that the balance between beta-adrenoceptor-mediated vasodilation and alpha-adrenoceptor-mediated vasoconstriction is therefore unchanged in the elderly.

Adult↗

Spinal cord schistosomiasis: a case report and review of the literature.

Spinal cord involvement by Schistosomiasis is considered to be rare. We report a case of acute transverse myelitis due to Schistosoma mansoni in which treatment with praziquantal and steroids was started three days after the onset of a paraparesis, with complete neurological recovery.

Adult↗