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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 649 records · Page 36Linked to original sources

X-ray induced mitotic delay and death of cells in different phases of the cell cycle. An autoradiographic study on jejunal crypt cells of the mouse using double labelling with 3H- and 14C-thymidine.

The cell-cycle phase specific effect of an X-ray absorbed dose of 1.9 Gy on jejunal crypt cells of the mouse was studied in terms of mitotic delay and in terms of radiation induced cell death. A double labelling method with 3H-and 14C-thymidine was used in order to discriminate the cells in the different phases of the cell cycle. Cells irradiated during G2 phase are most radiosensitive, i.e. they exhibit the longest mitotic delay, followed in decreasing order by cells irradiated during early S and during the middle and end of S phase. Even some of the cells irradiated during G1 phase reach mitosis with a certain delay. A similar pattern of radiosensitivity is derived from the results on cell death. The death of cells irradiated at a higher phase age (G2 and S) is predominantly associated with the mitotic process, while the majority of cells irradiated during G1 and early S phase die out of interphase. A rough estimate has led to a mean life span of about 1 hr for radiation induced necrotic cells within the crypt.

Animals↗

An enzymatic system for removing heparin in extracorporeal therapy.

The need to fully heparinize patients undergoing extracorporeal therapy often leads to hemorrhagic complications. To enable heparinization of only the extracorporeal circuit, a blood filter containing immobilized heparinase was developed. This filter degraded 99 percent of heparin's anticoagulant activity within minutes in both canine and human blood.

Extracorporeal Circulation↗

Nucleation-controlled polymerization of human monoclonal immunoglobulin G cryoglobulins.

The kinetics of the polymerization of human monoclonal cryoimmunoglobulins at low temperature was investigated in temperature jump experiments by monitoring the changes in turbidity resulting from the scattering of incident light by the polymers. Above a critical concentration between 2 and 3 mg/ml, depending on the ionic strength, the kinetics were characterized by a concentration-dependent lag phase and initial rate of self-assembly. Under equilibrium conditions which favored polymerization, the only stable intermediate detected by analytical ultracentrifugation was the dimer. Although purified monomers were unable to self-associate at 4 degrees C, addition of trace amounts of autologous dimers promoted polymerization. The apparent rate of polymerization was shown to be slow (k = 4.7 X 10(-4) M-1 s-1), and the process was governed by an equilibrium constant of 4.6 X 10(4) M-1. The initial rate of self-assembly was proportional to the product of the monomer concentration and the concentration of promoter (i.e. dimer). The rate of depolymerization was three orders of magnitude greater than the rate of polymerization and was proportional to the concentration of polymers present. These results suggest that the polymerization of monoclonal cryoimmunoglobulins is a nucleation-controlled process in which dimerization is the rate-limiting step. Kinetic studies on the polymerization of Fab and F(ab')2 fragments from cryoimmunoglobulins and a comparison of cryogel ultrastructure by electron microscopy suggested that the interaction site between monomers is located in the Fab region. Since the polymerization of monomers was only induced by autologous dimers and not dimers from other cryoimmunoglobulins, it was concluded that the hypervariable regions play a specific role in the condensation reaction. The fact that one cryoimmunoglobulin has a well defined antibody activity against streptolysin O argued against a low temperature-induced auto-anti-idiotype mechanism. Reduction of the interchain disulfide bonds of the Fab fragments abolished their ability to polymerize, probably by inducing a conformational change a considerable distance away in the variable domains of the molecules.

Cryoglobulins↗

Circulating immune complexes in patients with progressive systemic sclerosis.

Forty-one patients with progressive systemic sclerosis were studied for the presence of immune complexes by the fluid- and solid-phase C1q binding, C1 activation, and the fluid-phase conglutinin assays. Complement activation and autoantibodies were also studied. Immune complexes were detected in only 6 patients (15%); activation of complement was found in 5 others. The clinical and serologic features of patients with complexes were compared with those in whom complexes were not identified. No significant difference was found with respect to serology. Organ involvement was generally more frequent in the group with immune complexes, but the difference was statistically significant only with respect to lung involvement. The present data suggest that, although complement-fixing immune complexes are infrequently detected in progressive systemic sclerosis, they may play a role in the pathogenesis of lung lesions associated with the disease.

Adult↗

Clinical relevance of verapamil plasma levels in stable angina pectoris.

Plasma levels of verapamil and norverapamil were evaluated in 77 patients who received oral verapamiL for treatment of angina pectoris. There was a sixfold interpatient variation in verapamil plasma concentrations, but plasma concentrations were linearly related to doses of the drug (240 to 480 mg/day) in the same patient (r = 0.81). Plasma concentrations of norverapamil, the major active metabolite of verapamil, were similar to those of verapamil. Although verapamil produced a significant improvement in exercise tolerance in most patients, the increase in exercise time was not related to plasma levels of the drug; however, most patients with improvement had plasma levels exceeding 100 ng/ml. An increase in the dose of verapamil from 320 to 480 mg daily produced a substantial (71%) increase in plasma levels of the drug but no significant increase in exercise tolerance (4%). The average increase in the P-R interval with 480 mg of verapamil in these 77 patients was small (8%) (161 +/- 18 to 174 +/- 22 ms); on.y six patients had first-degree heart block. These minor effects on atrioventricular conduction were noted despite plasma verapamil concentrations in 76 patients that exceeded 100 ng/ml, a level that successfully converts supraventricular tachycardias after intravenous drug administration. We differences between the effects of oral and intravenous verapamil on atrioventricular conduction may be the result of stereoselective hepatic inactivation of verapamil's I-isomer. Determination of plasma levels of verapamil is of limited value in the management of patients with angina pectoris, but may be useful in the identification of nonresponders with plasma levels less than 100 ng/ml who may benefit from a further increment in drug dose.

Administration, Oral↗

Anticonvulsant and antiaggressive properties of di-n-propyl acetate after repeated treatment.

Swiss albino mice were treated twice daily with 200 mg/kg (i.p.) di-n-propylacetate (DPA), for 14 days and sacrificed 15 hr after the last injection, with or without an additional injection of 400 mg/kg at 45 min before death. Without the additional injection, the brain distribution of GABA followed closely that of control mice; with the additional injection, the pattern of regional increase of brain GABA was very similar to that following an acute injection of DPA. The anticonvulsant and antiaggressive properties of DPA were similar in rodents treated acutely or additionally after repeated DPA treatment. Neither the anticonvulsant nor the antiaggressive properties could be observed 15 hr after the last of the repeated injections of DPA. A residual effect of DPA against seizures induced by pentetrazole was shown, i.e. a potentiation of the anticonvulsant properties of the second of two successive injections of DPA, the latter being given after the decrease of the GABA levels in whole brain to control values.

Acoustic Stimulation↗

Serotonin modulates a specific potassium current in the sensory neurons that show presynaptic facilitation in Aplysia.

Serotonin exerts a long-lasting excitatory action on sensory neurons of Aplysia californica by decreasing outward K+ current. The depression of outward current delays repolarization of the action potential and extends the duration of Ca2+ influx into the presynaptic terminals, thereby contributing to the facilitation of transmitter release that underlies behavioral sensitization. We have extended the analysis of serotonin's action and find that it acts on a specific serotonin-sensitive K+ current (S current), which is different from the early K+ current (IA), the delayed K+ current (IK), the Ca2+-dependent K+ current (IC), and the muscarine-sensitive M current. The serotonin-sensitive current in these cells persists when IA and IK are reduced by conditioning depolarization or channel-blocking agents. The S current is not activated by intracellular injection of Ca2+, nor is it affected by substitution of Ba2+ for Ca2+, a treatment that reduces IC. Moreover, intracellular injection of cyclic AMP exerts an effect indistinguishable from that of serotonin. This observation and the insensitivity of the current to Ba2+ distinguishes the S current from M current. S current is activated at the resting potential and does not inactivate with steady-state depolarization. It is active sufficiently early during an action potential to contribute to the repolarization of the action potential and therefore accounts for the physiological effects of serotonin.

Animals↗

[Energy maintenance requirements and energy requirement for protein retention in growing rats and broilers. 1. Energy maintenance requirements of growing rats].

In 4 experiments with 3 times 3 male Wistar rats each, which received rations with different protein contents (10; 25 and 40% crude protein in the dry matter), in the growth range between approximately 65 and 180 g live weight and with an environmental temperature of 30 degrees C, a total of 226 measurings of the total metabolism were carried out on the energy level maintenance, partly also with the insertion of a fasting day. The most important results were: On the energy level maintenance with the simultaneous catabolisation of body fat there was considerable protein energy retention, which amounted to between 30 and 40% of the retention achieved in the growth periods. The energy maintenance requirement can be determined with good reproducibility (standard mean deviation: +/-6%). The average energy requirement directly measured at the feeding level maintenance of 437 kJ metabolizable energy (ME)/kg live weight 0,75.d (n=224) differs insignificantly from the average value obtained by means of multiple regression analysis from experiment periods with feeding for growth 423 kJ ME/kg live weight 0,75.d (n=437). Consequently it is not necessary to differentiate between energy requirement for maintenance and energy requirement connected correlatively with the live weight (metabolic weight of the body) under conditions of growth. Energy maintenance requirement proved to be insignificantly dependent on the amount of protein in the feed. The relative values of protein quotas of 10, 25 and 40% in the feed were 100, 101 and 103%; the expected values (derived from the efficiency of ATP synthesis in the oxidation of carbohydrates and protein) amount of 100, 104 and 109%. The problem of the thermogenous effect of protein, which is also of great importance to human nutrition urgently requires further experimental investigation. For growing rats the best adaptation of the energy maintenance over the investigated period of development is achieved if the 2/3 potence of the live weight is chosen as the expression of the metabolic body weight. With high probability this can also be transferred to the characterisation of protein metabolisation.

Animals↗

[Energy maintenance requirement and energy requirement for protein retention in growing rats and broilers. 3. Energy requirement for protein retention in rats].

In 4 experiments with 3 X 3 male Wistar rats each, which received rations with different protein content on 3 levels (10-40%), a total of 240 measurings of the total metabolism with the purpose of ascertaining the energy requirement for protein retention were carried out under the conditions of ad libitum feeding in the growth range between approximately 65 and 200 g live weight at a temperature of the environment of 30 degrees C. With 25% crude protein (caseine supplemented with methionine) in the feed mixture, with an energy content of the ration between 18 and 20 kJ/kg dry matter, the N-retention capacity of the animals was largely exhausted. When 150 g live weight were exceeded, the N-retention capacity of the animals decreased considerably. Energy retention in % of gross energy depended on the protein level of the feed rations; in all 4 experiments the rats achieved the highest energy retention with 10% crude protein in the feed. The level of energy utilisation decreased with the increasing protein content of the feed mixture. Requirement values of metabolisable energy per 1 J protein energy retention of 1.69; 1.93; 1.81 and 1.74 J were derived by means of multiple regression analysis for all 4 experiments, assuming the exponent 0.75 for the variable metabolic body size. The application of multiple regression analysis to the values of energy retention measuring in all 4 experiments results in the mean energy requirement of 1.67 J/J protein retention, which completely coincides with previous investigations. When the exponent 0.67 was assumed for the variable metabolic body size, the energy requirement data for the individual experiments resp. after the joint evaluation of all 4 experiments were 1.56; 1.75; 1.68 and 1.56; 1.53 J/J resp. The significant influence of the live weight, the consumption quota of digested nitrogen (protein level of feeding) and the protein retention quota on the value of protein requirement for protein retention was proved. This evidence is discussed with respect to further research for the factorial assessment of the bioenergetic of protein retention.

Animals↗

[Energy maintenance requirement and energy requirement for protein retention in growing rats and broilers. 4. Energy requirement for protein retention in broilers].

The results of measurings of the total metabolism from experiments with 6 male broilers (origin: Tetra B) each, which mainly served the ascertainment of energy maintenance requirement (cf. 2) in the growth range between 100 and 2,000 g with alternating experiment phases on the maintenance and growth level, have also undergone interpretation for the further characterisation of the energy requirement for protein retention. Caused by the sequence of periods chosen, there were compensatory growth effects. Energy retention in % of gross energy varied between the experiments in the limits of 24 and 39%, and concerning energy retention per animal and day there were differences up to 100% between the experiments. The share of protein energy retention in energy retention on average amounted to 38% after a medium-high protein supply and 54% after a high protein supply. The utilisation of metabolisable energy for energy retention was significantly lower from rations of a high protein level (40% crude protein) than from those of a medium-high protein level (20% crude protein). Assuming an energy requirement for fat retention of 1.2 J metabolisable energy per J retention, a requirement of metabolisable energy for 1 J protein retention of 1.68; 1.66 and 1.86 was ascertained in the 3 experiments by means of regression analysis. An energy requirement for maintenance of 423 (30 degrees C), 511 (25 degrees C) and 432 kJ metabolisable energy/kg live weight 0 75 X d (30 degrees C) correlated with these requirement values. Energy requirement for protein retention increased significantly with N-intake and decreased significantly with the daily protein retention rate. There was no dependence on the live weight of the broilers.

Animals↗

Geriatric psychiatry in the emergency department: characteristics of geriatric and non-geriatric admissions.

A study was made of the Emergency Department records of 49 elderly (65 years old or older) and 49 middle-aged (40-64 years old) patients seen in an urban hospital's psychiatric emergency service. The data were compared for demographic and admission information, psychiatric treatment history, presenting complaints, symptoms, diagnoses, and final disposition status. For the elderly patients, the referral was more likely to be their first contact with psychiatric treatment, and they were more likely to be referred (accompanied) by family or friends than to be self-referred. Among the middle-aged patients, "substance abuse" (e.g., drugs, alcohol) disorders and schizophrenic disorders were more common. The elderly, however, were much more likely to be regarded as having an organic brain syndrome of unspecified cause (34.7 per cent vs 0). Access to treatment was fairly consistent for both groups as measured by the hospital's priority code, total time spent in the emergency department, and final disposition. These results raise important issues concerning the unique psychosocial characteristics and psychiatric treatment needs of elderly patients. This applies particularly to the emergency-department medical clearance of elderly patients with symptoms of organic brain syndrome.

Adult↗

Epidemiologic features of Strongyloides stercoralis infection in an endemic area of the United States.

The epidemiologic features of Strongyloides stercoralis infection in Kentucky were studied by an analysis of clinical cases at the University of Kentucky Medical Center (UKMC); by an analysis of parasitologic records of the Kentucky Bureau for Health Services (KBHS); and by a prospective stool survey of school children in Clay County, located in southeastern Kentucky, an area of the state previously found to be highly endemic for intestinal parasites. S. stercoralis was the most common parasitic infection diagnosed at UKMC. The patients were predominantly white male adults who were over 50 years old, had an associated chronic or debilitating medical illness, were of low socioeconomic background, and resided in southeastern Kentucky. S. stercoralis was a common parasitic infection at KBHS ad the patients showed a similar geographic distribution. Of 561 Clay County children surveyed, 23.7% harbored one or more intestinal parasite pathogens and 3.0% had S. stercoralis. Thus, S. stercoralis remains highly endemic in Kentucky and may cause disease even in geriatric patients.

Adolescent↗

Noncovalent association of heavy and light chains of human immunoglobulins. III. Specific interactions between VH and VL.

Mildly reduced monoclonal human IgM proteins have been cleaved at cysteinyl residues to give VH fragments after S-cyanylation with 2-nitro-5-thiocyanobenzoic acid. The noncovalent interaction between the VH fragments and autologous kappa-chains was studied by ultraviolet difference spectroscopy and circular dichroism. A bimolecular complex was formed with an association constant in excess of 10(7) M-1 at 23 degrees C. Complex formation was accompanied by burial of tryptophan and tyrosine side-chains. In contrast to the studies with autologous species, the VH fragments did not associate with heterologous kappa-chains as judged both by difference spectroscopy and gel filtration using radiolabeled VH fragments. This specificity in the association between VH and VL has been attributed to interactions contributed to by residues in the third hypervariable region of VH encoded by the DH and JH genes.

Binding Sites, Antibody↗