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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 505 records · Page 28Linked to original sources
PubMed1989

Cyclosporine-induced deterioration in patients with AIDS.

Eight patients with AIDS (acquired immune deficiency syndrome) but free of life-threatening infection were treated with the immunosuppressive drug cyclosporine for a mean of 53.9 days. The serum cyclosporine levels were maintained in the desired therapeutic range. All eight patients experienced severe toxic symptoms, which necessitated discontinuation of cyclosporine therapy in six. The serum levels of creatinine, urea and potassium rose during treatment and fell after therapy was stopped. The total leukocyte count, hemoglobin level, platelet count, total T-cell count, and T4- and T8-cell counts all fell markedly during treatment. The total leukocyte count, platelet count, and T4- and T8-cell counts rose after therapy was stopped, but the hemoglobin level remained low. No patient experienced resolution of symptoms during therapy, and the condition of all patients improved after treatment was stopped. The results of this pilot study indicate that cyclosporine does not alleviate, and may worsen, the symptoms and laboratory findings in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The effect of prototypic sigma ligands on the binding of [3H]dextromethorphan to guinea pig brain.

We studied the effects of several prototypic sigma site ligands on the binding of [3H]dextromethorphan ([3H]DM) to guinea pig brain. Haloperidol, 3-(-3-Hydroxyphenyl)-N-(1-propyl)piperidine [+)-3-PPP) and (+)-N-allyl-N-normetazocine [+)-NANM or (+)-SKF10,047), which are potent sigma site ligands, showed high affinity for [3H]DM binding sites. The rank order of potency of sigma ligands, as indicated by the Ki values for the high-affinity sites is: haloperidol greater than (+)-pentazocine greater than (+)-cyclazocine greater than (+)-SKF10,047 greater than (-)-butaclamol much greater than (+)-butaclamol greater than (-)-SKF10,047. This rank order of potency is similar to that for the sites labeled with [3H](+)-3-PPP and [3H](+)-SKF10,047. The (+)-isomers of several benzomorphans displayed higher affinity than the (-)-isomers. (-)-Butaclamol competed against [3H]DM binding more effectively than the (+)-isomer, displaying the same stereospecificity shown for sigma sites. The findings reported here demonstrate that there are previously unrecognized similarities between DM and sigma sites. It is evident that further exploration of the DM, sigma and phencyclidine (PCP) sites will be necessary to establish the physiological role and therapeutic potential of these sites.

Animals↗
PubMed1989

The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation.

Using the knee joints of New Zealand White rabbits, a baseline study was made to determine the intrinsic capability of cartilage for healing defects that do not fracture the subchondral plate. A second experiment examined the effect of autologous chondrocytes grown in vitro on the healing rate of these defects. To determine whether any of the reconstituted cartilage resulted from the chondrocyte graft, a third experiment was conducted involving grafts with chondrocytes that had been labeled prior to grafting with a nuclear tracer. Results were evaluated using both qualitative and quantitative light microscopy. Macroscopic results from grafted specimens displayed a marked decrease in synovitis and other degenerative changes. In defects that had received transplants, a significant amount of cartilage was reconstituted (82%) compared to ungrafted controls (18%). Autoradiography on reconstituted cartilage showed that there were labeled cells incorporated into the repair matrix.

Animals↗
PubMed1989

Should elective lymph node dissection be used for treatment of primary melanoma?

A bicenter study compared survival probability in patients with malignant melanoma clinical stage I, treated by wide excision only or wide excision with elective lymph node dissection (ELND). ELND improved the survival only in men with primary tumors of 1.51-3.0 mm thickness. In female patients those without ELND showed a better survival. Thus, the total group of patients did not benefit from ELND, i.e. its value for the improvement of survival from malignant melanoma stage I could not be statistically proven.

Female↗
PubMed1989

Dextromethorphan and sigma ligands: common sites but diverse effects.

There is increasing evidence that sigma ligands and dextromethorphan (DM) bind to at least one common high-affinity site. DM and other antitussives do not produce psychotomimetic effects. This suggested that sigma ligands may produce their characteristic effects through another site, and prompted us to review critically the literature on the side effects of sigma opiates. Contrary to what is generally accepted, the dysphoric and psychotomimetic side effects of sigma opiates are mediated by the levo-and not by the dextrorotatory isomers. Moreover, these effects are unequivocally naloxone-reversible. Therefore, the current version of the "sigma receptor", with high affinity for the dextrorotatory sigma opiates, cannot explain the psychotomimetic effects of the levorotatory enantiomers. Thus, neither the "sigma ligands" nor its newly defined "receptor" are involved in the psychotomimetic effects of sigma opiates. Further experimentation with more selective drugs and with a combination of different methods will be necessary to identify the different binding sites, and to establish their physiological role and therapeutic potential.

Animals↗
PubMed1989

Irradiation-induced duodenal ulcer disease refractory to ranitidine: healing by omeprazole.

In two patients duodenal ulcer refractory to high dose H2-blocker treatment started several months after irradiation therapy following right nephrectomy because of renal adenocarcinoma. Established antiulcer drugs like ranitidine, famotidine, sucralfate, pirenzepine, and antacids alone or in combination were unable to control ulcer pain and failed to induce ulcer healing. Initiation of omeprazole treatment at dosages to produce complete achlorhydria were necessary for ulcer healing and maintenance therapy. We suggest that (a) irradiation may cause duodenal ulcer disease indistinguishable from idiopathic duodenal ulcer; (b) radiation-induced ulcers in the duodenal bulb are refractory to various antiulcer drugs but may heal after administration of omeprazole in dosages that completely suppress acid secretion.

Aged↗
PubMed1989

Single-step purification of pertussis toxin and its subunits by heat-treated fetuin-sepharose affinity chromatography.

A general procedure for purifying biologically active pertussis toxin from Bordetella pertussis fermentation broth using affinity chromatography on heat-treated fetuin-Sepharose CL-4B is described. Diethanolamine is used as eluent in this single-step purification to prepare endotoxin-free pertussis toxin in good yield (70%) and high purity (greater than 95%). This one-step affinity chromatography procedure can be easily applied for large-scale preparation of pertussis toxin S1 subunit and its B-component. The affinity-purified S1 subunit is devoid of any of the histamine-sensitizing activity normally associated with pertussis toxin. The chromatographically purified pertussis toxin and its subunits retained their immunogenicity and could induce high levels of anti-toxin neutralizing antibodies.

Animals↗
PubMed1989

Relations of spanking and other parenting characteristics to self-esteem and perceived fairness of parental discipline.

Punishment has long been a controversial topic in psychology, perhaps partly because its effects are different under different circumstances. This study used retrospective reports from college students to examine the effects of spanking, a common aversive punishment, on self-esteem and perceived fairness of parental discipline, while taking the effects of other parental characteristics into account. No parental characteristic interacted with the slightly negative effect of spanking on self-esteem and fairness. However, controlling for positive communication or for a parent-oriented motivation for spanking eliminated the negative effects of spanking, suggesting that the negative effects reflected use of spanking as a replacement for positive communication with the child.

Adolescent↗
PubMed1989

Diagnostic potential of cardiotocography (CTG) for silent uterine rupture.

We report on 3 patients with silent rupture of previous uterine scars. Despite continuous monitoring by cardiotocography, diagnosis was not made until the time of surgery. The cesarean section was indicated by the obstetrical-clinical examination, while CTG offered no evidence of uterine rupture.

Adult↗
PubMed1989

Comparison of the effects of cetamolol and atenolol on epinephrine- and isoproterenol-induced hypokalemia in anesthetized dogs.

Epinephrine-induced hypokalemia is a beta 2-adrenoceptor-mediated effect known to occur in patients after acute myocardial infarction. Cetamolol and atenolol are beta-adrenoceptor antagonists that possess cardioselectivity. They were studied for their ability to inhibit epinephrine- and isoproterenol-induced hypokalemia in anesthetized dogs at equipotent beta 1-adrenoceptor blocking doses. Cetamolol was able to block epinephrine-induced hypokalemia completely, in a dose-related manner, and to block isoproterenol-induced hypokalemia partially. On the other hand, atenolol could produce only partial blockade of epinephrine-induced hypokalemia in a dose-related manner and had essentially no effect on isoproterenol-induced hypokalemia. These results showed that cetamolol was less cardioselective than atenolol and suggest cetamolol would be more beneficial than atenolol in preventing epinephrine-induced hypokalemia in patients who have an acute myocardial infarction.

Acetamides↗
PubMed1989

High affinity dextromethorphan binding sites in guinea pig brain. Effect of sigma ligands and other agents.

Dextromethorphan (DM), a non-narcotic antitussive, binds in the guinea pig brain to specific high- and low-affinity sites with Kd values of 57 nM and 24 microM, respectively (Musacchio et al., 1988). The antitussives carbetapentane, caramiphen, butamirate and dimethoxanate competed with the high-affinity binding of [3H]DM at pH 7.4 with nanomolar Ki values. Sigma site ligands showed high affinity for [3H]DM binding sites. The rank order of potency was: haloperidol greater than (+)-pentazocine greater than (+)-cyclazocine greater than 3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine greater than (+)-N-allylnormetazocine greater than (-)-butaclamol much greater than (+)-butaclamol (-)-N-allylnormetazocine. The antipsychotic perphenazine competed with low nanomolar Ki values, whereas rimcazole was weaker. The antidepressant opipramol and the benzomorphan (+)2'methoxyphenazocine were the most effective drugs tested, with Ki values of 0.4 nM. By contrast, MK-801 and phencyclidine hydrochloride were very weak competitors for [3H]DM binding. The diphenylalkylamines were the most effective competitors of the calcium channel blocking agents: prenylamine and cinnarizine had Ki values of 17 and 22 nM, respectively. Lidoflazine and hydroxyzine were slightly less potent, but nifedipine and the benzothiazepine diltiazem were much weaker. Potassium channel blockers inhibited DM binding in pharmacologically relevant concentrations: primaquine was the most effective with a Ki of 0.5 microM. Other antimalarial potassium channel blockers tested inhibited binding in the micromolar range. 4-Aminopyridine and tetraethylammonium had Ki values of 0.76 and 1.40 mM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A comparison of growth regulation of mammalian with amphibian lens epithelium.

In frogs hypophysectomy causes cell proliferation in lens epithelium to subside entirely, with better than 95% of the cells arresting in G1. The phenomenon has been traced to the action of insulin-like growth factors (IGFs) whose synthesis depends on anterior pituitary hormones, most notably GH. Both GH and purified somatomedin C can reinitiate mitosis in the lenses of hypophysectomized frogs. The present studies were done to determine if growth of rat lenses is controlled as is that of amphibia. It appears this may not be so because hypophysectomy has no effect on division in the rodent system. Protein calorie malnutrition (PCM) reduced the mitotic index and this effect is much enhanced by pituitary ablation. Of interest too, were the observations that the glucocorticoid, dexamethansone, is inhibitory in frog; the effect in rat is uncertain. Injection of bovine pituitary powder has no influence on rat while stimulating the amphibian material. It is therefore possible to modify growth of rat lens epithelium in vivo but the regulating mechanism(s) appears to be distinct from that operating in frogs. Whether the difference(s) is inherent in the cells themselves or is to be sought in the access routes through which they are reached by blood borne factors (e.g. permeability of blood-aqueous barriers) is, at present, unclear.

Animals↗
PubMed1989

Effects of dextromethorphan site ligands and allosteric modifiers on the binding of (+)-[3H]3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine.

Equilibrium binding analysis demonstrated that (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-[3H]3-PPP] binds in guinea pig brain homogenates to high and low affinity sites with Kd values of 25 nM and 0.9 microM, respectively. Competition studies with dextromethorphan (DM) site ligands and other drugs against (+)-[3H]3-PPP demonstrated that their Ki values and rank order of potency are identical to those found previously against [3H] DM. Most significant, ropizine produced a concentration-dependent increase in the binding of (+)-[3H]3-PPP, with an inhibitory component at high concentrations, as described previously for [3H]DM. Similarly, phenytoin increased the binding of (+)-[3H]3-PPP in the same fashion as that of [3H]DM. Computer-assisted analysis of equilibrium binding of (+)-[3H]3-PPP in the presence of 10 microM ropizine demonstrated that the binding increase produced is due to a 3-fold increase in the affinity for (+)-[3H]3-PPP. These results, and our previous finding that sigma ligands inhibit [3H] DM binding with a rank order of potency similar to that for sites labeled with (+)-[3H]3-PPP or (+)-[3H]SKF10,047 strongly suggest that sigma ligands bind to the high affinity DM site. These findings, and the inability of DM and other antitussives to produce psychotomimetic side effects, suggest that the high affinity DM sites can mediate only the nonpsychotomimetic effects of sigma ligands. However, further studies are necessary to determine the physiological role and therapeutic potential of the DM high affinity sites.

Allosteric Regulation↗