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M H Klapper

Publications and source records attributed to M H Klapper.

At least 19 recordsLinked to original sources
PubMed1999

Clinical and quantitative EEG studies of mania.

BACKGROUND: Earlier EEG studies reported essentially normal findings during acute manic episodes but some atypical EEG characteristics and distinctions between familial and sporadic cases were described. Recently quantitative EEG (qEEG) studies differentiating mania from schizophrenia and depression have been published. METHODS: Clinical EEGs were obtained in 202 patients hospitalized for acute mania. EEGs were repeated in 75 patients rehospitalized for subsequent manic attacks. Quantitative EEGs were recorded in 37 patients who were able to cooperate after drug washout and again on completion of randomly assigned pharmacotherapy. RESULTS: Normal EEGs were obtained in most patients. Moderately abnormal EEGs in 16% were significantly associated with absent family histories of affective disorder. Left sided abnormalities were more common than right. "Small sharp spikes" and "microsleep" were encountered in 17% and 10% respectively of patients who drowsed. EEG findings during subsequent episodes did not suggest increasing CNS vulnerability. qEEGs showed significant differences between each of the therapeutic agents compared-lithium, carbamazepine, and lithium combined with carbamazepine, haloperidol or risperidone. Nonresponders at baseline had significantly more diffuse theta activity than responders. During pharmacotherapy nonresponders had higher amplitudes in the left temporoparietal areas. LIMITATION: Clinical EEG findings confirmed previous reports but did not contain original observations. Applications of qEEG were limited by requirements for patient cooperation.

Adult↗
PubMed1998

Topographic EEG studies of mania.

QEEG findings from 39 hospitalized manic patients were accomplished after a drug free period and following pharmacotherapy with lithium or carbamazepine alone or lithium combined with carbamazepine, haloperidol or risperidone. A subsample of 10 drug-free manic patients was compared with normal controls, which revealed lower qEEG amplitudes in the left anterior and midtemporal regions in the patients. Comparisons of drug therapies showed increased delta amplitudes and total power with lithium compared with carbamazepine. Increased fast frequencies were observed in the lithium and carbamazepine plus lithium groups compared with carbamazepine alone. Comparisons of the three drug combination groups revealed increased alpha and beta 1 amplitudes, most with risperidone and least with carbamazepine. Anterior delta and beta 2 amplitudes and interhemispheric coherence were increased directly proportional to plasma lithium levels. Nonresponders to treatment were identified at baseline by increased generalized theta amplitudes. After treatment, the nonresponders had higher amplitudes in the left temporal areas. Numerous qEEG associations with individual ratings of manic symptoms were found, more at baseline than after treatment. In general levels of psychopathology were negatively correlated with qEEG amplitudes. The qEEG findings appear to implicate dominant temporal lobe dysfunctions in mania.

Adult↗
PubMed1996

Comparison of therapeutic modalities for mania.

The results of sequential therapeutic trials in hospitalized manic patients conducted over a 16-year period are summarized, followed by an analysis of pooled data to assess relative efficacy. No clinically important baseline differences were found in the patients admitted to these studies despite the long time span. They were not overly "difficult to treat" or treatment resistant, and most were discharged to the community. Nearly all outcome measures showed statistically significant differences between groups after 8 weeks of treatment. The best responses occurred in the patients who received a mean series of nine electroconvulsive therapy (ECT) treatments with sparing use of neuroleptics followed by lithium maintenance. The next best outcome was observed with lithium combined with low doses of standard neuroleptics or risperidone. The combination of carbamazepine and lithium had significantly fewer neurological side effects than moderate doses of haloperidol with lithium, with equivalent therapeutic results. Monotherapy with either lithium or carbamazepine was less effective than the combination treatments. Minor differences in study design may contribute to the variance in outcome.

Adult↗
PubMed1995

Lithium combined with carbamazepine or haloperidol in the treatment of mania.

Hospitalized manic patients were withdrawn from psychoactive medications for 2 weeks after which they were randomized to double-blind treatment with carbamazepine plus lithium [CBZ-Li] or haloperidol plus lithium [HAL-Li] with benztropine. Unit dosages of Li 300 mg, CBZ 200 mg and HAL 2 mg were titrated to therapeutic plasma levels and maintained for 8 weeks. No rescue medications were permitted after 3 weeks. Standard ratings of psychopathology and side effects were accomplished weekly. Sixty patients entered the study but only 33 remained for randomization after drug washout. By 8 weeks both groups were improved from baseline without statistically reliable differences between them. However HAL-Li patients had more extrapyramidal side effects that were major reasons for dropout, whereas CBZ-Li patients were more often noncompliant and initially required more rescue medications. We conclude that either combination treatment can be beneficial but CBZ-Li has the advantage because of fewer neurologic side effects.

Adult↗
PubMed1992

Long range electron transfer along an alpha-helix.

The many observations of long range electron transfer in proteins raises the question of whether a protein's structure can influence the rate or path of such transfers, and if so, then how. To answer these questions requires information on which of the various structural elements composing proteins support long range electron transfer. In this report, we present evidence for long range electron transfer along the alpha-helix of a synthetic leucine zipper dimer. We also present electron transfer rate data obtained with other helical peptides.

Amino Acid Sequence↗
PubMed1991

Long range electron transfer between tyrosine and tryptophan in hen egg-white lysozyme.

The azide, dibromide and dichloride radicals oxidize one or more tryptophan side chains in hen egg-white lysozyme. The indolyl radical produced in this second-order 1-electron oxidation subsequently oxidizes a tyrosine side chain to the phenoxy radical in an intramolecular reaction with a rate constant of 130 +/- 10 s-1 at pH 7, 25 degrees C. The final indolyl and phenoxy equilibrium mixture then decays with a t1/2 approximately 2 s. The faster intramolecular reaction exhibits a pH dependence; on decreasing the pH from 9 the first-order rate constant increases to a maximum near pH 5.4 and then declines as the pH is lowered further. In contrast, the first-order rate constant for the intramolecular electron transfer between the tyrosine and tryptophan of the peptide trpH-pro-tyrOH remains unchanged between approx. pH 11 and 6.5 and then increases as the pH is lowered further. This difference in the observed pH dependence suggests that changes in structure or ionization state influence the protein electron transfer rate. We also discuss the radiation inactivation of lysozyme in light of these observations.

Animals↗
PubMed1991

Carbamazepine compared with lithium in the treatment of mania.

Fifty-two hospitalized manic patients were randomized to treatment with either carbamazepine or lithium carbonate after a 2-week drug withdrawal period. All of the probands were tertiary referrals with a high proportion of failures of previous lithium and other treatment. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for 8 weeks, and responders were followed up for up to 2 years. One third of patients responded favorably. Double-blind assessments revealed no statistically reliable differences between the two treatment groups. Patients receiving carbamazepine were somewhat more manageable than patients treated with lithium early in the study, whereas lithium-treated patients remained longer in the follow-up phase. However, numbers of long-term survivors were too small to be conclusive. This study adds to the growing body of evidence that acutely manic patients respond as well to carbamazepine as to lithium. However, monotherapy with either drug is not sufficient for the majority of manic patients who are referred for tertiary care.

Acute Disease↗
PubMed1990

Semiquinone radicals of methylamine dehydrogenase, methoxatin, and related o-quinones: a pulse radiolysis study.

Methoxatin is a novel o-quinone coenzyme found in a variety of dehydrogenases and oxidases. In this paper we present the visible absorption spectra, apparent pKa, and midpoint potentials of the methoxatin and two analogous phenanthrolinedione semiquinones. We have also obtained absorption spectra for the semiquinone forms of the methoxatin-containing holoenzyme methylamine dehydrogenase and of its resolved methoxatin-containing subunit. The two protein and the methoxatin semiquinone spectra all differ from one another.

Benzoquinones↗
PubMed1990

Intramolecular long-range electron transfer in the hemerythrin monomer: a pulse radiolysis study.

The single sulfhydryl group (Cys-50) of the methemerythrin from Phascolosoma gouldii reacts with 5,5'dithiobis(2-nitrobenzoic acid) to form a mixed disulfide. The pulse radiolytically generated formate radical reduces this mixed disulfide to its radical anion. In turn, the disulfide radical anion reduces the protein two-iron center over a nominal distance of 13 A. The rate constant for this intramolecular electron transfer is approximately 15 s-1 at room temperature, pH 7. Between the two redox centers there is an equilibrium driving force of 0.78 V, measured by differential pulsed polarography.

Animals↗
PubMed1989

Pulse radiolytic measurement of redox potentials: the tyrosine and tryptophan radicals.

With the technique of pulse radiolysis we have measured the redox midpoint potentials of the tryptophan side chain neutral indolyl radical (1.05 +/- 0.01 V vs NHE, pH 7.0 and 25 degrees C) and the tyrosine side chain neutral phenoxy radical (0.94 +/- 0.01 vs NHE, pH 7.0 and 25 degrees C). These potentials were obtained by using a variety of inorganic reference compounds in both kinetic and equilibrium protocols. We compare these results with others already in the literature, and we also present data useful in establishing a pulse radiolysis redox reference scale over the range 0.42-1.28 V.

Free Radicals↗
PubMed1988

Electroconvulsive treatment compared with lithium in the management of manic states.

Thirty-four hospitalized manic patients were randomized to treatment with either lithium carbonate or an average series of nine bilateral electroconvulsive treatments (ECTs), followed by maintenance with lithium carbonate. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for eight weeks, and patients were followed up monthly for up to two years. Ratings by nonblind and blind observers indicated that the patients who underwent ECT improved more during the first eight weeks than did patients who were treated with lithium carbonate. This was especially true of patients with mixed symptoms of mania and depression and/or extreme manic behavior. Clinical ratings after eight weeks showed no significant differences between the lithium carbonate- and ECT-treated patients. Likewise, the two groups had comparable rates of relapse, recurrence, and rehospitalization during the follow-up period.

Adult↗
PubMed1986

Permeable membrane/mass spectrometric measurement of solvent 1H/2H, 12C/13C, and 16O/18O kinetic isotope effects associated with alpha-chymotrypsin deacylation: evidence for reaction mechanism plasticity.

We have measured, by permeable membrane/mass spectrometry, the 16O/18O, 12C/13C, and solvent H2O/D2O kinetic isotope effects (kie) associated with acyl-alpha-chymotrypsin hydrolysis and transesterification. The hydrolysis of alpha-chymotrypsinyl 2-furoate has a 12C/13C kie of approximately 1.06. Transesterification of the same acyl enzyme shows 16O/18O, 12C/13C, and solvent H2O/D2O kinetic isotope effects of 1.015 (0.003), 1.01-1.02, and 2.226 (0.007), respectively. From the temperature independence of the 16O/18O transesterification kinetic isotope effect and kinetic data reported elsewhere [Wang, C.-L. A., Calvo, K. C., & Klapper, M. H. (1981) Biochemistry 20, 1401-1408], we conclude that there are two active forms of acylchymotrypsin. We also propose that formation of the tetrahedral intermediate is the rate-limiting step in both hydrolysis and transesterification and that the position of the transition state in the transesterification is closer to the starting enzyme ester while that for the hydrolytic reaction is closer to the tetrahedral intermediate. These results are discussed in terms of reaction mechanism plasticity.

Acylation↗
PubMed1986

The methoxatin semiquinone: a pulse radiolysis study.

Methoxatin is a novel o-quinone found in bacterial dehydrogenases and mammalian plasma amine oxidase. This is the first report of the redox potential and spectrum of the 1-electron reduced methoxatin semiquinone obtained by the method of pulse radiolysis in aqueous solution.

Kinetics↗
PubMed1986

Methylamine dehydrogenase and cytochrome c552 from the bacterium W3A1.

We describe a two-step purification of the methoxatin-containing enzyme methylamine dehydrogenase from crude extracts of the bacterium W3A1, and a longer purification of cytochrome c552 from the same organism. Some of the kinetic properties of the dehydrogenase are presented, together with the demonstration that c552 is an electron acceptor for this enzyme. Cytochrome c552 is the only hemeprotein we observed in the visible spectrum of intact W3A1 cells that were grown under the same culture conditions used for the protein purifications. Addition of methylamine to whole cells causes an increase in the rate of O2 uptake together with an abrupt reduction of c552. We propose that, in vivo, the electrons from the amine reach the hemeprotein through the dehydrogenase.

Bacteria↗
PubMed1985

Intramolecular electron and proton transfer in proteins: CO2- reduction of riboflavin binding protein and ribonuclease A.

The formate radical (CO2-) reacts with ribonuclease A to form the cystine disulfide radical as one of the products. CO2- reacts with the riboflavin binding protein of chicken egg white with the ultimate product being the neutral flavin semiquinone. Formation of the disulfide radical in ribonuclease is slower than the reaction between protein and CO2-; formation of the flavin semiquinone in the riboflavin binding protein is slower than the protein-CO2- reaction. We conclude for both proteins that CO2- must reduce an as yet unidentified group or groups, which in turn reduce(s) the disulfide of RNase or the flavin of riboflavin binding protein. This conclusion is supported in the case of ribonuclease by the observation of a transient, broad absorption band centered between 350 and 370 nm. The CO2--initiated reductions of the disulfide in ribonuclease and the flavin in the riboflavin binding protein are mixed first- and second-order processes. We propose that the transfer of an electron from the unknown intermediate(s) to the final product involves both inter- and intramolecular paths between groups that may not be in van der Waals contact. With the hydrated electron, in contrast to CO2-, as reductant of the riboflavin binding protein, the anionic semiquinone is observed as an intermediate. The anionic semiquinone is then rapidly protonated, yielding the stable neutral semiquinone. From the reaction kinetics and protein concentration dependence, we conclude that a group or groups on the protein donate(s) a proton to the anionic semiquinone by both inter- and intramolecular paths.

Animals↗
PubMed1985

Steady-state carbon-13 nuclear magnetic resonance spectra of acyl-alpha-chymotrypsin.

When [13C]carbonyl-enriched p-nitrophenyl 5-n-propyl-2-furoate is incubated with alpha-chymotrypsin, a new peak appears in the 13C NMR spectrum. On the basis of its position and the fact that it is "chased" with unlabeled substrate, we conclude that this new signal is due to the acyl-enzyme intermediate. In spectra taken during steady-state turnover, the acyl-enzyme ester carbonyl 13C chemical shift displays a pH dependence that fits to a titration curve with an apparent pK of 7.1 (0.1). The apparent pK of the kcat vs. pH curve for enzyme-catalyzed hydrolysis of the same substrate under conditions differing only in reactant concentration is 7.0 (0.1). We have found no spectral evidence for a tetrahedral intermediate.

Carbon Isotopes↗
PubMed1985

Manic symptoms: an indication for bilateral ECT.

As a follow-up to pilot observations that six manic patients who failed to respond to unilateral electroconvulsive therapy (ECT) recovered rapidly when switched to bilateral treatment, a retrospective study was conducted. Twenty-five patients who responded after switchover from unilateral to bilateral ECT, 25 age- and sex-matched controls, and 25 concurrent controls who responded to right unilateral ECT alone were evaluated. Demographic variables and DSM-III diagnosis did not discriminate between the groups, nor were they different in terms of electroencephalographic (EEG) findings, neuropsychological test results, numbers of ECT, and duration of seizure discharges. Standard assessments of psychopathology performed by independent psychiatrists showed no differences in ratings of psychosis or depressive phenomena. However, scales assessing manic symptoms showed highly significant differences with many more features of unrestrained behavior, elevated mood, hurried speech, and other typical features of mania in the patients who were switched from unilateral to bilateral ECT. Although there were no differences in prescribed drugs, the use of prn medications for sleep was greater in the experimental-switched patients than in controls. Patients who responded to unilateral ECT alone exhibited virtually no manic features, whereas those who demonstrated these characteristics failed to respond to unilateral ECT but benefited when switched to bilateral treatment.

Adult↗