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M Reiter

Publications and source records attributed to M Reiter.

At least 73 records · Page 4Linked to original sources
PubMed1989

Labile disulfide bonds and free thiol groups in human IgG. IV. Use of the "sigma S" value for postoperative monitoring of gynaecological malignant tumors.

"sigma S" comprises both disulfide bonds reactive to dithionitrobenzoate, as well as free SH groups of serum immunoglobulin G. In 38 cases of invasive gynaecological tumors, the value of sigma S was ascertained to be 1.04 +/- 0.25 (mean +/- SD), which, in accordance with former results, differs significantly from the reference value of 1.51 +/- 0.36 (2 p less than 0.001). 14 days after surgery, at the latest, sigma S significantly increased to an average value of 1.33 +/- 0.26 (2p less than 0.001). This increase was apparently influenced by both the localisation, as well as by the completeness of removal of the tumors. Of 15 squamous cell carcinomas of the cervix uteri, 14 were radically removed and showed a highly significant postoperative increase in the sigma S value (2p less than 0.001). All of the 12 adenocarcinomas of the corpus uteri were totally removed and the sigma S increased significantly (2p = 0.05). Of 11 cystocarcinomas of the ovary, only 3 cases were completely operable. The remaining 8 cases had residual tumors with diameters greater than 5 cm. The postoperative increase in sigma S in these cases was not of statistical significance.

Adenocarcinoma↗
PubMed1989

Cough-cardiopulmonary resuscitation in the cardiac catheterization laboratory: hemodynamics during an episode of prolonged hypotensive ventricular tachycardia.

Cough-CPR, a deep rhythmic forceful cough repeated 30-60 times per minute, can be an effective resuscitative technique during emergencies occurring in the cardiac catheterization laboratory. We provide documented evidence on the potential of cough-CPR to maintain adequate systemic arterial blood pressure and consciousness during malignant ventricular arrhythmias, including the longest cough-CPR episode (75-90 sec), with continuous hemodynamics recorded. Results in three patients disclose that 1) mean arterial pressure during cough-CPR was 47-66% of nonarrhythmic baseline at a cough rate of 38-46% of normal sinus rhythm heart rate; 2) mean arterial pressure during hypotensive ventricular tachycardia was 17-60 mm Hg higher with than without cough-CPR; 3) at comparable diastolic pressures (33 vs. 31 mm Hg), systolic arterial pressure during cough-CPR was 40 mm Hg higher than basic CPR; and 4) consciousness can be maintained with cough-CPR during prolonged malignant ventricular arrhythmias. Thus cough-CPR can be a valuable adjunct in maintaining patient stability while definitive therapy for the malignant ventricular arrhythmia is administered.

Aged↗
PubMed1989

Isolation of human monoclonal antibody isoproteins by preparative isoelectric focusing in immobilized pH gradients.

A method for preparative isolation of human monoclonal antibody isoproteins is described in the present paper. A human monoclonal antibody directed against the transmembrane protein gp 41 from the human immunodeficiency virus (HIV-1) was used in this study. The antibody belongs to the IgG1 subtype and exhibits antibody dependent cellular cytotoxicity. The resolving power of conventional preparative protein separation techniques such as ion-exchange chromatography, chromatofocusing and lectin affinity chromatography is too poor for a complete separation of isoproteins. The more sophisticated technique of chromatofocusing on FPLC-based material (Mono P, Pharmacia) did not satisfy our expectation. With semipreparative IEF in immobilized pH gradients we were able to prepare the different isoproteins of a human monoclonal antibody in milligram amounts. No significant difference between the single isoproteins with respect to specificity and avidity to the recombinant antigen (rec gp 160) was detected. Therefore, we assume that the separation conditions did not influence the immunochemical nature of the antibody and significant denaturation and/or precipitation of the IgG did not occur. Furthermore the method affords preparative separation with resolution equivalent to analytical runs. Experiments for scale up and further characterization of isoproteins (carbohydrate composition, amino acid analysis, half life times etc.) are in progress.

Animals↗
PubMed1989

[Proof of a disulfide bridge accessible to disulfide exchange between the heavy chains of IgG].

The paper deals with the direct experimental proof that human immunoglobulin G1 (IgG1) contains a reactive disulfide bond that can be opened by 3,3'-dithiobis(6-nitrobenzoate) (DTNB) within 24 h by a SH-catalysed disulfide exchange reaction. These results were obtained with the purified IgG1 myeloma protein and confirm earlier indirect evidence based on correlation analysis of DTNB reactivity and quantitative IgG1 determination. The reactive disulfide bond is most likely the one between Cys235 of the heavy chains in the "hinge"-region, activated for the disulfide exchange by the protonated amino groups of Lys231 as turned out by analysis of IgG1. As with the whole molecule, one mol of reactive disulfide was found per mol of the Fc-fragment. 0.8 mol of labile S-S bonds was detected per mol of F(ab)2. After separation of the excess of reagent, the sedimentation pattern still corresponded with the dimer. The unaltered antigenic properties as well as the crystallizability speak against any severe conformational changes. Therefrom it was concluded that in approximately 80% of the F(ab)2 molecules one of the two inter heavy chain-bridges was opened. With the isolated F(ab)-fragment a reaction with DTNB was ascertained to an extent of 20%, which is probably due to an altered stability of the heavy-light chain-SS-bridge. However, no influence on the sedimentation pattern was observed. The intrachainar disulfide bonds of neither the heavy nor the light chain reacted with DTNB to a measurable extent.

Disulfides↗
PubMed1988

[Drug therapy of migraine].

Out of the knowledge of various headache syndromes the physician has to develop a clear diagnostical and therapeutical concept. This is especially true for migraine. Relevant pathophysiological hypotheses are presented e.g. the neurogenic-vascular model of migraine. Metoclopramide and domperidone in combination with mono-analgesics, ergotamine and nonsteroidal-antiinflammatory drugs are favoured in the treatment of the acute migraine attack. 2 to 4 mg ergotamine for the attack, respectively 16 to 20 mg per month should not be exceeded. Mixed compounds, containing ergots, analgesics, codeine, caffeine, tranquilizers and barbiturates should be avoided as these drugs may induce rebound-headache. A prophylaxis of migraine is indicated if a migraineur suffers from at least 2 attacks per month or if a migraine attack lasts longer than 4 days. In the first place, beta-blockers and flunarizine, in some cases verapamil or naproxen, should be used; the effect of dihydroergotamine is questionable. Because of its severe side effects, methysergide should only be given if all other prophylactic drugs fail. Naproxen is standard medication in the short time prophylaxis of menstrual migraine.

Adrenergic beta-Antagonists↗
PubMed1987

[Labile disulfide bonds and free thiol groups in human IgG. III. The "sigma S value" in gynecologic neoplasms].

The immunoglobulins G contain labile disulfide bonds which can easily be opened by dithionitrobenzoic acid in the subclass G1, and free SH groups in the subclass G2. The "sigma S value" is a photometrically determined quantitative measure of both groups added together. 57 cases of different gynaecological malignant tumours gave a mean sigma S value of 1.02 +/- 0.24 and 7 cases of stage 0 a sigma S of 1.05 +/- 0.25, whereas in 45 cases of benign diseases the sigma S was found to be 1.45 +/- 0,21. The difference between the values in the malignant and benign cases was highly significant (p less than 0.001). The sigma S in the benign cases lies within the normal range ascertained with healthy serum donors. These results are in accordance with results formerly obtained with malignant tumours in other locations. This leads us to the assumption that the shift in sigma S may be functionally and/or symptomatically associated with malignancy. The decrease in sigma S is interpreted in terms of a decrease in the percentage of subclass G1 in the total IgG.

Disulfides↗
PubMed1986

Labile disulfide bonds and free thiol groups in human IgG. I. Assignment to IgG1 and IgG2 subclasses.

The content of free SH groups (about 0.24) and labile S-S bonds (about 0.64) per mole human IgG can be differentially determined by the reaction with 5,5'-dithio(2,2'-dinitro)benzoate (DTNB) for 30 min and 24 h, respectively. Highly significant linear correlations were found between the number of labile S-S and the percentage of IgG1, and the number of free SH and the percentage of IgG2 of the total IgG fraction. It is concluded that the IgG1 molecule contains one S-S bond which is opened during the 24 h interaction with DTNB by a disulfide exchange reaction. This was also confirmed by the investigation of pure monomeric IgG1. The splitting of this bond does not alter molecular weight, antigenic properties or antigen binding activity, but reduces significantly the complement binding activity of IgG. On the other hand, one free SH group could be found in the IgG2 molecule. Changes have been observed in SH and S-S levels of total IgG in patients with various malignant diseases that are to be explained by corresponding changes of the percentages of IgG1 and IgG2.

Disulfides↗
PubMed1986

Labile disulfide bonds and free thiol groups in human IgG. II. Characteristic changes in malignant diseases corresponding to shifts of IgG1 and IgG2 subclasses.

As recently shown, the measurement of labile disulfide bonds and free thiol groups of human IgG using 5,5'-dithio(2,2'-dinitro)benzoic acid (DTNB) provides direct information about the relative concentrations of IgG1 and IgG2, respectively. Furthermore, using this technique data have been obtained that show a decrease in labile S-S (corresponding to IgG1) and increase of free SH (corresponding to IgG2) in IgG from patients afflicted with various malignant diseases. In the present study a total of 280 sera from patients with malignancies of various tissue origin was investigated. Significantly reduced sigma S values, i.e. the sum of free SH and labile S-S, were obtained with IgG from cases of carcinoma of the mammary gland, urinary bladder, skin and prostate, as compared to cases with benign diseases of the respective organs. Most pronounced differences were observed between benign and malignant disorders of the prostate. It was confirmed with this group of patients that the reduction of sigma S was due to the decrease of S-S bonds, whereas the number of free SH groups remained unchanged or was increased. The cases of mammary gland carcinoma were grouped according to clinical stage. A clear correlation between reduction of sigma S and tumor size was observed. The possible theoretical and clinical implications of these results are discussed.

Breast Neoplasms↗
PubMed1985

Diffusion-controlled receptor occupancy determines the rate of inotropic action of some cardioactive steroids.

In guinea-pig myocardium the rates of onset and offset of the inotropic effects of digitoxigenin-monodigitoxoside, digitoxin, ouabain, digoxin, digoxigenin, and dihydroouabain correlated negatively, and independently of the lipophilicity of the steroids, with their intropic and Na-K-ATPase inhibitory potencies. The intropic potency of ouabain was considerably higher than that of dihydroouabain whereas its inotropic effect developed much more slowly (T50 17 min v. 3 min). By contrast, the inhibition of sarcolemmal Na-K-ATPase by equieffective concentrations of these steroids appeared at similar rates within a few minutes. The homogeneity of the effects, as shown by parallel concentration-effect curves with similar order of potencies of the inotropic and the Na-K-ATPase inhibitory effects, excluded the different activation of inhomogeneous receptor populations. The correlation between the geometry of the papillary muscles and the rates of onset of the inotropic ouabain effect or tissue/medium ratios of 3H-ouabain indicated the relevance of diffusion. The discrepancy between the rates of action in sarcolemmal preparations and in papillary muscles could thus be related to the different diffusion distances. The apparently contradictory results in which receptor occupation (dependence of T50 on EC50) appeared as the rate-limiting step are explained by diffusion-controlled receptor occupancy: the reduced rate of diffusion due to an affinity-dependent reduction of the free drug concentration (receptor occupancy as a temporal 'site of loss') accounted for the slow onset of the inotropic effect of the highly potent cardioactive steroids.

Animals↗
PubMed1985

Potassium changes the relationship between receptor occupancy and the inotropic effect of cardiac glycosides in guinea-pig myocardium.

K+ (2.4-15.6 mmol l-1) antagonized the positive inotropic effect of dihydro-ouabain. The concentration-effect curves became steeper with the shift to higher concentrations of the glycoside. At 1.2 mmol l-1 Ca2+, an increase in K+ from 2.4 to 12 mmol l-1 required tenfold higher concentrations of dihydro-ouabain to produce equal inotropic effects. This factor was reduced to four at 3.2 mmol l-1 Ca2+. The same change in K+ concentration, at 1.2 mmol l-1 Ca2+, diminished the inotropic effect of ouabain on rested-state contractions by a factor of six. The positive inotropic effect of Ca2+ was also antagonized by K+ (1.2-12 mmol l-1). Reduction of Na+ from 140 to 70 mmol l-1 abolished the antagonistic action of K+ (1.2-8.0 mmol l-1). Moreover the inotropic effect of Ca2+ was enhanced. Reduction of Na+, from 140 to 70 mmol l-1, antagonized the positive inotropic effect of dihydro-ouabain more at low (2.4 mmol l-1) than at high (8.0 mmol l-1) K+. Accordingly, the extent of the dihydro-ouabain-K+ antagonism was reduced. When the K+ concentration was increased from 2.4 to 12 mmol l-1, [3H]-ouabain binding was reduced by a factor of three. This is less than the reduction in the inotropic effectiveness of ouabain or dihydro-ouabain. Reduction of stimulation frequency from 1 to 0.1215 Hz did not significantly alter the antagonistic effect of K+. Diminution of Vmax of the action potential was observed only at K+ concentrations greater than 5.9 mmol l-1, whereas the resting membrane potential was continuously depolarized over the entire range of K+ concentrations. The results support the view that the reduction in receptor affinity cannot be the sole cause of the antagonism between the glycoside and K+. Impairment of passive Na+ influx during diastole, due to the K+-dependent depolarization of the resting membrane potential, contributed to about one half of the glycoside-K+ antagonism.

Animals↗
PubMed1985

Family members as monitors in a state mental hospital.

In 1983 the cooperative efforts of the Western Massachusetts Alliance for Mentally Ill Citizens and the Massachusetts Department of Mental Health led to the development of a program in which family members of patients at Northampton State Hospital monitor conditions at the hospital. The authors describe the process that generated the program, the training and duties of the family monitors, the role of the hospital administration and staff in the monitoring process, and the program's outcomes. They believe that the program gives families a much-needed role in the care of mentally ill relatives and that the staff-family collaboration it fosters strengthens the power of advocacy.

Adult↗
PubMed1985

Relaxant effects on tracheal and ileal smooth muscles of the guinea pig.

The effects of volatile oils of 22 plants from 11 different families and of some of their constituents on tracheal and ileal smooth muscles were investigated. The results were compared with the relaxant effects of catecholamines and phosphodiesterase inhibitors. All of the oils had relaxant effects on the tracheal smooth muscle, the most potent were angelica root, clove, elecampane root, basil and balm leaves oil. 16 oils inhibited the phasic contractions of the ileal myenteric plexus-longitudinal muscle preparation, the most potent were elecampane root, clove, thyme, balm leaves and angelica root oil. 2 oils (anise and fennel) increased the phasic contractions, and 4 oils (bitter orange, caraway, mace, pepper) produced a marked increase in resting force (i.e. contracture). In regard to the relaxant effects, most of the 16 oils were more potent on the ileal than on the tracheal muscle. However, a small group of 4 oils (angelica root, clove, basil, black caraway) had a higher relaxant effect on the tracheal than on the ileal muscle. This was also found to be the case with eugenol, eugenol acetate and cinnamic aldehyde as well as with isoprenaline and phosphodiesterase inhibitors.

Animals↗
PubMed1984

UD-CG 115--a cardiotonic pyridazinone which elevates cyclic AMP and prolongs the action potential in guinea-pig papillary muscle.

The mechanism of the positive inotropic effect of a benzimidazole-pyridazinone, UD-CG 115, was analysed in the isolated guinea-pig papillary muscle contracting isometrically at a frequency of 0.2 Hz. UD-CG 115 produced a slowly developing and poorly reversible positive inotropic effect increasing with concentration (3-300 mumol/l). The effect amounted to 30 and 74% of the maximum inotropic effect of a standard, dihydroouabain, at 34 and 300 mumol/l, respectively. Low concentrations shortened and 300 mumol/l UD-CG 115 significantly prolonged the duration of contraction. The enhancement of the maximum rate of relaxation, S2, was intermediate between those produced by isoprenaline and dihydroouabain, respectively. UD-CG 115 prolonged the duration of the transmembrane action potential (90% repol .) by up to 22% at 300 mumol/l, whereas an equieffective concentration of isoprenaline did not consistently alter action potential duration. UD-CG 115 increased Vmax and overshoot, and prolonged the duration, of slow action potentials elicited at 24 mmol/l [K]0. The inotropic potency of UD-CG 115 was not significantly changed by reserpine pretreatment of the guinea pig or by the presence of 1 mumol/l(-)-propranolol, 3 mumol/l phentolamine or 10 mumol/l cimetidine. Neither was it reduced by 10 mumol/l TTX. The inotropic effect of 100 mumol/l UD-CG 115 remained unchanged when [K]0 was elevated from 3.2 to 12.0 mmol/l. A sarcolemmal preparation of guinea- pig ventricular Na,K-ATPase was only slightly inhibited by the highest concentration of UD-CG 115.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Excitation-contraction coupling in rested-state contractions of guinea-pig ventricular myocardium.

Different types of rested-state contractions were examined under the influence of various inotropic agents. In magnesium-free solution, in low sodium (40 mmol/l) solution or in the presence of dihydroouabain, an "early" rested-state contraction developed without delay after stimulation. A distinctive "late" rested-state contraction was observed under the influence of noradrenaline. It is characterized by a latent period of about 100 ms between stimulation and onset of contraction. This latency was not reduced by increasing the catecholamine concentration, despite a concentration-dependent increase in the height of the "late" rested-state contraction. The late rested-state contraction under the influence of noradrenaline was suppressed by the slow inward current inhibitor nifedipine whether or not the nifedipine-dependent shortening of the action potential duration was prevented by caesium. When the slow inward current was not inhibited, the prolongation of the action potential duration by caesium resulted in an increase of the late rested-state contraction because of a prolongation of the time to peak force. High concentrations of dihydroouabain led to the appearance of an early contraction component without appreciably influencing the noradrenaline-dependent late component. From this it was deduced that the activator calcium for the late rested-state contraction was not stored intracellularly during rest prior to stimulation and, consequently, could not have been released by inflowing calcium. Instead, it is proposed that the activator calcium for the late rested-state contraction entered the sites of the sarcoplasmic reticulum and subsequently released from its release sites as long as the cell was depolarized. The "early" rested-state contractions in Mg2+-free solution, in low sodium solution or in the presence of dihydroouabain were not influenced in their contraction velocity by high concentrations of nifedipine which fully inhibited the late rested-state contractions. Nifedipine caused only a slight reduction in peak force due to a shortening of the time to peak force as a result of a shortening in action potential duration. This indicates that the activator calcium for the "early" rested-state contractions had accumulated in the sarcoplasmic reticulum during rest prior to stimulation and that it was released immediately by depolarization without a participation of the slow inward current.

Action Potentials↗
PubMed1982

Free thiol groups and labile disulfide bonds in the IgG fraction of human serum.

The IgG fraction was isolated from freshly taken blood serum of health persons (male and female) by column chromatography on QAE-Sephadex. After 30 min incubation with DTNB (5,5'-dithio-(2,2'-dinitro)-benzoate) the average photometrically determined quantity of thio-anions was 0.24 +/- 0.02 SH/mole IgG. Since this result remained unchanged even after 24 h incubation with DTNB, interaction with masked thiol groups cannot be assumed. If, however, the serum was incubated with DTNB for 24 h and the IgG fraction then isolated and treated with thioglycolate, an average of 1.51 +/- 0.39 moles of thio-anions were liberated per mole of IgG. This indicates that on 24 h interaction with IgG, DTNB not only reacts with free SH groups, but also opens S-S bonds by a disulfide exchange reaction. The amount of thio-anions resulting from such opened disulfide bonds was calculated as the difference between 1.51 0.24, i.e., 0.64 S-S/mole IgG. This would be accounted for if approximately 54% of the IgG fraction is composed of a subfraction containing 1 labile disulfide bone per mole. The average of 1.51 thio-anions per mole IgG resulted from 130 single values with an essentially normal statistical distribution and standard deviation well within the usual biological range.

Chemical Fractionation↗