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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 415 records · Page 23Linked to original sources
PubMed1992

Overexpression and structure--function analysis of a bioengineered IL-2/IL-6 chimeric lymphokine.

A synthetic chimeric IL-2/IL-6 gene was synthesized to engineer a bifunctional lymphokine which was overproduced in Escherichia coli. Following denaturation of the inclusion bodies in 6 M guanidine and refolding and reoxidation in the presence of a redox system, the fusion protein (rIL-2/IL-6) was purified to homogeneity and shown to react with both monospecific anti-IL-2 and anti-IL-6 antisera. A collagen-like spacer was introduced between the two cytokine moieties to generate IL-2 and IL-6 molecules upon collagenase digestion. After cleavage, the two subunits, purified in a single-step procedure, were found to be correctly reoxidized and functionally as active as their native counterparts. Circular dichroism studies of rIL-2/IL-6 revealed that both cytokine subunits refolded independently and exhibited the alpha-helical structures characteristic of the corresponding wild-type lymphokines. The chimera displayed full IL-2 activity in the CTLL-2 cell proliferation assay. It also retained the IL-6 property to enhance IgM synthesis in SKW6.4 cells, induce the proliferation of B-cell hybridomas and stimulate the production of fibrinogen in hepatocytes. Because IL-2 amplifies the cellular immune response and IL-6 up-regulates the humoral response, this bifunctional lymphokine represents a potentially useful therapeutic adduct and may serve as an immunomodulator to enhance the host's response to vaccination.

Amino Acid Sequence↗
PubMed1992

Identification of T- and B-cell epitopes of the S2 and S3 subunits of pertussis toxin by use of synthetic peptides.

To design an optimized synthetic vaccine against whooping cough, we have studied the biological and immunological properties of three peptides of the S2 subunit and nine overlapping synthetic peptides covering the entire sequence of the S3 subunit of pertussis toxin (PT). Synthetic peptides corresponding to sequences 18 to 41, 78 to 108, 134 to 154, and 149 to 176 of S3 were found to be consistently capable of stimulating the proliferation of PT-specific T-cell lines primed with pertussis toxoid in both BALB/c and A/J strains of mice. All synthetic peptides were recognized by rabbit antisera raised against PT or pertussis toxoid. Both S2 and S3 peptide-keyhole limpet hemocyanin (KLH) conjugates in the presence of complete Freund's adjuvant induced peptide-specific antibody responses in rabbits, and the antisera raised against S2(1-23), S3(18-41), S3(37-64), and S3(149-176) peptide-KLH conjugates cross-reacted with both subunits in the immunoblots. All antisera except those against S2(123-154) and S3(103-127) reacted with native PT in an enzyme-linked immunosorbent assay (ELISA) with PT directly coated onto microtiter wells. In contrast, antisera raised against S2(123-154), S3(1-23), S3(18-41), S3(37-64), S3(60-87), and S3(103-127) peptide-KLH conjugates recognized native PT in a fetuin-PT capture ELISA. S2(78-98), S3(1-23), and S3(149-176) peptide-KLH conjugates elicited good PT-neutralizing antibody responses as judged by the antitoxin CHO cell assay. Identification of these B-cell neutralization epitopes and T-cell immunodominant determinants represents a first step towards the rational design of a synthetic vaccine against whooping cough.

Amino Acid Sequence↗
PubMed1992

Influence of valve surgery on female fertility.

Pregnancies following cardiac valve surgery represent a considerable maternal and fetal risk. The present paper is a report of 163 women in child-bearing age who underwent cardiac valve surgery. Congenital (14.7%) and acquired (85.3%) cardiac defects required a total of 72 alloplastic and 16 bioprosthetic valve implantations. In 69 patients, purely instrumental correction was performed, in 6 patients conduits were placed. Thirty-four pregnancies were observed and led to the delivery of 18 healthy infants. The birth weight was always in the 2-sigma normal range or slightly above. Three cesarean sections were performed due to the cardiac defect, in 6 patients vacuum extraction or forceps delivery was done, and in 9 patients delivery was spontaneous. We observed 4 cases of spontaneous abortion, and in 12 cases interruption of pregnancy. 75.1% women never became pregnant. Potential risks in terms of endocarditis, repeated valve implantation and anticoagulation are emphasized, methods to decrease the physical strain during delivery are discussed.

Bioprosthesis↗
PubMed1992

Energetic metabolism in hypothyroid skeletal muscle, as studied by phosphorus magnetic resonance spectroscopy.

Phosphorus nuclear magnetic resonance spectroscopy was used to investigate the muscle bioenergetics in different hypothyroid states. Using the thenar muscle group as reference, 2 patients with chronic and severe hormonal deficiency, 3 patients with subacute hypothyroidism, and 8 patients with moderate thyroid insufficiency with isolated high blood TSH levels were studied at rest, during exercise, and during subsequent recovery. The patients were compared with 15 control subjects. Only 1 patient presented a clinical myopathy. The intracellular pH and the relative measurements of inorganic phosphate, phosphocreatine, phosphodiesters, and ATP were directly calculated from phosphorus spectra. Resting muscle showed a significant rise in the inorganic phosphate to ATP ratio. In working hypothyroid muscle, a more important decrease in phosphocreatine levels was noted in patients with chronic and subacute thyroid deficiency, while the intracellular pH fall was greater in all hypothyroid patients than in control subjects. The phosphocreatine recovery rate was lower in all deficient patients, reflecting a probable mitochondrial metabolism impairment. These results are consistent with a defect of the high energy phosphate metabolism in hypothyroidism, even in moderate or recent hormonal deficiency.

Adenosine Triphosphate↗
PubMed1992

High-affinity dextromethorphan and (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine binding sites in rat brain. Allosteric effects of ropizine.

Dextromethorphan (DM) binds to high- and low-affinity sites in the rat brain. The high-affinity DM binding is inhibited by nonnarcotic antitussives, opipramol and sigma ligands with nanomolar affinities. Computer-assisted modeling of homologous and heterologous competition studies between DM and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP] were performed at pH 8.4. These experiments confirmed the existence of the common high-affinity DM1/sigma 1 site (R1) for which DM and (+)-3-PPP have Kd values of 20 and 10 nM, respectively. DM also binds to a second high-affinity site (R2, Kd, 20 nM) for which (+)-3-PPP has only micromolar affinity. Similarly, (+)-3-PPP binds to another high-affinity site (R3, Kd, 60 nM) for which DM has micromolar affinity. The common high-affinity DM1/sigma 1 site is allosterically modulated by the anticonvulsant ropizine, and is (+)-pentazocine sensitive, as is the homologous site in the guinea pig. However, in the rat the common DM1/sigma 1 site is 10 times smaller than in the guinea pig. This explains the apparently different effects of the allosteric modifiers in both species. The multiplicity of binding sites for DM and (+)-3-PPP resolved in this investigation will help to establish the physiological role and the pharmacological potential of the different sites. Meanwhile, the pharmacological effects of DM and sigma ligands cannot be summarily attributed to any particular binding site or receptor. This investigation also demonstrates that the use of multiple labeled and unlabeled ligands, combined with computer-assisted modeling, is essential to resolve multiple binding sites with similar affinities and to characterize the complex effects of allosteric modifiers.

Allosteric Regulation↗
PubMed1992

[Hypothyroid myopathy. Physiopathological approach].

Patients with thyroid deficiency often complain of muscular weakness, exercise intolerance, cramps and excessive fatiguability. Hypothyroidism induces a metabolic myopathy, with a fall of the energetic production, and especially of the mitochondrial metabolism. This is due to a global inhibition of the main oxidative pathways (substrate incorporation, substrate oxidation) and of the respiratory chain. A diminished energetic consumption is partially related to a transition in the myosin isoforms, which express a slower ATPase, and to an impairment of the trans-sarcolemic transports. Exercise intolerance could be due to an abnormal recruitment of several metabolic pathways, such as glycolysis, related to the mitochondrial metabolism impairment, and including an abnormal accumulation of protons and monovalent phosphate ions, which are involved in the alteration of the actin-myosin interaction, and also by an abnormal Ca++ metabolism. The decreased number of NA+/K+ ATPase dependent pumps could imply an abnormal intracellular Na+ level and explain the frequent disorders of the membrane excitability.

Energy Metabolism↗
PubMed1992

[Magnetic resonance imaging in lupic chorea].

A case of disseminated lupus erythematosus with chorea is reported. CT was normal. Magnetic resonance imaging showed multiple focal lesions on T2-weighted sequences, predominating in the periventricular white matter. This MRI pattern did not change in a second MRI investigation, 7 months later. The contribution of MRI to our understanding of the neurolupus pathophysiology is discussed.

Adolescent↗
PubMed1992

[Traumatic tricuspid insufficiency with a right-to-left shunt and heart luxation].

Traumatic tricuspid insufficiency (TTI) with a right-to-left shunt through a patent foramen ovale associated with a cardiac herniation was identified in a 39-year-old man with severe hypoxemia. All reported cases of TTI with a right-to-left shunt are reviewed, the technical aspects of repair described and the physiologic mechanisms discussed.

Adult↗
PubMed1992

Examinations of the relative fluidity in cerebrovascular disease patients.

Parallel with the increasing incidence of cerebrovascular diseases, and the limitations of possible surgical methods, the importance of drug therapy has significantly increased. Due to our knowledge of haemorheology the effectiveness of therapies may be measured by means of useful circulatory markers. In course of our research activities of one and a half decades the changes in blood viscosity were measured during vinpocetine therapy, and were compared to the changes of haematocrit and mean corpuscular volume (MCV) values. The effect of vinpocetine and secale alkaloids or vinpocetine and pentoxifylline were compared by sequential analysis in other cases. The results of these examinations proved that vinpocetine is effective in both short and long-term therapy.

Adult↗
PubMed1992

[Heart-skin syndrome and cardiac myxoma: presentation of a case and clinical experience of 17 years].

Between 1971 and 1988, cardiac myxoma was identified in 13 (0.003%) of 4000 patients who underwent open-heart surgery at the hôpital du Sacré-Coeur in Montreal. One patient with multiple right atrial tumours also had abnormal cutaneous pigmentation compatible with the recently identified syndrome of "Carney's complex." This syndrome has also been associated with endocrine abnormalities such as primary nodular adrenal hyperplasia, with or without Cushing's syndrome. The authors review the literature and compare the findings with their experience in the surgical treatment of cardiac myxomas.

Adult↗