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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 307 records · Page 17Linked to original sources
PubMed1995

Modulation of ion currents and regulation of transmitter release in short-term synaptic plasticity: the rise and fall of the action potential.

Up and down-regulation of calcium and potassium conductances are associated with several forms of short-term synaptic modulation. Detailed investigation of synaptic plasticity in the marine gastropod Aplysia, and in other mollusks, indicates that synaptic transmission can be influenced in a number of ways by modulatory neurotransmitters acting through several second-messenger cascades. Modulation at the synapse itself occurs by means of the regulation of calcium current as well as through effects on processes directly involved in transmitter mobilization and exocytosis. Modulation of potassium current plays a major role in controlling neuronal excitability and may contribute to a lesser extent to the regulation of transmitter release through actions on the resting potential and on action potential configuration.

Action Potentials↗
PubMed1995

Undetectable luteinizing hormone levels using a monoclonal immunometric assay.

Previous studies have shown wide discrepancies among the results obtained with different immunometric assays. We present five cases (out of 4000 women) whose plasma luteinizing hormone was not detected using a LH immunometric assay (LH Stratus Baxter) but was recognized by other kits. These cases concerned one 28-year-old woman presenting with infertility and four postmenopausal women. The LH Amerlite kit gave detectable but low results. The results obtained with the other kits were > 7 IU/l. FSH levels were > 7 IU/l. In one case, sera were taken before and after the menopause; differences between the LH results increased. Discrepancies among LH assay kits have been attributed to variation both in standard curve calibration and in epitope specificity of the kit monoclonal antibodies. The Baxter kit might misrecognize some isoforms present in postmenopausal women. The present data illustrate the potential false results with such immunoassays in routine clinical laboratory testing. When undetectable LH results are not clinically explained or when disparities between LH and FSH are observed, we suggest using a second methodology or a bioassay if necessary. Improvement in LH assays and standardization might resolve the problem of discrepancies between the LH results.

Adult↗
PubMed1995

Use of P-wave-triggered, P-wave signal-averaged electrocardiogram to predict atrial fibrillation after coronary artery bypass surgery.

Atrial fibrillation occurs commonly after coronary artery bypass surgery. However, despite numerous attempts at prediction, no accurate and generally accepted method exists to predict its occurrence. P-wave-triggered P-wave signal averaging was performed on 54 patients before coronary artery bypass surgery to evaluate the utility of this method to predict atrial fibrillation after coronary artery bypass surgery. After excluding six patients with unevaluable P-wave signal averages and three patients with postoperative arrhythmias other than atrial fibrillation, the P-wave signal averages of 45 patients were analyzed. Sixteen patients had postoperative atrial fibrillation and 29 did not. The mean P-wave duration of the filtered, signal-averaged P wave was 163 +/- 19 msec in the 16 patients with atrial fibrillation and 144 +/- 16 msec in the 29 patients without (p < 0.005). Left atrial enlargement on the surface electrocardiogram (ECG) was the only other statistically significant variable that correlated weakly with the onset of postoperative atrial fibrillation (p = 0.04). Other clinical variables such as P-wave duration in ECG lead II, left ventricular hypertrophy on ECG, age, sex, hypertension, and left ventricular ejection fraction were not significantly different between the two groups. With a cut point of 155 msec, chi-squared analysis revealed a p value of < 0.005, yielding a sensitivity of 69%, a specificity of 79%, a positive predictive value of 65%, and a negative predictive value of 82%. Signal-averaging of the P wave in patients before coronary artery bypass surgery provides a good predictor of postoperative atrial fibrillation.

Aged↗
PubMed1995

[Gaucher's disease: current aspects].

Gaucher's disease is an autosomal recessive inherited disorder, characterized by genetic deficiency of lysosomial glucocerebrosidase. Its substrate (glycosylceramide) subsequently accumulates in cells of monocyte/macrophage origin, resulting in enlargement of the spleen and liver, skeletal lesions, and, in the most severe phenotypes, in neurological disorders. Thirty-six mutations have been at present documented in the gene encoding for the glucocerebrosidase, but four of them (N370S, L444P, 84GG and IVS2+1) are really frequent, particularly in ashkenaze population. Gaucher's disease is diagnosed by the presence of Gaucher cells, especially in bone marrow aspirate, and by assessing the glucocerebrosidase activity. The prognosis has been considerably improved by enzyme replacement therapy.

Gaucher Disease↗
PubMed1995

Hemodialysis urea rebound: the effect of increasing dialysis efficiency.

Urea rebound has been documented to occur after hemodialysis, but the magnitude and causes are not clearly defined. In this study we evaluated the effect of high-flux hemodialysis on urea rebound and Kt/V. Blood urea nitrogen samples were obtained before, immediately after, and 30 minutes after hemodialysis in 49 patients. Rebound was evaluated with respect to dialysis efficiency, dialysis treatment time, the occurrence of hypotension, and hematocrit. Urea rebound was significant and resulted in an overall decrease in Kt/V from 1.2 +/- 0.3 to 1.0 +/- 0.2 (P < 0.001). Of the 45 patients with a measured Kt/V of greater than 1.0, 40% had an actual delivered Kt/V of less than 1.0 once rebound was taken into account. Urea rebound correlated strongly with dialysis efficiency but not with hypotension, suggesting that rebound resulted primarily from delayed urea mass transfer across cell membranes. We conclude that increasing dialysis efficiency increases urea rebound and increases the error in Kt/V determinations from single pool urea kinetics.

Analysis of Variance↗
PubMed1995

HIV-1 recombinant poxvirus vaccine induces cross-protection against HIV-2 challenge in rhesus macaques.

Rhesus macaques were immunized with attenuated vaccinia or canarypox human immunodeficiency virus type 1 (HIV-1) recombinants and boosted with HIV-1 protein subunits formulated in alum. Following challenge with HIV-2SBL6669, three out of eight immunized macaques resisted infection for six months and another exhibited significantly delayed infection, whereas all three naive controls became infected. Immunizations elicited both humoral and cellular immune responses; however, no clear correlates of protection were discerned. Although more extensive studies are now called for, this first demonstration of cross-protection between HIV-1 and -2 suggests that viral variability may not be an insurmountable problem in the design of a global AIDS vaccine.

AIDS Vaccines↗
PubMed1995

[Histopathologic findings of the trophoblast and tubal wall after medicamentous therapy of tubal pregnancies].

The purpose of the study was to evaluate the effects of drug therapy on the throphoblast and on the tubal wall when protaglandin F2 alpha (PGF2 alpha) was administered in cases of tubal pregnancies. 42 patients were divided into two groups: women of group I (n = 30) were secondarily treated by surgery because of raising serum HCG levels. Group II (n = 12) consisted of patients who were operated on because of acute symptoms (abdominal pains, intraabdominal haemorrhage), despite already failing HCG values. In group I in 66% (n = 20) of the histological specimens an intact (vital) trophoblast was found. Five cases (17%) showed partly necrotic gestational tissue, whereas in another five cases (17%) the whole trophoblast was necrotic. In patients of group II all ectopic pregnancies showed histological signs of necrosis. In the histopathology of the Fallopian tubes no signs of trophic regression could be found. However, ten out of 22 cases showed ruptured tubal pregnancies. In this analysis we could show that the instillation of PGF2a electively destroys the ectopic trophoblast and does not exercise any necrotic action on the tubal wall.

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Impact of trophoblast penetration through the basal membrane on the efficacy of drug therapy in tubal pregnancies.

Concentrations of beta-human chorionic gonadotrophin (HCG) of 2500 IU/l are generally considered to be maximal for successful drug therapy of tubal pregnancies [instillation of prostaglandin-F2 alpha (PGF2 alpha) or hyperosmolar glucose]. The purpose of our study was to ascertain if there was an association between the significantly higher failure rates above this threshold value and the histologically determined anatomopathological substratum. We therefore evaluated the impact of trophoblast penetration through the basal membrane of the Fallopian tube on the efficacy of drug therapy. Pre-operative serum beta-HCG concentrations were compared with the histologically determined trophoblast penetration, distinguishing between ectopic pregnancies with intra-luminal growths up to the myosalpinx, and those with extra-luminal growths going beyond the basal membrane and penetrating the myosalpinx. Basic data were obtained from a group of patients who received primary surgical treatment but it had never been the intention for them to receive drug therapy (independently of their initial beta-HCG values; group I, n = 43). These reference data were compared with the findings in preparations from another group of patients obtained during secondary surgical intervention, performed to achieve final cure of tubal pregnancy after failure of primary PGF2 alpha instillation (group II, n = 30). Group I patients showed a significantly higher rate of intra-luminal trophoblast growths (P = 0.0001) at beta-HCG values < 2500 IU/l; above this threshold value, extra-lumina spread was found significantly more often (P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗
PubMed1995

Proliferative activity in ectopic trophoblastic tissue.

Clinical observations have shown that tubal pregnancies develop individually different biological activities such as different growth rates, levels of beta human chorionic gonadotrophin (beta-HCG), or rates of tubal wall destruction. In the present study, we evaluated the proliferative activity of ectopic cytotrophoblastic tissue using immunocytochemistry with antibodies to Ki-67 (clone MIB-1). The rates of proliferation obtained were related to the maternal serum beta-HCG values. Reference data were obtained from placentas of intact intrauterine pregnancies (group I, n = 14). The proliferative activity of this tissue was compared to that of cytotrophoblastic tissue of tubal pregnancies (group II, n = 27). Ki-67-immunostained as well as non-stained cytotrophoblastic nuclei of the villi and the trophoblastic columns were counted separately, and results were expressed as percentage of positive cells. Serum beta-HCG values were determined twice, 48 h and immediately before operation. The cytotrophoblastic cells of intact intrauterine pregnancies (group I) showed uniform and high proliferative activities (80% on average in villi, 84% on average in columns). The average Ki-67 proliferation rate was significantly lower (P < 0.001) in trophoblastic tissue of tubal pregnancies (group II; 42% on average in villi, 61% on average in columns). Within the group of tubal pregnancies, higher intragroup differences were observed. The number of Ki-67-labelled cells was independent of the absolute preoperative serum beta-HCG values in both groups, yet they were clearly related to the relative increase of beta-HCG in maternal serum. At higher proliferation rates, there was a significant, growing increase of beta-HCG values (P < 0.01). We have found immunohistochemical evidence to support the previous clinical speculations that tubal pregnancies develop more heterogeneously and more slowly than intact intrauterine pregnancies. The development of the beta-HCG concentrations may be taken as an indirect parameter, reflecting proliferative activity of the trophoblast.

Cell Division↗
PubMed1995

Multicenter trial of cefpodoxime proxetil vs. amoxicillin-clavulanate in acute lower respiratory tract infections in childhood. International Study Group.

Acute lower respiratory tract infections in children are a worldwide public health problem, with an estimated 4 million potentially preventable deaths every year. Until recently, penicillin and related drugs were the treatment of choice for empiric therapy of paediatric lower respiratory tract infections. However, concerns over the emergence of penicillin-resistant strains of Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis have led physicians to turn increasingly towards alternatives, such as the third generation cephalosporins. The oral extended spectrum cephalosporin cefpodoxime proxetil is highly active against the bacterial pathogens commonly associated with childhood lower respiratory tract infections. In order to evaluate its clinical efficacy in children with acute febrile lower respiratory tract infections, an international, multicenter, comparative, randomized open study was conducted in children ages 3 months to 11.5 years. Of 348 cases enrolled, 234 were randomized to cefpodoxime proxetil (8 mg/kg/day twice daily) and 114 to amoxicilin/clavanulate (amoxicillin 40 mg/kg/day 3 times a day). The duration of treatment was 10 days. Pretreatment diagnosis was pneumonia in 292 patients, bronchiolitis in 19 patients and acute bronchitis in 37 patients. Pathogens isolated from 59 cases included H. influenzae (47.5%), S. pneumoniae (23.7%), M. catarrhalis (11.9%) and Haemophilus parainfluenzae (6.8%). Clinical efficacy was evaluable in 278 children at the end of treatment when 95.2% of patients in the cefpodoxime proxetil group and 96.7% of patients in the amoxicillin/clavanulate group showed a satisfactory clinical response (cured or improved). The improvement was sustained at the follow-up visit, 10 to 20 days after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Immunogenicity of synthetic peptides of Haemophilus influenzae type b outer membrane protein P1.

To identify the B- and T-cell epitopes of P1 of Haemophilus influenzae type b, 13 peptides covering 90% of the protein were chemically synthesized. Mouse, guinea pig, and rabbit antisera raised against purified native P1 were tested for their reactivities against the peptides in peptide-specific enzyme-linked immunosorbent assays (ELISAs). Six immunodominant linear B-cell epitopes were mapped to residues 103 to 137, 189 to 218, 248 to 283, 307 to 331, 384 to 412, and 400 to 437 of the mature P1 protein. When P1 peptides were screened for their reactivities with three human convalescent-phase serum specimens, peptides corresponding to residues 39 to 64, 226 to 253, and 400 to 437 reacted strongly with the antisera. Four regions (residues 39 to 64, 226 to 253, 339 to 370, and 400 to 437) contained murine T-cell epitopes. Rabbit antipeptide antisera were tested for their reactivities with the immunizing peptides and P1 protein by ELISA and immunoblots. All anti-P1 peptide antisera except those raised against peptide HIBP1-8 (residues 279 to 312) or HIBP1-8-keyhole limpet hemocyanin conjugate were shown to be specific for their respective immunizing peptides by ELISA. In addition, rabbit antisera raised against the synthetic peptides corresponding to residues 1 to 29, 39 to 64, 103 to 137, 189 to 218, 226 to 253, 248 to 283, 307 to 331, and 400 to 437 of the mature P1 protein recognized the P1 protein from both typeable and nontypeable isolates. These results suggest that these peptides contain epitopes highly conserved among typeable and nontypeable strains of H. influenzae. However, none of the antipeptide antisera have bactericidal activity, nor were they protective against H. influenzae type b in the infant rat model of bacteremia.

Amino Acid Sequence↗
PubMed1995

Requirement of N-terminal amino acid residues of gp41 for human immunodeficiency virus type 1-mediated cell fusion.

An expression vector was designed to test the structural requirements of the gp41 N terminus for human immunodeficiency virus type 1-induced membrane fusion. Mutations in the region coding for the N terminus of gp41 were found to disrupt glycoprotein expression because of deleterious effects on the Rev-responsive element (RRE). Insertion of an additional RRE in the 3'-noncoding sequence of env made possible efficient glycoprotein expression, irrespective of the mutations introduced into the RRE in the natural location. This permitted the insertion of the unique restriction site SpeI within the N-terminal sequences of gp41, allowing convenient and efficient mutation of the gp41 N terminus by using double-stranded synthetic oligonucleotides. Mutants with deletions of 1 to 7 amino acids of the N terminus were constructed. Expression and cleavage of all mutants were confirmed by Western immunoblot analysis with anti-gp41 antibodies. The capability of mutants to induce membrane fusion was monitored following transfection of HeLa-T4+ cell lines with wild-type and mutant expression vectors by electroporation and microinjection. The efficiency of cell-fusing activity decreased drastically with deletion of 3 and 4 amino acids and was completely lost with deletion of 5 amino acids. Cotransfection of the parent and mutant expression vectors resulted in reduced cell-fusing activity. The extent of this dominant interference by mutant glycoprotein paralleled the decrease in cell-fusing activity of the mutants alone. This suggests the existence of a specific N-terminal structure required for fusing activity. However, there does not appear to be a stringent requirement for the precise length of the N terminus. This finding is supported by the length variation of this region among natural human immunodeficiency virus type 1 isolates and is in contrast to the apparent stringency in the length of analogous N-terminal structures of influenza A virus and paramyxovirus fusion glycoproteins.

Amino Acid Sequence↗
PubMed1995

Alterations in the visual cortex receptor pattern by operant conditioning in a reward paradigm.

The aim of the study was to investigate the impact of operant conditioning on the receptor pattern in the visual cortex of calves. A reward paradigm was used to induce conditioned preference for colours. Binding sites in visual cortex specimens from conditioned and naive animals were assayed in vitro on cellular basis after dissociation of the tissue by collagenase, incubation with fluorescent ligands and flow-cytometry for fluorescence analysis. The cellular counts were subdivided according to sedimentation at 200 g as well as via the flow-cytometrical histogram by size and granularity. Binding sites of dopamine D1 and D2 receptor subtypes, glucocorticoids, opioids, casein as well as glycine and N-methyl-D-aspartic acid (NMDA) were detected by fluorescent molecular probes. In displacing naloxone fluorescein from NMDA- and mu-opioid receptors NMDA and meth-enkephalin were used. Comparisons between portions of fluorescent cellular counts from visual cortex tissue of conditioned and naive animals revealed a small increase (1.2-fold, P < 0.05) in opioid receptors of large and high granulated counts, bearing > 80% D1 receptors, and a decrease (0.70-fold, P < 0.05) in less granulated counts with variable portion of D1 receptors. Conditioning resulted in higher and lower displacing rates by meth-enkephalin and NMDA, resp., and in a reduce in counts with dopamine D1 (0.8-fold, P < 0.05), glycine and glucocorticoid binding sites (0.6-fold in both cases, P < 0.01). A tendency of elevated phagocyte marker expression occurred in high granulated counts. The data suggest that conditioning is accompanied with significant and in part marked change in binding sites studied. Induction of scavenger activity may parallel this process. As cellular portion with glycine and glucocorticoid receptors were most markedly altered by conditioning, the neurochemical needs of the used paradigm seem to focus to motility-related functions.

Animals↗
PubMed1995

[Physiological role of PTHrP].

Parathyroid hormone related protein (PTHrP) is the aetiological factor for the syndrome of humoral hypercalcemia of malignancy. The PTHrP gene encodes three isoforms of respectively 139, 141 and 173 amino acids with N-terminal homology to parathormone (PTH). PTHrP, which has a wide tissue distribution, appears to be a polyhormone with different physiologic functions that depend on the particular fragment secreted. PTHrP may act in an autocrine, a paracrine or an endocrine fashion. There is evidence for a role in the growth and development of both embryonic and mature tissues, in cellular differentiation, in smooth muscle relaxation, lactation and calcium and magnesium transport. The best known PTHrP functions are those mediated by the N-terminal domain fixation on the classical PTH/PTHrP receptor. Nevertheless, several other functions are mediated by different fragments of PTHrP such as midregion fragments or carboxy-terminal forms. Each of these functional forms of PTHrP has one or several physiological function(s) which is (are) mediated by his own specific receptors and signal transduction pathways, some of which may be tissue specific.

Animals↗
PubMed1995

[Heart and thyroid].

Thyroid hormones may exert cardiovascular actions by direct effects on the myocardium, by interacting with the sympathetic nervous system and through alterations of the peripheral circulation. Then, thyroid hormones increase myocardial contractility and relaxation, sensitise the myocardium to sympathetic nervous system and decrease arterial resistance. Hyperthyroidism results in an enhanced myocardial contractility, an increased cardiac output and a fall in systemic vascular resistance. Nevertheless "high output" cardiac decompensation may occur. Thyrotoxicosis may trigger arrythmia and disease seems to be associated with an increase in the frequency of mitral valve prolapse. Even in mild or subclinical hyperthyroidism complication may occur. Sympathetic blocking agents are the treatment of choice in addition to aetiologic treatment. Hypothyroidism is associated with bradycardia, a decreased cardiac output, increased vascular resistance and perhaps a decreased sensitivity of the sympathoadrenal system. An increase in cholesterolemia leads to an additional risk for the development of atherosclerosis. Main cardiovascular complications of hypothyroidism are angina pectoris, diastolic hypertension, atrio-ventricular blocks or pericarditis. Mild hypothyroidism might also be correlated with an increase in adverse effects.

Cardiovascular Diseases↗
PubMed1995

The use of a particulate, microporous, calcified copolymer as a ridge maintenance device in dogs.

HTR polymer Synthetic Bone was found to be an osteoconductive, biocompatible, reliable nonresorbable matrix ridge maintenance material (Ridge Preservation). When used as socket implants immediately after the extraction of teeth over a one-year period in 16 beagle dogs, HTR was observed clinically and radiographically and compared with controls (unimplanted, sutured) extraction sites. As the control areas resorbed, the stability and effectiveness of the synthetic bone material in the operative sites became more clearly delineated. Quantitative analyses could not be made using radiographic techniques, but radiographs supported by subjective clinical observations as well as study casts taken of the height and width of the implanted areas, showed greater ridge retention compared with controls. Histological sections demonstrated dense laminar bone gradually forming into and around the HTR particulate material.

Alveolar Bone Loss↗