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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 433 records · Page 24Linked to original sources
PubMed1991

Activation of neurohumoral systems following acute myocardial infarction.

Previous studies have indicated that patients with an acute myocardial infarction have marked activation of all neurohumoral systems on admission to the hospital. This activation begins to subside within the first 72 hours so that by 7-10 days, all plasma neurohormones have returned to normal. The only documented exceptions were found to occur in patients with left ventricular dysfunction and overt heart failure, where both plasma renin activity and atrial natriuretic peptide were increased, and in patients with left ventricular dysfunction but no overt heart failure, where only atrial natriuretic peptide was increased. Although these studies suggest that neurohumoral activation rarely occurs at the time of hospital discharge, they were small and may have missed an important subgroup of patients with persistent neurohumoral activation. In the Survival and Ventricular Enlargement (SAVE) study, 522 patients had plasma neurohumoral levels measured at a mean of 12 days postinfarction. All SAVE patients had left ventricular dysfunction (left ventricular ejection fraction less than or equal to 40%), but no overt heart failure. In this group of patients, all neurohumoral levels (plasma renin activity, norepinephrine, arginine vasopressin, and atrial natriuretic peptide) were found to be increased compared with age-matched control subjects. These results indicate that, in fact, a subgroup of patients without overt heart failure has persistent neurohumoral activation at the time of hospital discharge postinfarction, and that this activation involves several neurohumoral systems. Since patients with persistent neurohumoral activation postinfarction are likely those most at risk of developing complications and the ones most likely to benefit from pharmacologic interventions blunting the effects of neurohumoral activation, measurement of predischarge neurohumoral levels may be useful.

Humans↗
PubMed1991

Acute respiratory infections as an important cause of childhood deaths in South Africa.

Compared with other major preventable childhood diseases, such as diarrhoea, acute respiratory infections (ARI) have received comparatively little attention as an important cause of death in children. In this study of mortality from ARI in South Africa, national data was examined for the period 1968-1985, and data for Greater Cape Town for 1987. Almost 90% of ARI deaths were attributable to pneumonia and large inter-group differences were found that favoured whites and Asians over blacks and coloureds. For example, during 1980-1985 the mortality rate for pneumonia in coloured infants under 1 year of age was 11 times that observed in whites (88 v. 981/100,000). Pneumonia accounted for 14.5% of coloured and 12.7% of black deaths under 1 year of age during this period, compared with 6.7% of white and Asian deaths. The mortality rates from pneumonia declined substantially (50%) over the 18-year period in whites, coloureds and Asians. Sequential data for blacks is not available. There was a marked seasonality of deaths among coloured and Asian infants, with rates peaking in winter months. In Cape Town, pneumonia is now a more important cause of death among white and coloured children than diarrhoea, while it ranks with diarrhoea as a cause of death in black children. In all population groups, death rates from ARI are from 7 times to 270 times greater than those recorded in Western European countries. Studies are urgently required to discover why South African children suffer such a high mortality from ARI and how these deaths can be prevented.

Acute Disease↗
PubMed1991

Identification of a gene fragment which codes for the 364 amino-terminal amino acid residues of a SecA homologue from Bacillus subtilis: further evidence for the conservation of the protein export apparatus in gram-positive and gram-negative bacteria.

A DNA fragment that codes for the 364 amino-terminal amino acid residues of a putative Bacillus subtilis SecA homologue has been cloned using the Escherichia coli secA gene as a probe. The deduced amino acid sequence showed 58% identity to the amino-terminus of the E. coli SecA protein. A DNA fragment which codes for 275 amino-terminal amino acid residues of the B. subtilis SecA homologue was expressed in E. coli and the corresponding gene product was shown to be recognized by anti-E. coli SecA antibodies. This polypeptide, although only about 30% the size of the E. coli SecA protein, also restored growth of E. coli MM52 (secAts) at the non-permissive temperature and the translocation defect of proOmpA in this mutant was relieved to a substantial extent.

Adenosine Triphosphatases↗
PubMed1991

SKF 525-A and cytochrome P-450 ligands inhibit with high affinity the binding of [3H]dextromethorphan and sigma ligands to guinea pig brain.

The DM1/sigma 1 site binds dextromethorphan (DM) and sigma receptor ligands. The broad binding specificity of this site and its peculiar subcellular distribution prompted us to explore the possibility that this site is a member of the cytochrome P-450 superfamily of enzymes. We tested the effects of the liver microsomal monooxygenase inhibitor SKF 525-A (Proadifen), and other P-450 substrates on the binding of [3H]dextromethorphan, [3H]3-(-3-Hydroxyphenyl)-N-(1-propyl)piperidine and (+)-[3H]1,3-Di-o-tolyl-guanidine ([3H]DTG) to the guinea pig brain. SKF 525-A, l-lobeline and GBR-12909 inhibited the binding of the three labeled ligands with nM affinity. Each drug has identical nM Ki values for the high-affinity site labeled by the three ligands. This indicated that they displaced the labeled ligands from the common DM1/sigma 1 site. Debrisoquine and sparteine, prototypical substrates for liver debrisoquine 4-hydroxylase, displayed Ki values of 9-13 and 3-4 microM respectively against the three labeled ligands. These results, the broad specificity of the DM1/sigma 1 binding site, and its peculiar subcellular distribution, raises the possibility that this binding site is a member of the cytochrome P-450 superfamily of isozymes, rather than a neurotransmitter receptor. These findings may have important implications for the understanding of the therapeutic, side effects and toxicity of several neurotropic drugs.

Animals↗
PubMed1991

Structural and functional analysis of the S1 subunit of pertussis toxin using synthetic peptides.

Pertussis toxin (PT) is a major virulence factor of Bordetella pertussis, and also an important protective antigen. PT is an oligomeric A-B type toxin in which the S1 subunit has the ADP-ribosyltransferase activity whereas the B-oligomer mediates its binding to target cell receptors. To analyze the immunological properties of S1 and to generate probes to localize and characterize S1 functional domains, we synthesized four sets of peptides and peptide analogs corresponding to potentially critical regions of the S1 subunit. Two peptide-KLH conjugates were found to be capable of inducing PT-neutralizing antibodies in rabbits as judged by the CHO cell clustering assay. These peptides comprise residues 1-18 (N18-S1) and 121-138 (NAD-S1), respectively. Immunization with the unconjugated C-terminal peptide C35-S1 (residues 201-235) in the presence of Freund's adjuvant also elicited PT-neutralizing antibodies, indicating that the C-terminal region of S1 contains a potent functional T-helper cell epitope. Using truncated peptide analogs of N18-S1, we have demonstrated that the first three N-terminal residues are essential for inducing neutralizing antibodies. The NAD-S1 peptide elicited a neutralizing antibody response when coupled to KLH via its N-terminal end but not via its C-terminal residue. Identification of these B-cell neutralization epitopes represents a first step towards the rational design of a synthetic vaccine against whooping cough.

Amino Acid Sequence↗
PubMed1991

Evaluation of the immunogenicity and protective efficacy of a candidate parainfluenza virus type 3 subunit vaccine in cotton rats.

A parainfluenza virus type 3 (PIV3) subunit vaccine consisting of detergent-solubilized, affinity-purified haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins was tested in cotton rats for immunogenicity, short-term effects on virus-induced immunopathology and protective efficacy. Groups of animals were immunized twice, 4 weeks apart, with graded doses of vaccine administered either alone or with aluminium phosphate (AlPO4). The minimum immunogenic dose of vaccine was 0.1 microgram HN and F when the vaccine was given alone and 0.01 microgram when the vaccine was administered with AlPO4 adjuvant. Antibody responses in animals immunized with 1 microgram HN and F mixed with adjuvant were similar to those in control animals infected with live PIV3 intranasally. Pulmonary and nasal wash PIV3 titres generally were inversely correlated with serum antibody levels. Virus titres were significantly reduced in all groups of animals immunized with greater than or equal to 0.1 microgram HN and F compared with control animals immunized with vehicle only. Four days after virus challenge, there was no evidence of enhanced histopathology in lung sections from animals immunized with the candidate vaccine.

Adjuvants, Immunologic↗
PubMed1991

[PAP IV in pregnancy--a retrospective multicenter study].

An analysis was made of the procedure when PAP IV occurs in pregnancy. 63 patients between 1. 1. 1985 and 1. 4. 1990 from 6 main hospitals in Vienna were included in this study. In 30 cases, a cone biopsy was made during pregnancy, whilst in 33 cases, the operation was performed after delivery. In both groups, the tissue showed in the histological examination nearly the same incidence rate of carcinoma stage Ia, carcinoma in situ as well as mild, moderately severe, and severe dysplasia. A significant frequency was found for a delivery before the 35th week of gestation, if conisation was done during pregnancy. An increased negative foetal outcome was also found if the operation was performed after the 16th week of gestation. Conservative procedure showed a better foetal outcome with the same security, in that carcinoma stage Ib was never overlooked. On-target biopsy under colposcopic control, combined with a conisation 8 to 10 weeks after delivery, is therefore recommended.

Adolescent↗
PubMed1991

[Implantation of a cardiac pacemaker in the 25th week of pregnancy in acquired 3d degree AV-block].

It is well documented, that bradycardiac electrical heart activity disturbances occur very rarely in women of reproductive age. Therapy is in fact redundant in congenital AV-block. However, acquired AV-block in pregnancy constitutes a risk for both mother and child. In the following case, we report on an acquired third-degree AV-block, which worsened during the pregnancy from N.Y.H.A stage I to stage III, and hence required the implantation of a pacemaker during pregnancy.

Adult↗
PubMed1991

[Significance of surgically corrected heart valve diseases on fertility].

We report on 111 patients, who were operated for heart valve failure. The influence of the operation on fertility was examined. Only 24 women became pregnant. From 34 pregnancies, 4 resulted in early abortion; in 12 cases abortion was performed (8 times for medical reasons), therefore 18 children were born. The remaining 87 operated patients (78.4%) never became pregnant, although only 29 patients were advised against pregnancy. 27 patients decided on various contraceptive methods by themselves.

Abortion, Induced↗
PubMed1991

[The diagnostic potential of amniocentesis in the first 12 weeks of pregnancy].

Prenatal diagnosis of chromosomal and biochemical defects is accepted as a routine in high-risk patients. To eliminate the disadvantages of traditional amniocentesis (late diagnosis) and of chorion villus sampling (placentar mosaics, higher fetal loss rate) we evaluated the facts on amniocentesis during the first 12 weeks of pregnancy. 42 samples were analysed. 21 amniotic fluid samples were from pregnancies before the 13th week of gestation, 21 further punctures were performed between the 13th to 15th week and served as comparative figures. Of 21 samples, diagnosis was possible in 16 cases. Four cultures did not show any growth of cells; in one case, amniotic fluid could not be aspirated. In the comparison group chromosomal diagnosis could be done in every case. An average of 12.3 ml of amniotic fluid were taken. Chromosomal disorders found, included a translocation in chromosome 13/14 as well as a trisomy of chromosome 18. Biochemical defects such as Gaucher's disease and Niemann-Pick disease were excluded. 30 pregnancies without pathological symptoms were seen (mean birth weight 3200 g, mean duration of pregnancy 39 weeks). One case of abortion following amniocentesis was found in the 16th week of gestation. One case of premature delivery occurred in the 34th week and the pregnancy of a 40-year old women was complicated by EPH gestosis while 9 pregnancies were terminated by interruption following the patients' wish. Because chromosomal diagnosis could not be performed in five of 21 cases, amniocentesis during the 13th week of gestation cannot be recommended as a routine method. Early amniocentesis, however, is an alternative to the traditional amniocentesis at the 16th week of gestation.

Abortion, Spontaneous↗
PubMed1991

[Conization in pregnancy and its significance for the further course of pregnancy].

The influence of cold knife conisation on further progression of pregnancy was analysed in 28 patients, who underwent the operation during pregnancy. 13 women were operated on within the first 16 weeks of gestation (group I) and were compared to 15 patients, where conisation was done in the 17th week or later (group II). In the first group, deliveries were found in the 39th week of pregnancy compared to 34 weeks in the second group (p.05). A statistical significant difference concerning the further duration of pregnancy after conisation was found: 25 weeks in group I vs. 11 weeks in group II (p. 0012). There was no difference, however, in radicality whether conisation was done in early or late pregnancy. Our final conclusion is, that a preterm delivery occurs significantly more often in women who underwent conisation after 16th week of gestation.

Abortion, Spontaneous↗
PubMed1991

[Energy metabolism of growing rats in relation to the environmental temperature].

8 experiments were carried out with 9 albino rats each (Wistar line, bred at the institute) in the live weight range between 70 and 200 g and at environmental temperatures (ET) of 34, 32, 30, 28, 26, 24, 22 and 20 degrees C. In the course of each individual experiment the rats were alternatively fed for maintenance and weight gain (semi ad libitum) with feed mixtures containing 10, 25 and 40% crude protein (3 animals/variant). Energy metabolism was measured according to the method of indirect calorimetry over a total of 780 metabolism periods. In the temperature range studied there was no compensation between thermoregulatory heat and heat from other processes of the metabolism. The partial utilization of metabolizable energy for energy retention in the body was independent of ET and ranged between 73 and 80% for the 7 experiments with ET between 32 and 20 degrees C. Energy utilization depended on the protein content of the feed and decreased from 81 to 79 or 73 resp. when the protein content increased from 10 to 25% or to 40% resp. Energy requirement for protein retention varied between 1.61 and 2.09 kJ metabolizable energy/kJ and was independent of ET. Energy maintenance requirement (measured at 28, 30 and 32 degrees C) increased with the growing protein content from 415 to 439 and 447 kJ/kg LW0.75.d resp. (regression analysis) and from 411 to 420 and 432 kJ/kg LW0.75.d (measuring at maintenance level). The relative weight gain with the increased protein content of the feed largely corresponds to the expected values according to the efficiency of ATP synthesis in the oxidative degradation of nutrients. The relationship between heat production and ET is parabolic. In the live weight range studied the average thermoneutral temperature (TNT) was 32 degrees C. It decreased during the course of development from 34 to 30 degrees C. TNT decreased with the growing protein content of the feed. Thermoregulatory heat production depended on both environmental temperature and the stage of development. Its average value in the development range studied decreased with an increase of the environmental temperature by 2 K each, starting from 20 degrees C and rising to 32 degrees C, in the following linear sequence: 23.3, 21.0, 16.8, 12.5, 8.3, 4.0 and 0.3 kJ/kg LW0.75.d.K.

Animal Feed↗
PubMed1991

[Energy metabolism of growing broilers in relation to the environmental temperature].

7 experiments with 6 chickens each (origin Tetra B) in the live weight range between greater than 100 and less than 300 g and up to 1800 g were carried out at environmental temperatures (ET) of 35, 30, 25 (2 experiments) 20 (2 experiments) and 15 degrees C. In the course of each experiment the chickens alternatively received feed mixtures containing 20 and 40% crude protein (3 animals/variant) for maintenance and weight gain (semi ad libitum). Energy metabolism was measured according to indirect calorimetry over a total of 645 metabolism periods. In the temperature range studied there was no compensation between thermoregulatory heat and heat from other metabolic processes. The partial utilization of metabolizable energy for energy retention in the body was independent of ET and remained in the limits between 71 and 73%. Energy utilization was dependent on the protein content of the feed. It decreased from 75 to 69% with the increase of the protein content from 20 to 40%. Energy requirement for protein retention varied between 1.67 and 1.89 kJ metabolizable energy/kJ and was independent of ET. Energy requirement (metabolizable energy) for the maintenance of the energy balance was independent of the protein content of the feed. It increased from 433 kJ/kg LW0.75.d at 35 degrees C to 693 kJ/kg LW0.75.d at 15 degrees C ET. The relationship between heat production and ET is parabolic. The thermoneutral temperature decreased from 35 to 25 degrees C in the course of development. In the live weight range of 300-500 g thermoregulatory heat production had its maximum with 19 kJ/kg LW0.75.d.K and decreased in the further development to 10-13 kJ/kg LW0.75.d.K.

Animal Feed↗
PubMed1991

[Determination of kinetic parameters of protein metabolism in growing rats in conjunction with measurement of energy metabolism. 1. Determination of kinetic parameters of protein metabolism in relation to body weight and protein content of the feed].

The digestibility, the N balance, the rate of protein synthesis and other parameters, characterising the protein metabolism in dependence on live weight, protein- and energy supply are estimated on Wistar rats (4-5 animals/group). These experiments were done in 5 alternating consecutive growth and energy maintenance periods at 4 different levels of protein (6, 10, 17, 26% CP) during the live weight period of 70 to 230 g. The rate of protein synthesis was calculated from the course of renale 15N excretion by means of the end product method after giving a single dose of a mixture of 17 15N labelled amino acids. N deposition, rate of protein synthesis and flux rate increased with the protein level of the ration. During maintenance these data were much lower, but showed the same dependence on the protein level. The absolute protein synthesis (g/d) increased up to the live weight of 130... 180 g and decreased afterwards according to the age. The reutilization rate varied between 44 and 87% and decreased with increasing dietary protein level by 27% and during proceeding age by 8 ... 12%. In contrast to the absolute metabolism rates (g/d) the fractional rates (%/d) clearly decreased with the age of the animals. The stimulation of these rates by the dietary protein level resembled that for the absolute rates of synthesis. The protein deposition showed the typical course of a growing curve according to the N intake and the protein synthesis showed practically the same course but on a higher level. The break down remained constantly (approximately 140 mg N/d) up to an N intake of about 360 mg and afterwards it increased too.

Amino Acids↗
PubMed1991

[Determination of kinetic parameters of protein metabolism in growing rats in conjunction with the measurement of energy metabolism. 2. Determination of the energy requirement for protein retention in conjunction with measurement of the protein synthesis rate at different levels of protein supply].

Energy metabolism-by means of indirect calorimetry-and kinetic parameters of the protein metabolism on the basis of the 3-compartment model were measured with 4 groups of 4 or 5 male Wistar rats in the growth range of between 70 and 230 g live weight in a total of 5 alternately successive periods at the feeding levels growth and energy maintenance as well as 4 different levels of protein supply (6, 10, 17 and 26% crude protein in the feed). The partial energy requirement values for protein retention (bp) for every animal and every period are calculated from the data of energy metabolism. On an average of the 3 growth periods they amounted to 1.75 +/- 0.37 kJ/kJ. A statistically significant linear relation with a slope of approximately 1 could be derived regressively between the protein synthesis rate and the protein retention rate, including all 5 test periods. There was no proven relation between the bp values and the corresponding individual values of the ratio of protein synthesis rate-diminished by the regressively derived protein synthesis rate in the N balance-to the protein retention rate. The results do not permit proven statements on the quantitative relations between protein turnover and energy requirement for protein retention, which is first of all due to methodical shortcomings in measuring both protein metabolism and energy metabolism. They indicate, however, that the heat production from protein synthesis has only a relatively low share in the additional energy expenditure for protein retention and does not considerably surpass the necessary minimal cost for the synthesis of the deposited protein in growing rats.

Animal Feed↗