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Biomedical subjects

I Witt

Publications and source records attributed to I Witt.

At least 55 records · Page 3Linked to original sources

Synthesis of rat-liver lactate dehydrogenase and characterization of its mRNA.

Rat liver lactate dehydrogenase (LDH) has been synthesized in hepatocytes and in a cell-free translation system. The subunit synthesized in both systems displayed the same electrophoretic mobility upon sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis. Sequence analysis of the subunits translated in vitro and synthesized in vivo indicated N-acetyl-alanyl-alanine for both N termini. Thus, the newly synthesized subunit does not exhibit an amino-terminal extension. The mRNA for the lactate dehydrogenase subunit was exclusively found in free polysomes. A size of 2120 +/- 240 nucleotides was estimated for the mRNA. Only about 50% of these nucleotides are needed to code for the polypeptide chain of the enzyme.

Amino Acid Sequence↗

N-terminal amino acid sequences of precursor and mature forms of alpha-1-antitrypsin.

alpha-1-Antitrypsin is found in hepatocytes as a high-mannose glycoprotein (Mr 49 000), extracellularly as a complex-type glycoprotein (Mr 54 000). Deglycosylation of both forms with peptide: N-glycosidase led to proteins of identical app. Mr (41 000). The sequence of 26 N-terminal amino acids of rat alpha 1-antitrypsin was determined. A high content of polar amino acids was found. The partially characterized presequence of in vitro synthesized alpha 1-antitrypsin showed a cluster of hydrophobic amino acids. A pre-peptide of 24 amino acids is proposed. There is no evidence for the existence of a propeptide.

Amino Acid Sequence↗

Glucosephosphate-isomerase type Kaiserslautern. A new variant causing congenital nonspherocytic hemolytic anemia.

In a 13-year-old German girl a GPI deficiency was found to be the cause of a chronic nonspherocytic hemolytic anemia with recurrent hemolytic crises. The hemolytic crises usually occurred after a feverish infection. Only once did the patient require blood transfusion during a crisis. Examination of the family indicated that the patient is doubly heterozygous for the deficiency. The investigation of the biochemical properties of the deficient enzyme revealed an altered electrophoretic migration, a pronounced thermolability, an increased affinity for G-6-P and slightly changed pH optima for both substrates. The described properties of the deficient GPI indicate that we are dealing with a new variant designated GPI-Kaiserlautern.

Adolescent↗

[alpha 2-Macroglobulin in serum and plasma: reference values with carbobenzoxy-valyl-glycyl-arginine-p-nitroanilide, a chromogenic substrate].

alpha 2-Macroglobulin can be determined using the amidolytic activity of the alpha 2-macroglobulin-trypsin-complex. Reference values are reported using a commercially available kit for continuous assay at 25 degrees C. Reference ranges obtained in a population of 235 children and adults aged between 1 day and 61 years were found to be age-dependent. Reference ranges established for the different age groups of children were grouped together in order to obtain useful guide values. The following values were obtained for serum: 1 to 10 days: 5-11 kU/l 11 days to 18 years: 8-16 kU/l The reference values (5th to 95th percentile) determined for juveniles and adults were as follows: 19 to 25 years: 4.1-12.2 kU/l (serum); 4.0-11.2 kU/l (citrated plasma) greater than or equal to 25 to 61 years: 4.1-8.1 kU/l (serum); 3.7-7.4 kU/l (citrated plasma) No variation according to sex was observed, nor was any difference noted between preprandial and postprandial catalytic concentrations, or between values in smokers and non-smokers or between values in the group of women taking hormonal contraceptives and the group not taking such drugs. If the dilution of the blood sample with citrate solution is taken into account when calculating the catalytic concentrations in citrated plasma, the values in plasma are higher than those in serum (median 11%). Measurement of the alpha 2-macroglobulin-trypsin complex in plasma is assumed to give a more realistic reflection of the in vivo activity than measurement in serum. Comparison with two immunological methods (radial immunodiffusion and kinetic nephelometry) revealed that there is a linear relationship between the measurement of the catalytic concentration of the alpha 2-macroglobulin-trypsin complex and the immunological concentration of alpha 2-macroglobulin. Therefore mutual conversion is possible for the described concentration range.

Adolescent↗

Renal metabolism of corticosteroid hormones.

IK and STF from male and female rats have been used to study in vitro the renal metabolism of B. in male rat tissue four lipid soluble metabolites (I-IV) have been found, I + II being more polar and III + IV being less polar than B. I and II have been identified as 11-dehydro-20-hydroxy-B and 20-hydroxy-B. The structure of III and IV remains to be determined. Renal tissue from female rats produced predominantly III indicating sexual variations of steroid metabolism in kidneys.--The literature has been reviewed which documents that the kidneys in addition to B metabolize A, cortisol, progesterone and other corticosteroids.

Adrenal Cortex Hormones↗

[Lung functions in children with marked alpha 1-antitrypsin deficiency (Pi-Z type) (author's transl)].

Various lung volumes and flows were measured in five children (aged 9-11 years), a male adolescent and one adult, all carriers of the homozygotic form of alpha 1-antitrypsin deficiency (Pi-Z type). In five patients lung function tests demonstrated overdistention, in three decreased CO diffusion capacity, as an expression of pulmonary emphysema at an early stage. Airway obstruction was not demonstrable in any of the patients (normal values for FEV 1, Tiffeneau test, peak flow and V25, V50 and V75). There was a correlation between the level of alpha 2-macroglobulin and the CO diffusion capacity, as well as between alpha 1-antitrypsin level and residual volumes. In one child there was evidence of minor liver involvement; in the other six patients, all liver-dependent serum enzymes were within normal limits. The findings suggest that the lung changes typical of adult homozygotic carriers of alpha 1-antitrypsin deficiency have their beginning in childhood.

Adult↗

[Joint study to establish reference values for clinical chemical parameters in childhood (author's transl)].

The working group 'Pädiatrische Klinische Chemie' undertook a joint study to satisfy the need for more reliable reference values for clinical chemical parameters in childhood. In 15 different pediatric hospitals data for the most important clinical chemical parameters were determined for children of different age groups. The children included in the study fulfilled the required minimal criteria concerning their health state. The data were listed according to parameter and age group and the percentiles and mean values with 95% confidence intervals are presented. From these values, reference ranges are derived that are suitable for daily routine analyses.

Alanine Transaminase↗

[alpha 1-antitrypsin: reference values in serum and plasma with benzoyl-D,L-arginine-p-nitroanilide, a chromogenic substrate].

Reference values for alpha 1-antitrypsin were determined using a commercially available kit for continuous assay at 25 degrees C. With a population of 100 probands aged between 20 and 60 years, a reference range of 1.4-2.4 kIU/l (1.9-3.4 g/l) was obtained for serum, and 1.4-2.1 kIU/l (1.9-3.0 g/l) for plasma. In each case, these ranges correspond to the 5th to 95th percentile. No variations according to age or sex were observed, or was any difference noted between preprandial and postprandial activities, or between values in smokers and nonsmokers. Significantly different values were found in the group of women taking oral steroid contraceptives and the group not taking such contraceptives. If the dilution of the blood sample with citrate solution is taken into account in calculating the activity in citrated plasma, it is apparent that higher values are found in plasma than in serum (median 13%): Hence, the in vivo-alpha 1-antitrypsin activity can most probably be better determined using a plasma sample.

Adult↗

Decreased production or increased turnover of antithrombin III in severe acquired coagulopathy?

During the course of severe coagulopathy in an infant suffering from septicaemia and shock, antithrombin III levels were determined repeatedly before and during substitution therapy with human antithrombin. By mathematical analysis of these data, using a biexponential function, the plasma elimination half-life of the antithrombin III was estimated to be 7.5-10.5 h. Compared with known plasma half-lives of radioactively labelled antithrombin III in adults the increase was five-to ten-fold. This indicates that the significantly decreased levels of antithrombin III in this case of coagulopathy were at least partly due to an accelerated consumption of antithrombin III. The estimation of the plasma elimination half-life of antithrombin III helps to differentiate decreased production from increased consumption in cases of severe coagulopathy. Thus, a more precise diagnosis of disseminated intravascular coagulation can be made whilst taking advantage of substitution therapy and avoiding the hazards of radioactive tracer proteins.

Antithrombin III↗

Twenty-four-hour pattern of growth hormone secretion in the rhesus monkey: studies including alterations of the sleep/wake and sleep stage cycles.

The 24-h pattern of GH secretion and its possible relation to the sleep/wake cycle and to sleep stages were studied in 12 male rhesus monkeys. Blood samples were drawn every 15 min for 96 h, 24 h, or shorter periods of time through chronic right atrial catheters which extended through the wall into the adjacent room. In addition, activity rating (daytime) and determination of sleep stages from electroencephalogram recordings (nighttime) were done. GH profiles were obtained during undisturbed conditions and during deprivation of nap, 5 h total sleep, slow wave sleep (SWS), and rapid eye movement (REM) sleep. GH secretion was episodic, with peak concentrations often exceeding 20 ngeq/ml and nadirs mostly below 1 ngeq/ml. Autocorrelation analysis demonstrated a circadian and an ultradian rhythm during undisturbed conditions. However, the cycle length of the ultradian rhythm showed large inter- and intraindividual variations (from 3--6 h). Neither cross-correlation analysis between hormonal and activity/electroencephalogram sleep stage time series nor results of deprivation experiments produced evidence for a link between nap phases, the sleep/wake cycle, or the SWS/REM sleep stage cycle on the one hand and the GH secretory pattern on the other hand. However, while SWS deprivation was highly effective, REM deprivation did not substantially reduce total REM sleep time due to frequent entries into abortive REM sleep epochs. During the daytime, there was no significant correlation between activity/arousal and GH, but during the night, there was a significant positive correlation between stage waking and GH. A direct or indirect synchronizing effect of the matutinal light change is suggested by the pattern of the 24-h curve of mean GH concentrations during undisturbed conditions: a steep increase from very low concentrations at light onset, followed by a succession of nadirs and peaks at approximately 4.5-h intervals. However, the nadirs became progressively more shallow until there was no apparent periodicity during the night due to the loss of synchronization. It is concluded that GH in the rhesus monkey shows a circadian and an ultradian periodicity. However, in contrast to man, sleep and SWS are not important determinators of the 24-h GH pattern.

Animals↗

Pattern of thyrotropin and thyroxine plasma concentrations during the 24-hour sleep-wake cycle in the male rhesus monkey.

The 24-h pattern of the plasma TSH concentration was investigated in five male rhesus monkeys prepared chronically with right atrial catheters and electroencephalogram (EEG) electrodes. The preparation allowed frequent blood sampling (every 15 min), TV monitoring, and EEG recording from the adjacent room for extended periods of time from undisturbed animals. In addition, nap deprivation, 5 h total sleep deprivation, and specific sleep stage deprivation experiments were performed in order to test their influence on the TSH pattern. T4 was also determined in approximately half of the profiles during undisturbed conditions. Both TSH and T4 patterns consisted of low amplitude, high frequency fluctuations which, however, did not exceed the assay variation. TSH showed superimposed higher amplitude spikes at unpredictable times (0-5/24-h). Intra- and interanimal variabilities of both TSH and T4 patterns were high. Power spectral maxima of the TSH time series indicated periodicities between 30-75 min which were not significant. No nyctohemeral difference in the TSH or T4 pattern or their mean concentrations was found, and there was no consistent pattern of a circadian cycle. Independent changes of average TSH and T4 concentrations were seen in 5 of the 16 profiles during undisturbed conditions, under which both hormones were determined. Cross-correlation analysis of the hormonal time series revealed no significant relation between TSH and T4 patterns. The deprivation procedures had no significant influence on the day or nighttime pattern of TSH. Cross-correlation analysis showed no relation between TSH and either activity during the day or sleep stages during the night. It is concluded that in the rhesus monkey, in contrast to man, TSH secretion shows no circadian variation and is not influenced by the sleep-wake cycle.

Animals↗