Enzyme diagnosis of liver diseases.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to E Schmidt.
Explore the source record for details and available documents.
Flinders Island spotted fever (FISF), a spotted fever group (SFG) rickettsial disease first described in 1991, occurs in south-eastern Australia. The isolation of the aetiological agent is described for the first time having been obtained from the blood of two patients. An additional 22 cases are also reported. Of these patients four had positive initial serology, and 20 showed seroconversion (using Rickettsia australis as antigen). Acute phase blood specimens taken from seven patients caused neonatal mice to seroconvert to R. australis and a blood specimen from one of these patients (and one other) yielded rickettsiae. A field survey for possible reservoir and vector animals on Flinders Island, Tasmania and in Gippsland, Victoria (both in south-eastern Australia) yielded 217 vertebrates and 1445 invertebrate ectoparasites, mostly ticks. Ixodes cornuatus from humans and dogs in Gippsland produced seroconversion to SFG rickettsia when inoculated into mice but no invertebrate pools from Flinders Island produced seroconversion in mice. Haemolymph from an individual I. cornuatus removed from a human in Gippsland, yielded a SFG rickettsia on tissue culture. Sera from several species of native vertebrates, especially the bush rat, Rattus fuscipes, were positive for antibodies to SFG rickettsia.
Of the ten class I tRNA synthetases, those for methionine and isoleucine are among the most closely related. In recent work we showed that the 676 amino acid E. coli methionine tRNA synthetase has one zinc bound per polypeptide. Zinc may be replaced by spectroscopically observable cobalt with retention of full activity. Bound zinc has been localized to a cysteine cluster within an insertion into the nucleotide binding fold that characterizes all class I enzymes. Mutations which interfere with metal ligation to these cysteines yield proteins that are defective in activity. Additional data presented here show that change of the cobalt oxidation state and coordination geometry of the Co(II)-substituted enzyme results in a complete loss in activity, and that mutations which replace any one of the zinc-binding cysteine sulfhydryls have a small but measurable effect on protein stability. These results further support the importance of the metal for the active site. We also show that, in contrast to methionine tRNA synthetase, the closely related but larger 939 amino acid E. coli isoleucine tRNA synthetase contains 1.5 to 2 molecules of zinc bound per polypeptide. The cobalt-substituted enzyme is active and shows the expected spectrum for tetrahedral coordination to sulfur ligands. Although the site(s) for metal coordination in isoleucine tRNA synthetase has not been rigorously established, one likely sequence element is in a region of the primary structure different from the known metal binding site in methionine tRNA synthetase. Thus, these two closely related proteins have incorporated metal binding sites into distinct parts of their related sequences.
The authors report the results of two EEG studies on adult patients with phenylketonuria (PKU) who had been treated early. Part I: the authors followed the EEGs of 34 PKU patients from birth to age 21. The frequency of abnormal EEG findings (especially epileptiform activity) steadily increased until age 12, then decreased. IQ correlated significantly with quality of dietary control during follow-up. Part II: frequency analysis of the EEG and neuropsychological testing were performed on eight adult patients after periods of four weeks with low and high levels of phenylalanine. Only five patients followed the strict dietary regulations. With high levels of phenylalanine, the dominant peak of EEG background activity shifted to the slower frequency spectrum in all patients; in addition, neuropsychological testing revealed impairment of cognitive function. The significance of different approaches of EEG examinations is discussed with respect to the problems of monitoring PKU patients and the pathogenic mechanisms of CNS damage in phenylketonuria.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Traditional monoamine oxidase inhibitors (MAOIs) have long been associated with tyramine-related hypertension--the cheese effect. Despite their undoubted clinical efficacy, this problem has restricted their use. New, selective, and reversible MAO-A inhibitors--which act only on the A isoenzyme--appear not to have this effect. Our investigations of these drugs, exemplified by brofaromine, have shown a reduced and more rapidly reversed tyramine pressor sensitivity. Moreover, we were unable to detect any clinically significant food interaction, following ingestion of a quantity of cheese containing sufficient tyramine to increase systolic blood pressure by at least 30 mm Hg. These results confirm the improved safety of brofaromine, and other drugs in this class, when compared with classic MAOIs.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Hypercholesterolemia is one of the major risk factors for ischemic heart disease and for the development of atherosclerotic plaques. Water soluble plant fibers do exert a binding of intestinal cholesterol and are not digested or metabolized. We have investigated the effect of a highly water soluble fiber containing oat brain on serum cholesterol concentrations in 14 volunteers (nine males, five females, age 39 to 67 years, serum cholesterol concentration: 7.14 +/- 0.80 mmol/l; x +/- SD) during an intervention with 50 g oat brain per day for nine weeks. We have documented in the whole study population a modest, but significant reduction of serum cholesterol levels of 4.2% (p less than 0.05) at six weeks; however at nine weeks the efficacy of this regimen was less pronounced (3.2%, p = n.s.) speaking for a decreased compliance although this regimen was well tolerated and accepted. In subsets of high risk volunteers for coronary heart disease of male gender (n = 9), with hypercholesterolemia (n = 8) or essential hypertension (n = 8) the reduction of serum cholesterol levels was more consistent (5.6%, p less than 0.05) with no change in normolipemic volunteers.
In vitro and animal experiments suggest that a constitutional increase in vascular responsiveness to serotonin (5-HT) may play a role in the development of essential hypertension. We have studied the potential alterations in vascular responsiveness to the direct and catecholamine-potentiating effects of exogenous 5-HT in patients with essential hypertension, by comparing in vivo responsiveness of superficial hand veins to local infusions of 5-HT or to coinfusions of 5-HT and noradrenaline in unmedicated hypertensive patients and in healthy control subjects. The dorsal hand vein compliance technique was employed. There was no significant difference between patients and control subjects in the maximal 5-HT-induced venoconstriction or in the doses required for half-maximal venoconstriction (ED50) for 5-HT. Coinfusions of a constant dose of 5-HT caused a significant leftward shift in the dose response curve for noradrenaline as compared with noradrenaline alone. This was indicated by a 9.7 +/- 13.7 fold and a 10.4 +/- 13.8 fold increase in the ED50 for noradrenaline in the patient and control groups, respectively (p = 0.89 between study groups). Our results argue against a generalized increase in responsiveness to the direct or catecholamine-potentiating effect of 5-HT in vivo in vascular smooth muscle, associated with hypertension.
In a retrospective study, 34 early treated, normally intelligent adolescents with phenylketonuria (PKU) and their parents were tested with several psychometric personality inventories and self-developed questionaires concerning their psychosocial situation and their disease- and diet-specific knowledge. Results show that the patients are characterized by less autonomy, a more negative evaluation of their scholastic ability, less achievement motivation, low frustration tolerance, more negative self description, less extraversion and impulsiveness, a feeling of not being quite healthy, more grave and a higher level of dependency from their families. The patients saw their whole social situation as being distinctly restricted. Their knowledge concerning disease and diet was alarmingly poor and the majority had great difficulties in managing the diet satisfactorily without parental help. Up to the age of 15 years the serum phenylalanine levels were persistently above the desired range.
The influence of smoking on serum IgE (s-IgE) was studied in a selected nonatopic population. The variation in s-IgE was followed during 1 year of smoking abstinence. The study included 287 smokers and 137 never smokers. IgE was higher in smokers compared with IgE in never smokers (p less than 0.005). Male smokers had higher s-IgE than female smokers (p less than 0.01). S-IgE was independent of age and claims of atopy among first-degree relatives. Weighted pack-years consumption was defined for cigarette smokers by modifying pack-years consumption by nicotine content of the brand smoked. Weighted pack-years consumption was associated with level of s-IgE (p less than 0.05). S-IgE was higher in smokers with airway symptoms compared with that in smokers without symptoms (p less than 0.01). In smokers older than 50 years of age, there tended to be decreased FEV1 residuals (0.05 less than p less than 0.06), and presence of airway symptoms was (p less than 0.03) associated with high levels of s-IgE independent of each other. In 92 quitters, s-IgE increased during the first 26 weeks of abstinence (p less than 0.05), and after 1 year, s-IgE had returned to baseline. The increase was only observed in smokers younger than 40 years and had no relation to variations in FEV1 during the 1-year follow-up. The increase in s-IgE after smoking cessation was transient, of minor clinical importance, and probably caused by a relief from an immunosuppressive influence.
(R)-2-Hydroxy-4-phenylbutyric acid, an intermediate in the manufacture of inhibitors of angiotensin converting enzyme, can be produced continuously in an enzyme membrane reactor by enzymatic reduction of its corresponding alpha-keto acid. D-Lactate dehydrogenase (D-LDH) from Staphylococcus epidermidis was chosen as the most appropriate enzyme to carry out the NADH-dependent reduction. Formate dehydrogenase (FDH) was used for NADH regeneration. Detailed kinetic measurements and a mathematical model for the coupled enzyme reactions were applied to calculate the optimal conditions for continuous production of the alpha-hydroxy acid. A mass of 1 kg [corrected] (R)-2-hydroxy-4-phenylbutyric acid was synthesized in a 220 ml enzyme membrane reactor over a period of 4 weeks. A mean space-time-yield of 165 g l-1 d-1 was achieved at low enzyme consumptions of 150 U kg-1 alpha-hydroxy acid for FDH and D-LDH.
An osteoid osteoma of the styloid process of the radius mimicking de Quervain's tenovaginitis in a 28-year-old man is reported. As the clinical presentation and X-rays of the wrist were not typical of an osteoid osteoma, only the histological examination led to the correct diagnosis.
Explore the source record for details and available documents.
DBP, a liver-enriched transcriptional activator protein of the leucine zipper protein family, accumulates according to a very strong circadian rhythm (amplitude approx. 1000-fold). In rat parenchymal hepatocytes, the protein is barely detectable during the morning hours. At about 2 p.m., DBP levels begin to rise, reach maximal levels at 8 p.m. and decline sharply during the night. This rhythm is free-running: it persists with regard to both its amplitude and phase in the absence of external time cues, such as daily dark/light switches. Also, fasting of rats for several days influences neither the amplitude nor the phase of circadian DBP expression. Since the levels of DBP mRNA and nascent transcripts also oscillate with a strong amplitude, circadian DBP expression is transcriptionally controlled. While DBP mRNA fluctuates with a similar phase and amplitude in most tissues examined, DBP protein accumulates to high concentrations only in liver nuclei. Hence, at least in nonhepatic tissues, cyclic DBP transcription is unlikely to be controlled by a positive and/or negative feedback mechanism involving DBP itself. More likely, the circadian DBP expression is governed by hormones whose peripheral concentrations also oscillate during the day. Several lines of evidence suggest a pivotal role of glucocorticoid hormones in establishing the DBP cycle. Two genes whose mRNAs and protein products accumulate according to a strong circadian rhythm with a phase compatible with regulation by DBP encode enzymes with key functions in cholesterol metabolism: HMG-coA reductase is the rate-limiting enzyme in cholesterol synthesis; cholesterol 7-alpha hydroxylase performs the rate-limiting step in the conversion of cholesterol to bile acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Colchicine as well HOE 077 were found to be effective in the inhibition of hepatic collagen accumulation after bile duct ligation in rats. The effect was additive and was truly reflected by changes in the serum PIIIP and 7s-collagen (IV) concentration. Extrahepatic effects on collagen synthesis were not detected when HOE 077 was used. Thus further studies on the potential clinical usefulness of these compounds are clearly indicated.