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Biomedical subjects

M Schumacher

Publications and source records attributed to M Schumacher.

At least 19 recordsLinked to original sources
PubMed1995

Progesterone synthesis and myelin formation by Schwann cells.

Progesterone is shown here to be produced from pregnenolone by Schwann cells in peripheral nerves. After cryolesion of the sciatic nerve in male mice, axons regenerate and become myelinated. Blocking either the local synthesis or the receptor-mediated action of progesterone impaired remyelination. Administration of progesterone or its precursor, pregnenolone, to the lesion site increased the extent of myelin sheath formation. Myelination of axons was also increased when progesterone was added to cultures of rat dorsal root ganglia. These observations indicate a role for locally produced progesterone in myelination, demonstrate that progesterone is not simply a sex steroid, and suggest a new therapeutic approach to promote myelin repair.

Animals↗
PubMed1995

[Thrombosis of a prosthetic mitral valve in the anticardiolipin syndrome].

A 40-year-old woman in whom the mitral valve had to be replaced with a prosthetic one (St. Jude's) had to be reoperated 8 months later because of endocarditis on the second prosthetic valve (Carbo-Medics). Four months later her general condition deteriorated progressively with cough and dyspnoea, requiring hospitalization. Auscultation revealed moist rales over both lung bases; heart sounds were distant but otherwise normal. The "international normalized ratio" was 2.5, while erythrocyte sedimentation rate, white cell count and C-reactive protein were normal. Transthoracic echocardiography demonstrated a hardly moving mitral valve prosthesis with an opening area of 0.8 cm. Subsequently this decreased further and measurement of the anticardiolipin antibody titre revealed an IgG fraction of 37.9 U/ml (normal up to 12 U/ml). Within 48 hours thrombolysis with streptokinase had increased the valve's opening area to 1.8 cm. The patient made an uneventful recovery under strict anticoagulation. This case illustrates that the anticardiolipin syndrome can be a cause of an otherwise unclear genesis.

Adult↗
PubMed1995

Synthesis and characterization of polyamides containing unnatural amino acids.

We describe the synthesis of several polyamides that retain the secondary structure of proteins and contain derivatizable side chains. The derivatizable side chain allows for further reaction of the polymer chain (e.g., chain cross-linking or addition of pendant groups). Polymers of alpha-amino acids containing a terminal unsaturated bond on the side chain have been synthesized. Poly-L-pentenyl glycine, poly-L-propargyl glycine, and poly-L-allyl glycine were synthesized chemically via Leuchs' anhydrides and enzymatically using subtilisin Carlsberg. Poly-L-propargyl glycine and poly-D,L-allyl glycine folded into the beta-sheet configuration whereas poly-L-pentenyl glycine assumed a helical conformation. The secondary structure of poly-L-allyl glycine and poly-D,L-pentenylglycine could not be determined conclusively. Comparison of properties between the polymers obtained chemically and enzymatically is provided.

Amino Acids↗
PubMed1995

Stereoselective increase of plasma concentrations of the enantiomers of propranolol and atenolol during exercise.

OBJECTIVE: In vitro studies have shown that, like catecholamines, both propranolol and atenolol are taken up by and released from adrenergic cells. We performed this study to investigate whether this may also play a role in humans and whether stereoselective aspects are important. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study of two groups of 12 healthy volunteers. Subjects received single oral doses of 80 mg (R,S)-, 40 mg (R)-, and 40 mg (S)-propranolol; 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol; and placebo at intervals of 1 week. Exercise was performed at 4 and 9 hours after drug intake, and blood samples were taken before and at the end of each exercise period. The plasma concentrations of the (R)- and (S)-enantiomers of propranolol and atenolol, as well as those of epinephrine and norepinephrine, were determined by HPLC. RESULTS: Effects of exercise on the plasma levels of the enantiomers of propranolol and atenolol were similar. When the optically pure enantiomers were administered, exercise caused a marked and significant increase of the plasma concentrations of the (S)- but not of the (R)-enantiomers. When the drugs were administered in the racemic form, the plasma levels of both the (R)- and (S)-enantiomers were elevated to the same extent. The increase of norepinephrine levels during exercise was more pronounced than that of epinephrine and paralleled that of the (S)-enantiomers of the beta-blockers. CONCLUSION: Bearing the in vitro data in mind, we conclude that (S)-propranolol and (S)-atenolol are taken up into and released from adrenergic cells together with norepinephrine during exercise. The reason why the plasma concentrations of (R)-propranolol and (R)-atenolol are increased only during exercise in the presence of the corresponding (S)-enantiomers remains to be determined.

Administration, Oral↗
PubMed1995

Transient reduction of autoantibodies against oxidized LDL in patients with acute myocardial infarction.

Fifteen consecutive patients (mean age 66 +/- 14, range 31-82) with an acute myocardial infarction (MI) suitable for thrombolytic therapy were included in this study. Autoantibodies against oxidized low-density lipoprotein (LDL) were determined by enzyme-linked immunosorbent assay (ELISA). Patients (n = 10) with marked elevation of the MB isoenzyme of creatinine kinase (CK-MB)-mass had significant decreases of oLDL-Ab during the acute phase, with a minimum after 8 h following the onset of thrombolytic therapy (within-group significance: p < .001; between groups: p = .01). Patients (n = 5) with CK-MB-mass values less than 70 ng/ml did not show this phenomenon. Furthermore, significant correlations existed between CK-MB-mass and oLDL-Ab after 6 and 8 h (n = 15; r = .72; p = .003) and the time of the highest CK-MB-mass values (after 12 h) and the time of the maximal decrease of oLDL-Ab (after 8 h) (r = .74; p = .003). Our observations provide further evidence for the release of free radicals and for increased lipid peroxidation during reperfusion after prolonged ischemia. The decrease of oLDL-Ab appears to be a marker for the severity of MI.

Adult↗
PubMed1995

Changes in thyroid hormone parameters after acute myocardial infarction.

Abnormalities in circulating thyroid hormone levels are very common in systemic nonthyroidal illnesses, such as acute myocardial infarction. In this study, thyroid parameters were determined in a series of 16 consecutive infarction patients treated by thrombolysis. Blood samples were taken before therapy as well as 2, 4, 6, 8, 12 and 72 h following admission. Total and free serum thyroxin and triiodothyronine decreased and reverse T3 increased significantly showing no major variations up to 72 h, whereas thyroid-stimulating hormone values remained almost unchanged during the observation period. Subjects with CK-MB levels of more than 150 ng/ml (n = 10) revealed similar changes in thyroid parameters in comparison to those with lower values (n = 6; NS). Thus, although hormone modifications very often occur following acute infarction, thyroid status may not serve as a marker for the extent of left ventricular dysfunction in the early phase of myocardial infarction.

Aged↗
PubMed1995

Poststroke depression. Is there a pathoanatomic correlate for depression in the postacute stage of stroke?

BACKGROUND AND PURPOSE: This study is aimed at the pathoanatomic correlates of depression in the postacute stage of patients with stroke. METHODS: Of a consecutive series of 104 stroke patients, a subgroup of 47 patients with single demarcated unilateral lesions was selected. Clinical examination, neuroradiological CT scan examination, and psychiatric assessment were performed within a 2-month period after the acute stroke. Depression was assessed with the Cornell Depression Scale, the Montgomery-Asberg Depression Rating Scale, and according to modified DSM-III-R criteria. The neuroradiological examination of all patients was performed on the same scanner, and lesion location, lesion volume, and ventricle-to-brain ratio were analyzed. RESULTS: We found no significant differences in depression scores between patients with left and right hemisphere lesions and no correlation between the severity of depression and the anteriority and the volume of lesion or brain atrophy. Major depressive disorders were only found in nine patients with left hemisphere lesions, all involving the basal ganglia, whereas none of the patients with right hemisphere stroke exhibited major depression. CONCLUSIONS: Lesions in the vicinity of the left hemisphere basal ganglia tend to play a crucial role in the development of major depression after the acute stage of stroke. The pathophysiological implications of this finding are discussed.

Brain↗
PubMed1995

(Apo)lipoprotein(a) concentrations at birth and in the first days and months of life--studies on the distribution of serum levels and the predictive value of measurements made at this time.

This study was carried out on 625 newborns delivered between July 1993 and December 1994 and 221 children visiting the clinic in the first year of life using an immunoluminometric assay specific for apolipoprotein(a), but calibrated with lipoprotein(a), hence the use of the term (apo)lipoprotein(a) for neonatal values. (Apo)lipoprotein(a) concentrations were measured in 278 neonates over the first 12 days of life (median observation time 6 days). A further 64 children were followed up over a period of 1-10 months (median observation time 5 months). The median (apo)lipoprotein(a) concentration at birth was 14.7 mg/l (males 14.6, females 14.7 mg/l). The range of concentrations measured was between 1 and 433 mg/l. The correlation coefficient between maternal and neonatal lipoprotein(a) at birth was 0.509 for 483 data pairs. The behaviour of serum concentrations of (apo)lipoprotein(a) during the first days of life varied greatly and was independent of the birth level. Eighty-four babies showed a decrease, 107 an increase and 87 no change in (apo)lipoprotein(a) levels; over the first months of life was more unified with 50 children showing an increase in serum lipoprotein(a), a decrease in 4 cases and no change in 10 cases. In these 64 children the median increase in serum (apo)lipoprotein(a) was from 15.8 mg/l at birth (range 1 to 364 mg/l) to 38.5 mg/l at 6 months. The median lipoprotein(a) concentrations in the children under 1 year (median age 6 months) was 37.0 mg/l (males 37.1, females 37.0 mg/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Hypertension and hemorheology].

A number of epidemiologic studies have provided evidence for an increased blood viscosity in hypertensive patients. Increased viscosity could result either from hemoconcentration, thus constituting a secondary phenomenon, or, alternatively, result directly from increased intracellular calcium concentrations in erythrocytes. The latter would augment the aggregating potential of these cellular blood compounds. This currently hypothetic view remains to be elucidated. Enhanced viscosity, however, may result in increased peripheral resistance and lead to hypertensive complications. The evaluation of antihypertensive therapy should therefore take possible effects upon blood viscosity into account.

Antihypertensive Agents↗
PubMed1995

[What are the therapeutic consequences of evaluating hypertensive patients with 24-hour blood pressure monitors and blood pressure self-measurement?].

Arterial hypertension is an important risk factor for excessive cardiovascular morbidity and mortality due to its high prevalence of about 20% in the adult population. Causal readings, which have been obtained for diagnosis and control of treatment in hypertension are of limited value. They are not reproducable due to physiologic variability of blood pressure, which causes a rise of blood pressure, if a straining situation (e.g. in doctor's office) occurs (white-coat-hypertension). Furthermore, no correlation between causal readings and signs of endorgan-damage (EOD) such as left ventricular hypertrophy (LVH) can be observed. Especially the development of LVH comprises an independent risk factor and worsens prognosis. Results of ambulatory monitoring and self-measurement of blood pressure are reproducable and show an excellent correlation to EOD. Both methods are able to exclude white-coat-hypertension. Furthermore, ambulatory blood pressure monitoring allows to obtain blood pressure values during sleep, which may give further information concerning secondary hypertension, EOD and prognosis. Self measurement of blood pressure reinforces compliance of the patient and gives the possibility of self-titration and long-term control of antihypertensive drug treatment. The non-consensus concerning normal values is one limitation of both methods, but the cut-off level of office blood pressure recordings appears arbitrary, too. For optimal concomittance of hypertensives both methods have to reach more importance for diagnosis, evaluation of prognosis as well as treatment control.

Adult↗
PubMed1995

[Thrombolytic therapy of acute myocardial infarct in advanced age (based on 2 case reports)].

The introduction of thrombolysis has reduced the mortality of acute myocardial infarction (MI) by 25%. Large-scale studies have revealed that especially patients over 65 benefit from this therapy. Nevertheless, many centers apply an age limit for thrombolytic therapy due to the higher risk of stroke or bleeding in elderly patients. In 1993 181 patients suffering from acute MI were admitted to the intensive care unit of the University Clinic of Internal Medicine, Graz, and 54 (29.4%) of them were treated with fibrinolytic drugs. In this paper we report on the successful thrombolytic management of acute MI in two male patients (87 and 88 years old) who were treated with 100 mg recombinant tissue-type plasminogen activator complex. As a sign of successful reperfusion a rapid increase in plasma creatinine kinase levels and fast amelioration of the ischemia-related ECG changes were observed. In the follow-up examination after four months the first patients showed only minimal exertional dyspnea and was otherwise well. The second patient died one month after MI following a laparotomy for ileus. We draw the conclusion that patients of advanced age also benefit from thrombolytic treatment of acute myocardial infarction, but the indications and contraindications have to be carefully observed.

Aged↗
PubMed1994

Outcome-oriented cutpoints in analysis of quantitative exposures.

In the analysis of epidemiologic data in which exposure has been measured on a continuous scale, cutpoints can be defined to delineate categories or exposure can be modeled as a continuous covariate by assuming a special functional shape of the effect on disease status. Rules for classifying exposure into two or more categories range from a priori selection of cutpoints to data-oriented rules. The risk estimates may vary, however, with the choice of cutpoint. If the cutpoint selected is that for which the most impressive effect of exposure on outcome is observed, the final result must be qualified by adjustment. In this paper, the authors propose a method for adjusting results which are derived by varying the cutpoint on a specified selection interval. Adjustment is derived from the null distribution of the maximally selected test statistic. The method should be applied to correct p values if the cutpoint used to define different levels of exposure is selected in such a way that the measure of difference between two risk groups, such as the odds ratio or relative risk, is maximized. No method is yet available for adjusting the resulting risk estimate and the corresponding confidence limits. The authors illustrate the statistical method by applying it to data from a case-control study of the association between exposure to magnetic fields and risk of cancer in children which was conducted recently in Denmark.

Adolescent↗
PubMed1994

Characterization of al-2, the phytoene synthase gene of Neurospora crassa. Cloning, sequence analysis, and photoregulation.

We have cloned the al-2 gene of Neurospora crassa and have analyzed its structure and regulation. The gene encodes a 603-residue polypeptide with a segment homologous to prokaryotic and other eukaryotic phytoene synthases. RNA measurements showed that the level of al-2 mRNA increased over 30-fold in photoinduced mycelia compared with dark-grown mycelia. This observation is consistent with the fact that carotenoid biosynthesis is induced by blue light during growth of N. crassa mycelia. The photoinduced increase in al-2 mRNA levels was not observed in two Neurospora mutants, wc-1 and wc-2, that are defective in all physiological photoresponses.

Alkyl and Aryl Transferases↗
PubMed1994

Actions of steroid hormones- and growth factors on glial cells of the central and peripheral nervous system.

Primary cultures of oligodendrocytes and astrocytes and purified cultures of Schwann cells were prepared respectively from forebrain and sciatic nerves of newborn rats. The effects of steroid hormones and growth factors on glial cell growth and on the production of myelin-specific proteins and lipids were investigated. Progesterone (P, 100 nM) decreased the proliferation of glial cells of the central nervous system. This inhibitory effect of P was abolished by the simultaneous administration of the antagonist RU486, thus suggesting a receptor-mediated action of the hormone. The expression of myelin-specific proteins, including the myelin basic protein (MBP) and the 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase), and of a myelin-specific lipid, galactocerebroside (Gal C), was also measured during cell differentiation under different hormonal conditions. The expression of MBP in oligodendrocytes was increased by P, and this effect was not blocked by RU486. The combined application of P and insulin promoted a synergistic stimulation of MBP expression. Insulin, by itself, also increased the number of MBP-positive oligodendrocytes in culture. The effects of P and insulin appeared to be selective as dexamethasone, dehydroepiandrosterone, pregnanolone and epidermal growth factor (EGF) had no effect. Only estradiol (E2, 500 nM) increased the number of MBP-immunoreactive cells, but in contrast to P, only a small synergism between E2 and insulin on MBP expression was observed. The expression of CNPase, another myelin-specific protein, was also increased by P and, here again, a synergy between P and insulin could be observed. In contrast, the expression of Gal C, a myelin-specific lipid, was not modified by P or other steroid hormones. Moreover, the increase in Gal C-positive cells observed in response to insulin alone was not further potentiated by P. Glial cells of the peripheral nervous system, namely Schwann cells, are also sensitive to steroid hormones. Schwann cells contain estrogen receptors, and E2 stimulates their proliferation in the presence of forskolin or dibutyryl cyclic AMP (dbcAMP). The mitogenic effect of E2 was abolished by the pure antiestrogen ICI-164,384. Insulin, at micromolar concentration, also stimulated Schwann cell growth when forskolin or dbcAMP were present in the culture medium. The mitogenic effect of insulin was mediated by insulin-like growth factor I (IGF-I) receptors. Indeed, at a physiological nanomolar concentration, IGF-I but not insulin or IGF-II, increased the proliferation of Schwann cells in synergy with forskolin. In addition, Schwann cells express receptors for IGF-I.

Animals↗