Control of cell proliferation by heparan sulfate and heparin-binding growth factors.
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Animals↗
Biomedical subjects
J Zimmermann
Publications and source records attributed to J Zimmermann.
[The Gitelman syndrome--a differential diagnosis of Bartter syndrome].
BACKGROUND: Hypokalemia due to renal potassium wasting in the absence of hypertension, moderate metabolic alkalosis, hyperreninism and hyperaldosteronism suggest the presence of Bartter's syndrome. The underlying cause is an inherited defect of sodium chloride reabsorption in the thick ascending limb of Henle. A differential diagnosis of Bartter's syndrome is Gitelman's syndrome, another hypokalemia-hypomagnesemia syndrome, which is thought to be caused by a transport defect in the distal tube. PATIENTS AND METHODS: We report 3 patients presenting with signs primarily suggestive of Bartter's syndrome, who turned out to have Gitelman's syndrome after determining the excretion of calcium in the urine. RESULTS: Two women, 36- and 55-year old, suffered from paresthesias in the hands and feet and from tetanic convulsions. The brother of the 36-year old woman presented in our hospital because of an accidentally discovered hypokalemia without any clinical symptoms. In all patients the outstanding biochemical features were hypokalemia, hypomagnesemia and moderate metabolic alcalosis. The renin and aldosterone values were inappropriately high. The most characteristic finding in the urine, besides the presence of hyperkaliuria was the diminution of calcium excretion, despite normocalcemia. CONCLUSION: The association between sodium and calcium reabsorption in the loop of Henle predicts hypercalciuria in patients with a defect in salt reabsorption in this segment, as in Bartter's syndrome. In Gitelman's syndrome the laboratory features resemble the findings in Bartter's syndrome, except for the presence of hypocalciuria. Since hypocalciuria follows also the administration of thiazide diuretics, which act in the early part of distal tube, a transport defect in this part of the tube is thought to be responsible for the electrolyte disturbances in Gitelman's syndrome. The measurement of the urinary calcium excretion in patients with an unclear hypokalemia-hypomagnesemia-syndrome allows easily the differentiation between Bartter's and Gitelman's syndrome.
Adult↗
Design, synthesis and investigation of mechanisms of action of novel protein kinase C inhibitors: perylenequinonoid pigments.
A series of perylenequinonoid pigments (PQPs) and related compounds were synthesized and screened for the inhibition of protein kinase C (PKC), a key enzyme involved in cellular differentiation and proliferation, and a potential target for anticancer and antiviral chemotherapeutic drugs. This study has established PQPs as efficient PKC inhibitors, and elucidated aspects of the light-enhanced action mode of the PKC inhibitors. Comparative studies between natural and synthetic PQPs led to the recognition of the effect of certain structural features of PQPs on PKC inhibition, including the skeleton of the 3,10-dihydroxy-4,9-perylenequinonoid chromophore and the configuration of the two side chains at positions 1 and 12. Calphostin C was identified as a superior PKC inhibitor of the POP class, and with the latter as a representative structure, we investigated the mechanism of PKC inhibition by PQPs via electron paramagnetic resonance spectroscopy in conjunction with the spin-trapping technique, absorption and fluorescence spectroscopy, photochemical and photobiological studies, and enzyme methodology. Multiple modes of action are suggested for PKC inhibition, comprising the following steps: (1) the binding of PQPs to the PKC regulatory domain via complexation; (2) the photobonding between mercapto groups of PKC cysteine residues and the PQP quinonoid moiety; and (3) the PQP-sensitized photodamage of PKC via Type I and/or Type II photosensitization.
Antibiotics, Antineoplastic↗
[Photo-brine therapy in patients with psoriasis and neurodermatitis atopica].
The effectiveness of salt water baths and subsequent selective ultraviolet phototherapy (SUP) was investigated in a prospective study on 40 patients with psoriasis vulgaris and atopic dermatitis. There were two groups with 20 patients each. The first group was treated with salt water (15%) that contained synthetic Dead Seas salt called "Psorisal"; the patients in the second group had a bath in a 3% NaCl solution. After 4 weeks of daily treatment, we found that 80% of the patients in the group treated with "Psorisal" had significantly better results than the second group. The subjective feeling of being ill had decreased significantly in both groups by the end of the study. The only side effect we found was the occurrence of sunburn in few cases, but this occurred significantly less in the "Psorisal" group. Both groups generally accepted the balneophototherapy, so it can easily be employed on an outpatient basis.
Adolescent↗
Toxic acute renal failure in the rat: effects of diltiazem and urodilatin on renal function.
Beneficial effects of natriuretic peptides have been reported in different models of acute renal failure (ARF). Calcium antagonists can also improve renal function, especially in ischemic models of ARF. The aim of our study was to investigate the effects of urodilatin and diltiazem alone and in combination in uranyl nitrate-induced toxic ARF in the rat. Three hours after induction of ARF glomerular filtration rate (GFR) was clearly diminished to about 50% compared to basal values. Intravenous infusion of diltiazem and urodilatin revealed a significant increase of GFR that even continued after cessation of drug delivery. Combined administration of urodilatin and diltiazem had no additional effect, probably due to a more pronounced fall in blood pressure in this group. Besides their vasorelaxing and blood pressure lowering effects both drugs also revealed diuretic activity. In conclusion both urodilatin and diltiazem are able to elevate GFR in the early phase of toxic ARF in the rat.
Acute Kidney Injury↗
Role of L-arginine-derived NO in ischemic acute renal failure in the rat.
Nitric oxide (NO) is involved in the regulation of renal perfusion and glomerular hemodynamics under basal conditions. We examined the hypothesis that L-arginine-derived NO modifies ischemic acute renal failure (ARF) in the rat. After a basal period ischemia was induced by clamping of both renal arteries (40 min). Thereafter, in the reperfusion period, we intravenously infused L-arginine (Arg, 300 mg/kg/60 min), or L-monomethylarginine (MeArg, 30 mg/kg/60 min), or Arg + MeArg (300 mg/kg/60 min, 30 mg/kg/60 min, resp.). Besides monitoring of urinary flow rate and arterial blood pressure, and determination of sodium excretion, glomerular filtration rate (GFR, mL/min/100 g) was estimated at the end of the infusion period and again after another 30 and 120 min by inulin clearance (fluorescence-marked inulin). In the basal period GFR showed no differences between the groups (Arg: 0.86 +/- 0.07, MeArg: 0.92 +/- 0.06, Arg + MeArg: 0.89 +/- 0.08, control: 0.84 +/- 0.07). At 180 min after the beginning of the reperfusion period, GFR was 0.13-0.02 in the control group. After administration of Arg, a remarkable and persistent increase in GFR was observed (0.28 +/- 0.03), whereas infusion of MeArg showed no significant effects (0.13 +/- 0.04). Combined administration of Arg + MeArg revealed a moderate increase of GFR (0.19 +/- 0.05), ranging between the Arg and the control group. Also, 60 and 90 min after the beginning of the reperfusion period, the highest values for GFR were obtained in the Arg group. We conclude that in this model of ischemic ARF in the rat, L-arginine-derived NO is capable of improving renal function. These data underline the regulatory role of the L-Arg-NO pathway for renal function, not only under normal conditions, but also in ARF.
Acute Kidney Injury↗
Improved fluorescent cycle sequencing protocol allows reading nearly 1000 bases.
Recently available thermostable DNA polymerases result in enhanced resolution and accuracy compared to thermal enzymes used previously in fluorescent cycle sequencing. These new enzymes produce less variations in peak intensities, enhance gel resolution and are less sensitive to unspecific termination caused by either DNA structure or impurities in the DNA preparation. Optimization of nucleotide ratios and the usage of high concentrations of detergents in the sequencing reaction result in sequence readings up to 1000 bases and improve overall reliability of the sequencing protocol; this works successfully in about 90% of cases.
DNA-Directed DNA Polymerase↗
Separation of up to 1000 bases on a modified A.L.F. DNA sequencer.
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Base Sequence↗
Sequencing and analysis of 51.6 kilobases on the left arm of chromosome XI from Saccharomyces cerevisiae reveals 23 open reading frames including the FAS1 gene.
We have sequenced two segments containing a total of 51.6 kb of the left arm from chromosome XI of Saccharomyces cerevisiae. The first segment of 38.5 kb contains 18 open reading frames (ORFs) of more than 100 amino acid residues. Five ORFs encode known yeast genes, including the fatty acid synthase gene (FAS1). Three new yeast genes were discovered with homologies to non-yeast genes and ten new genes without homologies to any known sequences. The second segment of 13 kb contains five ORFs with two known yeast genes and three unknown genes. The sequences from cosmid pUKG041 were obtained entirely with the walking primer strategy resulting in a very low overall sequence redundancy of 2.8 and an average reading length of 443 bases.
Base Sequence↗
Outbred mice infected by an encephalomyocarditis virus variant: a model for studying chronic viral heart disease.
Male 8 to 20-week-old NMRI mice (an outbred strain) infected with the encephalomyocarditis virus (EMCV) plaque variant (PV) 7 consistently develop a distinct myocarditis with a relatively low mortality (21%). Myocarditis occurs in essence independent of the virus dose applied, and other internal organs are not affected. Nevertheless, 3.5-week-old NMRI mice perished within 5 days of virus inoculation and exhibited disseminated myofibrillar degeneration (MFD); this obviously virus-induced myocardial damage was accompanied by scanty inflammatory infiltrates. EMCV PV7 infection of adult male C57Bl/6 and DBA/2 mice causes myocarditis comparable to that seen in NMRI mice. In DBA/2 mice, however, the virus-induced myocardial necrosis is complicated by subtotal calcification. This strain has a genetically determined "spontaneous" calcification of the myocardium, as shown by the study of uninfected controls. EMCV PV7-infected NMRI mice appear a promising model for study of long-term effects of viral myocarditis, possibly including cardiomyopathy. Furthermore, this outbred mouse strain offers the possibility of examining the pathogenesis of direct viral cytolysis and its relation to MFD as well as immunologically mediated cell damage.
Age Factors↗
Sequencing reactions for ALF (EMBL) automated DNA sequencer. European Molecular Biology Laboratory.
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Automation↗
Automated low-redundancy large-scale DNA sequencing by primer walking.
Low-redundancy automated DNA sequencing by primer walking is described. T7 DNA polymerase is used together with computer-selected walking primers and fluorescein-dATP as internal label to sequence large plasmids or cosmids directly on a standard DNA sequencer with an error rate below 1% up to 500 bases (in the unedited raw data). The low error rate allows efficient sequencing with low (2-3 times) redundancy. Plasmid subclones covering 20 kb of a cosmid insert were sequenced with an overall redundancy of 2.7 in the course of the European community Saccharomyces cerevisiae genome sequencing project. Neighboring plasmid subclones were linked by direct cosmid sequencing. Sets of ten walking primers are synthesized on the EMBL multiple segmental DNA synthesizer at low costs and used for sequencing with greater than 95% efficiency. The accuracy of the directed approach is improved by simultaneous walking on both strands by designing two primers in opposite directions in the same starting region. One primer is used to confirm sequence data on the opposite strand, and the other primer to obtain new sequence data.
Autoanalysis↗
[Perioperative cardiovascular reactions and the noradrenaline plasma level in patients on chronic antidepressant medication].
UNLABELLED: It is still controversial whether the perioperative incidence of cardiovascular complications is increased in patients on chronic treatment with cyclic antidepressants (AD) and whether AD medication should be discontinued prior to surgery. METHODS. We measured perioperative cardiovascular variables in 31 patients on chronic treatment with tri- and tetracyclic AD and 31 patients without AD medication. Heart rate, blood pressure, and noradrenaline plasma concentrations were compared between the two groups at nine points in time. During induction of anaesthesia, the ECG was recorded continuously. After the administration of 0.01 mg/kg atropine i.v., all patients received opiate-supplemented enflurane anaesthesia. RESULTS: Re-uptake inhibition of noradrenaline by AD resulted in significantly higher noradrenaline plasma concentrations before and during anaesthesia in the AD-treated group. The incidence of arrhythmias, blood pressure elevations, and tachycardia was not increased in patients in AD treatment. Arrhythmias during induction of anaesthesia were seen in 6 of the AD-treated patients and 5 of the controls. Blood pressure elevations by more than 35% were seen in 10 patients on AD treatment and 8 controls. The heart rate prior to induction of anaesthesia and 2 h after the end of surgery was significantly higher in the AD-treated group. During anaesthesia the heart rate was higher at two points in time only. The incidence of tachycardia was similar in both groups. Intravenous administration of 0.01 mg/kg atropine prior to induction of anaesthesia increased the heart rate of the patients on chronic AD medication by 11.4%. This increase was significantly higher in the control group (16.2%), suggesting that patients with chronic AD treatment do not have a higher sensitivity to atropine. CONCLUSION: The elevated noradrenaline plasma levels in patients on chronic AD treatment did not result in a higher incidence of arrhythmias, blood pressure elevations, or tachycardia perioperatively. Taking these results into account, we do not consider it necessary to discontinue chronic AD medication prior to surgery in patients without cardiovascular disease.
Antidepressive Agents↗
Hemodynamic responses to noxious stimuli in brain-dead organ donors.
The case report presents evidence for the spinal origin of the marked hypertensive responses to noxious stimuli that may occur in organ donors who fulfill the commonly accepted criteria of brain death. Cardiovascular spinal reflex activity does not invalidate these criteria. For the first time, the catecholamine plasma concentrations have been determined during spinal pressor reflex activity. Circulating epinephrine increased more markedly than norepinephrine in both cases, rising to 4.7 and 44 times the baseline concentration respectively. The relation between plasma norepinephrine and epinephrine suggests involvement of the adrenal medulla in the reflex arc. The literature on spinal hemodynamic reflexes is reviewed.
Adult↗
Acute endocrine failure after brain death?
After brain death, 32 potential organ donors were studied to determine serum and plasma concentrations of hypothalamic-pituitary hormones, thyroid hormones, and cortisol over a period of up to 80 hr. Diagnosis of brain death was established either on the basis of clinical criteria (n = 16) or by angiography (n = 16). While 78% of the organ donors developed diabetes insipidus, none of the circulating hormones of the anterior pituitary gland showed a progressive decline in concentration according to their plasma half-lives. With the exception of arginine vasopressin (AVP), no hormone concentration was found to be subnormal due to the onset of brain death. The subnormal free triiodothyronine (FT3) values in 62% of cases (median FT3 of 2.2 pmol/L within the first 24 hr) and the cortisol concentration of 6.9 micrograms/dl correlate with the frequency of similar findings in patients with severe head injuries. While the adrenocorticotropic hormone (ACTH) concentrations of 10-53 pg/ml remained constant during the study period, thyroid-stimulating hormone (TSH) and human growth hormone (hGH) concentrations showed a 12- and 35-fold increase from baseline values after 30-40 hr. These results suggest that, despite the now generally accepted criteria of brain death, there is still some residual function, and thus also perfusion of the hypothalamic-pituitary neuroendocrine system. This residual function appears to be sufficient to maintain hormonal plasma levels at least in the low reference range in most donors. Hormonal depletion in organ donors subsequent to brain death, as suggested repeatedly in the literature, could not be confirmed. The analysis of serum or plasma concentration patterns of a number of hormonal parameters following brain death does not support the rationale for a routine replacement therapy of total triiodothyronine (TT3) or cortisol to maintain endocrine homeostasis prior to organ harvest. However, dexamethasone therapy may be followed by suppression of the adrenal cortex of the organ donor. In these cases, cortisol substitution may be indicated.
Adrenocorticotropic Hormone↗
[Musical-verbal hallucinations and their correlation with electroencephalography and PET findings. Case report].
A case is reported of an organic auditory hallucinosis and depressive episode in a man aged 52. A new finding is the correlation of the musical hallucinosis to a central nervous disorder as shown by pathological sphenoidal EEG and 18FDG-PET-examination and not to acquired peripheral hearing deficit as often reported before.
Blood Glucose↗
Structure of the gene encoding human casein kinase II subunit beta.
Casein kinase II (CKII) is a ubiquitous serine/threonine protein kinase with numerous key functions in cell metabolism and growth. The human CKII has a tetrameric structure; two catalytic subunits (alpha and alpha') form the holoenzyme together with two presumably regulatory subunits (beta). The gene encoding CKII subunit beta was isolated from human genomic DNA and analyzed for its primary structure using exclusively nonradioactive procedures. The gene was found to span 4.2 kilobase pairs and to be composed of seven exons. Exon sizes range from 76 (exon 5) to 329 base pairs (bp) (exon 1), intron sizes from 145 (intron V) to 965 bp (intron II). All exon-intron junctional sequences conform to the canonical GT-AG rule. Primer extension analysis determined three transcription initiation sites, at 951, 919, and (minor) 840 bp upstream of the translation start site. The translation start is located early in the second exon; exon 1 is untranslated. The 3'-cleavage/polyadenylation signal sequence (AA-TAAA) is in the last exon at position 4173 bp relative to the first transcription initiation site. The coding sequence for CKII beta comprises 648 nucleotides identical to the published CKII beta-cDNA sequence (Jakobi, R., Voss, H., and Pyerin, W. (1989) Eur. J. Biochem. 183, 227-233). The upstream promoter region of the CKII beta gene contains multiple potential gene regulatory sequence elements, noticeable DNA structures, and the characteristics of a housekeeping gene (more than one transcription initiation site, lack of a TATA-box, presence of a CpG island, occurrence of multiple GC boxes and of nonstandard positioned CCAAT boxes). The CKII beta gene promoter shares common features with that of mammalian protein kinases and is closely related to the regulatory subunit gene promoter of cAMP-dependent protein kinase.
Amino Acid Sequence↗
Measurement of plasma catecholamines by high-performance liquid chromatography with electrochemical detection in intensive care patients after dobutamine infusion.
A procedure for the determination of plasma catecholamine concentrations in critical care patients after dobutamine infusion is presented. A modified chromatographic system is required with an additional washing procedure to achieve maximum sensitivity and stable chromatographic conditions. The influence of storage time on the catecholamine concentrations of plasma samples is reported in detail. A time-dependent decrease in catecholamine concentrations of up to 12 and 39% was found within two and ten months, respectively.
Catecholamines↗