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Biomedical subjects

K Voigt

Publications and source records attributed to K Voigt.

At least 73 records · Page 4Linked to original sources
PubMed1995

Characterisation of the processing by human neutral endopeptidase 24.11 of GLP-1(7-36) amide and comparison of the substrate specificity of the enzyme for other glucagon-like peptides.

The post-secretory processing of the potent insulinotropic peptide hormone, GLP-1(7-36)amide, probably involves one or more of a small group of membrane-bound ectopeptidases. Reported here, is the characterisation of the endoproteolysis of human GLP-1(7-36)amide by the recombinant human form of neutral endopeptidase (NEP) 24.11, which is one of the best characterised and widely-distributed of ectopeptidases and is involved in the processing of other peptide hormones. The products of the limited endoproteolysis were characterised by mass and primary structure following fractionation using high performance liquid chromatography. The rate of this endoproteolysis by NEP 24.11 was estimated and compared to that of GLP-1(7-36)amide-related peptides. GLP-1(7-36)amide appears to be good substrate for NEP 24.11 with most, but not all potential target bonds being cleaved. Also, the structurally-related peptides, secretin and glucagon appear to be good substrates whereas GIP and exendin-4 are very poor substrates. That the GLP-1(7-36)amide super-agonist, exendin-4 is a poor substrate for NEP 24.11 is significant for the possible use of this peptide as a prototype for the development of clinically-useful peptide agonists. Further studies should reveal whether NEP 24.11 is important for the metabolic clearance of GLP-1(7-36)amide and will be highly relevant for the attempts to realise the suggested therapeutic value of GLP-1(7-36)amide.

Amino Acid Sequence↗
PubMed1995

Toxicology databases in the metadatabank of online databases.

Databases in science and technology dealing with toxicology subjects are of great and increasing interest to the scientific community. International hosts pay their tribute in creating toxicology clusters as a user-aid. Toxicology clusters of DataStar, DIALOG, DIMDI and STN are listed and compared. At the German National Research Centre for Environment and Health an 'Information System for Environmental Chemicals' has been developed. Within this research project approximately 400 online databases have been evaluated and the results are stored in the Metadatabank of Online Databases called DADB. A further step in this project is to assist the users of these metadatabases to choose the most appropriate database(s) for a special query. The retrieval of information out of a multitude of differently structured databases can be optimized using different evaluation criteria. We distinguished three groups of evaluation criteria: (1) general evaluation criteria, e.g. size of database, update frequency, cost of online search, etc., (2) evaluation criteria based on the characterization of environmental chemicals, and (3) evaluation criteria based on environmental-relevant data-types. We studied the influence of a number of different criteria in order to rank a set of objects, in this particular case toxicology databases. We used a six-number scoring system. The scoring is carried out using the scientific background of lattice theory and its graphical evaluation. The application of this scoring system for toxicologically-relevant databases, which is still in an early development stage, is useful in selecting the most appropriate database(s) in accordance with special items of interest. Applying our five chosen criteria, the databank CA (Chemical Abstracts) turns out to be the best, followed by four other databanks, which cannot be compared with each other.

Databases, Factual↗
PubMed1995

Genetic variability in Gibberella fujikuroi and some related species of the genus Fusarium based on random amplification of polymorphic DNA (RAPD).

One of the most important rice pathogens is Fusarium moniliforme (perfect stage: Gibberella fujikuroi), the causal agent of the super-elongation ("bakanae") disease. Thirty-seven strains of this species from different geographical regions were analyzed for their ability to produce gibberellins (GA) and for genetic relatedness by random amplified polymorphic DNA (RAPD). All GA-producing isolates showed nearly identical RAPD patterns using 51 oligonucleotide nona- and deca-mers as arbitrary primers. On the other hand, large differences between GA-nonproducing isolates were obtained. Comparison of the RAPD patterns with those of the tester strains of the six known mating populations (A, B, C, D, E, F) of G. fujikuroi showed that all producer strains belong to mating population C and all nonproducer isolates to other mating populations. Evidence for the usefulness of the RAPD technique to distinguish between mating populations was provided by sexual crossings. Consensus phylogenetic trees based on RAPDs were constructed by the Phylogenetic Analysis Using Parsimony (PAUP) system. In combination with morphological analysis, RAPD can distinguish between different species of the genus Fusarium. These investigations may find an application in the diagnosis of unknown Fusarium spp. and in distinguishing isolates of G. fujikuroi within the section Liseola.

Base Sequence↗
PubMed1995

The combination of Gilbert/Maxam chemical sequencing and the dideoxynucleotide chain termination approach facilitates the construction of species specific PCR-primers based on diagnostic RAPD bands.

The randomly amplified polymorphic DNA technique (RAPD) is a modification of PCR that uses short, arbitrarily generated single primers to amplify genomic DNA. Amplified DNA-fragments are often polymorphic and can be used as individual, population- or species-specific markers. Because the RAPD technique requires a very high degree of reproducibility at the instrumentation level and with regard to buffer conditions, we propose to synthesize highly specific conventional PCR primers, the sequence of which is based on the primary diagnostic RAPD bands. In this communication we present a fast and convenient experimental strategy for converting the non-stringent RAPD conditions with their low annealing temperatures to stringent PCR conditions. Diagnostic RAPD bands were sequenced by a combination of chemical (Gilbert/Maxam) and chain termination (Sanger) techniques. Based on this sequence information, highly specific oligonucleotide primers were synthesized. The value of this approach was demonstrated for the molecular diagnosis of the important rape seed (Brassica napus) pathogen Leptosphaeria maculans.

Ascomycota↗
PubMed1995

Preprotachykinin-A gene expression occurs transiently in the developing rat endocrine pancreas and can be regulated in RINm5F cells.

We have reported previously that the rat insulinoma cell lines, RINm5F and RINr1046-38, express the preprotachykinin(PPT)-A gene, which encodes the tachykinin peptides, substance P and neurokinin A. Because endocrine cells of the adult rat pancreas do not appear to express PPT-A, we investigated whether the gene is expressed by rat pancreatic endocrine cells during development. We used immunohistochemistry, employing different substance P and neurokinin A antibodies, to show that many endocrine cells of the fetal and neonatal rat pancreas synthesise these products of PPT-A gene expression. Colabeling experiments revealed that a significant number of both insulin-containing and non-insulin-containing cells express tachykinins. After postnatal day 20, the number of tachykinin-immunoreactive pancreatic islet cells declines and, as already reported, none were detected in the adult rat pancreas. The transient expression of PPT-A by the developing endocrine pancreas is a novel finding. Substance P and neurokinin A are known to have trophic actions and may serve as growth factors during pancreatic islet development. PPT-A gene expression by RINm5F and RINr1046-38 cells is further evidence that these cells resemble developing pancreatic endocrine cells. They are potentially valuable as unique models for studying the regulation of tachykinin biosynthesis. We provide evidence in this study, using quantitative PPT-A messenger RNA analysis, that PPT-A expression in RINm5F cells may be up-regulated by activation of protein kinase C, down-regulated by activation of glucocorticoid receptors, and is not significantly affected by changes in intracellular cAMP levels.

Animals↗
PubMed1995

Intra-extradural hemangioblastoma of the cauda equina.

This is a case report of a hemangioblastoma of the cauda equina with intra-extradural extension in the form of a dumbbell tumor. For the first time diagnosis of an intra-extradural spinal hemangioblastoma was made by computerized tomography (CT) and magnetic resonance imaging (MRI). A total excision was performed with microneurosurgical techniques and application of Nd:YAG laser. Clinical appearance, neuroradiological diagnostic procedures and neurosurgical therapy of intra-extradural hemangioblastomas of the cauda equina and of spinal hemangioblastomas of other localization were compared.

Adult↗
PubMed1994

Variations in ploidy among isolates of Botrytis cinerea: implications for genetic and molecular analyses.

Field isolates and laboratory strains of Botrytis cinerea, an ascomycetous fungus causing considerable economic losses, e.g., as "grey mould" of vine, were compared for differences in ploidy level by determining their DNA content per nucleus. Strain SAS56, an ascospore line used routinely for genetic analyses, is probably polyploid, since treatment with benomyl causes a significant reduction in DNA content per nucleus. This conclusion is substantiated by the increased sensitivity of the putative haploid derivatives to mutagens (UV and EMS). Molecular analyses (RAPD) of the haploidized strains indicate a very limited degree of heterozygosis of the parent strain SAS56. Analysis of field isolates of B. cinerea showed that their DNA content per nucleus varied considerably, indicating that aneuploidy/polyploidy is a widespread phenomenon in this species. This can explain both the variability and phenotypic instability of many field isolates of this fungus and the unusual difficulties faced by researchers in recovering stable recessive laboratory mutants. Since the haploid derivatives of SAS56 resemble the parent strain in their parasitic and physiological properties they should provide a good basis for classical and molecular genetic studies.

Base Sequence↗
PubMed1994

The "dural tail" adjacent to meningiomas studied by dynamic contrast-enhanced MRI: a comparison with histopathology.

We examined 32 patients with intracranial tumors (17 meningiomas, 8 neuromas, 7 pituitary adenomas) by conventional and dynamic contrast-enhanced MRI. Our aim was to clarify whether the pathological dural contrast enhancement adjacent to meningiomas (the "dural tail") is specific to meningiomas and, more important, whether it represents neoplastic dural infiltration or hypervascularization as a tumor accompanying reaction. A "dural tail" was found in 9 of 17 meningiomas. None of the other extra-axial tumours (neuromas, pituitary adenomas) showed comparable dural enhancement. Dynamic examinations with an ultrafast single slice imaging technique (snapshot-FLASH) after a bolus injection of contrast medium showed a "dural tail" in seven out of these nine meningiomas, while in two cases the "dural tail" turned out to be a cortical vein with a characteristic dynamic contrast enhancement pattern. In the dynamic study all seven "dural tails" were found to have earlier, steeper contrast enhancement than the corresponding tumours. All the tumours and part of the adjacent dura mater in four of the seven meningiomas with dural enhancement were examined histopathologically. In none of these four cases was neoplastic tissue found more than 2 mm away from the main tumour. The results strongly support the suggestion that the "dural tail" adjacent to meningiomas represents a hypervascular, non-neoplastic dural reaction.

Adenoma↗
PubMed1994

Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT.

Sixteen patients with a clinical diagnosis of probable multiple system atrophy (MSA) were examined clinically by MRI and by 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT). The clinical records of another 16 patients were also analysed retrospectively. On the basis of their clinical presentation, patients were subdivided into those with prominent parkinsonism (MSA-P, n = 11) and those with prominent cerebellar ataxia (MSA-C, n = 21). Autonomic symptoms were present in all patients and preceded the onset of motor symptoms in 63% of patients. Calculated median lifetime and the median time to become wheelchair bound after onset of disease were significantly shorter for MSA-P than for MSA-C (lifetime: 4.0 v 9.1 years; wheelchair: 3.1 vs 5.0 years) suggesting a better prognosis for cerebellar patients. A significant loss of striatal dopamine receptors (below 2 SD threshold) was detected by IBZM-SPECT in 63% of the patients (56% below 2.5 SD threshold). There was no difference between patients with MSA-C and those with MSA-P in the proportion with significant receptor loss and the extent of dopamine receptor loss. Planimetric MRI evaluation showed cerebellar and brainstem atrophy in both groups. Atrophy was more pronounced in patients with MSA-C than in those with MSA-P. Pontocerebellar hyperintensities and putaminal hypointensities on T2 weighted MRI were found in both groups. Pontocerebellar signal abnormalities were more pronounced in MSA-C than in MSA-P, whereas the rating scores for area but not for intensity of putaminal abnormalities were higher in MSA-P. MRI and IBZM-SPECT provide in vivo evidence for combined basal ganglia and pontocerebellar involvement in almost all patients in this series.

Adult↗
PubMed1993

Demonstration of giant MCA aneurysm by transcranial duplex sonography and color Doppler imaging.

Transcranial color Doppler sonography is a new diagnostic technique which allows real-time, color-coded imaging of basal cerebral arteries, with simultaneous demonstration of parenchymal structures in the B-mode scan. With this technique we were able noninvasively to show a giant fusiform aneurysm of the middle cerebral artery (MCA) in an 11-year-old boy. Transcranial color Doppler sonography through the intact temporal bone demonstrated the size and location of the aneurysm and provided real-time imaging of the pulsating intra-aneurysmal flow. Additionally, duplex sonographic measurements of intravascular flow velocities within the aneurysm and the feeding and draining artery were possible. Postoperatively, patency of the MCA with reduced flow velocities after excision of the aneurysm could be shown. This is the first transcranial color Doppler report in a patient with an intracerebral aneurysm. In our opinion, transcranial color Doppler sonography offers new diagnostic possibilities in patients with cerebrovascular disorders.

Blood Flow Velocity↗
PubMed1993

[Therapy control of theophylline evening dosage in patients with sleep-related respiratory disorders--follow-up study].

We conducted a prospective study to perform classification according to responder types and follow-up during theophyllin treatment (500 mg/d) in a group of (up to now) 65 patients suffering from sleep apnoea. Changes in the apnoea index (AI) and clinical symptoms were taken as response criteria. A significant AI reduction was seen during a follow-up period of 3 months. At the last control measurement after 6 months no significant change has been detected so far. 10 patients were classified as Type I responders (improvement in initial AI 60%, over the total period at least 25%). No patient had a responder type II profile. 13 patients were nonresponders (improvement in initial AI and over the whole period not more than 25%, no improvement in the pattern of clinical symptoms). 13 patients dropped out of the trial due to non-compliance. Side effects typical of theophyllin leading to discontinuation of the treatment course occurred in 5 patients. 22 patients have not yet completed the course at the time of writing. Standardised questioning of patients showed a definite improvement in feeling tone, especially with regard to the tendency to fall asleep during the day and refreshed feeling in the morning. Nocturnal complaints occurred in only a few isolated cases. Hence, administration of theophyllin retard preparations in evening doses of 500 mg/d remains a meaningful therapeutic approach to sleep apnoea.

Adult↗
PubMed1992

Characterisation of the expression and post-translational processing of the preprotachykinin-I gene and the regulated release of tachykinins by the RINm5F cell-line.

Normal transcription and postranslational processing of the preprotachykinin (PPT)-I gene and regulated release of substance P and neurokinin A by the rat pancreatic endocrine cell-line, RINm5F, has been demonstrated, using radioimmunoassays (RIAs), reversed-phase (rp)HPLC and Northern blot analysis. This is the first stable cell-line found to express the PPT-I gene and provides an opportunity for investigating PPT-I gene expression and tachykinin biosynthesis. RIN5mF cells are a model for the pancreatic beta-cell, which is not known to exhibit PPT-I gene expression which may, therefore, be a feature of the transformed state of these cells. These data may imply that the tachykinins are important in pancreatic islet embryogenesis.

Animals↗
PubMed1992

MR imaging of experimental meningeal melanomatosis in nude rats.

MR imaging of the rat brain has become an increasingly frequently used method in experimental neuroradiology. On a generally available 1.5 T whole body tomograph, supplemented with an individually made small coil and a special SE sequence we obtained fairly fine images of the structures of the rat brain. With gadolinium-DTPA, we were able to visualize posterior fossa and cervical leptomeningeal growth of intrathecally injected B16 melanoma in nude rats. Using MRI to follow experimental leptomeningeal metastasis, may provide a new means for diagnostic evaluation and preclinical testing of treatment modalities.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Effective suppression of luteinizing hormone and testosterone by single doses of the new gonadotropin-releasing hormone antagonist cetrorelix (SB-75) in normal men.

In rats and nonhuman primates the new GnRH antagonist cetrorelix (SB-75; [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]GnR H) has been shown to suppress testosterone secretion effectively and persistently. A clinical phase I study was performed to assess the hormonal effects of this highly potent antagonist in normal men. After 2 control examinations 30 young male volunteers were randomly assigned to 6 treatment groups (n = 5/group), and single doses of 0 (placebo), 0.25, 0.5, 1.0, 2.0, and 5.0 mg cetrorelix were administered sc. Blood samples were obtained over the course of 7 days postinjection. After maximal cetrorelix serum levels were achieved 1 h postinjection, the GnRH antagonist serum levels decreased with a terminal t1/2 of 29.8 +/- 4.2 h (mean +/- SE). LH secretion was suppressed dose- and time-dependently; maximal suppression occurred 4-6 h postinjection. Suppression of FSH did not reach statistical significance. Doses of 1.0, 2.0, and 5.0 mg cetrorelix significantly suppressed testosterone secretion compared to that in the placebo group. After the administration of 1.0 mg cetrorelix, maximal suppression was seen 8 h after injection, with testosterone levels of 7.5 +/- 1.1 nmol/L compared to 15.8 +/- 2.2 nmol/L in the placebo group. Maximal testosterone suppression by 2.0 and 5.0 mg cetrorelix occurred 12 h after injection, with testosterone concentrations of 4.9 +/- 0.5 and 2.2 +/- 0.4 nmol/L, respectively, compared to 16.5 +/- 1.7 nmol/L in the placebo group. Twenty-four hours after the injection of 1.0 and 2.0 mg cetrorelix, testosterone values were no longer significantly different from those in the placebo group, whereas in the 5.0-mg dose group testosterone concentrations increased slightly and reached serum concentrations in the lower normal range after 48 h. The only side-effect observed after the administration of cetrorelix was a transient local erythema at the injection site that disappeared within 30 min. No local induration or pruritus, or any adverse systemic side-effect occurred in any volunteer. In conclusion, the new GnRH antagonist cetrorelix effectively decreases serum LH and testosterone concentrations in a dose- and time-dependent manner and, therefore, has potential for treatment of sex hormone-dependent diseases and male contraception.

Follicle Stimulating Hormone↗
PubMed1991

Different modulation of the perioperative stress hormone response under neurolept-anaesthesia or enflurane for cholecystectomy.

Two groups of 13 patients, randomly allocated to receive either enflurane or neurolept anaesthesia for cholecystectomy, were compared in their cardiovascular and neuroendocrine response to surgery and in the postoperative period. There were no significant differences in blood pressure or heart rate. Catecholamine values were higher under neurolept anaesthesia towards the end of surgery and postoperatively. Median values for adrenaline during suture of peritoneum were 342 pg/ml and 88 pg/ml, respectively, P less than 0.05. In contrast, ACTH and cortisol rose to higher levels in enflurane treated patients. At the end of surgery median ACTH values were 75 pg/ml in NLA patients and 322 pg/ml in enflurane patients (P less than 0.01). Vasopressin increments during surgery were similar under both regimens, while prolactin was higher following induction of neurolept anaesthesia. It is discussed whether the differences in stress hormone secretion patterns under either form of anaesthesia reflect different stress protective properties or direct pharmacological effects of certain anaesthetics. We conclude that the hormonal stress response to surgery is critically dependent on the type of anaesthesia and may be discordant in different hormonal systems.

Adrenocorticotropic Hormone↗