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Biomedical subjects

H Zühlke

Publications and source records attributed to H Zühlke.

At least 19 recordsLinked to original sources

Cardiovascular multimorbidity, emerging coalescence of the integrated panvascular approach.

Cardiovascular diseases are systemic processes frequently involving multiple vascular beds. Cardiovascular multimorbidity, arbitrarily defined as a clinically relevant disease of at least two major vascular beds in a single individual is frequent occurring in 30% to 70% of patients depending on the patient population. Management of patients with cardiovascular multimorbidity is complex requiring an interdisciplinary consensus and coordination. A panvascular concept of an interdisciplinary integrated management of these patients is introduced.

Cardiovascular Diseases↗

DGAT1, a new positional and functional candidate gene for intramuscular fat deposition in cattle.

Intramuscular fat content, also assessed as marbling of meat, represents an important beef quality trait. Recent work has mapped a quantitative trait locus (QTL) with an effect on marbling to the centromeric region of bovine chromosome 14, with the gene encoding thyroglobulin (TG) being proposed as a positional and functional candidate gene for this QTL. Recently, the gene encoding diacylglycerol O-acyltransferase (DGAT1), which also has been mapped within the region of the marbling QTL, has been demonstrated to affect the fat content of milk. In the present study, the effects of a 5'-polymorphism of TG and of a lysine/alanine polymorphism of DGAT1 on the fat content of musculus (m.) semitendinosus and m. longissimus dorsi in 55 bovine animals (28 German Holstein and 27 Charolais) has been investigated. Significant effects were found for both candidate genes in both the breeds. These effects seem to be independent of one another because the alleles of the two polymorphisms showed no statistically significant disequilibrium. The DGAT1 effect is mainly on the m. semitendinosus. The TG polymorphism only affects m. longissimus dorsi. However, both intramuscular fat enhancing effects seem to be recessive. The possibility of two linked loci, acting recessively on intramuscular fat content, will require special strategies when selecting for higher marbling scores.

Acyltransferases↗

[Which factors are responsible for postoperative mortality in colorectal cancer patients?].

INTRODUCTION: The postoperative decease is the most severe complication in surgery. PATIENTS AND METHOD: Within the framework of a multicentre study between January 1 (st) and December 31, 1999, 3,756 patients, 1,463 of them suffering from rectal cancer and 2 293 from colon carcinoma, from 75 clinics were documented with the help of a standardized questionnaire. We compared data of 211 patients who died postoperatively with data of 3,484 patients who survived after surgical treatment of colorectal cancer. Logistical regressions, under inclusion and exclusion of intra- and postoperative complications, show independent influence factors on the postoperative decease and provide models for the prediction of the postoperative death. RESULTS: Compared to the patients who survived, the postoperative deceased patients were significantly older. They had a poorer risk profile and therefore a higher ASA-score (p < 0.001). 20.4 % of the patients underwent an emergency operation. General and specific postoperative complications occurred significantly more frequently. The model of a logistical regression allowed the prediction of postoperative decease with a sensitivity and specificity of 91 %. General postoperative complications such as pulmonary embolism (relative risk: 30.3), cardiac (relative risk: 24.1), renal (relative risk: 22.1), and pulmonary complications (relative risk: 12.0) are crucial for lethality. DISCUSSION: The postoperative decease is influenced by several factors. It is impossible to reduce the number of influence factors for the prediction of outcome. The general postoperative complications, however, represent a crucial problem. It is important to avoid these problems in order to reduce postoperative lethality.

Adolescent↗

[Can intuition in surgery by learned?].

Intuition, even at the end of the 20th century, has decisive significance in the field of medicine. Intuition within the medical field is understood to be a type of thinking based on experience, but without conscious recourse to its situations and thought processes; rather, it represents an act without reflection and one determining our medical actions to some extent. It is a cognitive process, an intuitive gain in recognition on the basis of experiential values called up from memory. Intuition is a combination of knowledge, ability, endurance, intellectual abilities, and discoursive methods of recognition, in short, the abilities of an expert. To become an expert, one must go through the stations of surgical training. In these the knowledge is imparted, which leads via decision-making to diagnosis and therapy. Intuition in the sense of the definition as experiential thinking cannot be learnt, but it can be schooled. The prerequisites for this are analytic thinking, expert knowledge, and metacognitive knowledge.

Clinical Competence↗

Maternally-inherited diabetes and deafness: report of two affected German families with the A3243G mitochondrial DNA mutation.

In two German families four patients containing the A3243G mutant in the mitochondrial DNA suffered from maternally-inherited diabetes and deafness (MIDD). DNA was isolated from oral mucosa cells. Using the polymerase chain reaction with not yet published primers, we obtained after digestion with the restriction endonuclease BSP 1201 two oligonucleotides of comparable size increasing the sensitivity of our method two times. Under these conditions we were able to detect 0.8% of the mutated DNA. In general, the patients show the characteristics proposed for MIDD by Maassen et al. (1997), however, there are some differences: age at onset (in our study 36-45 y), body mass index (>26 kg/m2). In addition, our study shows that MIDD may be combined with neuronal disorders (M. Parkinson, epilepsy) and/or endocrinopathies (M. Addison). Our data indicate that MIDD is a heterogeneous disease. On the other hand, in one family there are healthy probands with a high concentration of mutated mitochondrial DNA.

Adolescent↗

Expression of two proopiomelanocortin mRNAs in the islets of Langerhans of neonatal rats.

Proopiomelanocortin-(POMC) derived peptides have been found in pituitary and in nonpituitary tissues including the endocrine pancreas. However, only a truncated 800-base POMC-like mRNA is demonstrable in most nonpituitary tissues. The functional relevance of this RNA is doubtful, because it lacks the sequences of translation initiation and signal peptide (exon 1 and 2). Recently we have demonstrated the truncated POMC-like mRNA in pancreatic islets. Using PCR techniques in this paper we prove the existence of a full-length POMC mRNA in this tissue. This RNA contains the sequences of exon 1 and 2, as shown by Southern blot technique and by sequencing parts of the PCR products. We suppose that this RNA is the source of the POMC peptides in islets despite of its small amount.

Animals↗

The neuropeptide galanin occurs in two conformations.

The secondary structure of the six known species forms of galanin was predicted using a statistical method. In the region between positions 13 and 20 the model predicts alpha-helical structures in human, cow, and chicken galanin, whereas the model does not predict alpha-helical structures in the same region of pig, rat, and sheep galanin. Based on the different conformational states of galanin, the species forms of galanin could be divided in two groups: galanin A (= human, cow, chicken galanin) and galanin B (= pig, rat, and sheep galanin). A chemical explanation might thus be provided for the observed differences in potency between different species forms of galanin (A or B) to inhibit insulin secretion.

Amino Acid Sequence↗

In vitro effect of vanadate on content, secretion and biosynthesis of insulin in isolated islets of normal Wistar rats.

In in vitro experiments the effect of (Na-ortho)vanadate (1-50 mumol/l) on content, secretion and biosynthesis of insulin was investigated in isolated islets of normal Wistar rats. Compared with controls insulin content is unchanged, but insulin secretion and biosynthesis rate are significantly reduced; secretion is significantly more reduced in the basal than in the stimulating glucose medium. Our results support the view that vanadate exhibits its influence on insulin metabolism in the beta cell already.

Animals↗

Presence and regulation of a truncated proopiomelanocortin gene transcript in rat pancreatic islets.

The demonstration of proopiomelanocortin-(POMC-) derived peptides in the endocrine pancreas suggests a local biosynthesis of these peptides. Using Northern blot analysis we demonstrated a 800 nucleotide POMC-like mRNA species. The POMC-like mRNA was demonstrable in a part of the pancreatic islets by the in situ hybridization technique. A small number of single cells within the exocrine pancreas were also found to give positive hybridization signals. Isolated islets were incubated under normoglycemic conditions with dibutyryl-cAMP (3mM) or dexamethasone (0.1mM) for 4 h. Dibutyryl-cAMP significantly (p < 0.01) increased the POMC-like mRNA content to 177 +/- 39.1% of the control whereas dexamethasone decreased it to 66.9 +/- 11.4% of the control. In vivo treatment of adult rats with 80 micrograms dexamethasone over 3 days showed also a reduction of the POMC-like mRNA level in the islets. In conclusions, the POMC gene is expressed in adult rat islets and can be regulated by dexamethasone and dibutyryl-cAMP. Whether the truncated POMC-like mRNA reported here is the source of the biosynthetic POMC-like products detected in the islets is not yet known.

Animals↗

Expression of exogenous DNA in rat liver cells after liposome-mediated transfection in vivo.

Liposomes containing the expression vector pRSVneo coding for neomycin phosphotransferase-II were used for a gene transfer into rat liver cells in vivo. After intravenous application of liposomes to male Wistar-rats, non-integrated vector DNA was detected by blot-hybridisation in isolated nuclei of hepatocytes. Presence of messenger RNA specific for the transferred construct was demonstrated by Northern analyses of poly(A)+RNA. The biological activity of the neomycin phosphotransferase-II gene and its enzyme could be demonstrated in hepatocytes for at least 7d post injection. Liposome-mediated gene transfer into adult animals is discussed as a model system to study the expression and fate of transferred genes in adult rat hepatocytes under physiological conditions.

Animals↗

DQ beta restriction fragment length polymorphism in insulin dependent diabetes mellitus.

HLA DQ beta restriction fragment length polymorphisms (RFLP's) were compared in 43 patients with insulin dependent diabetes mellitus (IDDM), 51 healthy first grade relatives of IDDM patients and 27 controls without IDDM heredity in their families. We were able to demonstrate an association between the presence of a 12 kb BamHI restriction fragment (p less than 0.001) and 12 kb/4 kb (p less 0.01) or 12 kb/4.4 kb (p less than 0.001) BamHI fragment combinations and IDDM. But for these fragments and fragment combinations we also found increased frequencies in the healthy first grade relatives of IDDM patients. That means for the evaluation of the importance of the characterised "risk fragments" in practice it is necessary to follow up the manifestation of IDDM in this risk group.

Adolescent↗

Bgl II-restriction fragment length polymorphism of the insulin receptor gene in patients with type-II diabetes mellitus.

As an approach to estimate the involvement of the insulin receptor gene in the etiopathogenesis of type-II diabetes mellitus we determined the distribution of the alleles of a restriction fragment length polymorphism of this gene (Bgl II-RFLP) in a group of type-II diabetics. The patients had been characterized by insulin and C-peptide values during OGTT and insulin receptor binding indices. The difference in allelic distribution to a healthy control group (10% "+"-allele in diabetics versus 18% in control persons), was not significant in chi 2-analysis.

Alleles↗

Expression of the insulin gene is regulated by opioid peptides.

The effects of the opioid peptides Met- and Leu-enkephalin on the expression of the insulin gene in isolated adult rat islets of Langerhans were examined. Isolated rat islets were maintained under various culture conditions for 26 h. The contents of islet preproinsulin mRNA and the amounts of (pro)insulin biosynthesis were assayed. In the presence of 5 mM glucose the preproinsulin mRNA content was increased by 10(-8) M Met-enkephalin to 198% (p less than 0.001) and by Leu-enkephalin to 145% (p less than 0.001) of the control without enkephalins. The preproinsulin mRNA content was raised in the presence of 5 mM glucose by 10(-10) M significant. These results corresponded with an increase in the (pro)insulin biosynthesis under the same conditions. The biosynthesis of (pro)insulin was strongly decreased by actinomycin D at the glucose and enkephalin concentrations tested. The results demonstrated that there is a dose-dependent stimulation of the insulin gene expression by enkephalins and that the increase in (pro)insulin biosynthesis in isolated pancreatic islets by endogenous opioid peptides occurs mainly on the pretranslational level.

Amino Acid Sequence↗

Genetic manipulation of rat hepatocytes in vivo. Implications for a therapy model of type-1 diabetes.

The successful expression of transferred insulin genes in non-pancreatic somatic cells could be an important step towards a somatic gene therapy of type-1 diabetes. Hepatocytes are potential target sites of a genetic manipulation. Using liposomes as a gene carrier system a method was established to manipulate rat hepatocytes in vivo. To prove this model, a bacterial marker gene (pRSVneo) was used which is normally absent in the mammalian genome. The genetic material was encapsulated into reverse-phase evaporated vesicles (REV). Using a sonication step for 60-90 s during vesicle preparation no significant loss of genetic information was observed. 70% of the liposomes were taken up by the liver within 10 min after i.v. application to male Wistar rats (1.5 mumol lipid and 10-15 micrograms DNA per 100 g b.w.). The transferred vector was detected in isolated nuclei of hepatocytes by Southern hybridisation up to 7 days. Integration events into the host genome were observed already 48 h after injection. The transcription of the transferred DNA (mRNA) as well as the translation (NPT-II activity) were demonstrated.

Animals↗

Immunohistochemical investigations of beta-endorphin in human pancreatic islets.

The PAP technique was used to examine adult human pancreata (corpus) immunohistochemically for the presence of beta-endorphin containing cells. These cells were found to account for 4.8% of the islet cells. They are irregularly distributed within the islets, where they occur singly or in groups of 3 to 5 cells between the acini (0.4% of the parenchyma). Investigations designed to detect the simultaneous presence of beta-endorphin and somatostatin or glucagon revealed that beta-endorphin occurs in somatostatin cells (1.0% of the islet parenchyma). This is the 1st proof that these 2 hormones appear together. The simultaneous presence of beta-endorphin and glucagon in the same cell was also observed in 0.9% of the islet parenchyma. Earlier studies undertaken by us have shown that beta-endorphin is synthetized in the islets of Langerhans. Possible functions of beta-endorphin in the islets are discussed.

Aged↗

Spontaneous recovery of streptozotocin diabetes in mice.

With the aim of developing a model of experimental diabetes by which spontaneous recovery processes can be investigated, we used a lower (1) and a higher (2) dose of streptozotocin (SZ) to find out the lowest possible dose definitely inducing diabetes in mice through beta cell loss but preventing excessive damage to the endocrine pancreas which would exclude restoration processes. After application of SZ (1) to neonatal mice only male animals showed an overt diabetes in adult life. 70 percent of these mice had recovered 15 weeks after appearance of diabetes. Recovery was indicated by normalization of blood glucose, serum insulin, insulin secretion and biosynthesis of isolated pancreatic islets and a reenhancement of the pancreatic insulin content from lower than 10 to 30 percent of control values. After SZ (2) both sexes became hyperglycaemic, and the recovery rate was lower, but was increased by pregnancy in female mice. By means of this model it will be possible to investigate mechanisms and promoting factors of such restoration processes in more detail.

Animals↗