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Biomedical subjects

R Günther

Publications and source records attributed to R Günther.

At least 37 records · Page 2Linked to original sources

Direct detection of domains in phospholipid bilayers by grazing incidence diffraction of neutrons and atomic force microscopy.

The geometry of domains in phospholipid bilayers of binary (1:1) mixtures of synthetic lecithins with a difference in chain length of four methylene groups has been studied by two independent, direct and complementary methods. Grazing incidence diffraction of neutrons provided gel domain sizes of less than 10 nm in both the gel and the coexistence phase of the mixture, while no domains were detected for the fluid phase. For the coexistence region, the neutron data suggest that domains grow in number rather than in size with decreasing temperature. Atomic force microscopy was used to study gel phase size and shape of the domains. The domains imaged by atomic force microscopy exhibit a rather irregular shape with an average size of 10 nm, thus confirming the neutron results for this phase. The good agreement between atomic force microscopy and neutron results, despite the completely different nature of their observables, has potential for the future development of refined models for the interpretation of neutron data from heterogeneous membranes in terms of regularly spaced and spatially extended scatterers.

Calorimetry, Differential Scanning↗

[The vaginal stump recurrence rate in endometrial carcinoma in relation to the target volume of postoperative HDR-afterloading brachytherapy].

BACKGROUND: Basis for adjuvant strategies for patients with endometrial carcinoma is a postoperative staging including criteria such as myometrial tumor infiltration and histological grading. Such adjuvant strategies include afterloading therapy of the vagina as a long-established therapeutic concept. Our aim was to investigate the influence of the target volume on treatment results (i.e. local tumor control, side effects) in these patients. PATIENTS AND METHOD: At Jena University, Department of Radiotherapy, from 1981 to 1990 108 patients with endometrial carcinoma were postoperatively treated with high dose radiation brachytherapy of the vagina without additional percutaneous radiotherapy. Histology showed more or less differentiated adenocarcinoma in 90% of all patients, all patients were postoperatively stage I or II without proven lymphatic metastases. Dependent on individual figures patients were distributed to 3 different groups: group A: 4 x 10 Gy, tissue-thickness of 1 cm (vaginal apex) respectively 0.5 cm (lower vaginal walls); group B: 4 x 10 Gy, tissue thickness of 1 cm (upper vaginal wall); group C: 4 x 10 Gy, tissue-thickness of 0.5 cm (both excluding the lower vaginal walls). RESULTS: Both 3-year survival rates (group A: 96.6%, group B: 96.9%, group C: 97.7%) and tumor relapse rates of the vaginal apex (group A: 0, group B: 3.1%, group C: 2.2%) don't show significant differences. No case of local tumor recurrence was seen in the upper 2/3 of the vagina and the pelvic walls. Late side effects concerning bladder and rectum (grade III to IV, EORTC/RTOG) could be minimized by reducing the treatment volume (group A: 6.8%/12.6%, group B: 6.2%/3.1%, group C: 2.2%/0). CONCLUSIONS: Our results show the value of postoperative afterloading brachytherapy in patients with endometrial carcinoma, the brachytherapy of the upper vaginal wall is a sufficient therapeutic concept. Radiotherapy of the lower vaginal walls does not contribute to better tumor control, while it does significantly increase the number of unwanted side-effects in our investigation.

Adenocarcinoma↗

[Comparison of findings with 18-FDG PET and CT in pretherapeutic staging of malignant lymphoma].

AIM: Comparison of diagnostic efficiency of FDG-PET and CT regarding localisation, histology, size and FDG-uptake of a lesion. METHODS: CT- and FDG-PET studies of 27 patients with histologically confirmed malignant lymphoma as primary disease or relapse were evaluated retrospectively. In CT lesions with a diameter (DCT) > 15 mm were regarded as positive. Focal accumulations of FDG, not explained by physiological metabolism, found by visual interpretation in iterative reconstructed PET-scans, were quantified for diameter (DPET) and corrected standardized uptake value (SUV), corrected for partial-volume-effect. Lesions were classified depending on histology and lesion quality (lymph nodes, bulks, extranodal lesions). RESULTS: CT detected 78 lesions in 26 patients, all confirmed by FDG-PET. PET localized 18 additional lesions (+23%); in high grade NHL +25%. Both methods were equally efficient in cervical lymph nodes and lung lesions, in all other regions of lymphatic nodules and in case of liver and spleen lesions PET localized more lesions. SUV was significantly higher in high-grade NHL (19.0) than in low-grade NHL and Hodgkin's disease (10.6 resp. 11.1). DCT and DPET correlated significantly (r = 0.75). CONCLUSION: Diagnostic efficiency of FDG-PET is equivalent or superior to CT in staging of malignant lymphoma before therapy. Qualitative interpretation seems sufficient for staging, quantitative analysis may add information about malignancy grade in NHL.

Fluorodeoxyglucose F18↗

Pituitary adenylate-cyclase-activating polypeptide stimulates proto-oncogene expression and activates the AP-1 (c-Fos/c-Jun) transcription factor in AR4-2J pancreatic carcinoma cells.

Pituitary adenylate-cyclase-activating polypeptide (PACAP) has been shown to possess mitogenic activity in various tumor cells. The present study was designed to investigate signal transduction mechanisms and expression of the proto-oncogenes c-fos and c-jun linked to the mitogenic effect of PACAP in the pancreatic carcinoma cell line AR4-2J. PACAP-(1-27)-peptide and PACAP-(1-38)-peptide, but not the structurally related vasoactive intestinal polypeptide (VIP), potently stimulated [3H]thymidine incorporation and cell number at doses of 0.1-10 nM. Both molecular forms of PACAP strongly increased formation of cAMP and inositol trisphosphate, elevated cytosolic Ca2+ levels and induced mitogen-activated protein (MAP) kinase activity. Quantitative reverse-transcription PCR revealed that PACAP-(1-27)-peptide and PACAP-(1-38)-peptide elevated c-fos mRNA levels 50-100-fold, whereas c-jun mRNA levels increased only moderately (2-3-fold). The effect of PACAP on c-fos and c-jun expression in AR4-2J cells was rapid (20 min), transient (1-2 h), dose-dependent IC50, 0.5 nM) and was abolished by the specific PACAP receptor antagonist PACAP-(6-38)-peptide or inhibitors of protein kinase C or tyrosine kinases. Compared with PACAP, epidermal growth factor and gastrin equipotently stimulated c-fos transcription whereas VIP, secretin, forskolin or phorbolester showed only marginal effects. Both PACAP (1-27)-peptide and PACAP-(1-38)-peptide strongly increased the DNA binding activity of the c-fos/ c-jun heterodimer transcription factor AP-1 at 10 nM and also stimulated AP-1 transcriptional activity up to 20-fold in AR4-2J cells. These findings indicate that the mitogenic effect of PACAP mediated via activation of the GTP-binding protein coupled PACAP/VIP-1 (PV1) receptor is linked to the MAP kinase cascade, increased expression of the proto-oncogenes c-fos and c-jun and activation of the heterodimeric transcription factor AP-1.

Animals↗

PACAP stimulates transcription of c-Fos and c-Jun and activates the AP-1 transcription factor in rat pancreatic carcinoma cells.

Pituitary Adenylate Cyclase Activating Peptide (PACAP) strongly induces proliferation of the rat pancreatic carcinoma cell line AR4-2J via interaction with the G-protein coupled type 1 PACAP/VIP (PVI) receptor. RT-PCR analysis revealed that this mitogenic effect of PACAP is preceded by a rapid and transient increase of transcription of the protooncogene c-fos and to a lesser extent of c-jun. Transcriptional activation is abolished by a specific PACAP antagonist and by inhibitors of PKC and PKA. In parallel to c-fos/c-jun induction, PACAP rapidly activates the heterodimeric transcription factor AP-1, as shown by electrophoretic mobility shift assay. These findings demonstrate that signal transduction of a growth-stimulating G-protein-coupled receptor involves the c-fos/c-jun/AP-1 cascade, a pathway mainly linked to classical growth factor receptor tyrosine kinases.

Animals↗

Hamming chromatography.

Selection of molecules with desired properties from random pools of biopolymers has become a powerful tool in biotechnology. On designing an evolution experiment, a certain knowledge of the concomitant fitness landscape is clearly helpful to set up the optimal experimental conditions. The correlation function is a useful means of characterizing a given landscape, since it can be efficiently measured if one has a method of separating a pool of random sequences according to their Hamming distance from a moderately small number of test sequences. In this paper we describe a special type of hybridization chromatography, where a mixture of oligomers (partially) complementary to a given test sequence is hybridized to the test sequence, covalently bound to a matrix. DNA oligomers are eluted in an 'effective temperature gradient' using conditions that minimize the differences of effects of GC versus AT pairs on the melting temperatures. This method should be a means to quickly separate error classes and thus be the crucial step in characterizing fitness landscapes of biopolymers through an experimental approach. It would also be a useful tool to design sequence pools with a bias towards desired mutant spectra.

Bacteriophage T7↗

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. Part VI. Evaluation of psychomotor training programs in schizophrenic patients.

Parts I-III of this series established signs of disturbed motor performance--the "psychotic motor syndrome" (PMS)--in schizophrenic and endogenous depressed patients, which was not found in neurotic/reactive depressed nor healthy persons. Part IV yielded EEG signs of concomitant brain dysfunction in these patients, which were demonstrated by other (SPECT/PET) neuroimaging methods also. In part V we engaged in the development of motor-training programs applied both actively and mentally, using the PMS as target syndrome in depressed patients. We hypothesized that motor training would not only improve disturbed motor behaviour, but ameliorate other symptoms of psychopathology additionally, which was supported for these patients. Part VI is the final paper of this series demonstrating favourable results of our motor-training programs in 96 schizophrenic inpatients in two separate investigations. A general discussion to the whole series attempts to link motor symptoms to neuroimaging findings of brain dysfunction during motor challenge and to modern three- and four-factor models of schizophrenic symptomatology. A final version of our complete training programs will be published as an appendix to this paper along with information regarding the abbreviated test battery.

Adolescent↗

[Epidemiologic data on eating disorders in Hungary: recent results].

The authors carried out a two-stage survey (screening and interview phase) among 538 medical students (248 males, 290 females) relating to eating attitudes and eating disorders. In the screening phase detection of eating disorders based upon body weight data, the Anorexia Nervosa Inventory for Self-rating, the Eating Disorder Inventory, and the Eating Behaviour Severity Scale. The screening did not revealed anorectic subjects, while subclinical anorexia nervosa could be found in 0.4% of males, and in 0.3% of females. The prevalence of bulimia nervosa was 0% in males, 0.3% in females, that of subclinical bulimia nervosa was 1.2% in males, 3.8% in females. Interview was performed with 38 high risk subjects, corroborating screening data. The results correspond well to former Hungarian data, and reach the morbidity of Western industrialized countries.

Adult↗

Functional replacement of the Saccharomyces cerevisiae Trg1/Pdi1 protein by members of the mammalian protein disulfide isomerase family.

The TRG1/PDI1 gene of Saccharomyces cerevisiae is essential for growth and encodes a lumenal endoplasmic reticulum (ER) glycoprotein that is structurally related to thioredoxin and is involved in the secretory pathway. We have tested whether the yeast Trg1/Pdi1 protein can be replaced in vivo by three members of the mammalian thioredoxin-related protein family, protein disulfide isomerase (PDI), ERp72, and ERp61. Multicopy plasmids containing galactose-inducible rodent PDI and ERp72 genes support germination and growth of haploid trg1 null mutants in galactose-containing media, whereas the ERp61 gene is inactive. Strains expressing PDI or ERp72 instead of Trg1 are thermosensitive. An overproduced mutant Trg1 protein lacking the HDEL retention signal supports growth, whereas a truncated version of the protein containing only one thioredoxin-like domain is inactive. The mammalian proteins were localized to both the soluble and microsomal membrane fraction of yeast cells. Our observations indicate that the two unglycosylated mammalian proteins PDI and ERp72 are capable of replacing at least some of the critical functions of Trg1, in spite of the fact that the three proteins diverge considerably in sequences surrounding the thioredoxin-related domains.

Animals↗

[Osteomyelitis today--diagnostic imaging and therapy].

Plain radiography, bone scan and especially in infants sonography belong to the primary imaging methods for posttraumatic osteomyelitis. For further diagnostic check up of osteomyelitis CT, MRI and leukocyte scintigraphy are excellent methods. Treatment of posttraumatic osteomyelitis is today a combination of operation, local and systemic antibiotic therapy.

Adolescent↗

Accurate high-speed liquid handling of very small biological samples.

Molecular biology techniques require the accurate pipetting of buffers and solutions with volumes in the microliter range. Traditionally, hand-held pipetting devices are used to fulfill these requirements, but many laboratories have also introduced robotic workstations for the handling of liquids. Piston-operated pumps are commonly used in manually as well as automatically operated pipettors. These devices cannot meet the demands for extremely accurate pipetting of very small volumes at the high speed that would be necessary for certain applications (e.g., in sequencing projects with high throughput). In this paper we describe a technique for the accurate microdispensation of biochemically relevant solutions and suspensions with the aid of a piezoelectric transducer. It is suitable for liquids of a viscosity between 0.5 and 500 milliPascals. The obtainable drop sizes range from 5 picoliters to a few nanoliters with up to 10,000 drops per second. Liquids can be dispensed in single or accumulated drops to handle a wide volume range. The system proved to be excellently suitable for the handling of biological samples. It did not show any detectable negative impact on the biological function of dissolved or suspended molecules or particles.

Base Sequence↗

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. V. Evaluation of psychomotor training programs in depressed patients.

Parts I-III of this series used psychometric assessment of motor performance in psychiatric patients and indicated a "psychotic-motor syndrome" (PMS) in schizophrenic and affective psychoses, which was not found in "neurotic"/reactive or healthy persons. Part IV yielded signs of concomitant brain dysfunction in these patients, demonstrated by EEG mapping as well as other (SPECT/PET) neuroimaging methods. Apart from this "basic science" interest into the pathophysiology of endogenous psychoses we engaged in the development of motor training programs using the PMS as "target" syndrome. We hypothesized, that motor training would not only improve disturbed motor behaviour, but ameliorate other symptoms of psychopathology also. These assumptions were supported in the first two independent studies involving n = 45 and n = 31 ICD-9 mono- and/or bipolar endogenous depressed patients, respectively (the studies on schizophrenic patients being reported finally as part VI of this series, along with the final version of our modified motor test battery). Examples of the motor training programs are provided in this paper, although the final version of the complete programs will be published separately for space reasons and for better availability for routine clinical use.

Adult↗

The Saccharomyces cerevisiae TRG1 gene is essential for growth and encodes a lumenal endoplasmic reticulum glycoprotein involved in the maturation of vacuolar carboxypeptidase.

We have isolated and mapped to the left end of chromosome III a single-copy gene (TRG1) encoding a 72-kDa glycoprotein, by screening a yeast genomic library with a DNA probe specifying the catalytic center (APWCGHCK) of thioredoxin-related proteins. the TRG1 gene sequence predicts an amino-terminal leader peptide, two thioredoxin-like domains, five N-glycosylation sites and a carboxyl-terminal HDEL retention signal. The TRG1 protein shows about equal sequence similarity to a mammalian multifunctional protein family residing in the lumen of the endoplasmic reticulum (ER), and to a putative cytosolic alpha form of phosphoinositide-specific phospholipase C. Haploid cells do not survive TRG1 gene disruptions, unless an additional wild-type copy is generated by interchromosomal transposition. Antibodies raised against synthetic amino- and carboxyl-terminal epitopes recognize a pair of lumenl ER glycoproteins (gp70/72) and a cytosolic 48-kDa protein. A 1.8-kilobase TRG1 transcript was translated by a reticulocyte lysate into a 60-kDa protein, which was translocated and processed to a 72-kDa glycoprotein in the presence of ER membrane vesicles. The TRG1 gene was placed under the control of the galactose-inducible and glucose-repressible GAL1 promoter, leading to growth arrest in glucose media. Glucose repression of the TRG1 gene caused the disappearance of gp72 and the accumulation of procarboxypeptidase. Our data indicate that the TRG1 gene encodes a growth essential lumenal ER glycoprotein involved the maturation of vacuolar carboxypeptidase.

Amino Acid Sequence↗