Biomedical subjects

R Nagel

Publications and source records attributed to R Nagel.

At least 19 recordsLinked to original sources

PubMed1992

[The long-term toxicity of polychemotherapy in successfully treated testicular carcinoma].

Of 55 patients with testicular cancer, treated by combination chemotherapy including cisplatin, 21 (mean age 35 [21-51] years) were reexamined for late sequelae of the chemotherapy 1-9 years later. No patient had a recurrence or second malignancy. They all had normal renal function (renal sequence scintigraphy; creatinine clearance). Seven of 20 patients had a polyneuropathy, nine of 18 had high-tone hearing loss. Two patients became fathers after treatment. In nine of 20 patients the serum concentration of follicle-stimulating hormone was raised to above 20 mU/ml, evidence of germ-cell damage. Six of 13 patients had an abnormal ejaculation following retroperitoneal lymphadenectomy or excision of a residual tumour. There was no evidence of any life-limiting toxicity of the chemotherapy.

Adult↗

PubMed1992

Deletion and insertion mutants of HBsAg particles.

We have found previously that hybrid 22-nm HBsAg particles can be created by insertion of short antigenic sequences into the HBV major envelope protein. We have now performed a detailed deletion mutagenesis of the S gene of HBV encoding HBsAg. Deletion of the 51 C-terminal amino acids including most of the third and all of the fourth hydrophobic domain of the S protein did not affect particle assembly and secretion. However, secretion of 22-nm particles was abolished by minor deletions in the N-terminal region. Insertion and deletion/substitution mutants carrying a poliovirus epitope at the N-terminus and the preS1 region at the C-terminus have been characterized.

DNA Mutational Analysis↗

PubMed1992

Transitional cell carcinoma of the renal pelvis and ureter: prognostic relevance of nuclear deoxyribonucleic acid ploidy studied by slide cytometry: an 8-year survival time study.

In 72 patients with urothelial carcinoma of the renal pelvis or ureter the ploidy, deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the tumor were analyzed by means of single cell DNA cytophotometry with the intention of finding new prognostic factors in addition to those already known (stage and grade). Followup ranged from 1 to 8 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumors and clinical course. Malignancy grade 1 tumors showed DNA frequency peaks in the diploid range, while tumors assessed as malignancy grade 2 showed heterogeneous DNA distribution patterns. Malignancy grade 3 tumors exhibited 71% aneuploid and 29% tetraploid DNA values. The proliferation rate of the tumor cells was statistically significantly higher in malignancy grades 2 and 3 than in malignancy grade 1. The prognosis for grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups (patients with grades 1 and 3 tumors) DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the other hand, are heterogeneous in respect to DNA ploidy although they exhibit the same histomorphological degree of differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive) tumors. There was also a positive correlation between T category and DNA ploidy. The cell lines were aneuploid in 38% of the patients with stage T1 tumors, 56% with stage T2 tumors and almost 85% with stage T3, N+ tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei had no metastases and no local tumor progression for up to 8 years, whereas patients with aneuploid tumor cell nuclei suffered metastasis and local tumor progression within 24 to 36 months. The patients died of the tumor 36 months after primary diagnosis on the average. The determination of DNA ploidy, tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry affords valuable clues as to prognosis.

Adult↗

PubMed1992

Deletions in the hepatitis B virus small envelope protein: effect on assembly and secretion of surface antigen particles.

The small envelope S protein of hepatitis B virus carrying the surface antigen has the unique property of mobilizing cellular lipids into empty envelope particles which are secreted from mammalian cells. We studied the biogenesis of such particles using site-directed mutagenesis. In this study, we describe the effect of deletions in the N-terminal hydrophobic and hydrophilic domains of the S protein. Whereas short overlapping deletions of hydrophilic sequences flanking the first hydrophobic domain were tolerated, larger deletions of the same sequences were not. Conversely, the hydrophilic region preceding the second hydrophobic domain was not permissive for even short deletions. Deletion of part or all of the first hydrophobic domain also completely blocked secretion, confirming that the entire apolar region serves an essential function. Most of the secretion-defective deletion mutants still entered the secretory pathway and translocated at least the second hydrophilic domain across the membrane of the endoplasmic reticulum. These mutants appeared to remain arrested in a membrane-associated configuration in the endoplasmic reticulum or the cis-Golgi compartment but preserved their capacity for oligomerization with the wild-type S protein. While secretion of wild-type S protein was specifically blocked by the formation of intracellularly retained mixed envelope aggregates, secretion of an unrelated protein (interleukin 9) was completely unaffected.

Base Sequence↗

PubMed1992

Nuclear DNA analysis: DNA heterogeneity in the monitoring of patients with locally advanced prostatic carcinoma.

Single-cell DNA cytophotometry was employed to analyze the tumors of 271 patients with locally advanced prostatic carcinoma as to DNA ploidy and heterogeneity and the distribution of the phases of the cell cycle before and during therapy, with the intention of establishing prognostic factors apart from those already known (stage, grade). Follow-up periods ranged from 1 to 9 years. 198 (73%) of the 271 patients had carcinoma stage T3 N0 M0, and 73 (27%) of them had carcinoma stage T3/T4 N+M1. The tumors were evaluated cytologically to establish the grades of malignancy. 11.8% were grade I carcinoma, 64.3% were grade II and 23.9% were grade III carcinoma. Single-cell DNA cytophotometry demonstrated aneuploidy rates of up to 73% and diploidy rates of up to 23.8% for the higher grades of malignancy, whereas the diploidy rate established for grade I carcinoma was 71% and the respective aneuploidy rate was 15.2%. These differences are significant (p < 0.001). There was a significant correlation between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei developed no metastases and no local tumor progression during the follow-up period of 9 years, whereas patients with aneuploid tumor cell nuclei showed metastases and local tumor progression within 8-22 months, despite changes in therapy. These patients died of carcinoma after an average 18 months following primary diagnosis.

Adult↗

PubMed1992

Teaching interviewing skills: the effect of instructors' academic department.

This study examines student evaluations of an interviewing and communications skills course taught in small groups by members of psychiatry and family medicine departments. Student course evaluations for two academic years were analyzed by means of t-tests and multiple regression analyses to explore if the group leader's academic department affected the student's learning experience. Students taught by family medicine instructors rated significantly higher three aspects of the course: the usefulness of the role playing session, the credibility and realism of the videotaping session, and the recommendation that the course be continued. This study found the family medicine instructors to be valued teachers of interviewing and communication skills.

Attitude↗

PubMed1992

[Rainbow trout and zebrafish, two models for continuous toxicity tests: relative sensitivity, species and organ specificity in cytopathologic reaction of liver and intestines to atrazine].

In order to elucidate cytopathological alterations in hepatic and intestinal cells, immature rainbow trout (Oncorhynchus mykiss) were exposed for five weeks to 10, 20, 40, and 160 micrograms/l of the herbicide atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine; model 1). For comparison, ultrastructural changes in female zebra fish (Brachydanio rerio) liver were studied after exposure to 100, 1,000 and 10,000 micrograms/l atrazine for three months (exposure from egg stage to sexual maturation; model 2). Neither epithelial nor glandular cells in the gastrointestinal tract of rainbow trout reveal cytological modifications following exposure to atrazine. In contrast, hepatocytes of rainbow trout and zebra fish clearly display dose-dependent and species-specific cytopathological effects at 40 and 1000 micrograms/l, respectively. In rainbow trout (model 1), rough endoplasmic reticulum (RER) appears of particular diagnostic value for the effects of atrazine, since it already shows a full spectrum of cytological alterations after 40 micrograms/l, and since in cells without RER modifications no further cytopathological symptoms can be revealed. At 40 micrograms/l atrazine, further changes include disturbance of the intracellular compartmentation, increased heterogeneity of mitochondria (longitudinally arranged cristae, branching, size), formation of myelinated bodies as well as immigration of macrophages and granulocytes along the biliary system and the space of Disse. The separation of peripheral storage areas from the central organelle-containing cytoplasm is no longer evident at 80 micrograms/l, and the phagocytic activity of invading macrophages is drastically increased. Following exposure to 160 micrograms/l atrazine, additional pathological changes comprise clubshaped deformation of mitochondria, formation of myelinated bodies in the intermembranous space of mitochondria, increase of degranulated ER cisternae and lysosomes, as well as perisinusoidal accumulation of lipid droplets. Deformation of the nuclear envelope, elevated mitotic activity and an increased number of nuclei with two or more nucleoli indicate interactions between atrazine and the nucleus. In the liver of female zebra fish (model 2), atrazine-induced alterations are limited to increased parenchymal variability, disturbance of the intracellular compartmentation, partial RER fractionation and vesiculation, club-shaped deformation of mitochondria and an increase in the number of lysosomes, myelinated bodies and invading macrophages at 1000 micrograms/l atrazine. After three months at 10,000 micrograms/l, mortality of zebra fish is increased to 100%. According to cytopathological alterations of hepatocytes following long-term exposure, susceptibility of the test model rainbow trout to atrazine appears higher than that of the model zebra fish.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

[Bladder tumors--Magnevist-assisted magnetic resonance tomography].

Magnetic resonance imaging (MRI, Magnetom 0.5 Tesla) using a high-resolution surface coil was performed on 10 healthy volunteers, 16 patients with bladder tumours, 2 patients with cystitis and 15 patients with bladder tumours and cystitis. Lesion delineation versus urine, bladder wall and surrounding organs was evaluated in plain and contrast-enhanced (IV Magnevist, 0.1 mmol/kg) T1-weighted, plain proton-density and T2-weighted spin-echo images. Surface-coil MRI proved very sensitive since all lesions were found in plain scans. Cystitis and 27 of 31 tumours exhibited contrast enhancement, however, differentiation of tumours and cystic lesions was not improved. Plain T2 and contrast-enhanced T1-weighted images demonstrated bladder wall disruption and perivesical tumour spread with equal sensitivity. Post-contrast images permitted unequivocal visualisation of perivesical tumour spread in surrounding peritoneal fat. The authors conclude that T2-weighted imaging may be restricted to non-enhancing bladder tumours thus significantly reducing imaging time.

Aged↗

PubMed1991

Transdermal fentanyl for the treatment of pain after major urological operations. A randomized double-blind comparison with placebo using intravenous patient-controlled analgesia.

Transdermal fentanyl 75 micrograms/h (Fentanyl-TTS) was compared with placebo in a randomized double-blind study in the early postoperative period, using 50 patients recovering from major urological operations. Analgesic efficacy was individually titrated with intravenous fentanyl by means of a PCA pump (demand dose 34 micrograms, lockout time 5 min). The test systems were applied 8 h before anaesthesia and were left in situ for 24 h. During the PCA period (18.2 h) patients with Fentanyl-TTS required significantly less additional fentanyl (0.48 vs 0.93 micrograms.kg-1.h-1) and reported less pain than patients in the placebo-group. Patient acceptance was high in both groups. Side-effects were of only minor intensity and did not differ between the two groups. In particular, there was no case of clinically relevant respiratory depression.

Administration, Cutaneous↗

PubMed1991

Bioconcentration, metabolism and toxicity of substituted anilines in the zebrafish (Brachydanio rerio).

The LC50 (96 h) values and the bioconcentration factors (BCF) for nine anilines (aniline; 2-, 3-, 4-chloroaniline; 2-, 3-, 4-nitroaniline; 2,4- and 3,4-dichloroaniline) in the zebrafish (Brachydanio rerio) were determined. Biotransformation products of anilines in the zebrafish were analyzed by HPLC. The aim of the investigations was to find relationships between accumulation/elimination/metabolism and toxicity on the one hand and between chemical structure and biotransformation on the other. We found a good correlation of log BCF and of log Pow with log LC50. This concurs with the assumption that the internal dose determines the toxicological effect. All anilines investigated, with the exception of 2- and 4-nitroaniline, were transformed into the corresponding acetanilides. The toxicity of the compounds was not altered by biotransformation. A comparison of the extent of acetylation confirms the supposition that substituents in the ortho position sterically hinder acetylation.

Aniline Compounds↗

PubMed1991

Effect of 3,4-dichloroaniline on the early life stages of the zebrafish (Brachydanio rerio): results of a comparative laboratory study.

An early life-stage (ELS) test was conducted with the zebrafish and 3,4-dichloroaniline (3,4-DCA) in eight laboratories. Based on the results from all eight laboratories, an LOEC of 200 micrograms 3,4-dichloroaniline/liter applies for the early life stages of the zebrafish. Effects observed were reduction of the survival rate and malformations. If the 100 micrograms/liter concentration additionally tested by one laboratory is included in the assessment, an LOEC of 100 micrograms 3,4-DCA/liter is obtained for the survival rate and increase in length. The NOEC is 20 micrograms/liter. The present results of a comparative laboratory study with the zebrafish show that a 42-day ELS test can be conducted with this species of fish, and affords meaningful results.

Aging↗

PubMed1991

Toxicokinetics of xenobiotics in zebrafish--comparison between tap and river water.

1. Uptake and elimination of lindane, 3,4-dichloroaniline, phenol and 4-nitrophenol by the zebrafish Brachydanio rerio were investigated in tap water and in water of the river Rhine. 2. The differences in bioconcentration of chemicals between the two water types did not exceed a factor of 2.5. 3. Elimination kinetics were comparable in tap and river water. 4. It can be concluded that water of the river Rhine does not influence the kinetics of the investigated xenobiotics.

Animals↗

PubMed1991

RecA-dependent increased precise excision of Tn10 in Salmonella typhimurium.

UV irradiation induced the precise excision of Tn10 inserted in met, trp or srl in a Salmonella typhimurium strain; mitomycin C was also found to induce the frequency of precise excision of Tn10 from srl or met. Precise excision of Tn10 was not increased by either UV or mitomycin C in a recA mutant. Similarly, a recA mutant derived from a uvrD strain showed a drastic reduction in the high spontaneous levels of precise excision of Tn10 of this strain. These results indicate that recA is involved in the increased precise excision of Tn10. In contrast to point mutations excision of Tn10 was found to be UV inducible in a top mutant.

Chromosome Deletion↗

PubMed1991

Calcium, magnesium, zinc, and iron balances in young women: effects of a low-phytate barley-fiber concentrate.

The effects of a low-phytate barley-fiber concentrate on calcium, magnesium, and zinc balances and on apparent iron absorption were measured by balance experiments. During the three experimental periods of 22 d each, all subjects consumed the basal diet alone, the basal diet with 15 g barley fiber (high-fiber, high-protein diet), and a modified basal diet containing less protein with 15 g barley fiber (high-fiber, low-protein diet), respectively. The mean daily intake of the cations was 24.4, 25.4, and 22.9 mmol Ca; 10.4, 10.1, and 10.0 mmol Mg; 165.2, 166.8, and 119.3 mumol Zn; and 154.0, 186.2, and 154.0 mumol Fe, respectively. Mean balances were 0.2, 1.9, and -0.8 mmol Ca; 0.3, -0.2; and -0.5 mmol Mg; 3.0, -4.6, and -18.4 mumol Zn. The mean apparent iron absorption was 16.1, 5.4, and -23.2 mumol when these three diets, respectively, were consumed.

Adult↗

PubMed1991

Prognostic relevance of DNA ploidy and proliferative activity in urothelial carcinoma of the renal pelvis and ureter. A study on a follow-up period of 6 years.

In 55 patients with urothelial carcinoma of the renal pelvis or ureter, the ploidy, the DNA heterogeneity and the counts of cell cycle phases in the tumor were examined by means of single-cell DNA cytophotometry in order to find more prognostic factors than those already known (stage and grade). Follow-up periods ranged from 1 to 6 years. At the time of first diagnosis, 42 (76%) of the patients had tumors of the renal pelvis, 13 (24%) of them had ureteral tumors. 23 (42%) patients were in stage pT 1 N 0, 15 (27%) in stage pT 2 N 0, 12 (22%) in stage pT 3 N 0, and 5 (9%) were in stage pT 3 N+. The histological malignancy grade most frequently seen in the patients examined--i.e. in 51% of cases--was malignancy grade II. 25% of the patients had grade III tumors whereas only 24% had grade I tumors. With malignancy grade I, DNA cytophotometry showed DNA frequency peaks to be in the diploid range while tumors with malignancy grade II showed heterogenous DNA patterns. 71% of the patients with malignancy grade III showed aneuploid DNA values; 29% of them had polyploid DNA values. For malignancy grades II and III, the proliferation rate of the tumor cells was statistically significantly higher than for malignancy grade I. The determination of tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry gives valuable clues regarding prognosis.

Adult↗

PubMed1991

[Acute pancreatitis--a free radical disease. Decrease in fatality with sodium selenite (Na2SeO3) therapy].

Malonic dialdehyde as an indirect marker of the lipid peroxidation was found increased in the acute pancreatitis compared with persons of the same age and sex. Its concentrations inversely correlated to those of the serum calcium during the course of the disease and additionally they proved to be indicator of the prognosis. Postulating that the acute pancreatitis must be a "free radical disease", in a randomized clinical study the adjuvant therapy of the acute necrotizing pancreatitis (n = 8) with sodium selenite was carried out in a daily dose of 500 micrograms. The lethality of the control group was 89% (8 out of altogether 9 patients), no patient died in the therapy group. By the selenium therapy within 24 hours a normalization of the serum calcium and a decrease of the increased MDA-values could be achieved. It was concluded that by selenium increased activities of the phospholipid-hydroperoxide-glutathione peroxidase were induced, by means of which a peroxidation protection of membrane fatty acids, an inhibition of the activity of phospholipase A2 and an interruption of the arachidonic acid cascade must have been reached.

Acute Disease↗

PubMed1991

[Tangier disease--a "free radical"-associated disease. Results of HDL and anti-oxidant therapy with selenium and D-alpha tocopherol].

In a 26-year-old patient there have been benign enlargements of the lymphatic nodes and a splenomegaly since the end of the adolescence. In the 21st year of age the diagnosis of a Tangier disease was made. Allogenic HDL-rich serum fraction (COHN IV/1-fraction, prepared according to the modified method 6) infused under therapeutic aspect led to a prolonged increase of the serum total cholesterol and of the thrombocytes. The results pled for an activation of the reverse cholesterol transport. Excessively high malonic dialdehyde concentrations in the serum were relating to a "free radical"-associated metabolic defect, which was caused by the hypocholesterolaemia, the reduced transport capacity of vitamin E in the plasma and the nutrition poor in selenium and cholesterol, respectively. Under a nutritive antioxidant supplementation with sodium selenite and D-alpha-tocopherol a slight increase of the total cholesterol, of the thrombocytes as well as a normalization of the MDA values could be reached. The chronic oxidative stress appeared in the patient in a distinct lipofuscinosis of the skin and formations of naevus-cell naevi as an expression of massive denaturations of protein-lipids. In the Tangier disease we must reckon with an increased mutagenic effect of free radicals with an additional DNS repair capacity as well as an increased sensitivity to radical-generating cancerogenic xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

[Primary hyperparathyroidism: studies of 4,000 urinary calculi patients treated with extracorporeal shockwave lithotripsy].

The incidence of primary hyperparathyroidism was determined in 4000 renal stone formers treated by ESWL at our institution from 1983 to 1990. Based on repeated measurements of serum calcium and serum parathyroid hormone an incidence of 2.8% was found. In 60% of patients with primary hyperparathyroidism stone disease occurred for the first time. The majority of patients (68%) were more than 50 years of age. 56% of patients were men, 44% were women.

Calcium↗