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Biomedical subjects

W Hofmann

Publications and source records attributed to W Hofmann.

At least 145 records · Page 8Linked to original sources

Extension of a generalized state-vector model of radiation carcinogenesis to consideration of dose rate.

Mathematical models for radiation carcinogenesis typically employ transition rates that either are a function of the dose to specific cells or are purely empirical constructs unrelated to biophysical theory. These functions either ignore or do not explicitly model interactions between the fates of cells in a community. This paper extends a model of mitosis, cell transformation, promotion, and progression to cases in which interacting cellular communities are irradiated at specific dose rates. The model predicts that lower dose rates are less effective at producing cancer when irradiation is by X- or gamma rays but are generally more effective in instances of irradiation by alpha particles up to a dose rate in excess of 0.01 Gy/day. The resulting predictions are compared with existing experimental data.

Animals↗

137Cs concentrations in lichens before and after the Chernobyl accident.

137Cs activities were measured in a variety of epigeic and epiphytic lichens in Austria before and after contamination by the Chernobyl fallout. For comparison, the activity of the naturally occurring 40K was also determined in each lichen sample. The high 137Cs activities found after Chernobyl suggest that lichens are suitable and inexpensive biological detectors of the fallout pattern.

Accidents↗

Radon progeny dosimetry in the rat lung.

Deposition, mucociliary clearance, and dosimetry for the inhalation of radon progeny in the rat lung have been simulated for a variety of inhalation conditions. Computations indicate that the exposure-dose conversion factor for the rat lung is approximately twice as high as the corresponding value for the human lung for the same exposure conditions. However, if typical aerosol characteristics are used for animal inhalation experiments and human indoor exposures, the resulting exposure-dose conversion factors are comparable, thereby suggesting similar lung cancer risks per unit exposure. The predicted relative effects of radon progeny disequilibrium and unattached fractions on bronchial doses agree with results from inhalation experiments with laboratory rats.

Administration, Inhalation↗

[The effectiveness of intravenous administration of large quantities of glucose in the treatment of bovine ketosis].

Glucose in a 40% (w/v) solution (200 g, 400 g or 600 g) was infused intravenously in clinically healthy cattle. On urinalysis, 13%, 19% and 26% respectively of the infused glucose was excreted. In cattle with elevated urinary ketone bodies, only the infusion of 400 or 600 g glucose led to a significant rise in the serum glucose concentration compared to initial values. Only the infusion of 600 g of glucose was followed by a significant decrease in serum beta-hydroxybutyrate 24 hours later compared to initial values. The present results indicate a possibility of improving the results of treatment of ketosis by infusion of high amounts of glucose.

3-Hydroxybutyric Acid↗

[Promoting competence in training courses--complementary curriculum in "population medicine and health sciences--public health" at the Hannover Medical University].

Public Health professionals should have various knowledge and abilities. The Public Health programme at Hannover Medical School offers a training with well-defined practice related elements. It includes also special courses of social medicine for both groups together, the medical students as well as the postgraduate public health students.

Curriculum↗

[Clinical indications of an auxiliary effect of antihistamines (parenteral benadryl) in the treatment of RSV infections of cattle].

The BRSV-infection belongs to the Bovine Respiratory Disease (BRD) complex. Because of its clinical features as well as pathomorphological and histopathological lesions it can be considered an independent disease. Therefore, concepts of treatment deviating from conventional BRD have to be applied. In addition to antibiotic therapy, therefore, the effect of treatment with the antihistamine Diphenylhydramin (Benadryl-parenteral, Parke Davis) was checked. For the evaluation the internal body temperature was used as measure. With the additional daily application of the antihistamine to the antibiotic therapy the animals were faster without fever. The difference was significant.

Animals↗

[BHV-1 intradermal test in cattle].

Investigations concerning an intradermal test for the diagnosis of BHV 1 infection were carried out in 221 cattle. In 16% of cases the result of the test was dependent on the time the test was read (48 or 72 h). Fifteen per cent of the animals older than 9 months showed no reaction to the intradermal test though humoral antibodies against BHV 1 were detectable by ELISA. Intradermal injection of test antigen resulted in seroconversion in seronegative cattle. The antibodies remained detectable in the ELISA for about 3 to 6 weeks.

Animals↗

Characterization of the transcriptional regulatory region of the human WT1 gene.

Specific control of the expression of the Wilms tumor gene WT1 is important for normal development of the kidney. In order to characterise the transcriptional control region of the WT1 gene we have isolated genomic clones spanning the upstream region, the first WT1 exon and the 5' end of the Wit1 gene. DNA sequencing revealed that the WT1 promoter lacks a TATA box or CCAAT motif and has a GC content of 71%. Four transcriptional start sites are clustered within a 32 bp region. GC-boxes are present at nucleotide positions -413, -160, +84 and +158. DNAase I protection assays with purified Sp1 protein revealed the existence of 11 different binding sites in the WT1 promoter. WT1 and Wit1 promoter activities were tested in COS-7 cells with luciferase reporter gene constructs either containing or lacking an SV40 enhancer. WT1 promoter activity was found in a fragment extending from 449 bp upstream to 201 bp downstream of the WT1 start site. It was 26 fold lower in the absence of the SV40 enhancer than in the presence. Cotransfection with a Sp1 expression vector stimulated both constructs 3-4 fold. Wit1 promoter activity was identified in a DNA fragment extending from 200 bp upstream of the putative Wit1 TATA box to 130 bp downstream. Several potential recognition sites for WT1/EGR, Pax-8, and GAGA-like transcription factors are present in the WT1 promoter.

Base Sequence↗

[Endocrinously active parathyroid cysts. Their diagnosis by the determination of intact parathormone in the cyst fluid].

A 53-year-old woman with recurrent nephrolithiasis was found to have hypercalcaemia of 3.12 mmol/l and an intact parathormone level of 166 pg/ml, indicating primary hyperparathyroidism. Preoperative ultrasound examination to localize the parathyroid adenoma revealed a clear fluid-containing cyst in the right lobe of the thyroid. The aspirated fluid had an intact parathormone level of 306 pg/ml, twice that in serum. The cyst was removed surgically. 14 days postoperatively calcium and parathormone levels in serum had become normal without any calcium administration. Measuring the concentration of intact parathormone in the aspirated cyst fluid made possible not only the distinction from a thyroid cyst but also the precise preoperative localization of the parathyroid cyst.

Body Fluids↗

Interaction of obidoxime with sarin in aqueous solution.

The interaction of obidoxime (Toxogonin) with sarin was shown by different analytical methods. The UV spectrum of obidoxime at pH 7.4 yields two absorption maxima, lambda 1 = 284 nm and lambda 2 = 353 nm. The peak at lambda 2 = 353 nm is representative for the amount of zwitter-ionic obidoxime, i.e. the active form of obidoxime. By addition of sarin, lambda 1 shifts immediately to 278 nm and the intensity at lambda 2 decreases, thus indicating an interaction. TLC and 31P-NMR evidence shows that both mono-phosphonylated and diphosphonylated obidoximes are present. Decomposition of phosphonylated obidoxime in MOPS (3-[N-morpholino] propanesulfonic acid) buffered D2O at pH 7.4 occurs with t1/2 = 13.3 min at 24 degrees C. Decomposition of di-phosphonylated obidoxime is faster. It is suggested that decomposition of di-phosphonylated obidoxime occurs through the mono-phosphonylated form. Formation and decomposition of mono- and di-phosphonylated obidoxime is pH dependent. We conclude that obidoxime exerts a detoxifying effect by capturing free sarin molecules and thus increasing its polarity. Thereby the transition of sarin through the blood-brain barrier is restricted and its renal elimination facilitated.

Chromatography, Thin Layer↗

Cryo-electron microscopy of vitrified muscle samples.

A great deal of information on the 3-dimensional structure of the protein assemblies involved in muscle contraction has been obtained using conventional transmission electron microscopy. In recent years, developments in cryo-electron microscopy have facilitated work with fully hydrated, non-chemically fixed specimens. It is shown how this technique can be used to visualize muscle sarcomere filaments in quasi-native conditions, to access hitherto inaccessible states of the crossbridge cycle, and to obtain new high resolution structural information on their 3-dimensional protein structure. A short introduction to the crossbridge cycle and its biochemically accessible states illustrates the problems amenable to studies using the electron microscope, as well as the possibilities offered by cryo-microscopy on vitrified samples. Work on vitrified cryo-sections and myosin filament suspensions demonstrates the accessibility of crossbridge states and gives implications on the gross structural features of myosin filaments. Recent studies on actin filaments and myosin (S1) decorated actin filaments provide the first high resolution data on vitrified samples. The use of photolabile nucleotide precursors allows the trapping of short lived states in the millisecond time range, thereby visualizing intermediate states of the crossbridge cycle.

Animals↗

Quantitative determination of urinary marker proteins: a model to detect intrarenal bioeffects after extracorporeal lithotripsy.

To detect the source of relevant acute intrarenal side effects after extracorporeal piezoelectric lithotripsy and its impact on repeat treatment, urinary excretion of highly specific marker proteins was determined before (day-1) and after (days 0, 1, 4, 7, 14 and 21) treatment. Marker proteins included high molecular weight alpha-2-macroglobulin, immunoglobulin G, albumin, alpha-1-microglobulin as well as the enzyme N-acetyl-beta-glucosaminidase. Of 50 patients who underwent 4,000 shock waves to caliceal stones (group 1) 15 were identically retreated after 5 (group 2) or 15 (group 3) days, respectively, to determine the shortest safe interval to repeat extracorporeal piezoelectric lithotripsy. The course of lithotripsy damage was also evaluated in 15 pre-damaged kidneys (group 4). The alpha-2-macroglobulin enhancement found in all groups on day 0 (p less than 0.005 to p less than 0.05) documented intrarenal bleeding from ruptured vessels. Ratios of alpha-2-macroglobulin/albumin greater than 2.00 on days 0 and 1 exclude a glomerular source of gross hematuria (groups 1 to 4). There was only slight acute tubular damage after extracorporeal piezoelectric lithotripsy (N-acetyl-beta-glucosaminidase increase, p less than 0.05 for groups 1 to 4). Retreatment after 5 days did not enhance the amount of proteinuria compared to the same patients from group 1 (statistically significant at p less than 0.45 to p less than 0.10). Group 3 also showed a similar elevation of proteinuria as the identical patients pretreated 15 days previously. Thus, the data seem to suggest that early repeat sessions of extracorporeal piezoelectric lithotripsy are as safe as delayed retreatments. The course of proteinuria in group 4 did not suggest enhancement of extracorporeal piezoelectric lithotripsy damage in pre-injured kidneys. The urinary marker alpha-2-macroglobulin detects intrarenal vessel ruptures, which are responsible for intrarenal hematomas, as evidenced by animal and human histology. A model is offered to understand and detect the most important parenchymal bioeffects to minimize the risk of injury.

Acetylglucosaminidase↗

Markers for the diagnosis and monitoring of renal tubular lesions.

Single proteins and tubular enzymes have been proposed as markers to detect and differentiate prerenal, glomerular, tubular and postrenal forms of proteinuria and hematuria. By quantitation of total protein, albumin, alpha 1-microglobulin, IgG, alpha 2-macroglobulin and N-acetyl-beta,D-glucosaminidase (beta-NAG) activity it has become possible to clearly separate these forms by analysis of a single sample of second morning urine. When this program was applied to screening of hospital patients, albumin, total protein and NAG proved to be sufficient to exclude clinically relevant disturbances. alpha 1-Microglobulin was useful to separate primary glomerulopathies from tubulo-interstitial diseases. Glomerular and postrenal hematuria could be clearly separated by their different excretion rates of alpha 2-macroglobulin, if urine albumin concentration exceeds 100 mg/l. The results imply that wider application of these techniques can help to detect renal abnormalities at an earlier stage and differentiate their various forms by less invasive techniques.

Acetylglucosaminidase↗

Liver transplantation for acute or chronic liver failure by hepatitis non-A, non-B and hepatitis C viral infections: a postoperative follow-up.

Orthotopic liver transplantation (OLT) was performed for liver failure related to hepatitis non-A, non-B (HNANB) or hepatitis C (HCV) infections in 12 patients. Of those, 8 patients had chronic and 4 acute hepatic failure. To determine the incidence of recurrent infection, the clinical course, histological findings and serological HCV markers (HCV-RNA and detection of anti HCV antibodies, respectively) were comparatively studied in these patients. Recurrent infection was apparent in 5 of 6 patients transplanted for liver cirrhosis attributable to chronic HCV infection and with HCV-RNA detectable in serum. The clinical course of infection after OLT varied considerably. Chronic active hepatitis, progressing to liver cirrhosis 13 months postoperatively and an acute hepatitis, resolving spontaneously were seen in one case each. Recurrent infection led to chronic persistent hepatitis in the remainder. None of the patients with acute liver failure experienced recurrent infection. HCV-RNA was detectable in all the patients after OLT, with HCV-RNA present pretransplant, however the presence of HCV-RNA in serum was not necessarily associated with clinical illness.

Budd-Chiari Syndrome↗