PubMed Health⌕ Search

Biomedical subjects

O Hoffmann

Publications and source records attributed to O Hoffmann.

At least 73 records · Page 4Linked to original sources
PubMed1989

Interferon gamma and calcitonin induce differential changes in cellular kinetics and morphology of osteoclasts in cultured neonatal mouse calvaria.

The present study compares the effects of calcitonin (CT) and interferon gamma (IFN-gamma) on the size, distribution, and ultrastructure of osteoclasts in cultured neonatal mouse calvaria. The number and cross-sectional area of osteoclasts in cultured bones was increased by the addition of parathyroid hormone (PTH) to the culture medium for 24-48 h. Prolonged treatment (up to 72 h) with PTH led to extensive rarefication and formation of holes in the mineralized matrix. PTH-activated osteoclasts exhibited an elaborate ruffled border and showed a typical zonal arrangement of intracellular organelles with the outer cytoplasmic region containing numerous membrane-bound vesicles. CT (20 mU/ml) within 90 minutes caused a complete loss of the ruffled border in PTH-activated osteoclasts. The typical zonal architecture disappeared with intracellular vesicles spread through the entire cytoplasm. Prolongation of CT treatment to 24-48 h led to the appearance of vesicles with dark granular content in inactivated osteoclasts. This morphologically distinct vesicle population allowed us to identify the latter cells as "postosteoclasts" and thereby to distinguish them from osteoclasts precursors. Small active osteoclasts that had originated very likely from these precursors appeared in calvarial bones coincidentally with escape from CT inhibition of bone resorption and resulted in increased total number of osteoclasts. In contrast, IFN-gamma (500 U/ml) acting as a proliferation inhibitor, reduced the total number of osteoclasts. In the presence of PTH it caused no immediate (90 minutes) change in the ultrastructure of PTH-induced osteoclasts apart from an increase in the number of autophagic vacuoles. After prolonged exposure (24-48 h) in the presence of PTH, osteoclasts with low resorbing activity exhibited intermediate borders at their contact zone with the mineralized matrix. In the absence of PTH, the short-term effect of the immune interferon on osteoclast morphology was almost comparable to that of CT. After prolonged treatment in the absence of PTH, postosteoclasts comparable in vesicle population and size to those after CT treatment were found.

Animals↗
PubMed1989

Differentiation in medulloblastomas: correlation between the immunocytochemical demonstration of photoreceptor markers (S-antigen, rod-opsin) and the survival rate in 66 patients.

Biopsy specimens of 66 medulloblastomas were investigated by means of S-antigen and rod-opsin immunocytochemistry. The patients were operated between 1969 and 1988 and the medical records were retrospectively evaluated to correlate the immunocytochemical features of the tumors to the course of the disease. S-antigen- and rod-opsin-immunoreactive tumor cells were found in 19 out of 66 cases. Since in the normal non-neoplastic state immunoreactive S-antigen and rod-opsin are restricted to retinal photoreceptors and a class of pinealocytes derived from photoreceptor cells, the occurrence of these proteins in certain tumor cells of medulloblastomas suggests a differentiation of these cells along the photoreceptor cell lineage and allows the identification of a special subtype of medulloblastoma displaying photoreceptor-specific characteristics. This subtype appears to be closely related to retinoblastomas and pineal cell tumors. The incidence of this subtype corresponds to approximately 30% of all medulloblastomas. Correlation between the demonstration of immunoreactive S-antigen and rod-opsin and the course of the disease revealed a 10-year survival rate of 50.6% for patients with medulloblastomas displaying photoreceptor-specific characteristics and maximally 11% for patients suffering from medulloblastomas devoid of these markers. Although the statistical evaluation does not provide a significant result, the estimated P-value of 0.085 indicates a distinct trend toward a better prognosis for patients suffering from medulloblastomas with photoreceptor-specific features. The validity of this trend needs to be proven in further studies with a greater number of patients.

Adolescent↗
PubMed1989

Comparison between the effects of forskolin and calcitonin on bone resorption and osteoclast morphology in vitro.

The adenylate cyclase activator forskolin (1-10 mumol/L) inhibited 45Ca release from parathyroid hormone (PTH; 10 nmol/L) stimulated prelabeled neonatal mouse calvaria in short term culture (24 h). This effect of forskolin was potentiated by rolipram, Ro 20-1724, and isobutyl-methylxanthine, three structurally different inhibitors of cyclic AMP phosphodiesterase. Forskolin (10 mumol/L) and calcitonin (30 mU/mL) inhibited the mobilization of stable calcium and inorganic phosphate as well as the release of the lysomal enzymes beta-glucuronidase and beta-N-acetylglucosaminidase from PTH-stimulated unlabeled bones. Osteoclasts in PTH-stimulated calvaria showed active ruffled borders with numerous membrane infoldings. Treatment of PTH-stimulated bones with forskolin and calcitonin resulted in a rapid (2 h) loss of the active ruffled border. In addition, forskolin and calcitonin induced similar changes with respect to the number and size distribution of cytoplasmic vesicles in PTH-activated osteoclasts. After 24 h, all signs of osteoclast inactivation were still prominent, whereas after 48 h of treatment with forskolin or calcitonin, the reappearance of a ruffled border on a number of osteoclasts signaled an escape from the inhibitory action of both calcitonin or forskolin. These data indicate that forskolin inhibits bone resorption by a cyclic AMP dependent mechanism and that the effect of forskolin and calcitonin on bone resorption and osteoclast morphology are comparable. These observations lend further support to the view that cyclic AMP may be an intracellular mediator of the inhibitory action of calcitonin on multinucleated osteoclasts.

Acetylglucosaminidase↗
PubMed1989

[Survey of the initial treatment of pulmonary tuberculosis in West Germany. A study by the German Central Committee for the Prevention of Tuberculosis].

1405 adult patients were selected for assessment who had been newly notified in the years 1986/87 with confirmed diagnosis of active progressive pulmonary tuberculosis who required treatment. Of these, 83.5% excreted tubercle bacilli in the sputum; radiographic lung cavities were confirmed in 53.6%, and 859 (61.1%) had a concomitant disease. 1173 patients (94.2%) were hospitalized for initial treatment and only 232 (5.8%) received outpatient treatment. The median duration of the hospital stay was 12 weeks. Isoniazid and rifampicin were prescribed in 96% and 93% patients, respectively, mostly all the time, ethambutol in 75% initially and in 50% throughout, streptomycin in 50% initially. Three or four drug regimens including pyrazinamide in the initial phase were employed in 76% of the patients. Premature discontinuation of therapy for different reasons was noted in 135 patients (9.5%). Of these, treatment was discontinued in 59 (4.2%) due to death; 37 (2.6%) patients died due to tuberculosis. Adverse reactions were observed in 193 patients (13.7%); 0.3% of the patients discontinued chemotherapy because of toxicity. The duration of chemotherapy was between 9 and 12 months in the majority of patients; 30%, however, were treated for more than 12 months. The chemotherapy of 6-months duration was performed only in about 10% of treated patients. Among the patients who completed the treatment, this proved effective in 98%. Although the majority received initially the rational chemotherapy with a three or four drugs regimen, it is concluded that the inpatient stay and the outpatient duration of chemotherapy in the routine clinical practice is too long, therapy control is insufficient.

Adolescent↗
PubMed1989

Effect of auranofin on resorption, prostaglandin synthesis and ultrastructure of bone cells in cultured mouse calvaria.

Auranofin (AF) in concentrations between 3 x 10(-7) and 3 x 10(-6) mol/l stimulated bone resorption in cultured neonatal mouse calvariae significantly with 1 x 10(-6) mol/l being most potent. Complete inhibition by 5 x 10(-7) mol/l indomethacin and increased medium concentrations of prostaglandin (PG) E2 and 6-keto-PGF1 alpha after 72 h indicate a PG mediated mechanism. Morphology revealed active osteoclasts. Cytotoxic effects were observed with 3 x 10(-6) and 1 x 10(-5) mol/l AF with osteocytes and osteoblasts being considerably more sensitive than osteoclasts. The latter concentrations inhibited bone resorption stimulated by parathyroid hormone (PTH) 1,25-dihydroxyvitamin D3, PGE2, thrombin and interleukin 1. The stimulatory effect of AF on PG production and subsequent bone resorption could limit its therapeutic usefulness.

Animals↗
PubMed1988

Comparison of the inhibitory effect of nonsteroidal antiinflammatory drugs on bone prostaglandin synthesis and resorption.

The biopotency of various nonsteroidal antiinflammatory drugs (NSAID) in inhibiting prostaglandin (PG) mediated bone resorption was evaluated in a neonatal mouse calvaria organ culture system. Thrombin stimulated formation of the osteolytic PG, PGE2 and PGI2 (measured as 6-keto-PGF1 alpha) and the concomitant stimulation of calcium release from cultured bone were inhibited by diclofenac much greater than indomethacin much greater than flurbiprofen greater than piroxicam greater than acemetacin much greater than acetylsalicylic acid. The relative potencies of the NSAID on PG synthesis in bone differs from that observed previously in other model systems.

Animals↗
PubMed1987

Gamma interferon inhibits basal and interleukin 1-induced prostaglandin production and bone resorption in neonatal mouse calvaria.

Production of the osteolytic arachidonic acid metabolites, prostaglandin (PG) E2, PGI2 and PGF2 alpha, by neonatal mouse calvariae was quantitated by gas chromatography/mass spectrometry. Mouse recombinant interleukin 1 (rIL-1) raised medium levels of PGE2 and PGI2 (measured as 6-keto-PGF1 alpha) in the dose range tested (1.0-10.0 U/ml culture medium), while an effect on PGF2 was only observed at 10 U/ml. Bone resorption in response to rIL-1 reached a plateau at 3.0 U/ml. Mouse recombinant gamma-interferon (rIFN-gamma) between 100-500 U/ml suppressed basal PG synthesis and spontaneous resorption of cultured bone. In addition, IFN-gamma at 100 U/ml prevented stimulation of PG synthesis by 3.0 U/ml rIL-1 and thereby reduced the bone resorbing activity of the cytokine by at least 60%. 5 X 10(-7) M indomethacin was equally effective in suppression of PG synthesis and bone resorption. The present study provides evidence that IFN-gamma inhibits PG synthesis and consequently resorption of cultured bone.

Animals↗
PubMed1987

Biomathematics of intracranial CSF and haemodynamics. Simulation and analysis with the aid of a mathematical model.

A mathematical model of the isolated intracranial system including autoregulation of cerebral blood flow with the aid of a variable cerebrovascular resistance is described. The rate of formation of cerebrospinal fluid is assumed to depend on the regional blood flow through the choroid plexuses. This model is extended by cardiovascular components including the left ventricle of the heart, the aorta and the peripheral resistance. Additionally the model contains control circuits to simulate the short-time behaviour of the blood pressure regulation with the aid of the baroreceptor reflex. Disturbances of central regulation of blood pressure are simulated depending on changes of the regional blood flow through the brain stem. The application of the model is demonstrated by the analysis of the influence of arterial blood pressure upon the intracranial pulse pressure relationship (PPR) and upon the pressure response to a volume pressure test. Theoretical considerations and simulations reveal an opposite effect of arterial blood pressure (ABP) and its amplitude upon PPR. The ICP amplitude rises with decreasing ABP or increasing ABP amplitude. Breakpoints and other deviations from a linear PPR over the whole ICP range are studied by the analysis of the transfer function. The application of the model concerning parameter estimation methods is demonstrated and discussed. Simulations of rhythmic phenomena with the aid of the extended model point out possible approaches to quantitative descriptions of disturbances of central regulation.

Brain↗
PubMed1987

The effect of intrathecal baclofen on electrical muscle activity in spasticity.

The efficacy of intrathecally administered baclofen was demonstrated in three patients with different types of muscular hypertonia (supraspinal rigidity, spasms shortly after spinal trauma, spasms for many years induced by multiple sclerosis) using integrated electromyography. Reduction of muscular electrical activity was accompanied by clinical improvement during long-term infusion via an implanted pump. The three patients have been observed for more than 1 year, during which time the antispastic activity of intrathecally infused baclofen has remained stable. Intrathecal application of baclofen may be considered as a possible alternative to surgery.

Adult↗
PubMed1987

Cyclosporine A inhibits bone resorption in cultured neonatal mouse calvaria.

The effect of the immunosuppressive agent cyclosporine A (CsA) on the resorption of neonatal mouse calvaria was examined in vitro. CsA, at concentrations of 10(-7) to 3 X 10(-5) M, inhibited bone resorption produced by 10(-8) M parathyroid hormone, 3 U/ml of mouse recombinant interleukin-1,5 X 10(-7) M prostaglandin E2, 14 U/ml of thrombin, 5 micrograms/ml of bacterial lipopolysaccharide or 10(-9) M 1 alpha,25-dihydroxyvitamin D3. The effects of CsA on resorption were maintained over 72 h of culture with parathyroid hormone or prostaglandin E2 with no evidence of "escape". Removal of CsA from the cultures resulted in recovery of the resorptive response after a 24-h delay. CsA did not affect thymidine incorporation into DNA in the calvaria. Our results demonstrate that CsA is a nonselective antiresorptive agent in bone, with actions that differ somewhat from those of calcitonin. The results confirm and extend our previous findings on effects of CsA in fetal rat limb bones, with the exception that the inhibitory effects of CsA were more rapidly and completely reversible in the limb bone system.

Animals↗
PubMed1986

Indomethacin inhibits thrombin-, but not thyroxin-stimulated resorption of fetal rat limb bones.

The bone-resorbing effects of thrombin and thyroxin, two agents that stimulate resorption in neonatal mouse calvaria by prostaglandin-dependent mechanisms, were examined in cultures of fetal rat limb bones. Thrombin produced maximal resorption in the limb bone cultures at a concentration of 100 U/ml when bones were cultured in BGJ supplemented with 1 mg/ml bovine serum albumin. The effects of thrombin were partially inhibited by 0.5 and 10 uM indomethacin. Thrombin failed to elicit resorption when the limb bones were cultured in DMEM with 15% horse serum. Thyroxin stimulated the resorption of limb bones in both BGJ-albumin and DMEM-serum media. Resorption was elicited by thyroxin concentrations of 10 nM-10 uM. 30 uM thyroxin failed to stimulate resorption. The dose-response curve to thyroxin was shallow, and the agent did not produce maximal resorption. The bone-resorbing effects of thyroxin were not affected by 0.5 or 10 uM indomethacin.

Animals↗
PubMed1985

Recombinant gamma-interferon inhibits prostaglandin-mediated and parathyroid hormone-induced bone resorption in cultured neonatal mouse calvaria.

A role of gamma-interferon in the bone remodeling process can be implicated from its interference with bone resorptive processes in cultured neonatal mouse calvaria. The immune interferon is an efficient inhibitor of endogenous prostaglandin synthesis, particularly after stimulation by thrombin or arachidonic acid, and, in addition, has a calcitonin-like inhibitory effect on PTH-induced osteoclastic bone resorption.

Animals↗
PubMed1985

Prostaglandin-related bone resorption in cultured neonatal mouse calvaria: evaluation of biopotency of nonsteroidal anti-inflammatory drugs.

The objective of this study was the development of an assay based on suppression of endogenous prostaglandin synthesis in cultured neonatal mouse calvaria for evaluation of the biopotency of nonsteroidal anti-inflammatory drugs in bone. In preliminary trials, osteolytic activity due to spontaneous prostaglandin production over a 72 h culture period was found highly variable, and could not be stabilized by addition of the common precursor arachidonic acid to the culture medium. Eventually, continuous exposure of mouse calvaria to moderate concentrations of thrombin (greater than or equal to 14 U/ml medium) proved to be satisfactory to achieve stable rates of bone resorption through continuous stimulation of prostaglandin synthesis from endogenous sources. Notably, the extent of net calcium release into the medium was highly reproducible in different experiments. As an example for possible applications of the bioassay, the ability of acemetacin to interfere with prostaglandin synthesis in bone, which had not been assessed before, was evaluated in a comparative assay with indomethacin and acetylsalicylic acid. While 1 X 10(-8) M acemetacin appeared to augment thrombin-induced bone resorption, as did 5 X 10(-6) M acetylsalicylic acid, a dose-dependent inhibition of calcium release was observed between 10(-7)-10(-5) M acemetacin. In this respect, the biopotency of indomethacin was 50 times higher than that of acemetacin and exceeded that of acetylsalicylic acid by a factor of more than 2000. These data could be useful for the appraisal of multiple effects of the investigated drugs on prostaglandin-related bone turnover.

Animals↗
PubMed1984

Application of statistics and frequency of statistical errors in articles in acta neurochirurgica.

Out of 395 contributions in the volumes 51 to 64 of Acta Neurochirurgica 141 reported numerical data. The frequency of procedures used for describing distribution, location or variability and the frequency of analytical methods were evaluated. Critical assessment of these articles revealed a considerable rate of fundamental errors in application of statistics. Considering only papers involving analytical methods 52% of these (33 out of 64) contained simple statistical errors which can be avoided without any statistician's help. Some rules for improving statistical quality of medical articles are presented.

Humans↗