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B Fischer

Publications and source records attributed to B Fischer.

At least 433 records · Page 24Linked to original sources
PubMedDate not supplied

Seizure induced C-Fos mRNA in the rat brain: comparison between young and aging animals.

The molecular mechanisms associated with age-related alterations in the pharmacological and physiological properties of hippocampal and cortical neurons in response to chemically induced seizure are largely unknown. Administration of pentylenetetrazole (PTZ) (50 mg/kg body weight) to rats of various ages evoked tonic-colonic seizures. Using RNA gel blot analysis we found that 1 h after the onset of seizure, the mRNA for the protooncogene c-fos was increased in the hippocampus and cortex of 3-month-old rats. The levels of c-fos mRNA in the hippocampus and cortex of 3-month-old rats returned to control levels by 3 h after PTZ administration. The levels of c-fos mRNA in the hippocampus and cortex of 20-month-old and 30-month-old rats peaked at 3 h and returned to basal levels by 15 h following PTZ treatment. These results suggest that the induction of immediate-early gene expression, as exemplified by c-fos, is not impaired in the aged rat brain. However, the aged rat brain responded more slowly to chemically induced seizure and the levels of c-fos mRNA induction are decreased by about 49% in the cortex and by 27% in the hippocampus of 30-month-old rats, as compared to the levels expressed by 3-month-old rats.

Aging↗
PubMedDate not supplied

Embryotoxicity of polychlorinated biphenyls (PCBS) for preimplantation embryos.

In a previous study oral administration of a commercial PCB mixture (Aroclor 1,260) to female rabbits (4 mg/kg b.wt. for 14 weeks) resulted in a significant accumulation of PCBs in 6-d-old blastocysts and increased preimplantation embryo mortality (1). In the present study, the direct toxicity of PCBs on preimplantation rabbit embryos was investigated during in vitro culture. One-day-old cleavage stages and 3-d-old rabbit morulae were cultured in BSM II medium supplemented with 1.5% BSA in a reduced oxygen concentration of 5% O2. They were exposed to 50, 5, or 0.5 microgram Aroclor 1,260/mL culture medium for 24 h. PCB (50 micrograms) led to a complete degeneration of the exposed embryos. Following exposure to 5 micrograms only 16% of the morulae developed into blastocysts. The others were either arrested in the morulae stage or were degenerated. Cell proliferation of the nondegenerated embryos was approximately 20% of that of corresponding control embryos. Compared with nonexposed controls, addition of 0.5 microgram PCB/mL showed either no or only a slight impairment of development. Preliminary embryo transfer experiments showed that morulae exposed to 5 micrograms PCB with clear signs of degeneration after 24 h in vitro culture were able to implant. Aroclor 1,260 is embryotoxic in a dose-dependent manner in cultured rabbit preimplantation embryos.

Animals↗
PubMedDate not supplied

Synaptic plasticity is preserved in the temporal cortex of 20-month-old rats.

The molecular mechanisms associated with age-related alterations in the plasticity of the cortical neurons in response to chemically-induced seizure are largely unknown. Administration of pentylenetetrazole (PTZ) (50 mg/kg body weight) to rats of various ages evoked tonic-clonic seizures. Using immunoblotting and in situ hybridization analysis we found that 72 h after the onset of seizure, the mRNA for microtubule-associated protein 1B (MAP1B), a marker of synaptic plasticity, was increased in the cortex of 3-month-old rats. The levels of MAP1B mRNA in the cortex of 3-month-old rats returned to control levels by 10 days after PTZ administration. The levels of MAP1B mRNA in the hippocampus and cortex of 20 months at later times (10 days) and returned nearly to basal levels by 20 days following PTZ treatment. Immunohistochemical analysis revealed that MAP1B-like immunoreactivity was confined to layer II and neuronal processes extending into layer I. In contrast, the staining of MAP1B in the temporal cortex of 20-month-old animals was restricted to neuronal cell bodies of layer II. Since synaptic plasticity is associated mainly with neuronal processes we conclude that synaptic plasticity is reduced in the temporal cortex of 20-month-old rats. Remarkably, the induction of MAP1B in neuronal extensions was not impaired in the temporal cortex of older animals following intense neuronal activity. However, the aged rat brain responded more slowly to chemically-induced seizure although the levels of MAP1B induction are not decreased as compared to the levels expressed by 3-month-old rats.

Journal Article↗
PubMedDate not supplied

"Cleavable trifunctional" approach to receptor affinity labeling: chemical regeneration of binding to A1-adenosine receptors.

A general approach for reversible affinity labeling of receptors has been developed. The objective is to carry out a series of chemical modifications resulting in a covalently-modified, yet functionally-regenerated, receptor protein that also may contain a reporter group. The ligand recognition site of A1-adenosine receptors in bovine brain membranes was probed to demonstrated the feasibility of this approach. Use of disulfide or ester linkages, intended for cleavage by exposure of the labeled receptor to either reducing reagents or hydroxylamine, respectively, was considered. Binding of the antagonist radioligand [3H]CPX was preserved following incubation of the native receptor with 3 M hydroxylamine, while binding was inhibited by the reducing reagent dithiothreitol (DTT) with an IC50 of 0.29 M. Hydroxylamine displaced specific agonist ([3H]PIA) binding in a noncovalent manner. Specific affinity labels containing reactive isothiocyanate groups were synthesized from XCC (8-[4-](carboxymethyl)-oxy]phenyl]-1,3-dipropylxanthine) and shown to bind irreversibly to A1-receptors. The ligands were structurally similar to previously reported xanthine inhibitors (e.g., DITC-XAC: (1989) J. Med. Chem. 32, 1043) except that either a disulfide linkage or an ester linkage was incorporated in the chain between the pharmacophore and the isothiocyanate-substituted ring. These groups were intended for chemical cleavage by thiols or hydroxylamine, respectively. Radioligand binding to A1-receptors was inhibited by these reactive xanthines in a manner that was not reversed by repeated washing. Hydroxylamine or DTT restored a significant fraction of the binding of [3H]CPX in A1-receptors inhibited by the appropriate cleavable xanthine isothiocyanate derivative.

Affinity Labels↗
PubMedDate not supplied

Synthesis, mechanism and fluorescence properties of 8-(aryl)-3-beta-D-ribofuranosylimidazo[2,1-i]purine 5'-phosphate derivatives.

The synthesis of new fluorescent nucleotides is described. This synthesis comprises two parallel reactions, the Kornblum oxidation and imidazole formation, which lead to 8-(aryl)-3-beta-D-ribofuranosylimidazo[2,1-i]purine 5'-phosphates 2 from AMP or ATP. A detailed mechanism is proposed based on monitoring the reaction by 1H- and 13C-NMR spectroscopy, MS, FAB, HPLC, and pH meter. The spectral and fluorescent properties of the new derivatives at various pH values are described. Excitation and emission maxima for 3 were observed at 290 and 420 nm, respectively, in both basic and neutral media. In acidic media, the emission maximum shifted to 410 nm, however, the fluorescence intensity increased 1.5-fold. ATP analogues 2b and 3b exhibited relative stability regarding hydrolysis by type II ATPDase. Compound 3b is relatively chemically stable at pH 10.4 and 7.4.

Adenosine Monophosphate↗
PubMedDate not supplied

An acidic microenvironment inhibits antitumoral non-major histocompatibility complex-restricted cytotoxicity: implications for cancer immunotherapy.

Local immunosuppression may explain the failure of an effective immune response against solid tumors. Although it is well known that the interstitial pH is significantly lower in solid tumors than in normal tissue, only a few studies in the mouse system have investigated the influence of this acidic milieu on the anti-tumoral cytotoxic response. Here the authors report the suppression of human non-major histocompatibility complex (MHC)-restricted cytotoxicity against tumor cells by an acidic extracellular pH (pHe). Unstimulated peripheral blood mononuclear cells, lymphokine-activated killer (LAK) cells, and natural killer cell clones were used as effector cells. According to pH measurements in solid tumors, representative pH values of 7.2 to 5.3 were chosen during the cytotoxic assays. Target cell lysis was measured using two nonradioactive fluorometric methods, namely two-color flow cytometry and a modified calcein-release assay, which allowed cell-mediated cytotoxicity to be measured and compared with that in adherent targets. Using K562, Daudi, or Raji as suspended target cell lines, the cytotoxic activity of unstimulated peripheral blood mononuclear cells and of LAK cells was markedly reduced by a decreasing pHe. An extracellular pH of 5.8 to 5.3 resulted in a nearly complete loss of the cytotoxic response. This pHe-dependent impairment of the killing activity could also be shown for killer cells stimulated with interleukins-7 and -12, phytohemagglutinin, or lipopolysaccharide. The lytic potential of homogeneous natural killer cell clones as effectors was also strictly influenced by the surrounding pH. The pHe dependence of the non-MHC-restricted killer cell functions against tumor cells seems to be a general phenomenon, because the cytolytic activity of LAK cells against six human adherent tumor cell lines (HeLa, HepG2, LS174T, LS174Te, MCF-7, and RT112) was also clearly reduced under acidic conditions. To initiate the killing process, adhesion molecules play an important role in recognition and binding of the target cell. However, flow cytometric analysis revealed that the expression pattern of relevant adhesion molecules was unaffected by acidic pHe. In conclusion, these data clearly indicate an inhibition of non-MHC-restricted cytotoxicity against tumor cells by an acidic pHe, which may contribute to the failure of immunosurveillance against solid tumors. Consequently, efforts to enhance the anti-tumoral cytotoxicity by immunotherapies may have limited success.

Acids↗
PubMedDate not supplied

Release of hyaluronan and laminin into pancreatic secretions.

BACKGROUND: Development of fibrosis characterizes chronic pancreatitis. As it results from deposition of extracellular matrix (ECM) proteins such as hyaluronan (HA) or laminin, the release of these ECM components into blood or pancreatic secretion may be enhanced during the course of chronic pancreatitis. PATIENTS, MATERIAL AND METHODS: Using immunoassays for HA and laminin, the concentration for these ECM components was measured in pancreatic juice and serum samples from 20 patients with and 20 patients without chronic pancreatitis. Pancreatic calculi of varying size and weight obtained from 13 patients with chronic pancreatitis were also examined for the content of ECM components. Tissue samples from normal pancreas and those showing chronic pancreatitis were investigated immunocytochemically with an antibody to HA synthetase (HAS). RESULTS: After stimulation with secretin high levels of ECM components were found in the initial washout period in chronic pancreatitis patients as well as in controls. HA levels, however, were seen seven times higher in patients with chronic pancreatitis (mean +/- SEM; 734 +/- 301 vs. 95 +/- 15 microg/l; p < 0.01). Serum HA levels correlated with the duration of chronic pancreatitis and with the levels of HA in pancreatic juice. HA and laminin were detected in the supernatants of pancreatic calculi (laminin 0.70 +/- 0.30 U/l; HA 275 +/- 85 microg/l). Immunocytochemically, strong staining for HAS was found in the duct epithelium and in centroacinar cells of chronic pancreatitis specimens. CONCLUSION: Demonstration of increased amounts of HA in pancreatic juice of chronic pancreatitis patients stimulated with secretin suggests enhanced production of this ECM component in the chronically inflamed pancreas. The source of HA appears to be the pancreatic ductal epithelium.

Calculi↗
PubMedDate not supplied

Dissemination of a continuing education program in diabetes to health care professionals.

A goal of the Diabetes Research and Training Centers (DRTCs) is to translate advances in diabetes research into improved patient care by providing innovative, state-of-the-art training for health care professionals. This paper is a report on a collaborative DRTC-AADE training project. A 2-day diabetes program developed by the Chicago DRTC was packaged as a Workshop Instructor's Guide with accompanying slides and materials. AADE faculty observed the workshop presented by DRTC faculty and subsequently presented the workshop themselves. The evaluation design involved comparing a workshop presented by the DRTC faculty with a workshop presented by faculty from AADE. Three components were included in the evaluation: the participants' evaluation, a commitment-to-change evaluation, and the faculty observations. When comparing workshops, few differences were observed in participants' or faculty observers' evaluations. Moreover, participants at both workshops were equally successful at meeting goals related to improving their diabetes education practice behaviors. Dissemination of the program has been expanded and the workshop has become part of AADE's national continuing education efforts.

Allied Health Personnel↗
PubMedDate not supplied

Comparing opiate users in methadone treatment with untreated opiate users: results of a follow-up study with a Toronto opiate user cohort.

Untreated opiate use is correlated with major social harms and costs in Canada. While methadone treatment has existed in Canada since the 1960s, there is little specific Canadian research on its effects. This paper reports on the one-year follow-up results of a Toronto cohort study of opiate users (N = 114) who were not in treatment at baseline. Sixty-nine people were recruited for re-interviewing. A number of these individuals (N = 29) had entered methadone treatment during the year between baseline and follow-up interviews. Comparisons with respect to social functioning, health status and health care utilization, drug use and related risks, and criminal justice system involvement were made between the follow-up subsample who remained untreated, and the subjects who entered methadone treatment. Differences were found with respect to illegal income generation, illicit opiate and other drug use, illicit drug market activities and emergency care and aspects of socio-economic integration, but no major effects on health and criminal justice status could be shown. Research and policy implications are discussed.

Crime↗
PubMedDate not supplied

[The first total hip prostheses in man (1890 - 1960)].

We owe the first total prosthesis to Th. Gluck from Berlin (1880-1890), (they were in ivory), and to Jules Pean from Paris (1890-1894) (they were in platinum and cemented with plaster and pumice). Hardly successful though they were, the idea of replacing an articulation by foreign material was born. It would take sixty years to come to a successful hip total prosthesis. In the 1930 ies, Smith-Petersen, from Boston, designed moulds to be set between the femoral head and a cotyle in glass, pyrex, Bakelite and eventually a metal cupule (vitallium) either set on to the cotyle or the femoral head. After 1940 Bohlmann and Moore were the first to replace the upper part of a femur bearing a tumour and a metal prosthesis. In 1947, Jean and Robert Judet proposed a femoral head in acrylic. The first successful femoral prosthesis (more than 50 % good results) was Moore's new metal prosthesis in 1950. In the 50ies, some surgeons had the idea of connecting the two prosthetic pieces (cupule and femoral prosthesis) to get a total prosthesis, mainly in metal (Mc Kee from Norwich in 1951 and Herbert from Aix les Bains around 1955). In 1960, Charnley used dentist's methalcrylate cement for a Moore femoral prosthesis. In 1962, Charnley used this cement for a total prosthesis, with the low-friction concept and a 22 millimeter femoral head, which could move in a polyethylene cupule. This prosthesis is still in use today, in 1999.

Hip Prosthesis↗
PubMedDate not supplied

Plasma pharmacokinetics and metabolism of 13-cis- and all-trans-retinoic acid in the cynomolgus monkey and the identification of 13-cis- and all-trans-retinoyl-beta-glucuronides. A comparison to one human case study with isotretinoin.

In order to compare the disposition and metabolism of 13-cis-retinoic acid (13-cis-RA) and all-trans-retinoic acid (all-trans-RA) in the nonpregnant female cynomolgus monkey, the plasma concentrations of the parent compound, the oxidized metabolites 4-oxo-13-cis-retinoic acid and 4-oxo-all-trans-retinoic acid, and the conjugate metabolites 13-cis-retinoyl-beta-glucuronide (13-cis-RAG) and all trans-retinoyl-beta-glucuronide (all-trans-RAG), were determined on day 1 and day 10 after oral dosing of 2 and 10 mg 13-cis- and all-trans-RA/kg/day. Both 13-cis-RAG and all-trans-RAG have been identified as major plasma metabolites in these studies using thermospray/HPLC/mass-spectrometry of the intact conjugates. AUC comparisons from 0-24 hr after administration indicated that 13-cis-RA treatment resulted in primarily cis metabolites and all-trans-RA treatment resulted in primarily trans metabolites, although low levels of isomerization products were observed. Comparison of the two doses (2 and 10 mg/kg, po) revealed that the AUCs were proportional to the dose administered. Although qualitatively similar, elimination of 13-cis-RA in the monkey was more rapid than in the human, and approximately a 10-fold greater dose of 13-cis-RA was required in the monkey to produce the AUC values comparable to the human. The elimination of all-trans-RA in monkey was faster than that of 13-cis-RA and tended to increase with repeated dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Cerebrovascular insufficiency and compliance with drug therapy].

Particularly elder multimorbid patients suffering from a cerebrovascular insufficiency need a long term therapy. One condition for success, however, is the regular intake of drugs by the patient. Therefore the final goal is the increase of drug-compliance. This is based on the enhancement of the knowledge of the actual drug-compliance, the subject we wanted to learn more about by empirical investigations. During one year the drug-compliance of each patient of the Special Clinic Klausenbach was tested over a period of 20 days. The results were taken by checking riboflavin fluorometrically (method according to Gundert-Remy). In this way the patients could be classified as "takers" and "non-takers". The following variables wee considered: diagnoses, marital status, age, nationality, profession, IQ, mood, subjective evaluation of success of cure and medication. since according to a pre-study foreigners show a lower rate of compliance we restricted the sample to the 892 german cure patients, 343 of whom suffered from cerebrovascular diseases. Their compliance-level was almost 50%. The results of the subgroups hardly differed. The cure patients suffering from cerebrovascular insufficiencies did not show any striking compliance behaviour: the values are far below the ideal value, however. Further multivariate statistical analyses are designed to contribute to the development of effective measures of intervention.

Aged↗
PubMedDate not supplied

Radiofrequency catheter ablation for AV nodal reentrant tachycardias (AVNRT).

Radiofrequency (RF) catheter ablation is the curative treatment of choice for atrioventricular (AV) nodal reentrant tachycardia (AVNRT). Analogous to the development of surgical techniques, catheter ablation has evolved from AV nodal ablation to selective "fast" and "slow" pathway ablation. "Slow" ablation is now the method of choice because of the lower incidence of associated AV block. Though slow pathway ablation can be achieved with equal success using either the anatomic or the electrogram-guided approach, fewer applications of RF energy are required for the potential-guided technique.

Catheter Ablation↗