[Computer-assisted parenteral feeding].
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Biomedical subjects
Publications and source records attributed to A Lang.
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Rabbit articular chondrocytes in monolayer culture were stimulated with human recombinant interleukin-1 beta. Under the influence of the cytokine the intracellular pool of the cysteine endopeptidase cathepsin B was increased by a 2-4-fold factor, while enzyme secretion was not stimulated at a significant level. Under the same conditions, the secretion of collagenase, measured as an internal control, was stimulated about 6-fold. The effects of interleukin-1 beta were compared to those caused by phenotypic modulation. Chondrocytes modulated by serial subcultures in monolayer secreted more cathepsin B, but less collagenase than differentiated cells (cultured within collagen gels). Thus, interleukin-1 beta and phenotypic modulation affected differently two endopeptidases which are relevant in the pathogenesis of osteoarthritis.
Rats with high and low exploratory activity in an elevated plus-maze model of anxiety were separated into subgroups termed 'non-anxious' and 'anxious' respectively according to the number of sectors the animals crossed and the total amount of time they spent in the open part of the plus-maze. The binding parameters of benzodiazepine and cholecystokinin octapeptide (CCK-8) receptors in frontal cortex and hippocampus of selected animals were studied and compared to an animal group representing the total mean scores and to home-cage controls. It was established that anxious rats had a significantly lower number of benzodiazepine receptors in frontal cortex as compared to non-anxious animals and in hippocampus as compared to home-cage controls. There was also a decreased number of CCK-8 receptors in hippocampus of anxious rats as compared to the non-anxious and control groups. Non-anxious animals had a significantly lower number of CCK-8 receptors in frontal cortex than anxious and control rats. Acute treatment of rats with anxiogenic benzodiazepine inverse agonist FG 7142 (10 and 20 mg/kg) did not influence benzodiazepine binding in brain regions under investigation but caused upregulation of CCK-8 receptor binding in frontal cortex. On the other hand, CCK-8 analogues caerulein and pentagastrin, administered in doses which inhibit exploratory activity in plus-maze (100 or 500 ng/kg respectively), decreased the number of benzodiazepine binding sites in rat frontal cortex if injected intraperitoneally but did not affect CCK-8 binding. The present findings indicate that benzodiazepine and CCK-8 receptor binding characteristics in brain undergo rapid and behaviourally specific changes during stressful events.
This study examined the effect of chronic diazepam administration on central benzodiazepine and CCK-8 receptor binding in rat brain. After a two-week treatment with diazepam (5 mg/kg per day) tolerance developed towards the sedative but not towards the anxiolytic action of this drug as determined using elevated plus-maze and open field tests. The % entries the rats made onto open arms and % time the rats spent in open arms were markedly decreased 24 h after the last dose of diazepam, probably indicating withdrawal anxiety. There were no changes in [3H]flunitrazepam binding either 30 min or 24 h after the last diazepam dose. However, 30 min after the last diazepam administration the apparent number of sulphated [3H]CCK-8 binding sites was significantly increased in the primary olfactory cortex. Acute diazepam treatment (5 mg/kg) had no influence on [3H]flunitrazepam or sulphated [3H]CCK-8 binding in any brain region studied. Cessation of chronic diazepam treatment was followed after 24 h by an increase in the number of CCK-8 receptors in frontal cortex and hippocampus as compared to the vehicle group. These results demonstrate that certain alterations in CCK-8 receptor characteristics may be important in the anti-anxiety effect, tolerance, and withdrawal reaction reaction after benzodiazepine administration.
The association of psychogenic neurological features with organic neurological disease is commonly acknowledged. However, the occurrence of psychogenic dyskinesias in patients with underlying organic movement disorders is not well recognized. Six cases of psychogenic dyskinesias complicating preexisting organic movement disorders are described. This possibility must be carefully considered and excluded before an unusual movement disorder can be considered entirely psychogenic.
Rabbit articular chondrocytes in monolayer culture are modulated away from their differentiated state and undergo morphological and biochemical changes. One of the characteristics of the modulated state is an abnormally high production of the cysteine endopeptidase cathepsin B. Addition to chondrocyte cultures of the protein biosynthesis inhibitor, cycloheximide, resulted in a concentration-dependent reduction of cathepsin B secretion, which was fully restored after removal of cycloheximide. Glycosaminoglycans added to the culture medium of modulated chondrocytes partially reduced the rate of secretion of cathepsin B, this effect being dependent on their structure, the degree of sulfation, and concentration. The age of the chondrocytes and the duration of the treatment also influenced this response. The switching off of cathepsin B release was apparently best favored by a high concentration of negatively charged sulfate groups attached to a polymeric glycosaminoglycan chain; this simulates the natural environment of the chondrocytes in articular cartilage.
Behavioral and biochemical experiments on male albino mice have revealed similar effects after the cessation of repeated (15 days) haloperidol (0.5 mg/kg daily IP) and caerulein (0.1 mg/kg daily SC) treatment. Tolerance developed to the action of muscimol (a GABA-A agonist, 1 mg/kg IP), caerulein (a CCK-8 agonist, 15 micrograms/kg SC) and flumazenil (a benzodiazepine antagonist, 10 mg/kg IP). Muscimol and caerulein were not able to suppress the motor activity of mice after 15 days treatment with haloperidol and caerulein. Flumazenil, which increased motor activity in saline-treated animals, also failed to affect activity after extended haloperidol or caerulein treatment. In contrast, the motor excitation induced by amphetamine (an indirect dopamine agonist, 3 mg/kg IP) was increased after haloperidol or caerulein administration. In radioligand binding studies the density of dopamine-2-receptors in striatum, opioid receptors in mesolimbic structures, and benzodiazepine and GABA-A receptors in brainstem was significantly elevated after long-term haloperidol or caerulein treatment. Simultaneously, the number of CCK-8, benzodiazepine and GABA-A receptors in cerebral cortex was decreased. It is probable that CCK-8-ergic mechanisms are involved closely in the action of repeated haloperidol treatment. CCK-8 seems to modulate the action of haloperidol through altering the sensitivity of dopamine, opioid, GABA-A and benzodiazepine receptors.
The optical performance of one monofocal and five multifocal lenses was evaluated in the laboratory and photographically. The laboratory testing included determination of the modulation transfer function (MTF), through focus response (TFR), resolution efficiency, and Strehl ratio of each lens. The photographic testing included photographs of the Regan high contrast acuity chart at ten feet with clearest focus and 18 additional photographs in which the image was defocused using minus trial lenses in 0.25 diopter increments. A color photograph of the Kodak color chart was also taken using each lens. All testing was conducted using a 3 mm artificial pupil under ideal implant conditions with no decentration or tilt. The laboratory and photographic results demonstrate that all the multifocal lenses had a two- to three-fold increase in the depth of field with at least a 50% lower contrast in the retinal image. The photographic testing revealed a one to two line better resolution limit with the monofocal lens, which corresponded to the 12% to 41% better MTF cut-off value with the monofocal lens by laboratory testing. The measured resolution efficiencies of all six lenses were comparable. The color photographs revealed color mixing of adjacent colors with the multifocal lenses, whereas the colors appeared unchanged from the original with the monofocal lens.
Rat-1 cells infected with a temperature sensitive mutant of RSV (ts LA 29 Rat-1) can be rendered quiescent by serum deprivation at restrictive temperature. Shift to permissive conditions activates the v-src protein tyrosine kinase within 10 minutes and either this stimulus, or serum addition at restrictive temperature, leads to progression of the cell from G0 to G1, S-phase and mitosis. The effects of serum and temperature shift are not synergistic, suggesting that they may operate by convergent mechanisms. However, the characteristic serum-stimulated transient increases in transcripts of three immediate early response genes, c-fos, c-jun and c-myc are absent or much reduced when mitogenesis in ts LA 29 Rat-1 is induced by pp60v-src. Nonetheless, upon activating the pp60v-src protein kinase there is a marked and rapid increase in the ability of ts LA 29 Rat-1 nuclear extracts to retard the gel migration of oligonucleotides containing the AP-1 binding site, indicating that pp60v-src activity leads to an enhanced functioning of Fos and Jun related proteins that may, in turn, affect their transcriptional activation. Furthermore, these findings, and comparison with those of other laboratories, suggest that the mitogenic and transforming activities of pp60v-src have different effects on the transcription of immediate early response genes.
We describe a long-term follow-up study (1-15 years) of 33 patients with Tourette syndrome who were treated with pimozide (2-18 mg), haloperidol (2-15 mg), or no drugs. Both drugs produced comparable relief of symptoms at follow up; however, significantly more patients on haloperidol (eight of 17), compared with those on pimozide (one of 13), discontinued treatment (p less than or equal to 0.05). Haloperidol produced significantly more acute dyskinesias/dystonias than pimozide (p less than or equal to 0.03); otherwise, the adverse effect profile was similar for the two drugs. In particular, we found no increased incidence of ECG abnormalities in patients treated with pimozide. A prospective, randomized, double-blind crossover trial is required to determine whether there are significant differences in efficacy between pimozide and haloperidol in treatment of Tourette's disorder.
In the translational termination step of protein synthesis the three termination codons UAA, UAG or UGA are recognized by so-called release or termination factors. The release factor RF-1 interacts with UAG and UAA whereas RF-2 is specific for UGA and UAA. Two mechanisms concerning the termination event have been discussed so far: recognition of the termination codon by the protein in a tRNA-like manner or double-strand formation between the codon and the 3' end of the 16S rRNA which is stabilized by the termination factor. Using equilibrium dialysis we show that 40% of the ribosomes can bind UGAA in an RF-2-dependent manner. The stability with the correct combination RF-2-UGA is tenfold higher as compared to the wrong termination codon UAG. We confirm prior findings that the termination factor RF-2 is bound to the A-site of the ribosome. In addition to the ribosomal proteins L2, L10, L7/L12 and L20 of the large subunit and S6 and S18 of the small subunit, the 16S rRNA became labelled when radioactive UGA was crosslinked to the ribosome in the presence of RF-2. Our data support a mechanism of termination in which a double strand between the termination codon and the 3' end of the 16S rRNA is formed as the starting event. The resulting RNA-RNA double strand in turn may be recognized and stabilized by the termination factor.
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We diagnosed 24 patients, 9 men and 15 women ranging in age from 15 to 78 years, with clinically established or documented psychogenic tremors. Clinical presentations were unique, with complex tremors (often resting, postural, and kinetic), unusual temporal profiles (abrupt onset with a variable course), absence of other neurologic signs, inconsistent and incongruous symptomatology, selective disability with ability to perform some functions despite severe tremors, distractibility that lessens or abolishes tremor, atypical tremorgraphic recordings with changing amplitude and frequency, unusual handwriting and drawing specimens, presence of multiple undiagnosed somatizations, unresponsiveness to all treatments, absence of documented disease by laboratory or radiographic tests, presence of psychiatric disease, spontaneous remissions, or recovery with psychotherapy. We present criteria for the diagnosis of psychogenic tremor.
Analysis of attendance of the German Cancer Screening Programme according to sex, age and federal state ("Land") reveals noticeable regional differences whereas in general participation is decreasing. It is shown that attendance is above average in the city states, Hesse, and Baden-Württemberg. The remaining Länder should, therefore, improve their rates. A decline in preventive activities and a reluctant attitude towards cancer screening must be taken seriously and be considered when developing the programme further.
Hairy cell leukemia (HCL) has been shown to be extraordinarily sensitive to treatment with alpha-interferon (IFN). In order to define clinically effective IFN doses associated with minimal toxicity, the therapeutic efficacy and side effects of recombinant IFN-alpha-2C treatment of HCL were compared for two different dose regimens: 18 patients (group A) received conventional doses of recombinant IFN-alpha-2C (2 x 10(6)U/m2) for a median time of 35 weeks (range 26-52 weeks), and 21 patients (group B) received optimum biological response-modifying doses of IFN-alpha-2C (0.2-0.6 x 10(6)U/m2) for a median time of 31 weeks (range 12-52 weeks). Interferon was administered daily subcutaneously for 3 months and then every second or third day. Induction of neopterin excretion was chosen as the marker for definition of biological response. The smallest IFN dose causing maximum in vivo induction of biosynthesis of the GTP-degradation product neopterin was deemed "biologically optimal." Both dose regimens were effective, but the low-dose regimen was almost free of toxicity. Thus, in HCL patients alpha-IFN related toxicity can be separated from its antineoplastic activity. Low doses of alpha-IFN should be considered for treatment of HCL patients who develop toxic side effects and for primary treatment of HCL patients with severe cytopenia.
Platelet-activating factor (PAF) is transformed in vivo rapidly into the biologically inactive lyso-PAF. This reaction as well as lipid parameters were quantified in serum from 40 survivors of myocardial infarction and 36 healthy controls matched for age and body weight. The PAF-degrading capacity was 23% (p less than 0.001) higher in patients compared with the control group. Using the degradation of PAF as an univariate discriminator more than 70% of subjects were classified correctly. This is comparable with the discriminatory value of the best lipid variables, apolipoprotein B and HDL-cholesterol. Statistically significant differences in the degradation of PAF were found also by comparing subgroups which were matched for plasma levels of total cholesterol, VLDL/LDL-cholesterol or apolipoprotein B. The ratio by 48% (p less than 0.0001) in the case group was identified as an additional good discriminator between both groups. In contrast, platelet aggregation tests which were performed in acetylsalicyclic acid treated platelet-rich plasma discriminated poorly between patients and controls.
We investigated the effect of human recombinant DNA-derived IFN-alpha-2 given in a dose of 1-2 X 10(6) units daily by subcutaneous injection to five patients with advanced idiopathic myelofibrosis (IM). Transfusion dependent anemia and symptomatic splenomegaly were taken as inclusion criteria for this pilot study. Two patients succumbed, one and three months after starting interferon-treatment because of pneumonia and traumatic cranial injury, respectively. While on IFN-treatment no improvement of cytopenia or reduction of splenomegaly was seen in four of the patients. In one patient, however, the requirement for erythrocyte transfusions decreased from 5 to 1.7 monthly upon IFN-treatment. After two, four and six months respectively IFN-treatment had to be stopped in these cases because of progressive thrombocytopenia and/or neutropenia. These observations suggest, that IFN-alpha might be of only marginal value in the treatment of advanced idiopathic myelofibrosis.
Rabbit articular cartilage does not secrete cathepsin B in organ culture. By established methods for modulating the chondrocyte phenotype in vitro, however, the synthesis, intracellular storage, and secretion of cathepsin B were followed up over a period of two months. With chondrocytes grown in monolayer cultures both the intracellular pool of the enzyme and its secretion were very small initially, but increased progressively to a factor of 110 after eight weeks. The secretion of cathepsin B was strongly depressed after transferring the cells from monolayer to collagen gel cultures. In contrast, collagenase was secreted in almost the same amounts during the whole period in both monolayer and collagen gel cultures. The cells cultured in collagen gels secreted more collagenase than those grown in monolayers. The reversible switch of cathepsin B secretion suggests that this enzyme, unlike collagenase, is a marker of the dedifferentiated chondrocyte phenotype. Cathepsin B was localised within cultured chondrocytes using antibodies raised against rabbit liver cathepsin B and shared with it many catalytic properties. Its Mr, however, was higher (34,000 compared with 27,000) and showed an unusual resistance to denaturation at neutral-alkaline pH, which may confer on this enzyme an important role in the degradation of cartilage matrix.