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Biomedical subjects

T Becker

Publications and source records attributed to T Becker.

At least 55 records · Page 3Linked to original sources

Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain.

The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.

Animals

Protein-protein recognition via short amphiphilic helices; a mutational analysis of the binding site of annexin II for p11.

Annexin II (p36) interacts with its ligand p11 via the short stretch of 12 amino acids (Ac-S-T-V-H-E-I-L-C-K-L-S-L) situated at the N-terminus. We have now synthesized some 37 tetradecapeptides, which differ from the original p11 binding sequence (Ac1-14) by single amino acid substitutions. The relative affinity of each peptide for p11 was determined by fluorescence spectroscopy using a competitive binding assay. The binding behaviour of the different peptides confirms the model of an amphiphilic alpha-helix induced upon binding to p11. The apparent affinities delta delta Gbind of the mutant peptides revealed that the N-acetyl group of serine 1 and the hydrophobic side chains at positions 3, 6, 7 and 10 contribute most to the binding. The observed destabilization of the complex upon removal of signal methyl groups from the hydrophobic side of the helix is comparable with the destabilization of proteins in which methyl groups have been removed from the inner core. We conclude that upon binding to p11 the hydrophobic side of the amphiphatic alpha-helix becomes fully buried.

Amino Acid Sequence

Clinical, biochemical and psychometric findings with the new MAO-A-inhibitors moclobemide and brofaromine in patients with major depressive disorder.

N = 53 inpatients with major depressive disorder have been treated with the reversible, selective MAO-A-inhibitors moclobemide (double-blind versus maprotiline) and brofaromine (open study), respectively. Clinically, significant improvement of depression and an activating profile of action could be observed, typical side effects were sleep disturbances, agitation and weight loss. The neurobiochemical data showed an increase of noradrenaline plasma concentrations under treatment with moclobemide. Visual reaction times improved with antidepressant treatment. MAO-A inhibitors proved to be effective antidepressants in the treatment of hospitalized patients with predominantly endogenous depressions.

Benzamides

Brofaromine (CGP 11 305 A): estimation of plasma concentrations by a biologic technique as compared to liquid chromatography.

In an open clinical trial 13 depressives significantly improved under the reversible and selective type-A monoamine oxidase (MAO) inhibitor brofaromine. The inhibitory potency of deproteinated plasma on a crude MAO preparation from human placenta was measured as a parameter for plasma brofaromine. There were no significant differences in plasma MAO inhibitory potency between responders (improvement greater than 50%; n = 5) and non-responders. MAO inhibitory potency significantly (p less than 0.05) increased parallel to the increase of the dosage from 50 mg b.i.d. to t.i.d. confirming the validity of this technique. The biologic assay, however, overestimated brofaromine by a factor of two in acute kinetic experiments with healthy volunteers as compared to a chromatographic technique, although both methods significantly correlated (r = 0.928).

Adult

"Physiological osteoporosis" and "osteoblast insufficiency" in old age. Comparative radiological-morphometric and statistical studies on the spongy bone of lumbar and cervical vertebral bodies.

To investigate the expectation of general insufficiency of osteoblasts with increasing age, we studied autotopsy material from 105 deceased persons of both sexes who had died between 16 and 91 years and in whom clinically manifest diseases of the bone had been excluded. Quantitative morphometric examination of the structure of the spongy bone of the 3rd-5th lumbar vertebral bodies (LVBs) and of the 5th-7th cervical vertebral bodies (CVBs) was carried out in frontal and sagittal planes, the parameters analysed being volumetric density (Vv), surface density (Sv) and specific surface area (S/V), and the results were subjected to statistical evaluation. The results showed that in the three LVBs, Vv, Sv and S/V behave in a similar manner, Vv and Sv decreasing after the age of 50 years by more than one-third while S/V remains constant throughout life. The three lower CVBs had higher values than the LVBs for all three structural parameters. In the 7th CVB somewhat lower Vv and Sv values and higher S/V values were found than in the 5th and 6th. The age-related changes, by contrast, were very small. This differing behavior of the spongy bone in the two regions of the spinal column is an expression of the different characteristic loading forces in each regions: LVB loading is predominantly static, CVB loading mainly dynamic. Thus, from the functional point of view, what is known as "physiological osteoporosis due to ageing" is nothing more than adaptation by an ageing bone to physical activity, reflecting--like the bone of the young adult--the current loading of the cancellous bone by the actions of the musculoskeletal system. Since such physical activity is often age-related, the performance of the osteoblasts does not depend upon age per se, but merely on the remaining functional adaptive capacities of the ageing organism as whole.

Adaptation, Physiological

MRI findings in medial temporal lobe structures in schizophrenia.

In an MRI volumetric study of 10 young male schizophrenics (DSM-III-R 295.9x) a temporal lobe segment, corresponding hippocampal formation and parahippocampal gyrus were found smaller as compared with healthy controls while temporal horn was enlarged. Temporal lobe segment and parahippocampal gyrus were larger on the right in patients and controls, reversed asymmetry was found for the hippocampus.

Adult

Brofaromine (CGP 11 305 A) in treatment of depression: biological estimation of plasma concentrations.

In an open clinical trial, 13 depressives were treated with the reversible and selective type-A monoamine oxidase (MAO)-inhibitor brofaromine (CGP 11 305 A), the inhibitory potency of deproteinated plasma on a crude MAO preparation from human placenta was measured as a parameter for plasma brofaromine and possibly active metabolites of brofaromine. Patients significantly (p less than 0.01) improved under brofaromine. There were, however, no significant differences in plasma MAO-inhibitory potency between responders (improvement greater than 50%; n = 5) and nonresponders and no correlations with the change from baseline of the total Hamilton Depression Score (HAMD) or with changes of sleep (change from baseline of the HAMD sleep items). MAO-inhibitory potency significantly (p less than 0.05) increased parallel to the increase of the dosage from 50 mg b.i.d. to t.i.d., confirming the validity of this technique. The biological assay applied is a simple and reliable alternative when estimating the plasma concentrations of brofaromine and, possibly, other reversible MAO inhibitors.

Adult

[Lumbosacral nerve root avulsion. Diagnosis using computed tomography, magnetic resonance tomography and myelography].

Root lesions in the lumbo-sacral region are rare, compared with injuries of the roots of the brachial plexus. They occur almost exclusively in association with serious injuries of the pelvis. The present case, without pelvic injury, is a rarity. The appearances on myelography and CT are well known, but the findings on MRI are also described and the value of this non-invasive procedure is discussed.

Adult

Single cell transplantation reveals interspecific cell communication in Drosophila chimeras.

Cell-cell communication is not only a common strategy for cell fate specification in vertebrates, but plays important roles in invertebrate development as well. We report here on experiments testing the compatibility of mechanisms specifying cell fate among six different Drosophila species. Following interspecific transplantation, the development of single ectodermal cells was traced in order to test their abilities to proliferate and differentiate in a heterologous environment. Despite considerable differences in cell size and length of cell cycle among some of the species, the transplants gave rise to fully differentiated clones that were integrated into the host tissue. Clones comprised cells of epidermal and/or neural histotypes, indicating that mechanisms mediating the epidermal/neural dichotomy in the ectoderm are conserved between the species. Cells of the neural lineages differentiated into neurones, glia, or both. Moreover, heterologous neurones sent out axons that followed major pathways along nerves and within the neuropile, demonstrating their ability to recognize positional cues in the heterologous CNS of the host.

Animals

[Comparative structural analyses of the spongy bone of lumbar and cervical vertebral bodies. Radiological-morphometric and statistical studies].

To investigate the question as to a possible insufficiency of the osteoblasts with increasing age, autopsy material obtained from 105 deceased of both sexes at an age of 16 to 91 in whom clinically manifest bone diseases had been excluded, was studied. The structure of the spongy bone of the 3rd to 5th lumbar vertebral bodies (LVB) and of the 5th to 7th cervical vertebral bodies (CVB) was examined quantitatively-morphometrically, and the results were submitted to a statistical evaluation. In the three LVB, Vv, Sv and S/V behave in a similar manner. Here, Vv and Sv decrease after the age of 50 by more than 1/3, while S/V remains constant throughout live. In all the structural parameters, the three lower CVB have higher values than do the LVB. The age-dependent changes, in contrast, are only very slight. This differing behaviour of the spongy bone in the two regions of the spinal column is an expression of the characteristic loading forces in the respective regions: LVB loading is predominantly static, CVB loading mainly dynamic. Thus, from this functional point of view, physiological osteoporosis due to aging, so-called, is merely an expression of an aging bone adapting - in the same way as the bone of a young adult - to the current loading forces acting upon it.

Adolescent

[Elimination of secretions in CF patients under amiloride inhalation].

Inhaled amiloride reduces active absorption of sodium of respiratory epithelium in CF patients and so, transiently, diminishes loss of water. 10 CF patients, 8 to 28 years of age, were examined on two days. First day, they inhaled in a randomised order isotonic saline and a solution of amiloride hydrochloride (0.3 mg/ml) one after another, each inhalation taking twenty minutes. Second day, inhalations were performed in an inverse order. To intensify the effect of inhalation, the inhalation procedure was combined with "autogenic drainage", a special kind of physiotherapy. Main criterion for evaluation was the amount of expectorated sputum. Mean increase of sputum during amiloride inhalation in comparison to saline was +50.4%. Patients and physiotherapist observed a liquefaction of secretion and a decrease of coughing by amiloride and a support of physiotherapy. These results suggest a beneficial clinical effect of regular amiloride inhalation in CF patients.

Absorption

The New Mexico experiment: educational innovation and institutional change.

Over the past ten years the University of New Mexico School of Medicine has conducted an educational experiment featuring learner-centered, problem-based, community-oriented learning. The experiment was introduced into an established institution by means of an innovative educational track running parallel to the more conventional curriculum. Students in the innovative track, compared with those in the conventional tract, tended to score lower on the National Board of Medical Examiners (NBME) Part I examination (basic sciences) and higher on NBME Part II (clinical sciences), received higher clinical grades on clinical clerkships, and experienced less distress. They were more likely than conventional-track students to retain their initial interest in or switch their preference to careers in family medicine. The parallel-track strategy for introducing curriculum reform succeeded in fostering institutional acceptance of continuing educational innovation. Generic steps in overcoming institutional barriers to change are identified.

Curriculum

Moclobemide and maprotiline in the treatment of inpatients with major depressive disorder.

A double-blind study with the substituted benzamide moclobemide, a novel reversible, short acting MAOI with predominant inhibition of MAO-A, and maprotiline, the most selective noradrenaline reuptake inhibitor available at present has been conducted in n = 40 severely depressed inpatients suffering from predominantly endogenous depressions. No significant differences between the two drugs were found using global HRSD, HAMA and self rating scales. Regarding the clinical profile moclobemide seemed to be more effective in retarded depressives, maprotiline was superior in alleviating depressive agitation and sleep disturbances. The latter symptoms were responsible for three cases of treatment withdrawal in the moclobemide group. No case of hypertensive crisis could be registered, though patients were not subject to food restrictions. Maximal concentrations of moclobemide in CSF were reached two hours after oral application, compared to tricyclic antidepressants a high CSF/plasma ratio could be detected.

Anthracenes