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Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 595 records · Page 33Linked to original sources

Astroglial and fibroblast growth factors have neurotrophic functions for cultured peripheral and central nervous system neurons.

Embryonic and neonatal neurons require specific trophic supplements for their survival and the induction of transmitter-synthesizing enzymes in vivo and in vitro. Acidic and basic fibroblast growth factor (aFGF, bFGF) and the closely related astroglial growth factors AGF-1 and AGF-2 were studied for putative neurotrophic functions using dissociated, highly neuron-enriched cultures from chick and rat peripheral ganglia and central nervous system tissues. Embryonic chick ciliary ganglion neurons were the only peripheral neurons that responded to bFGF and AGF-2 by enhanced survival equivalent to that obtained with ciliary neurotrophic factor. Half-maximal effects were achieved with bFGF at 360 pg/ml or AGF-2 at 3 ng/ml. Small effects seen with aFGF could be potentiated by adding heparin at 1 microgram/ml. bFGF, but not ciliary neurotropic factor, also promoted neuron survival after the factor was bound to polyornithine and laminin. Both AGF-2 and ciliary neurotropic factor induced choline acetyltransferase activity during 48 hr. AGFs and FGFs also enhanced the long-term survival of embryonic chick spinal cord neurons, including motoneurons that had been retrogradely labeled with rhodamine isothiocyanate. These results demonstrate the potency of a class of mitogenic growth factors as neurotrophic agents for embryonic ciliary ganglion and spinal cord neurons--adding to the emerging evidence that mitogenic and neuronal growth factors are not strictly separate entities.

Animals↗

Structure/activity relationships of polyfunctional diterpenes of the ingenane type. I. Tumor-promoting activity of homologous, aliphatic 3-esters of ingenol and of delta 7,8-isoingenol-3-tetradecanoate.

Eight skin irritant 3-esters with the homologous even number aliphatic acids (acetic to hexadecanoic acid) of the polyfunctional diterpene alcohol ingenol as well as the non-irritant 3-tetradecanoate of delta 7,8-isoingenol were tested for their initiation or (tumor)-promoting activity in the standardized semi-quantitative initiation/promotion assay on the back skin of NMRI mice. In a corresponding protocol over 48 weeks without preceding initiation, i.e. as a tumorigen, the 3-hexadecanoate of ingenol (3-HI) proved to be practically inactive as compared to the strong response elicited as promoter. Dose/response relations were shown to be positive for both 3-HI and 3-O-tetradecanoylingenol (3-TI), as representative ingenol-3-esters. In assays for structure/activity relations of promoting activity, it turned out that the group of 3-acetate, 3-butyrate and 3-hexanoate of ingenol are very weak to weak promoters. The group of 3-octanoate to 3-HI proved to be strong promoters. Maximal activity was exhibited by 3-TI and it is proposed that this be considered the prototype of the 3-esters of the ingenane type. In semi-quantitative terms it is slightly less active as a skin tumor promoter than the tigliane type 12-O-tetradecanoylphorbol-13-acetate. At the same dose level as 3-TI, the 3-tetradecanoate of delta 7,8-isoingenol was inactive as a promoter.

9,10-Dimethyl-1,2-benzanthracene↗

Identification and subcellular distribution of cornified envelope precursor proteins in the transformed human keratinocyte line SV-K14.

SV-40 transformed human foreskin keratinocytes (line SV-K14) develop under conditions of serum starvation the competence to form cornified envelopes that are characteristic of terminally differentiating epidermal cells. In this cell line, the final assembly of the envelope does not occur spontaneously but must be induced using a calcium ionophore. Five potential precursor proteins with molecular weights of 140K, 90K, 61K, 53K, and 36K, respectively, could be detected in the extracts of envelope competent and noncompetent cells. The 61 kD and the 36 kD precursors were specifically decorated in immunoblots when using an antiserum directed against the purified cornified envelope of SV-K14 cells. The 140 kD protein was identified as involucrin by means of a commercial anti-involucrin antibody. Part of the 61 kD protein was found to be inserted into the plasma membrane after the cells gained envelope competence. The set of precursor proteins used by SV-K14 cells differed markedly from those described in the literature for epidermal cells in vivo and for normal human keratinocytes in vitro. Furthermore, cyanogen bromide cleavage of purified envelopes from transformed and normal keratinocytes revealed a completely different peptide pattern. This indicates that the exact molecular composition of the cornified envelope may not be strictly determined and may vary according to the availability of potential substrate proteins at the very moment when the cross-linking enzyme, the plasma membrane associated transglutaminase, becomes functional.

Cell Line↗

Subcellular distribution of ependymins in goldfish brain measured by radioimmunoassay.

Goldfish CNS was fractionated by differential and density gradient centrifugation. The fractions obtained were characterized by marker enzymes typical of various subcellular organelles. They were further analyzed by radioimmunoassay for their contents of ependymins, two CNS glycoproteins known to participate in biochemical reactions after learning events. Ependymins were shown to be major constituents of the soluble cytoplasm (5.6% of the total protein content). The nuclear fraction was virtually devoid of ependymins (0.6% of protein). Small amounts were observed in the crude synaptosomal and microsomal fractions (1.0 and 3.5%, respectively). The highest steady-state concentration of ependymins, however, was measured in the brain extracellular fluid (15.6% of the protein), including the CSF. The specificity of the distribution was examined by intracerebroventricular injection of 125I-labeled ependymins as exogenous marker substances. No indication of an artificial redistribution of the radiolabel during homogenization and fractionation was obtained. The exogenous analogues of ependymins were, however, incorporated in vivo into organelles recovered in the nuclear and crude synaptosomal fractions. Our results suggest that ependymins may interact with synaptic membranes from the extracellular fluid, although so far no evidence for a specific receptor-type binding site could be obtained in vitro.

Animals↗

Changes in subcellular distribution of ependymins in goldfish brain induced by learning.

Goldfish were trained for 4 h to swim with an attached polystyrene foam float and tested for retention 3 days later. Intracerebroventricular injection of anti-ependymin antisera was shown to prevent long-term memory formation of this vestibulomotor learning task, as reported previously. In further experiments, fish were killed 4-14 h after the start of training. The brains were dissected, incubated in an isoosmolar solution for collection of proteins of the brain extracellular fluid (ECF), homogenized, and fractionated by differential centrifugation. The ECF, a supernatant fraction enriched in cytoplasmic constituents (S3), and various particulate subcellular fractions were analyzed for their ependymin contents by radioimmunoassay. No statistically significant changes that might be induced by the learning were revealed in any of the particulate fractions. Steady-state concentrations of ependymins in the cytoplasm, however, increased temporarily by 39% in fish that had mastered the training task as compared with nonlearning animals (passive and active controls). In the ECF, the specific concentration of ependymins first decreased to 88% of control levels (4-5 h after the start of training), but later on, it increased to 138% (8-14 h). Apparently, ependymins present in the ECF are used during biochemical reactions of memory consolidation. The resulting decrease in extracellular ependymin concentrations might trigger their resynthesis in the cytoplasm and lead to an increased release of these glycoproteins into the ECF.

Animals↗

Peripheral neural correlates of cutaneous anaesthesia induced by skin cooling in man.

The effect of local skin cooling on the behavior of low- and high-threshold mechanoreceptive afferents innervating glabrous and non-glabrous skin was studied in microneurographic recordings on awake human subjects. Cooling with ice or ethyl chloride to a skin surface temperature below 10 degrees C caused a reduction of receptor sensitivity in 49 out of 52 studied low-threshold afferents. This effect was reversible upon warning but some reduction often persisted for a few minutes after normal skin temperature had been reached. The subjects' sensations of application and removal of von Frey hair stimuli were more resistant than had reappeared before the sensation of sustained pressure. This could be explained by shorter recovery times for fast than for slowly adapting units and by a relative preservation of the dynamic responses of the slowly adapting units. During the recovery phase some low-threshold mechanoreceptive afferents exhibited a transient 'spontaneous' discharge in the absence of external mechanical stimulation. The suppression of afferent C-fibre responses to needle strokes was more pronounced and long-lasting than the effect on A-fibre responses and largely paralleled the recovery of sensation of pain. It is concluded that the local anaesthetic effect of skin cooling is to a large extent explicable in terms of receptor desensitization although other mechanisms may contribute.

Adult↗

Aneurysmal bone cyst arising in fibrous dysplasia during pregnancy.

A case of two secondary aneurysmal bone cysts arising in fibrous dysplasia during pregnancy is reported. Marked radiographic changes were seen in one lesion over a 3-week period. The development of these cysts during pregnancy strongly suggests that the hemodynamic and/or hormonal changes of pregnancy were responsible for their formation.

Acromion↗

Present state of hemorheology.

Hemorheological disturbances are present in more than 50% of cerebrovascular disease (CVD). An inverse relationship between cerebral blood flow (CBF) and viscosity has been established. There also exists an interaction of vessel wall changes, whole blood viscosity, and plasma fibrinogen. The acute ischemic episode is associated with hyperaggregability of the blood platelets, increased blood viscosity, hyperaggregability of the red cells and an increase in plasma fibrinogen. Hemorheological changes to a certain extend may occur not only in CVD but also in senile dementia of Alzheimer type (SDAT) and certain cases of Parkinson's disease. This fact allows to differentiate between idiopathic parkinsonism and Parkinson's disease with high hemodynamic risk.

Aged↗

[Aneurysm of the infrarenal abdominal aorta].

Preoperative and postoperative treatment as well as standardisation of surgical techniques over the past 20 years have helped to bring about considerable reduction of operative mortality in cases of asymptomatic aortic aneurysm. Yet, with all improvement, rupture of aneurysm has continued to be associated with high rates of mortality. At the Department of Surgery of Cologne University, between 1963 and 1985, operations were performed on 681 patients for abdominal aortic aneurysm. Asymptomatic aneurysm were surgically removed from 41.7 per cent of them, while 27.5 per cent underwent surgery in symptomatic stages. Aneurysm had ruptured in 210 patients. Operative mortality accounted for 5.3 per cent of all asymptomatic patients. High mortality rates among patients with ruptured aortic aneurysms were attributable to preoperative shock. Only 16.3 per cent of patients survived in this group. The mortality rate among patients without shock amounted to 39.5 per cent.

Adult↗

Immunological cross-reactivity of cultured rat hippocampal neurons with goldfish brain proteins synthesized during memory consolidation.

Ependymins are goldfish brain glycoproteins exhibiting a specifically enhanced rate of synthesis when the animals adopt a new pattern of swimming behavior. With specific antisera against ependymins it has become possible to look for ependymin-like immunoreactivity in other animal species, both qualitatively by immunofluorescence staining and quantitatively by radioimmunoassay. Ependymin-like immunoreactivity was detected not only in other fish but also in rat brain. In the rat radioimmunoassay measurements were highest for the hippocampal formation and for cultured neurons derived from the embryonic hippocampus. Immunofluorescence staining was performed on various cell culture systems derived from rat brain, in order to establish which cell type contains the antigen. Only neuronal cell populations reacted with the anti-ependymin antisera. Cells derived from embryonic rat brain hippocampus which resembled pyramidal neurons stained particularly bright for ependymin-like immunoreactivity. The antigenic material was distributed throughout the cytoplasm including the neuronal extensions. Various neuron-specific antisera have been used to counterstain the cells containing ependymin-like immunoreactivity.

Animals↗

[Clinical aspects of the use of the artificial kidney].

During the last years the haemodialysis treatment in chronic uraemia has been admirably developed and improved. At now as ever high expenditure for the chronic dialysis programme the capacity at our disposal must optimally be used. For this it is necessary to detoxicate the patients in relatively short times of treatment as effective as possible. But the increase of the efficacy of the haemodialysis is limited, which is revealed in the fact that the patient under the highly effective treatment shows complications such as decrease of blood pressure, muscle spasms, nausea and vomiting as well as headache. The clinical findings of the patient may further depend on the age, on the dialysis technique being at our disposal, on the composition of the dialysis solution, the biocompatibility of the dialysis membrane, the level of the retention values as well as on nutrition, training condition of the patient, psychic factors and others. The scientific efforts for optimization of the haemodialysis treatment have the aim to realize a haemodialysis treatment adapted individually to each patient, in order to treat the individual patient as effective as possible, however, without complications.

Adult↗

Incomplete epidermal differentiation of A431 epidermoid carcinoma cells.

A431 malignant keratinocytes, although derived from a muco-cutaneous carcinoma of the vulva, fail to achieve terminal epidermal differentiation in culture as shown by their inability to form cornified envelopes. Even after culture in a serum-free medium (MCDB 153) containing no retinoic acid and a high (10(-3) M) calcium concentration (conditions known to facilitate epidermal differentiation), the cells do not become competent as shown by the fact that subsequent treatment with a calcium ionophore is unable to provoke the formation of cornified envelopes. Nevertheless, A431 cells are able to synthesize the envelope precursor involucrin. The block in formation of cornified envelopes is thus not due to a lack in involucrin. The results described here suggest that the absence of cross-linking of this molecule is due to a lowered epidermal membrane-bound transglutaminase activity in A431 cells when compared to normal human keratinocytes. In other respects, EGF, which inhibits the proliferation of A431 cells, enhances involucrin accumulation in these cells, although in normal human keratinocytes it stimulates growth and reduces involucrin synthesis. These results suggest that involucrin synthesis is triggered by the arrest of growth.

Calcium↗

Destruction of the preganglionic nerves by beta-bungarotoxin does not interfere with normal embryonic development of the rat adrenal medulla.

Using beta-bungarotoxin (beta-BTX) as a tool to eliminate the preganglionic cholinergic nerve supply to the embryonic rat adrenal gland, we have investigated whether or not these nerves affect the differentiation of embryonic chromaffin cells (pheochromoblasts). Rat fetuses received a single injection of 1 or 2 micrograms beta-BTX or an identical volume of saline at embryonic day (E) 17 and were taken for morphological and biochemical analyses at E 21. Administration of beta-BTX caused a 15 to 20% reduction in body weight, crown-rump-length and adrenal weight. Spinal cord development was reduced and acetylcholinesterase-positive cells in ventral and lateral columns were virtually absent in toxin-treated animals. In adrenal glands, a decrease of choline acetyltransferase activity to 13% of control levels and a concomitant decrease of ultrastructurally identifiable nerve fibers and axon terminals revealed that application of 2 micrograms beta-BTX effectively reduced the neuronal input to E 21 adrenal glands. Values for total adrenal catecholamines, relative amounts of adrenaline and noradrenaline, tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities were unaltered. All ultrastructural features of pheochromoblasts (except the lack of synapse-like axon terminals) were inconspicuous. Corticosterone levels in adrenals and plasma were identical to controls. These data strongly suggest that normal embryonic development of adrenal chromaffin cells does not require an intact nerve supply.

Adrenal Medulla↗