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Biomedical subjects

K Hempel

Publications and source records attributed to K Hempel.

At least 91 records · Page 5Linked to original sources

Unresponsiveness to experimental allergic encephalomyelitis in Lewis rats pretreated with complete Freund's adjuvant.

A single injection of complete Freund's adjuvant blended with aluminum hydroxide gel (ALU-CFA) was successfully used to prevent clinical as well as histologic experimental allergic encephalomyelitis (EAE) in Lewis rats for more than 330 days. Adjuvant preparations with Mycobacterium tuberculosis were more potent than those with Mycobacterium butyricum. Neither the removal of the ALU-CFA inoculum nor a splenectomy 1 month after immunization arrested the adjuvant induced unresponsiveness. However cyclophosphamide restored responsiveness in more than half of the treated animals when applied 2 days before the encephalitogenic challenge at a dose of 20 mg/kg. Passive EAE was not prevented by the ALU-CFA pretreatment. The disease was induced by the transfer of 4 X 10(6) T lymphocytes of a cell line reactive against myelin basic protein. This indicates that the adjuvant prevents EAE at the inductive rather than at the effector phase of the autoimmune response.

Age Factors↗

Calmodulin content in specific brain areas.

A radioimmunoassay was used to measure the calmodulin content in eleven brain areas of the rat. Calmodulin showed an uneven distribution. Various cortical regions, striatum, hippocampus, amygdala and substantia grisea were highest in calmodulin content (15 micrograms/mg protein). Locus coeruleus, nucleus tractus solitarii (+A2 region) and A1 region, contained 7 micrograms calmodulin per mg protein and the cerebellum 4 micrograms/mg.

Animals↗

Radioimmunoassay of oxidized calmodulin in chloramine-T treated tissue samples.

We found that a short incubation of calmodulin with chloramine-T alters its antigenic structure. Antisera elicited by performic acid oxidized calmodulin only bind with chloramine-T treated calmodulin. Based on this finding we have developed an assay for the determination of calmodulin in small tissue samples. Tissue homogenates are incubated with 10 mmol/l chloramine-T before calmodulin quantification. Immune complexes are isolated by sodium sulphate precipitation. [125I]calmodulin is used as tracer.

3',5'-Cyclic-AMP Phosphodiesterases↗

Quantitative investigation on the urinary excretion and metabolism of 3,4-dimethoxyphenylethylamine in schizophrenics and normal individuals.

A quantitative method for the detection of DMPEA in urine was developed. It is based on the fluorometric determination of DMPEA in the form of its phosphopyridoxyl derivate. The limit of detection is 2 microgram DMPEA per 1 g creatinine. The DMPEA content was measured in urine from healthy persons, from schizophrenics, and from psychiatric patients without schizophrenia hospitalized with the schizophrenics. From each person five to ten 24-hr urine samples were investigated. DMPEA could be found neither in schizophrenics nor in controls or healthy persons. Finally, the urinary excretion of parenterally applied 14C-DMPEA was determined in three healthy volunteers and in three rats. In man about 25% of the label was excreted as DMPEA. The main metabolite in urine was homoveratric acid. Both compounds were excreted as conjugates.

Biotransformation↗

Myelin basic protein in cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases.

Cerebrospinal fluid (CSF) from 105 patients was analyzed by radioimmunoassay for the presence of material cross-reactive with peptide 89-169 of bovine myelin basic protein (BP). In a group of 72 multiple sclerosis patients, 52 showed higher BP content than the control group, i.e. more than 2 ng/ml CSF. Increased BP or BP fragments could be detected in CSF from almost all patients who recently (within 2 weeks) had had an acute episode, or after deterioration in the progressive form of the disease. Fifteen to 30 days after the onset of exacerbation or in a stable period, BP content decreases and in the slowly progressive form was in the range of the control group with one exception. BP content was also elevated in the CSF of patients with other neurological diseases. The presence of BP in the CSF from patients with isolated retrobulbar neuritis is of particular interest. Thus the presence of material cross-reactive with BP fragment 89-169 is not specific for multiple sclerosis, but is a useful parameter in diagnosis and evaluation of MS.

Cerebrovascular Disorders↗

Suppression of experimental allergic encephalomyelitis by transfer of lymph node cells from Lewis rats pretreated with complete Freund's adjuvant.

Experimental allergic encephalomyelitis (EAE) in Lewis rats was suppressed by pretreatment with complete Freund's adjuvant (CFA) 14-16 days before immunization with basic protein (BP) in CFA. Suppression of active EAE was also accomplished clinically and even histologically if lymph node cells from CFA-treated donors were passively transferred. Obviously this depends first on a certain amount of transferred lymph node cells (about 3 X 108) and secondly on the interval between CFA application and cell harvest (more than 14 days). No suppression was obtained by transfer of serum from CFA-treated donors. This indicates that there is a suppressor cell population which can be raised or stimulated by CFA and which is capable of suppressing the immune response EAE.

Animals↗

Studies on collagen metabolism in rats. I. Age-related changes in turnover and amino acid composition of the collagen of glomerular basement membrane and tail tendon.

To examine the effect of age on the collagen metabolism of glomerular basement membrane (GBM) and tail tendon, both structures were labeled in vivo by the injection of tracer amounts of radioactive proline. The analyses of the labeled proline and, especially, hydroxyproline revealed that synthesis and degradation are reduced in senescent rats. The calculated turnover rate for GBM-collagen is prolonged by about 40% with increased life span. The reduced catabolism is responsible for the age-related thickening of the GBM. In addition, compositional analyses of isolated GBM and tail tendon were performed. Substantial age changes were observed in the amino acid composition of both structures. The hydroxylated amino acids showed a progressive increase with age, while proline and lysine were found to decline.

Age Factors↗

Studies on collagen metabolism in rats. II. Turnover and amino acid composition of the collagen of glomerular basement membrane in diabetes mellitus.

The effects of streptozotocin diabetes on the collagen metabolism in rat glomerular basement membrane (GBM) have been investigated. The metabolic activity was measured in vivo by following the incorporation of 3H-proline into hydroxyproline over the course of 3 months. Under diabetic conditions, smaller amounts of labeled hydroxyproline were found in the GBM indicating that collagen synthesis is injured. The retarded disappearance of the tracer from the GBM is related to an additional alteration of the degradation resulting in a slower turnover. If collagen formation is reduced in streptozotocin diabetes, the thickening of the diabetic basement membranes can only explained by this disturbed catabolism. The amino acid composition of GBM was also altered after streptozotocin application. The diabetic animals showed an increase of hydroxylysine in this structure. The diabetic effects on the GBM presented were interpreted as a kind of accelerated aging of collagen.

Amino Acids↗

Glomerular basement membrane turnover in young, old, and streptozotocin-diabetic rats.

Diabetic and senile glomerulosclerosis consists of thickening of the glomerular basement membranes (GBM) and augmentation of the mesangial matrix. The pathogenesis of these alterations is still controversial. Therefore, an in vivo study of the metabolism and the chemical composition of the GBM in streptozotocin-diabetic and old rats reported here was conducted: The turnover rate of the GBM, determined by the incorporation of labeled hydroxyproline, is prolonged in preparations from diabetic and aging rats. This can be explained by the decreased synthesis and delayed degradation of the GBM material found in both experimental groups. The biochemical analyses of the GBM revealed a higher content of hydroxylated amino acids, especially OH-lys, in the old and diabetic animals. The findings suggest that diabetic and senile glomerulosclerosis results from a prolonged turnover of the GBM and GBM-like material under the altered metabolic conditions investigated in this study.

Age Factors↗

BAEE esterase (kallikrein-like) activity in parotid saliva of normal rats and rats with various forms of experimental hypertension (genuine, renovascular and DOCA salt hypertension).

A technique for continuous and quantitative collection of parotid saliva including salivary flow rate determination for in vitro experiments in rats is described. Kallikrein-like activity in parotid saliva of rats with various forms of arterial hypertension (genuine, renovascular and DOCA salt hypertension) was studied. Kallikrein-like excretion was measured by its estoerolytic activity using benzoyl arginine ethyl ester (BAEE) as a substrate. The levels of kallikrein-like activity in parotid saliva of normotensive control rats ranged between 2.5 and 4.0 mU/min during salivary flow stimulation with pilocarpine. In all forms of experimental hypertension kallikrein-like activity in saliva was increased two-to fourfold. This increase was not related to the activity of the renin-angiotensin system.

Animals↗

Decrease in motor activity - an early symptom in the course of experimental allergic encephalomyelitis (EAE).

Motor activity has been followed in rats during an experimental allergic encephalomyelitis (EAE). The disease was produced by transfer of lymph node cells from sensitized syngenic donors. Small and large movements were permanently registered by an electric activity meter. It could be demonstrated that a decrease of the motility is an early symptome of the disease. Therefore the measurement of the motoric activity might be a useful parameter in the classification of EAE.

Animals↗

[Influence of pyloroplasty and pyloric stenosis on motoric and secretory function of the stomach after selective proximal vagotomy--an experimental study (author's transl)].

In conscious fullgrown minipigs simple SPV alone, SPV and pyloric stenosis and SPV and pyloroplasty were performed. After a liquid test meal the motoric and secretory function of the stomach were examined simultaneously by a modified method of intestinal perfusion and aspiration. After simple SPV initially a marked decrease of gastric volume and normal emptying into the duodenum were found. With additional pyloric stenosis no significant change was found. The pyloroplasty lead to an increase of gastric volume and delayed emptying. The acid secretion after feeding reduced by SPV was not changed significantly neither by pyloroplasty nor by pyloric stenosis. The baseline values of serum gastrin were elevated after SPV as well as after SPV in combination with pyloric stenosis or pyloroplasty. After food stimulation there was a delayed increase of gastrin after SPV which differed from that after SPV with pyloric stenosis or pyloroplasty only during the first hour. These results show that after SPV no further improvement of the motoric and secretory function can be achieved by an additional pyloroplasty. Furthermore these findings permit the conclusion that even after SPV with additional artificial pyloric stenosis no delayed gastric emptying occurs and that there is no negative effect postoperatively on the acid secretion and gastrin production.

Animals↗

Influence of endogenous S-adenosylmethionine on the determination of catechol O-methyltransferase activity in red blood cells.

A double isotope method for the simultaneous determination of S-adenosylmethionine (SAM) and catechol O-methyltransferase (COMT) activity in red blood cells was developed. Healthy persons contained 7.9 +/- 1.9 nmol SAM per ml red blood cells and 1.9 to 3.8 nmol per ml plasma. Epinephrine increases the SAM biosynthesis rate in red blood cells. The possible influence of endogenous SAM on previous methods to determine COMT activity in red blood cells is discussed. The statement of Briggs and Briggs (Briggs, M.H. and Briggs, M. (1973) Experientia 29, 278--281) that COMT activity in red blood cells is lower during the last 3 months of pregnancy could not be verified by us.

Catechol O-Methyltransferase↗

Technique of continuous collection of parotid saliva in the rat.

A method is described, which is suitable to collect continuously and quantitatively saliva from both parotid glands in rats under in vivo conditions and which allows to investigate salivary electrolyte composition in relation to flow rate during several hours. This might be of expanding scientific interest in disturbances of transepithelial electrolyte transport in various pathophysiological situations (for instance different forms of experimental hypertension, endstage renal failure and so on).

Animals↗

Decreased cAMP content of the hypothalamus of genetically hypertensive rats.

In genetically hypertensive rats an altered catecholamine content of hypothalamic structures has been reported. In the present study cAMP was estimated in the hypothalamus and cortex of genetically hypertensive rats and compared with normotensive controls of the same strain. It is shown, that the cAMP content of the hypothalamus of the hypertensive animals was decreased to about 60% of control values, whereas there was no difference of the cAMP content in the cortical regions of the same animals. These results indicate an alteration of the adenyl cyclase-cAMP-phosphodiesterase system in hypothalamic structures of genetically hypertensive rats.

Animals↗