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Biomedical subjects

H H Lange

Publications and source records attributed to H H Lange.

10 recordsLinked to original sources

CD30 shedding from Karpas 299 lymphoma cells is mediated by TNF-alpha-converting enzyme.

CD30 is a costimulatory receptor on activated lymphocytes and a number of human lymphoma cells. Specific ligation of membrane-bound CD30 or cellular stimulation by PMA results in a metalloproteinase-mediated down-regulation of CD30 and release of its soluble ectodomain (sCD30). In this report, it is demonstrated that PMA-induced CD30 cleavage from Karpas 299 cells was mediated by a membrane-anchored metalloproteinase which was active on intact cells following 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate extraction of membrane preparations. Moreover, CD30 shedding was blocked by the synthetic hydroxamic acid-based metalloproteinase inhibitor BB-2116 (IC(50), 230 nM) and the natural tissue inhibitor of metalloproteinases (TIMP)-3 (IC(50), 30 nM), but not by the matrix metalloproteinase inhibitors TIMP-1 and TIMP-2. This inhibition profile is similar to that of the TNF-alpha- converting enzyme (TACE) and, indeed, mRNA transcripts of the membrane-bound metalloproteinase-disintegrin TACE could be detected in Karpas 299 cells. The ectodomain of TACE was expressed in bacteria as a GST fusion protein (GST-TACE) which cleaved CD30 from the surface of Karpas 299 cells and concomitantly increased the level of sCD30 in the cell supernatants. Hence, TACE does not only control the release of TNF-alpha, but also that of sCD30.

ADAM Proteins↗

Does hormone analysis predict the antihypertensive response of basic medical treatment?

The antihypertensive effect of 200 mg metoprolol per day was compared to 25 mg hydrochlorothiazide over a period of four weeks. Metoprolol reduced mean arterial blood pressure from 120 +/- 13 mm Hg after placebo to 109 +/- 8 at the end of the study (n = 18; 38 +/- 12 years) (p less than 0.01). The corresponding values in the hydrochlorothiazide group were 119 +/- 13 mm Hg and 107 +/- 13 (n = 20; 33 +/- 12 years) (p less than 0.01). No significant difference between the groups was found for blood pressure at the end of the study. When blood pressure responders or non-responders of the metoprolol group were compared with the respective subgroup of the hydrochlorothiazide treated patients, no difference could be found for plasma renin activity as well as for aldosterone and PGE2- and PGF2a-excretion rates. However, when blood pressure responders were compared with non-responders within the same treatment group, plasma renin activity and PGE2-excretion rates were higher in the responder group corresponding with younger age in both treatments. Therefore high PGE2-excretion rate and high plasma renin activity might reflect a favorable vascular response to antihypertensive therapy. However, the hormonal analyses do not seem to help in the selection between a beta-blocker or a diuretic as a drug of first choice.

Adolescent↗

[The spread and inhibition of epileptic processes, findings with the kindling model in the cat].

The study was undertaken to describe some characteristics of subcortical brain activity during the development of an experimentally induced seizure disorder in the cat, as well as to test inhibitory effects of caudate counterstimulation. A further objective was to assess the use of closed circuit TV monitoring for the evaluation of clinical symptoms in an experimental model of limbic epilepsy. The analysis of event related potentials, spectral coherences and phases was especially suitable in order to detect a gradual lowering of the seizure threshold during the establishment of a unilateral Nucl. amygdalae epileptic focus. The results demonstrated evidence for the proceeding importance of hippocampal involvement during the development of seizure activity originating in the ipsilateral amygdala. No evidence, however, could be found for the existence of inhibitory functions triggered by stimulation of the ipsilateral caudate nucleus. The simultaneous split-screen TV monitoring of EEG and partial complex symptoms proved to be a valuable tool for the documentation of seizure patterns during the kindling procedure.

Animals↗

Temporo-spatial patterns of pre-ictal spike activity in human temporal lobe epilepsy.

The statistical properties of pre-ictal EEG spike activity in medial temporal lobe sites were analyzed in 6 patients with medically refractory complex partial seizures. A total of 24 1 h pre-ictal periods (2-6 periods per patient) were evaluated by quantifying the rate of occurrence of individual spatial patterns of spike activity derived from a subset (n = 6) of the recording channels. The channels chosen for analysis always included those medial temporal lobe sites which were documented to be most likely to initiate seizures, as well as their respective contralateral homologues. Each 1 h pre-ictal period was divided into 360 10 sec bins which were then visually classified into 1 of 64 possible spatial patterns of spike activity. These patterns, in turn, were grouped into 1 of 5 general spatial patterns and evaluated for trends across 3 20 min pre-ictal segments. Pooling these data across patients yielded the following results: (1) Focal patterns of spike activity tended to decline significantly in rate of occurrence several minutes prior to seizures, while the rate of independent contralateral patterns did not change. (2) The rate of occurrence of patterns of bilateral loosely coupled spike activity (involving focal and contralateral sites) increased significantly across the 20 min pre-ictal segments and was clearly augmented during the 20 min prior to seizures. These findings indicate that the degree of bilateral independence in medial temporal lobe spike activity tends to decrease several minutes prior to the localized onset of temporal lobe seizures; such changes may reflect the mechanisms responsible for the inter-ictal-ictal transition.

Action Potentials↗

[Reduced urinary prostaglandin E2-excretion and diminished responsiveness of plasma renin activity in patients with essential hypertension (author's transl)].

Under basal conditions prostaglandin (PG) E2-excretion was significantly lower in 35 patients with essential hypertension studied than in 22 age- and sex-matched controls (p less than 0.02). PGF 2 alpha--excretion was similar in both groups. Within the first 15 minutes after furosemide i.v., PGE2-excretion rose substantially less in the patients than in the controls (p less than 0.001), while the increase in PGF 2 alpha-excretion was not different for both groups. The coincident rise of plasma renin activity was significantly lower in the hypertensive (167% +/- 11, SEM) than in the normotensive (386% +/- 46) group (p less than 0.001). Our results support the assumption that a decrease in renal cortical (vascular?) synthesis of vasodilatating PG's may be the cause for both, the diminished secretion of renin and the increase of vascular resistance in the kidney, which are often associated in essential hypertension.

Adult↗

[Pathogenetic, pathophysiological and biochemical aspects of essential hypertension (author's transl)].

Hereditary and environmental factors are involved in the pathogenesis of essential hypertension. Obesity, salt intake and stress are predominant among the environmental influences. Autonomous nervous dysfunction, increased contractility of vascular smooth muscle cells and impaired renal handling of sodium are major abnormalities in essential hypertension. At present it cannot be decided if alterations in the activities of systemic or renal hormonal systems reflect primary defects or adaptive changes in the regulation of blood pressure. In any case the kidney is regarded to have a key position in the long term increase of blood pressure in essential hypertension. Recent studies in essential hypertensive patients suggest that renin release decreases as renal vascular resistance increases. Studies from our laboratory have shown that renal prostaglandins are intrinsic to the renin release mechanism from the kidney. Additionally, there is evidence that renal prostaglandin synthesis is disturbed in essential hypertension, either primarily or secondarily, leading to unresponsive renin secretion. Further studies on the interrelationships of other hormonal systems and on hormone-receptor interactions in the vascular wall are necessary to delineate more precisely the mechanisms which are operative in the pathogenesis and manifestation of essential hypertension.

Adrenal Cortex Hormones↗

[Pre-renal failure due to villous adenoma of the colon].

A 68-year-old man with known villous adenoma of the rectum had recurrent severe episodes of dehydration and electrolyte loss, misinterpreted as being due to "chronic pyelonephritic". The dehydration proved, in fact, to be due to the adenoma and ceased after removal of the tumour.

Acute Kidney Injury↗