Biomedical subjects

G Heinen

Publications and source records attributed to G Heinen.

At least 19 recordsLinked to original sources

PubMed1995

Induction of beta 1 integrin synthesis by recombinant platelet-derived growth factor (PDGF-AB) correlates with an enhanced migratory response of human dermal fibroblasts to various extracellular matrix proteins.

Cell migration plays a major role during wound healing and is tightly controlled by a variety of growth factors and extracellular matrix proteins. The experiments reported here have been designed to study whether defined beta 1 integrins are involved in the platelet-derived growth-factor-AB (PDGF-AB)-modulated migratory response to collagen type I and to fibronectin. Preincubation of fibroblasts with PDGF-AB resulted in an up to 2.5-fold increase in the migratory response to collagen type I as well as fibronectin and to enhanced synthesis and cell surface expression of the alpha 2, alpha 3, alpha 5, and beta 1 integrin subunits. Function-blocking monoclonal antibodies against the common beta 1 integrin subunit dose-dependently inhibited the PDGF-AB-augmented migration of fibroblasts to collagen type I and fibronectin. The PDGF-AB-induced migration to collagen type I was also inhibited by antibodies against the alpha 2 integrin subunit, whereas the corresponding migration to fibronectin was almost completely blocked by the combined application of antibodies against the alpha 3 and the alpha 5 integrin subunits. Taken together, up-regulation of integrin synthesis and expression by human recombinant PDGF-AB correlate with an increase in the migratory response of dermal human fibroblasts to various extracellular matrix proteins and thus may contribute to an efficient regulation of cell migration during wound healing and tissue repair.

Cell Movement↗

PubMed1994

Calcium antagonists for treatment of diabetes-associated hypertension. Metabolic and renal effects of amlodipine.

In hypertensive diabetics a strict blood pressure control may decrease the incidence of cardiovascular and diabetic complications. Long-term experience with the use of calcium antagonists is still limited. The metabolic and renal effects of long-term (8 months) therapy with amlodipine, 5 to 10 mg daily, were studied in 15 hypertensive patients with uncomplicated diabetes mellitus as compared with 15 patients with essential hypertension. After a 4 week placebo phase, the diabetics and essential hypertensive patients did not differ in mean blood pressure (156/93 +/- 16/7 v 150/95 +/- 9/5 mm Hg), body weight, creatinine clearance, microalbumin excretion, and C-peptide and lipid levels, while serum fructosamine was higher in the diabetics. In both groups, amlodipine caused a significant and long-lasting decrease of arterial pressure (8%), but did not modify creatinine clearance, microalbumin excretion, and serum lipid levels. In diabetics indices of diabetic control and the insulin and glucose response to an oral glucose tolerance test were unchanged, whereas in essential hypertension the insulin response to a glucose load was decreased (P = .033). Amlodipine exerts a comparable and long-lasting antihypertensive effect in hypertensive diabetics and patients with essential hypertension. Despite the significant decrease in arterial pressure, there was no change in urinary microalbumin excretion. Lipid metabolism, quality of diabetic control, and the insulin response to a glucose load were not affected unfavorably.

Adult↗

PubMed1994

UVA-induced autocrine stimulation of fibroblast-derived collagenase/MMP-1 by interrelated loops of interleukin-1 and interleukin-6.

Previous work has shown that fibroblast-derived collagenase/matrix-metalloproteinase-1 (MMP-1), responsible for the breakdown of dermal interstitial collagen, was dose-dependently induced in vitro and in vivo by UVA irradiation and this induction was at least partly mediated by interleukin-6 (IL-6). We here provide evidence that UVA-induced IL-1 alpha and IL-1 beta play a central role in the induction of the synthesis both of IL-6 and collagenase/MMP-1. In contrast to the late increase of IL-1 alpha and IL-1 beta mRNA levels at 6 h postirradiation, bioactivity of IL-1 is already detectable at 1 h postirradiation. This early peak of IL-1 bioactivity appears to be responsible for the induction of IL-6 synthesis and together with IL-6 lead to an increase of the steady-state mRNA level of collagenase/MMP-1 as deduced from studies using IL-1 alpha and IL-1 beta antisense oligonucleotides or neutralizing antibodies against IL-1 alpha and IL-1 beta. Besides the early posttranslationally controlled release of intracellular IL-1, a latter pretranslationally controlled synthesis and release of IL-1 perpetuates the UV response. From these data we suggest a UV-induced cytokine network consisting of IL-1 alpha, IL-1 beta and IL-6, which via interrelated autocrine loops induce collagenase/MMP-1 and thus may contribute to the loss of interstitial collagen in cutaneous photoaging.

Aging↗

PubMed1993

Fluid absorption and circulating endotoxins during transurethral resection of the prostate.

Recent publications report increased cardiovascular morbidity and mortality after transurethral prostatic resection (TURP). Repeated breath-ethanol monitoring with a new infrared device permits a highly sensitive peroperative registration of fluid absorption. A prospective study in 52 patients revealed surprisingly high rates of intravascular fluid loads without clinical manifestations. Only 4 patients developed clinical signs of the TUR syndrome. Immunological work-up in 41 patients demonstrated circulating endotoxins and significant rise of endogenous tumour necrosis factor (TNF) in 3 of these patients. In 11 patients transient endotoxins could be detected during resection under prophylactic parenteral antibiosis. In the face of less invasive approaches to benign prostatic hyperplasia, close intraoperative monitoring and antibiotic coverage should be demanded as a routine procedure during TURP. Elective surgery should be delayed until appropriate antibiotic therapy has been given.

Absorption↗

PubMed1992

Antihypertensive mechanism of amlodipine in essential hypertension: role of pressor reactivity to norepinephrine and angiotensin II.

Calcium entry blockade may affect the pressor reactivity to vasoconstrictors. The pressor response to norepinephrine and angiotensin II, as well as several other blood pressure modulating factors, were studied in normal subjects (n = 9) and patients with essential hypertension (n = 10) before and after 8 weeks of treatment with the long-acting dihydropyridine amlodipine. In control subjects, calcium entry blockade did not modify blood pressure, the pressor and aldosterone response to angiotensin II, the activity of the renin-angiotensin and sympathetic nervous systems, or urinary dinoprostone (prostaglandin E2) excretion; however, the pressor response to norepinephrine was significantly decreased (p less than 0.01). In patients with hypertension, amlodipine decreased blood pressure (p less than 0.01) and the pressor response to both norepinephrine and angiotensin II (p less than 0.01), without changes in body weight, plasma renin, angiotensin II and catecholamine levels, dinoprostone excretion, or aldosterone responsiveness to angiotensin II. These findings suggest that calcium entry blockade modifies sympathetic-dependent vasoconstriction in both normal subjects and in patients with hypertension. Angiotensin II pressor response may be selectively decreased in essential hypertension.

Adult↗

PubMed1992

Migration of a human keratinocyte cell line (HACAT) to interstitial collagen type I is mediated by the alpha 2 beta 1-integrin receptor.

The migratory response of the human keratinocyte cell line HaCaT to collagen type I and the molecular mechanism underlying collagen-mediated migration have been analyzed. The migratory response of HaCaT cells to collagen type I consisted of a dose-dependent migration to insoluble step gradients of substratum-bound collagen (haptotaxis) and to gradients of soluble collagen (chemotaxis). Checkerboard analysis demonstrated a minor chemokinetic component. Denatured collagen type I was less chemoattractive than the native triple-helical form. Pre-treatment of cells with 25-250 micrograms/ml of synthetic peptides containing the fibronectin cell-recognition sequence RGD (Arg-Gly-Asp) resulted in a concentration-dependent inhibition of fibronectin-mediated chemotaxis, whereas chemotaxis to collagen was not affected. We then investigated the role of VLA/collagen-receptors for collagen type I-induced chemotaxis. Monoclonal antibody (MoAb) 5E8, which selectively blocks function of the alpha 2 subunit of the VLA-2/collagen receptor, dose-dependently inhibited the chemotactic response of HaCaT cells to collagen. This effect was specific for collagen-mediated chemotaxis because the chemotactic response to fibronectin remained unaffected. In contrast, a function blocking MoAb directed to the alpha 3 subunit of the coexpressed VLA-3 receptor, which is also capable of binding collagen, had no effect. However, function blocking MoAb directed to the beta 1-chain of integrins completely inhibited chemotaxis to collagen type I. Based on our results, we propose that the chemotactic migration of the human keratinocyte cell line (HaCaT) to collagen type I is specifically mediated by the RGD independent VLA-2/collagen receptor (alpha 2 beta 1) of the integrin family.

Amino Acid Sequence↗

PubMed1991

[The use of personal computers for the collection, storage and analysis of data from neurosurgical intensive care monitoring].

For data acquisition intensive care neurosurgery increasingly has recourse to modern electronics, which have become an integral part of many aspects of present-day neurosurgery. Despite their high technical standard, the devices in common use often lack flexibility. Their range of possible applications is defined by the manufacturer, and the user has little or no influence on them. Moreover, there are often no adequate interfaces to peripherals, and the storage capacity is limited. We would like to present a data acquisition system on a PC/AT basis, which operates up to 64 channels allowing parallel registration, storage, analysis, and of decisive importance, also various computations, i.e. correlation. Computation is rarely feasible on commercial devices, but it is essential for specific demands, such as implementation of PA/PM diagrams to determine intracranial compliance. In addition, the pertinent software permits implementation of Fourier analyses, offers separate statistical functions, and transfers data to other programs. The program is capable of automatic batch-processing, which greatly facilitates its use.

Computer Systems↗

PubMed1975

[New sequential therapy in the premenopause (author's transl)].

A report about the treatment of 85 women in the premenopause during 387 cycles is given. The treatment consisted in sequential therapy in form of conjugated Estrogens (Presomen) and a new synthetic Gestagen, which was given in three different modifications: from the fifth to the 24-th day of the cycle 1,25 mg Presomen a day, additionally on the last five, seven or ten days, during each period 6 respectively 5 mg Gestagen a day. It proved that both, the disfunctional haemorrhages as well as the climacteric syndrome, were favourably influenced. The mode 10+10, that is, 10 days Estrogens alone + 10 days combined with ;estagen, proved best. A sufficiently secure contraception is not guaranteed. This can be recognized by the occurence of biphasic basal temperature curves.

Adult↗

PubMed1974