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Biomedical subjects

F Kern

Publications and source records attributed to F Kern.

At least 55 records · Page 3Linked to original sources
PubMed1993

Expression of soluble and insoluble fibronectin in rat aorta: effects of angiotensin II and endothelin-1.

This study has investigated the influence of the vasoconstrictor peptides angiotensin II (Ang II) and endothelin-1 (ET-1) on fibronectin expression by vascular smooth muscle cells (VSMC). In confluent, quiescent cultures of VSMC, Ang II and ET-1 elevated fibronectin mRNA levels in a time- and dose-dependent fashion. ET-1 and Ang II also induced a time-dependent expression of immunoreactive fibronectin in cultures of aortic organoids, and for both peptides the fibronectin immunoreactivity was most prominent within those medial smooth muscle cell layers close to the vessel lumen. Immunoprecipitation of biosynthetically labelled fibronectin elaborated by cultured VSMC revealed a predominant expression of soluble fibronectin in response to Ang II, whereas for ET-1 the newly synthesized fibronectin was predominantly incorporated into the extracellular matrix deposit of the cells. These findings indicate that Ang II and ET-1 may exert disparate effects on smooth muscle cell phenotype and migration.

Angiotensin II↗
PubMed1993

The renin-angiotensin system and extracellular matrix.

A hallmark of vascular disease is the inappropriate proliferative and synthetic behaviour of vascular smooth muscle cells. This phenotypically immature behaviour arises as a consequence of the myocytes undergoing phenotypic conversion and/or clonal proliferation of a "fetal" type of smooth muscle cell preexisting in the vessel wall. De-differentiation and initiation of proliferation is not only induced by endothelial desquamation and acute exposure of smooth muscle cells to platelet-derived mitogens, but also occurs in the uninjured blood vessel. Therefore normal components of the blood vessel are implicit in the pathological process. These include vasoconstrictor peptides, growth factor peptides and extracellular matrix molecules. In vitro and in vivo experimentation has indicated that while some of these compounds individually are only mild stimulators of smooth muscle proliferative metabolism, they may act synergistically to induce robust responses. Here we discuss the effects of the vasoconstrictor peptide angiotensin II, which can be locally generated within the vessel wall itself, on the expression of extracellular matrix molecules in vitro and in vivo. We focus on the angiotensin II-modulated expression of extracellular matrix glycoproteins, e.g. thrombospondin, tenascin, fibronectin and laminin.

Angiotensin II↗
PubMed1993

Peptide vasoconstrictors, vessel structure, and vascular smooth-muscle proliferation.

The peptide vasoconstrictors angiotensin II (Ang II) and endothelin-1 (ET-1), originally thought to derive exclusively from the plasma renin-angiotensin system and vascular endothelium, respectively, have been demonstrated to be produced independently of such sources. Local tissue angiotensin-generating systems are well documented, and endothelin production has been demonstrated for a variety of nonendothelial cells, including vascular smooth-muscle cells (VSMC). There is increasing evidence from in vitro studies that local production of these vasoconstrictor peptides may contribute to blood vessel homeostasis and the development of vascular pathologies. Results obtained from pharmaceutical intervention in humans and animals of these systems strongly support this hypothesis. In addition to their vasoconstrictor properties, Ang II and ET-1 act as potent biological effectors. In vitro, both vasoconstrictor peptides appear to modulate the activity of autocrine feedback loops in VSMC. The activity of these feedback loops in vivo may represent a central mechanism for regulation and phenotypic differentiation of this cell type. The best-recognized autocrine feedback loops of VSMC are constituted by platelet-derived growth factor and transforming growth factor-beta, both of which are influenced by the action of Ang II and ET-1. Because both vasoconstrictors (via their induction of autocrine growth modulators) may influence the composition of the extracellular matrix of VSMC, the effects of the peptide vasoconstrictors on the (auto-) regulated feedback loops are of long-term structural importance. Ang II and ET-1 promote the synthesis and secretion of the glycoproteins thrombospondin, fibronectin, and tenascin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Effects of endothelin-1 on vascular smooth muscle cell phenotypic differentiation.

Endothelin-1 (ET-1) produced by vascular endothelial cells has been proposed to act in a paracrine manner on adjacent smooth muscle cells (SMCs) in vivo, exerting a variety of short- and long-term effects. Although some of the in vitro ET-1-mediated effects are related to growth-promoting events, the physiological significance of these observations remains to be clarified. Reported discrepancies of the mitogenic potential of ET-1 may relate to differences in culturing conditions (submitogenic levels of serum in combination with ET-1). Because ET-1 has been implicated in proliferation of vascular SMCs (VSMCs) at sites of vascular injury, as well as pathological events during atherogenesis, a clarification of the mitogenic effects of ET-1 is important. This study demonstrates the possible autocrine role for ET-1 in the regulation of the vasculature, its influence on VSMC cell cycle, and autocrine and phenotypic regulation of VSMCs. Stimulation of quiescent VSMCs with a variety of peptides resulted in the secretion of biologically active ET-1 by VSMCs. In contrast to previous reports, long-term exposure (12-15 days) of VSMCs to ET-1 in nonmitogenic medium did not promote cycling of cells. On the contrary, ET-1 attenuated the cycling of VSMCs in the S and G2/M phases and interrupted progression through the cell cycle at late G1/early S phase. Subsequent to ET-1 exposure, VSMCs expressed increased levels of smooth muscle-specific alpha-actin. Therefore, autocrine-produced ET-1 may contribute to phenotypic differentiation of VSMCs.

Actins↗
PubMed1992

Expression of tenascin by vascular smooth muscle cells. Alterations in hypertensive rats and stimulation by angiotensin II.

The extracellular matrix glycoprotein tenascin is associated with remodeling events in many embryonic and pathologic tissues. The expression of tenascin has been investigated by immunohistochemistry in blood vessels of Wistar-Kyoto (normotensive) and spontaneously hypertensive rats. Weak tenascin staining was present throughout the tunica media of large and small arteries from normotensive animals; strong staining was only detectable at branching sites. In arteries from hypertensive animals, foci of strong tenascin staining were scattered throughout the tunica media. The expression of tenascin mRNA and protein by rat aortic smooth muscle cells cultured in serum-free medium was induced by the vasoconstrictor peptide angiotensin II. Transforming growth factor-beta and platelet-derived growth factor also stimulated tenascin mRNA expression. Vascular smooth muscle cells attached specifically to a substratum of tenascin, but remained rounded. Thus, increased focal tenascin expression by vascular smooth muscle cells is associated with hypertension, and may mediate angiotensin II-induced changes in vascular structure in hypertension.

Angiotensin II↗
PubMed1992

The effect of temperature on cerebral metabolism and blood flow in adults during cardiopulmonary bypass.

The effect of temperature on cerebral blood flow and metabolism was studied in 41 adult patients scheduled for operations requiring cardiopulmonary bypass. Plasma levels of midazolam and fentanyl were kept constant by a pharmacokinetic model-driven infusion system. Cerebral blood flow was measured by xenon 133 clearance (initial slope index) methods. Cerebral blood flow determinations were made at 27 degrees C (hypothermia) and 37 degrees C (normothermia) at constant cardiopulmonary bypass pump flows of 2 L/min/m2. Blood gas management was conducted to maintain arterial carbon dioxide tension (not corrected for temperature) 35 to 40 mm Hg and arterial oxygen tension of 150 to 250 mm Hg. Blood gas samples were taken from the radial artery and the jugular bulb. With decreased temperature there was a significant (p less than 0.0001) decrease in the arterial venous-oxygen content difference, suggesting brain flow in excess of metabolic need. For each patient, the cerebral metabolic rate of oxygen consumption at 37 degrees C and 27 degrees C was calculated from the two measured points at normothermia and hypothermia with the use of a linear relationship between the logarithm of cerebral metabolic rate of oxygen consumption and temperature. The temperature coefficient was then computed as the ratio of cerebral metabolic rate of oxygen consumption at 37 degrees C to that at 27 degrees C. The median temperature coefficient for man on nonpulsatile cardiopulmonary bypass is 2.8. Thus reducing the temperature from 37 degrees to 27 degrees C reduces cerebral metabolic rate of oxygen consumption by 64%.

Aged↗
PubMed1991

Tumor growth dependent on Kaposi's sarcoma-derived fibroblast growth factor inhibited by pentosan polysulfate.

A neoangiogenic response is critical for the unrestricted growth of solid tumors beyond a few millimeters in diameter. Release of adequate growth-stimulating activity from tumor cells is obviously required for the stimulation of blood vessel growth, and blockade of such stimulatory activity should repress tumor growth at the microscopic level. To test this hypothesis and to study appropriate inhibitors, we used a human adrenal cancer cell line (SW-13/K-fgf) engineered to secrete Kaposi's sarcoma-derived fibroblast growth factor (K-FGF), which we previously showed to induce growth of highly vascularized subcutaneous tumors in animals by autocrine and paracrine stimuli. In the present study, we tested different polysulfates for their selective inhibition of proliferation induced by K-FGF versus proliferation independent of K-FGF. Suramin and dextran sulfate showed slight selective inhibition of K-FGF-induced proliferation, ie, inhibition three- and five-fold greater, respectively, than the inhibition of proliferation independent of K-FGF. In contrast, heparin was inactive. The heparin analogue pentosan polysulfate (PPS), however, showed selective inhibition that was more than 2000-fold greater. The inhibitory effects of PPS on growth of SW-13/K-fgf cells, as well as endothelial cells, were fully reversible by an excess of added FGF. Daily intraperitoneal injections of PPS were tolerated well by athymic nude mice and prevented growth of subcutaneous SW-13/K-fgf tumor xenografts. PPS will be a useful tool to elucidate the effects of FGFs in vitro and in vivo and appears to be a prototype for the development of tumoricidal therapy based on targeting of growth factors.

Adrenal Gland Neoplasms↗
PubMed1991

Ammoniated mercury ointment as a cause of peripheral neuropathy.

A 72-year-old Caucasian man with widespread psoriasis presented with a sensory-motor peripheral neuropathy following 40 years' use of an ammoniated mercury ointment. No clinical involvement of his central nervous system was noted and no other possible causative factors for his peripheral nerve disease were found. D-Penicillamine treatment induced mercuriuresis and blood levels of mercury fell to normal. His peripheral neuropathy improved slowly after normalisation of the serum mercury. It is believed that his condition was caused by percutaneous absorption of mercury. Ammoniated mercury ointments should have no role in the current management of skin disorders.

Administration, Topical↗
PubMed1991

Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism.

Our aim was to define mechanisms whereby conjugated estrogens (Premarin, exogenous estrogen; Ayerst Laboratories, New York) increase the risk of developing cholesterol gallstones and to determine the role, if any, of dietary cholesterol. We studied gallbladder motor function, biliary lipid composition and secretion, cholesterol absorption, cholesterol synthesis and esterification by peripheral blood mononuclear cells, the clearance of chylomicron remnants, and bile acid kinetics in 29 anovulatory women. 13 were studied on both a low (443 +/- 119 mumol/d) and high (2,021 +/- 262 mumol/d) cholesterol diet. Premarin increased the lithogenic index of bile (P less than 0.05), increased biliary cholesterol secretion (P less than 0.005), lowered chenodeoxycholate (CDCA) pool (P less than 0.001) and synthesis (P less than 0.05), altered biliary bile acid composition [( CA + DCA]/CDCA increases, P less than 0.005), stimulated cholesterol esterification (P less than 0.03), and enhanced the clearance of chylomicron remnants (P = 0.07). Increases in dietary cholesterol stimulated the biliary secretion of cholesterol (P = 0.07), bile acid (P less than 0.05), phospholipid (P = 0.07), and as a result, did not alter lithogenic index. The reduction in CDCA pool and synthesis by Premarin was reversed by increasing dietary cholesterol. Off Premarin, only 24% of the increase in cholesterol entering the body in the diet was recovered as biliary cholesterol or newly synthesized bile acid. On Premarin, 68% of this increase in cholesterol was recovered as these biliary lipids. We conclude that Premarin increases biliary cholesterol by enhancing hepatic lipoprotein uptake and inhibiting bile acid synthesis. These actions of Premarin divert dietary cholesterol into bile.

Adult↗
PubMed1991

Immunohistochemical studies on human pituitary gland and adenomas.

To study coexpression patterns in normal and adenomatous pituitaries, frozen (n = 4) and paraffin-embedded (n = 10), normal human glands and 34 pituitary adenomas were investigated, using immunoperoxidase and double-labeling immunofluorescence methods. Broad range monoclonal antibodies (mAB) against cytokeratins (CK) (lu-5, A45-B/B3, AE1/3, CAM 5.2) as well as anti-CK18 (DC10) and anti CK19 (A53-B/A2) were compared with mAB's against vimentin, epithelial membrane antigen (EMA), epithelial sialomucin (ESM 140 C1), GFAP (GF-2), neurofilament (2F11), Leu-7 (HNK-1) and polyclonal AB's against pituitary hormones (ACTH, FSH, LH, TSH, GH, PRL). CK and vimentin coexpressing endocrine cells, mainly of the ACTH type, were observed in the pars intermedia in 5 of 14 normal pituitaries. All hormone producing cells expressed CK. The mAB A53-B/A2 (CK19) stained selectively the folliculo-stellate cells in frozen and paraffin sections. EMA, sialomucin and Leu-7 antigen localized to different structures of normal pituitaries. 25 of 34 pituitary adenomas exhibited CK positive tumor cells. Coexpression of vimentin or neurofilament protein was rare (2 cases of each). 9 CK negative adenomas were also negative for other intermediate filament proteins. 6 hormone producing adenomas showed unusual positivity for CK19. Whereas EMA and sialomucin reactivity disappeared in adenoma tissues, an enhanced Leu-7 antigen expression in the GH and prolactin adenoma group was noted. The heterogeneity of antigen expression seen in normal and neoplastic pituitary cells calls for further functional studies and usage of a broad range of mAB's against intermediate filaments in immunohistochemical studies of the pituitary.

Adenoma↗
PubMed1988

Drug-induced pancreatitis.

We reviewed the English-language literature pertaining to drug-induced pancreatitis and attempted to determine whether the reported association between each drug and pancreatitis was valid. The following drugs seem to cause pancreatitis: azathioprine, chlorothiazide and hydrochlorothiazide, oestrogens, frusemide, 6-mercaptopurine, methyldopa, sulphonamides, sulindac, tetracycline and valproic acid. Less convincing but suggestive evidence exists for colaspase, chlorthalidone, combination cancer chemotherapy, cimetidine, cisplatin, corticosteroids, cytosine arabinoside, diphenoxylate, ethacrynic acid, iatrogenic hypercalcaemia, methandienone, metronidazole, nitrofurantoin, pentamidine, phenformin, piroxicam and procainamide. In general, pancreatitis is a very rare complication of treatment with these drugs. The pathogenesis of the pancreatitis is usually obscure, but is probably mediated by an immune response. Certain drugs such as oestrogens cause hypertriglyceridaemia, which in turn may lead to pancreatitis.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1988

Contraceptive steroids alter the steady-state kinetics of bile acids.

Contraceptive steroids increase the ratio of cholic acid to chenodeoxycholic acid in bile. This alteration may contribute to the development of cholesterol gallstones. The objective of this study was to measure the effects of contraceptive steroids on bile acid kinetics and to relate them to changes in cholesterol metabolism. Steady-state kinetics of bile acids were measured in 15 healthy women, on and off contraceptive steroids. Cholic acid synthesis increased 30.3% (P less than 0.025) and its pool increased by 37.4% (P less than 0.025). Chenodeoxycholic acid synthesis decreased 6.4% (P = 0.08) and its pool decreased by 11.8% (P less than 0.05) during use of contraceptive steroids. The fractional turnover rates of both primary bile acids did not change. The changes in kinetics of the primary bile acids were related to alterations in biliary lipid and cholesterol metabolism, separately reported. (J. Lipid Res. 1987. 28: 828-839). During use of contraceptive steroids, total bile acid pool and total bile acid synthesis correlated directly with cholesterol synthesis, assayed in mononuclear leukocytes (r = 0.50 and r = 0.54, respectively) but not with the plasma clearance of chylomicron remnants, measured with retinyl palmitate. The data indicate that contraceptive steroids directly alter the hepatic synthesis of bile acids and suggest that newly synthesized cholesterol may be a preferred substrate for bile acid synthesis during use of contraceptive steroids.

Adult↗
PubMed1988

[Optimizing puncture of the internal jugular vein. Effects and advantages of the Valsalva maneuver in catheterization].

Shortly after the publication by English et al. on catheterization of the internal jugular vein (VJI) in 1969, the first papers reporting complications appeared. To reduce the rate of puncture failures with their consequences and complications, we tried to find the optimal conditions for successful puncture by evaluating serial CT scans. The diameter increase of the VJI was studied in 8 women and 9 men with an average age of about 39 years with 30 mmHg pressure in the upper respiratory passages. The measurement was performed 2 cm below the level of the cricoid cartilage (the probable puncture point for posterior access). It was carried out first during normal respiration, then after forced inspiration and bearing down with the glottis open against a closed system consisting of a manometer. By means of continuous bearing down, a pressure of 30 mmHg was maintained during CT scanning. With this pressure in the upper respiratory passages, the mean increase in diameter of the VJI was 58% on the left side (P less than 0.002) and as much as 78% on the right (P less than 0.001), which is highly significant. In 12 of the 17 test persons (70.6%), the right VJI proved to be the dominant vessel, and the diameter increase achievable by the Valsalva maneuver likewise seems to be greater on the right side than on the left (Table 1). We now recommend a slight Trendelenburg position with the head rotated 45 degrees to the contralateral side. For the first puncture we consider the posterior approach (see Fig. 2) on the right side to be the best.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Development of a growth model for fetal head and body measurements].

Head parameters BPD, FOD and HC and abdomen parameters ATD, APD and AC have been ascertained in a prospective cross-sectional study in 515 healthy single fetuses between 13 and 40 weeks of gestation by ultrasound. In all cases ultrasound velocity was 1540 m/sec. From these data, a growth model was achieved for each parameter and corresponding growth curves with 5%, 10%, 50%, 90% and 95% percentiles were established.

Anthropometry↗