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Biomedical subjects

F C Luft

Publications and source records attributed to F C Luft.

At least 325 records · Page 18Linked to original sources
PubMed1996

Effect of strenuous exercise on agonist-induced platelet cytosolic calcium in man.

Hypertension, which is attenuated by regular aerobic exercise, is associated with an increase in cytosolic platelet calcium [Ca+2]i. How aerobic exercise might lower blood pressure is unknown. We tested the hypothesis that exercise would influence the agonist-induced effect on platelet cytosolic calcium [Ca+2]i. Twenty, healthy normotensive men between 20 and 60 years of age (five per decade) were studied while resting supine for 30 min and after bicycle ergometry at a work load sufficient to achieve a heart rate of 200 beats per min minus age in years. On the next day, the protocol was repeated with the subjects exercising at 75% their maximum heart rate for 6 min. Venous blood was obtained from an indwelling cannula. Exercise had no effect on total or ionised serum calcium values. Adrenaline values increased from 0.2 +/- 0.03 to 0.55 +/- 0.1 (s.e.m.) nmol/l (P < 0.05), while noradrenaline increased from 1.46 +/- 0.18 to 4.72 +/- 0.44 nmol/l (P < 0.05). Resting platelet [Ca+2]i concentrations were 95.4 +/- 3.9 and 94.4 +/- 3.0 nmol/l on the two study days. The values were not correlated with age or level of fitness. The platelet [Ca+2]i was 99.2 +/- 4.2 nmol/l after exercise, not different from the resting values. Platelet activation with adrenaline and thrombin across a wide range of doses resulted in prompt increases in [Ca+2]i, which were 50% less in platelets after exercise than at rest (P < 0.05). Activation with angiotensin (Ang) II, on the other hand, was less pronounced and less clearly influenced by exercise. We conclude that exercise influences the platelet activation state and reactivity. The decreased [Ca+2]i responses to adrenaline and thrombin suggest that [Ca+2]i stores were in part depleted at exercise compared to rest, an effect not observed with Ang II perhaps because of the smaller number of Ang II-operative receptors on platelets.

Adult↗
PubMed1996

Effect of antihypertensive treatment on qualitative estimates of microalbuminuria.

We tested the utility of qualitative microalbuminuria (MAU) screening in an office practice setting, in assessing the response of MAU to drug treatment. We enrolled general practitioners throughout Germany, who obtained histories, physical examinations, and routine laboratory values as clinically indicated on > 6000 non-treated hypertensive, nondiabetic patients. MAU was measured with an albumin-sensitive, immunoassay test strip. The patients were then assigned to monotherapy by their physicians with carvedilol, angiotensin-converting enzyme (ACE) inhibitors, beta blockers, calcium channel blockers, diuretics, and other single regimens in an open-label fashion. The goal was diastolic pressure < 90 mm Hg or at least a 10 mm Hg decrease in systolic (S) and diastolic blood pressure (DBP). The patients' mean age was 57 years and 51% were men. The mean known hypertension duration was 69 months. MAU was present in 37% of men and 34% of women. All regimens lowered BP. All regimens caused large numbers of MAU patients to revert by 3 months. MAU reversal occurred in patients less than 65 years as well as in those 65 years or older. Multiple regression analysis indicated that systolic and DBP reduction, duration of hypertension, and body size were most associated with MAU reversal. Thus, MAU determinations reverted to negative with antihypertensive treatment in many patients. BP reduction was the single most important variable in reversing MAU. All drug regimens were effective. We conclude that qualitative MAU detection is useful not only for screening, but also for follow-up nondiabetic patients with hypertension in an office practice setting.

Aged↗
PubMed1996

The role of hyperglycemia and hyperinsulinemia in the pathogenesis of diabetic angiopathy.

The small and large vessel disease associated with diabetes mellitus is responsible for its morbidity and mortality. Although much of the pathogenesis remains to be clarified, the role of hyperinsulinemia and hyperglycemia per se in the progression of vascular disease is beginning to emerge. Hyperinsulinemia increases the release of very low density lipoprotein (VLDL) and may also be responsible for the low HDL cholesterol levels in patients with diabetes. Hyperinsulinemia also contributes to increased blood pressure, which independently promotes vascular disease. High glucose concentrations have direct influence on intracellular signal transduction, including effects on sorbitol pathway and associated changes of pyridine nucleotides, the de novo synthesis of diacylglycerol with subsequent stimulation of protein kinase C, and possibly changes in the cellular generation of myoinositol. Hyperglycemia also exerts long-lasting changes in cellular function, which result from non-enzymatic glycosylation of matrix and membrane proteins with subsequent binding of these proteins to specific receptors. These receptors are termed the advanced glycosylation end-products (AGE) receptors. Their activation leads to an increased release of cytokines and growth factors including PDGF, interleukins, TNF-alpha, and TGF-beta, all of which may act concomitantly in the disease process.

Arteriosclerosis↗
PubMed1996

[Development of a model of human renin hypertension in rats].

The effective development of human renin inhibitors meets its major obstacle in the absence of a suitable experimental rodent model and the species-specificity of human renin, exclusively cleaving its natural substrate human angiotensinogen. We have reconstructed the human renin-angiotensin system in transgenic rats over expressing the human angiotensinogen gene TGR (hAOGEN) 1623 by chronically injecting i.v. human recombinant renin. We have first established new in vitro enzyme kinetic techniques to measure the various components of the chimeric renin-angiotensin system and distinguished the two human and rat-specific pathways of generating angiotensin I by the human specific renin inhibitor Ro 42-5892 (Hoffmann-La Roche). Male heterozygous TGR had plasma levels of rat angiotensinogen of 1.2 +/- 0.2 mg Ang l/ml while the plasma levels of the transgene were 141 +/- 98 mg Ang l/ml (n = 41; not normally distributed). Transgene expression was found in the liver kidney, aorta, heart and adrenals. Four rats were infused i.v. with human recombinant renin at 50 ng/h over 9 days which chronically increased their blood pressure to > 200 mmHg while total plasma renin activity increased by a factor of 300. Rat renin disappeared form the plasma. This new model of experimental human renin-induced hypertension in rats will facilitate the screening and characterization of human renin inhibitors.

Angiotensinogen↗
PubMed1996

The renin-angiotensin system and renal function in transgenic (mRen2)27 rats.

The transgenic rat (TGR)(mRen2)27 was the first hypertensive transgenic rat model developed. The model is unique in that it allows studying the effects of a single gene, namely the mouse salivary gland renin gene (mRen2), in the rat. The transgene is expressed in various rat tissues, including the central nervous system, adrenal gland, and the kidney. TGR exhibit a rightward shifted pressure-natriuresis curve that is overwhelmingly angiotensin II (Ang II) dependent. The mRen2 transgene, the rat's own renin gene, angiotensinogen, and the type 1 Ang II receptor, AT1, are all expressed in the kidneys of TGR. The rat's own renin gene is regulated normally in renal tissue, while the mRen2 transgene operates independently of blood pressure. These results, coupled with findings that the mRen2 transgene product converts rat angiotensinogen more effectively than endogenous rat renin, that the TGR may have high circulating mouse renin levels which increase with age, and the fact that high circulating prorenin concentrations are present in these TGR, shed light on the kidney's role in the blood-pressure-elevating mechanisms of TGR. The viewpoint that the kidneys are not mechanistically important in this TGR model must be revised.

Angiotensin II↗
PubMed1995

An angiotensin-converting enzyme gene variant is associated with acute myocardial infarction in women but not in men.

We believe our data may speak to the issue of sexual dimorphism with respect to MI. Most studies have concentrated on men with this disease. In a recent study, Lindpaintner et al10 could find no relationship between the D/D genotype and AMI in subjects of the Physicians Health Study. However, this study consisted entirely of men. The D allele may provide an avenue to discern differences in the pathogenesis of MI in men and women.

Adult↗
PubMed1995

Wegener's granulomatosis masquerading as breast cancer.

We describe a patient with Wegener's granulomatosis whose disease presented as pseudotumor of the orbit and a breast mass. Both findings were misinterpreted and errors in diagnosis resulted, despite the availability of rapid and accurate diagnostic tests for this disease. We report this case to emphasize the more unusual presentations of Wegener's granulomatosis.

Breast Neoplasms↗
PubMed1995

Tumefactive megalocytic interstitial nephritis in a patient with Escherichia coli bacteremia.

Megalocytic interstitial nephritis is rare and primarily affects the cortex in an otherwise normal kidney. We recently encountered a patient with Escherichia coli bacteremia and oliguric acute renal failure who died of gram-negative septicemia. At autopsy, this patient's kidneys displayed typical features of megalocytic interstitial nephritis. We were able to perform special stains suggesting that the histiocytic interstitial cells originated from infiltrating macrophages. Our patient illustrates that macrophage proliferation can result in interstitial inflammation sufficiently severe to cause anuric acute renal failure.

Acute Kidney Injury↗
PubMed1995

Diagnosis of iron deficiency anemia in renal failure patients during the post-erythropoietin era.

The purpose of this study was to evaluate the sensitivity and specificity of laboratory methods in the diagnosis of posterythropoietin-era, iron-deficient, chronic renal failure patients. The patient population comprised 25 anemic (hemoglobin < 11 g/dL) patients with creatinine greater than 3 mg/dL; 20 were dialysis patients, two were transplant patients, and three patients had renal failure from other causes. Criteria for study inclusion were as follows: bone marrow iron was the reference standard and was graded 0 to +4, ranging from absent to diffuse homogeneous iron staining; serum ferritin concentration and serum transferrin saturation were tested in terms of sensitivity and specificity. The reference standard indicated that iron deficiency existed in 40% of patients. Neither serum ferritin nor transferrin saturation were completely adequate diagnostic tools. Serum ferritin levels less than 200 ng/dL were 100% specific for the diagnosis but only 41% sensitive. Transferrin saturation of less than 20% was 88% sensitive, but only 63% specific. By excluding patients with hypoproteinemia (transferrin values of < 150 mg/dL), the sensitivity of the test increased to 100% and the specificity to 80%. We conclude that transferrin saturation is an adequate screening tool in anemic chronic renal failure patients, provided that hypoproteinemia is not present. By determining both the serum ferritin concentration and the transferrin saturation, a high sensitivity and specificity can be achieved, even in patients with hypoproteinemia. Furthermore, we believe that on this basis, iron therapy in patients with renal insufficiency can be improved.

Adult↗
PubMed1995

Correlates of health care satisfaction in inner-city patients with hypertension and chronic renal insufficiency.

Barriers to effective health care are potential contributors to the increased prevalence of hypertension and hypertension-related renal disease observed in black patients. We have enrolled 333 primarily elderly (mean age 69 years) black (87%) patients with hypertension and chronic renal insufficiency into a prospective randomized trial testing the effect of intense multidisciplinary management on progression of chronic renal insufficiency. These patients have an average 6 years of education and $400-$800 monthly household income: 57% have diabetes. Our baseline data include the Patient Satisfaction Questionnaire administered by home interviewers who also recorded sociodemographic data, medications and questionnaires regarding medication compliance and symptoms related to anti-hypertensive drugs. Inpatient and outpatient vital signs, test results and diagnoses came from patients' computerized medical records. We used multiple linear regression to identify correlates of overall satisfaction. We also analyzed three subscales: access to care, financial aspects and interpersonal manner of physicians. We included only variables with univariate correlations (P < 0.05) in the models. Decreased overall satisfaction correlated with more symptoms related to anti-hypertensive drugs (P < 0.001), lower medication compliance (P = 0.01), and higher diastolic blood pressure (P = 0.08). Decreased satisfaction with access to care correlated with more symptoms related to anti-hypertensive drugs (P < 0.001) and decreased medication compliance (P = 0.08). Decreased satisfaction with financial aspects of care correlated with more symptoms related to anti-hypertensive drugs (P < 0.001), lower medication compliance (P = 0.01) and more proteinuria (P = 0.02). Finally, decreased satisfaction with interpersonal manner of physicians correlated with lower medication compliance (P < 0.001), lower albumin (P = 0.01) and sodium (P = 0.04), and higher diastolic blood pressure (P = 0.04). These cross-sectional baseline data describe a group of mostly black inner-city patients with hypertension and chronic renal insufficiency in whom decreased satisfaction with care correlates with decreased medication compliance, increased symptoms related to anti-hypertensive drug therapy, higher diastolic blood pressure and more proteinuria. Our prospective study may help determine whether improving satisfaction improves compliance and blood pressure control, and forestalls complications in this high-risk population.

Aged↗
PubMed1995

High glucose concentrations and protein kinase C isoforms in vascular smooth muscle cells.

High extracellular glucose activates protein kinase C (PKC), a family of kinases vital to intracellular signaling. However, which PKC isoforms are involved and where in the cell they operate is unclear. We tested the hypothesis that only those PKC isoforms binding to diacylglycerol (DAG) are activated by high glucose. We also reasoned that the isoforms would translocate to different parts of the cell, where they presumably serve different functions. The PKC isoforms alpha, beta, delta, epsilon, and zeta were studied. Twenty mM glucose caused an increase in total PKC activity at six hours, which was maintained at 24 hours. High glucose decreased the angiotensin II-induced calcium signal. This effect was reversed by preincubating the cells with the PKC inhibitor staurosporine. Glucose induced a translocation of all PKC isoforms except PKC zeta by Western blot. Confocal microscopy showed that PKC alpha, beta, and epsilon were translocated into the nucleus. PKC delta showed strong association with cytoskeletal structures. The effects were sustained at 24 hours for PKC isoform beta and to a lesser extent for PKC delta and epsilon, but not for PKC alpha. Thus, PKC isoforms differ in their propensity to be activated by high glucose. Those isoforms binding to DAG are activated. Both cytoskeletal and nuclear signaling may be involved.

Alkaloids↗
PubMed1995

Monocyte infiltration and c-fms expression in hearts of spontaneously hypertensive rats.

To elucidate mechanisms of myocardial hypertrophy in spontaneously hypertensive rats (SHR), we examined by Northern blotting the expression of the proto-oncogenes c-myc, c-fos, c-sis, and c-fms in the hearts of 4- and 14-week-old SHR and normotensive Wistar-Kyoto (WKY) rats. No difference in c-myc or c-fos expression could be found between SHR and WKY rats. In SHR, c-sis gave a weak and c-fms a very strong signal at 14 weeks, whereas no signal for these oncogenes was found in either WKY rats or Sprague-Dawley controls. Since c-fms codes for the receptor of monocyte colony-stimulating factor, we next used in situ hybridization to localize the presence of c-fms in hearts of SHR at 14 weeks. We found strong signals for c-fms around small blood vessels and between cardiac myocytes in 14-week-old SHR but none in WKY rats. Immunohistochemical staining corroborated the presence of clusters of monocyte infiltration at these same perivascular sites in significantly greater numbers in SHR than in WKY rats. We conclude that c-fms expression and macrophage infiltration are increased in the perivascular space of hypertrophied hearts from SHR. We suggest that mononuclear cell recruitment and induction of c-fms may play a role in the development of hypertension-associated myocardial hypertrophy.

Animals↗
PubMed1995

Low-density lipoprotein induces vascular adhesion molecule expression on human endothelial cells.

We tested the hypothesis that low-density lipoprotein (LDL) and its acetylated form influence surface expression of vascular adhesion molecules on human endothelial cells. Vascular adhesion molecule surface expression was assessed with flow cytometry on cultured endothelial cells with a modified enzyme-linked immunosorbent assay. LDL acetylation was determined by chromatography. Monocyte adhesion to endothelial cells was assessed with U937 cells by direct counting. Tumor necrosis factor-alpha (10 ng/mL), a positive control, induced a time-dependent expression of vascular adhesion molecules (P < .05), which peaked at 5 hours. Incubation of endothelial cells with LDL (1.3 to 26.0 mmol/L) led to an increase in expression at 2 and 5 hours (P < .05). Prolonged (24-hour) exposure to LDL resulted in a second peak. The effect of acetylated LDL on expression was not different from that of native LDL. Incubation with the protein kinase C inhibitor staurosporine (5 x 10(-8) mol/L) blocked the effects of both native and acetylated LDL completely (P < .05). The calcium channel blocker nitrendipine (10(-7) mol/L) did not influence the expression of vascular adhesion molecule at 2 and 5 hours but did reduce the effect of LDL on expression at 24 hours. LDL (2.6 mmol/L) also induced a significant increase in the surface expression of intercellular adhesion molecule-1 but did not affect the expression of endothelial adhesion molecules. LDL (2.6 mmol/L) induced a significant increase in monocyte binding. We conclude that LDL can induce the expression of vascular adhesion molecules on endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockers↗
PubMed1995

Effects of bromocriptine on cardiovascular regulation in healthy humans.

Bromocriptine, a dopamine agonist with central nervous system actions, may reduce sympathetic nervous system activity. We tested this hypothesis by measuring arterial blood pressure, central venous pressure, heart rate, muscle sympathetic nerve activity, and forearm blood flow before and after unloading the arterial baroreceptors with sodium nitroprusside (0.5 to 1.5 mcg/kg per minute IV), before and after unloading the cardiopulmonary baroreceptors with incremental lower body negative pressure (0 to -15 mm Hg), and before and after immersion of the hand in ice-cold water for 2 minutes (cold pressor test). After obtaining basal responses to provocative maneuvers, we gave 20 healthy subjects either 5 mg oral bromocriptine (n = 10) or placebo (n = 10) in a randomized, double-blind fashion. Bromocriptine did not affect resting mean arterial pressure, heart rate, or forearm blood flow. Bromocriptine decreased resting central venous pressure by 1.2 mm Hg (P < .05) and tended to increase total integrated muscle sympathetic nerve activity (from 151 +/- 44 to 212 +/- 82 U/min, P = NS). The reflex increases in muscle sympathetic nerve activity to nitroprusside infusion and lower body negative pressure were unchanged by bromocriptine; however, vascular responsiveness to both maneuvers was impaired after bromocriptine administration compared with control. Without bromocriptine, the reflex increase in muscle sympathetic nerve activity after nitroprusside-induced hypotension maintained forearm blood flow at a constant level, whereas with bromocriptine the forearm blood flow increased from 1.9 +/- 0.3 to 2.8 +/- 0.6 mL/min per 100 mL (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗