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Biomedical subjects

Friedrich C Luft

Publications and source records attributed to Friedrich C Luft.

At least 37 records · Page 2Linked to original sources
PubMed2006

Posttransplantation malignancy in a patient presenting with weight loss and changed bowel habits: a case report.

BACKGROUND: Advancements in immunosuppressive therapy have significantly improved patient and graft survival following renal transplantation. This is paralleled by an increasing occurrence of posttransplantation malignancy. CASE PRESENTATION: We report on a patient who presented with a history reminding of colon cancer seven years after receiving a kidney transplant. Initial diagnostic imaging seemed to confirm this diagnosis showing a constricting colonic lesion. To our surprise, colonoscopy findings were unremarkable. Review of the imaging studies revealed that the tumor-like picture was caused by the renal graft impressing the intestine. The following search for malignancy in other locations resulted in the diagnosis of glioblastoma multiforme of which the patient died several weeks later. CONCLUSION: Follow-up of renal transplant patients must include screening tests directed at tumor detection. Imaging studies and other tests in this patient group should be interpreted by physicians who are familiar with transplant related peculiarities.

Aged↗
PubMed2006

Extrarenal Na+ balance, volume, and blood pressure homeostasis in intact and ovariectomized deoxycorticosterone-acetate salt rats.

Water-free Na+ storage may buffer extracellular volume and mean arterial pressure (MAP) in spite of Na+ retention. We studied the relationship among internal Na+, K+, water balance, and MAP in Sprague-Dawley rats, with or without deoxycorticosterone-acetate (DOCA) salt, with or without ovariectomy (OVX). The rats were fed a low-salt (0.1% NaCl) or high-salt (8% NaCl) diet for 5 weeks. DOCA salt increased MAP (161+/-14 versus 123+/-4 mm Hg; P<0.05), and DOCA-OVX salt increased MAP further (181+/-22 mm Hg; P<0.05). DOCA salt increased the total body Na+ by &40% to 45%; however, water-free Na+ retention by osmotically inactive Na+ storage and by osmotically neutral Na+/K+ exchange allowed the rats to maintain the extracellular volume close to normal. DOCA-OVX salt rats showed similar Na+ retention. However, their osmotically inactive Na+ storage capacity was greatly reduced and only partially compensated by neutral Na+/K+ exchange, resulting in greater volume retention despite similar Na+ retention. For every 1% wet weight total body water gain, MAP increased by 2.3+/-0.2 mm Hg in DOCA salt rats and 2.5+/-0.3 mm Hg in DOCA-OVX salt rats. Because water-free Na+ retention buffered total body water content by 8% to 11% wet weight, we conclude that this internal Na+ escape buffered MAP. Extrarenal Na+ and volume balance seem to play an important role in long-term volume and MAP control.

Animals↗
PubMed2006

Perivascular adipose tissue and mesenteric vascular function in spontaneously hypertensive rats.

OBJECTIVE: Perivascular adipose tissue of normotensive rats releases a transferable factor that induces relaxation by opening voltage-dependent K+ (Kv) channels. The relevance of these observations to hypertension is unknown. METHODS AND RESULTS: We characterized mesenteric perivascular adipose tissue from 3-month-old Wistar Kyoto rats (WKY) and aged-matched spontaneously hypertensive rats (SHR). Mesenteric bed (MB) weight and MB total lipid content were lower in SHR than in WKY. Freshly isolated MB adipocytes were smaller in SHR. Plasma triglycerides, glycerol, nonesterified free-fatty acids, and cholesterol were also lower in SHR. Plasma and mesenteric leptin were correlated with the quantity of mesenteric fat. To study vascular function, the MB was cannulated and perfused at a constant 2 mL/min flow. The Kv channel blocker 4-aminopyridine (4-AP; 2 mmol/L) increased perfusion pressure less in SHR MB than WKY and was directly correlated with the mesenteric fat amount. In isolated mesenteric artery rings, 4-AP (2 mmol/L) induced a contractile effect that was attenuated in SHR compared with WKY. The anticontractile effects of perivascular fat were reduced in SHR mesenteric artery rings compared with WKY. CONCLUSIONS: Differences in visceral perivascular adipose tissue mass and function may contribute to the increased vascular resistance observed in SHR.

4-Aminopyridine↗
PubMed2006

Fever-like temperatures affect neutrophil NF-kappaB signaling, apoptosis, and ANCA-antigen expression.

The neutrophil is pivotal to ANCA vasculitis pathogenesis. Fever frequently complicates ANCA diseases. This study investigated the effects of short-term heat exposure on apoptosis in neutrophils that were treated with LPS, GM-CSF, IL-8, and dexamethasone. All compounds delayed apoptosis. Heat abrogated the apoptosis-delaying effect of LPS without affecting constitutive apoptosis or delayed apoptosis by GM-CSF, IL-8, or dexamethasone. The heat effect was dose dependent over the 39 to 42 degrees C range. NF-kappaB but not extracellular signal-regulated kinase, p38 mitogen-activated protein kinase (MAPK), or phosphatidylinositol 3-kinase/Akt controlled LPS-delayed apoptosis. Furthermore, LPS-induced IkappaBalpha degradation, DNA binding, and NF-kappaB-dependent gene transcription activation were abrogated by short-term heat. When core temperatures were raised to 40.5 degrees C for 30 min in mice, LPS-induced neutrophil NF-kappaB activation also was prevented. Short-term heat removed heat-shock protein 90 from the IkappaB kinase complex, resulting in failure of LPS-induced IkappaB kinase activation. Despite delayed apoptosis, ANCA antigen expression was increased in LPS-treated neutrophils. ANCA antigen increase was prevented by p38 MAPK inhibition and by heat exposure. Heat exposure did not inhibit LPS-induced p38 MAPK phosphorylation. Instead, apoptosis-mediated p38 MAPK degradation was accelerated, thereby decreasing the p38 MAPK that was available for LPS-mediated ANCA antigen upregulation. These data suggest that fever-like temperatures modulate neutrophil behavior in this disease.

Animals↗
PubMed2006

Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects.

BACKGROUND: Sibutramine, a serotonin and norepinephrine transporter blocker, is used as adjunctive obesity treatment. Studies in healthy subjects suggested that sibutramine might have opposing effects on peripheral and central sympathetic activity; an increase in blood pressure has been claimed. Direct measurements of muscle sympathetic nerve activity (MSNA) in sibutramine-treated patients have not been conducted. METHODS AND RESULTS: Twenty nondiabetic obese men and women completed the study (mean body mass index, 35 +/- 3 kg/m2; mean age, 42 +/- 8 years). They were treated for 5 days with 15 mg sibutramine per day or matching placebo in a randomized, double-blind, crossover fashion. At the end of each intervention, heart rate, blood pressure, and MSNA were recorded. Patients underwent cold pressor testing and phenylephrine and nitroprusside infusions. RESULTS: The mean blood pressure (systolic/diastolic) was 118 +/- 13 mm Hg/70 +/- 9 mm Hg with placebo and 120 +/- 13 mm Hg/69 +/- 8 mm Hg with sibutramine (P = .29). The mean resting MSNA was 28 +/- 14 bursts/min with placebo and 12 +/- 10 bursts/min with sibutramine (P < .0001). Sibutramine attenuated the rise in blood pressure (25 +/- 9 mm Hg/9 +/- 9 mm Hg versus 31 +/- 12 mm Hg/14 +/- 9 mm Hg, P < .01) and MSNA (0.3 +/- 0.5 arbitrary units/min versus 1.0 +/- 1.1 arbitrary units/min, P = .01) in response to cold pressor testing. Baroreflex heart rate control was similar with sibutramine and with placebo. The sympathetic baroreflex was shifted such that at a given blood pressure, MSNA was substantially decreased (top, 44 +/- 1.23 bursts/min versus 58 +/- 2.99 bursts/min [P < .001]; center point, 65 +/- 0.32 mm Hg versus 67 +/- 0.81 mm Hg [P < .05]). CONCLUSIONS: Sibutramine treatment profoundly and selectively reduces sympathetic nerve traffic at rest and attenuates the responsiveness to sympathetic stimuli. Our data support the idea that sibutramine's peripheral sympathomimetic effect is counteracted by a central sympatholytic mechanism.

Adult↗
PubMed2006

Agonistic antibodies directed at the angiotensin II, AT1 receptor in preeclampsia.

Immune mechanisms and circulating mediators may be important in the pathogenesis of preeclampsia. We review our findings on agonistic antibodies against the angiotensin II (Ang II) receptor (AT1-AA) and their possible role in the pathogenesis of this disorder. AT1-AA appear in the course of preeclampsia and are largely gone by 6 weeks after delivery. AT1-AA detection relies on a bioassay using spontaneously beating neonatal rat cardiomyocytes. Their specificity has been documented by other methods, including Western blotting, co-localization, and co-immunoprecipitation experiments. AT1-AA induce signaling in vascular cells and trophoblasts including transcription factor activation. The signaling results in tissue factor production and reactive oxygen species generation, both of which have been implicated in preeclampsia. The role of AT1-AA in preeclampsia and other severe hypertensive conditions has not yet been proved with certainty. However, we believe the findings are compelling and warrant further study.

Angiotensin II↗
PubMed2006

Hemodynamic and metabolic responses to interstitial angiotensin II in normal weight and obese men.

OBJECTIVE: The expression of the AT1 receptor in adipose tissue is not decreased or even increased in obese subjects despite systemic activation of the renin-angiotensin system. Therefore, we hypothesized that peripheral tissues of obese subjects are hypersensitive to angiotensin (Ang) II. METHODS: We characterized the effect of locally applied Ang II in skeletal muscle and subcutaneous adipose tissue of healthy non-obese (n = 12) and obese (n = 11) men using the microdialysis technique. Tissues were perfused with Ringer's solution + ethanol and incremental doses of Ang II (0.01, 0.1 and 1 micromol/l). Dialysate ethanol, glycerol, glucose, lactate, and pyruvate concentrations were measured to assess changes in blood flow (ethanol dilution technique), lipolysis and glycolysis, respectively. RESULTS: In adipose tissue, basal ethanol ratio was significantly higher and dialysate metabolite concentrations were significantly lower in obese versus non-obese men. In muscle, basal dialysate glycerol was significantly higher in obese versus non-obese men. Ang II elicited small increases in ethanol ratio and decreases in dialysate glucose in adipose tissue and skeletal muscle in both non-obese and obese men. Dialysate lactate increased significantly in both tissues of obese, but not non-obese men. Dialysate glycerol increased in adipose tissue of non-obese (+ 40%) but not of obese and remained almost unchanged in muscle of both groups. CONCLUSIONS: Interstitially applied Ang II elicits subtle changes in tissue perfusion and metabolism. However, we did not find a major increase in interstitial Ang II responsiveness in obese men.

Adipose Tissue↗
PubMed2006

Angiotensin type 1 receptor antagonists induce human in-vitro adipogenesis through peroxisome proliferator-activated receptor-gamma activation.

OBJECTIVE: In clonal animal cells, certain angiotensin receptor blockers (ARB) activate the peroxisome proliferator-activated receptor-gamma (PPARgamma). The aim of this work was to validate that observation in human cells and humans. METHODS: We investigated the induction of in-vitro adipogenesis and the activation of PPARgamma-target genes, adiponectin and lipoprotein lipase, by ARB in human preadipocytes. We also studied PPARgamma response-element-driven luciferase reporter gene activation in human adipocytes. Finally, we treated 14 obese men for 10 days with placebo crossed over with 150 mg/day irbesartan. Subcutaneous fat was analyzed for mRNA expression of adiponectin and lipoprotein lipase. RESULTS: Telmisartan and irbesartan, and to a lesser degree losartan, induced adipogenesis and activated PPARgamma-target genes. This stimulation of PPARgamma-target genes was prevented by the PPARgamma antagonist GW9662. Eprosartan had no effect. Paradoxically, all ARB activated the luciferase reporter gene. PPARgamma activity increased approximately two-fold with pioglitazone and 1.5-fold with the ARB in all assays. In the cross-over clinical study, irbesartan lowered blood pressure but had no effect on adiponectin or lipoprotein lipase mRNA expression. CONCLUSIONS: Our data are the first to show that ARB induce adipogenesis and PPARgamma-target gene expression in human adipocytes. Pharmacokinetic differences may contribute to the heterogeneous effects on metabolism and preadipocyte differentiation. In humans, larger doses of ARB, longer treatments, or both may be required to activate PPARgamma in adipose cells.

Adipogenesis↗
PubMed2006

Retinol-binding protein 4 in human obesity.

Studies in mice suggest that adipocytes serve as glucose sensors and regulate systemic glucose metabolism through release of serum retinol-binding protein 4 (RBP4). This model has not been validated in humans. RBP4 was highly expressed in isolated mature human adipocytes and secreted by differentiating human adipocytes. In contrast to the animal data, RBP4 mRNA was downregulated in subcutaneous adipose tissue of obese women, and circulating RBP4 concentrations were similar in normal weight, overweight, and obese women (n = 74). RBP4 was positively correlated with GLUT4 expression in adipose tissue, independent of any obesity-associated variable. Five percent weight loss slightly decreased adipose RBP4 expression but did not influence circulating RBP4. In another set of experiments, we stratified patients (n = 14) by low or high basal fasting interstitial glucose concentrations, as determined by the microdialysis technique. Venous glucose concentrations were similar throughout oral glucose tolerance testing, and basal RBP4 expression in adipose tissue and serum RBP4 concentrations were similar in the groups with higher and lower interstitial glucose levels. Our findings point to profound differences between rodents and humans in the regulation of adipose or circulating RBP4 and challenge the notion that glucose uptake by adipocytes has a dominant role in the regulation of RBP4.

Adipose Tissue↗
PubMed2005

NO-dependent blood pressure regulation in RGS2-deficient mice.

The regulator of G protein signaling (RGS) 2, a GTPase-activating protein, is activated via the nitric oxide (NO)-cGMP pathway and thereby may influence blood pressure regulation. To test that notion, we measured mean arterial blood pressure (MAP) and heart rate (HR) with telemetry in N(omega)-nitro-l-arginine methyl ester (l-NAME, 5 mg l-NAME/10 ml tap water)-treated RGS2-deficient (RGS2(-/-)) and RGS2-sufficient (RGS2(+/+)) mice and assessed autonomic function. Without l-NAME, RGS2(-/-) mice showed during day and night a similar increase of MAP compared with controls. l-NAME treatment increased MAP in both strains. nNOS is involved in this l-NAME-dependent blood pressure increase, since 7-nitroindazole increased MAP by 8 and 9 mmHg (P < 0.05) in both strains. The l-NAME-induced MAP increase of 14-15 mmHg during night was similar in both strains. However, the l-NAME-induced MAP increase during the day was smaller in RGS2(-/-) than in RGS2(+/+) (11 +/- 1 vs. 17 +/- 2 mmHg; P < 0.05). Urinary norepinephrine and epinephrine excretion was higher in RGS2(-/-) than in RGS2(+/+) mice. The MAP decrease after prazosin was more pronounced in l-NAME-RGS2(-/-). HR variability parameters [root mean square of successive differences (RMSSD), low-frequency (LF) power, and high-frequency (HF) power] and baroreflex sensitivity were increased in RGS2(-/-). Atropine and atropine plus metoprolol markedly reduced RMSSD, LF, and HF. Our data suggest an interaction between RGS2 and the NO-cGMP pathway. The blunted l-NAME response in RGS2(-/-) during the day suggests impaired NO signaling. The MAP increases during the active phase in RGS2(-/-) mice may be related to central sympathetic activation and increased vascular adrenergic responsiveness.

Animals↗
PubMed2005

Plasma exchange for primary autoimmune autonomic failure.

We report on a patient with long-standing severe autonomic failure that affected his sympathetic and parasympathetic nervous systems. Antibodies against the ganglionic acetylcholine receptors were detected in the serum. Removal of the antibodies by means of plasma exchange resulted in a dramatic clinical improvement.

Adult↗