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Biomedical subjects

R B Sterzel

Publications and source records attributed to R B Sterzel.

125 records · Page 7Linked to original sources
PubMed1971

Relationship of nervous tissue transketolase to the neuropathy in chronic uremia.

Patients with chronic uremia develop neurologic defects which are similar to the demyelinating lesions seen in thiamine deficiency. The present study describes inhibitory effects of uremic material on nervous tissue transketolase, a thiamine-dependent enzyme of the pentose phosphate pathway which has been reported to have functional importance in the metabolism of myelinated nervous structures. Transketolase activity (TKA) of normal human brain and spinal cord was measured by the conversion of ribose-5-phosphate (R5P) to sedoheptulose-7-phosphate (S7P). TKA was significantly inhibited by plasma, cerebrospinal fluid and low molecular weight dialysate fractions obtained from patients with uremic neuropathy, but not by samples from normal subjects. The specific effect on transketolase by uremic material was established by showing suppressed formation of S7P from R5P also in the presence of excess cofactor thiamine pyrophosphate and of the other substrate xylulose-5-phosphate. Uremic plasma likewise inhibited a partially purified transketolase preparation from bakers' yeast.31 of 35 chronic uremic patients with inhibition values between 10 and 84% before or during the early phase of intermittent hemodialysis had evidence of neuropathy. Data of clinical grading of the neurologic deficits and values of motor nerve conduction velocity revealed a correlation between the extent of uremic neuropathy and the degree of nervous tissue transketolase inhibition. Hemodialysis markedly reduced the inhibitory effects of the patients' plasma and the data indicate that uremic patients who received effective long-term dialysis treatment show a parallel decline of transketolase inhibition and uremic neuropathy.The findings demonstrate that in patients with chronic renal failure, low molecular weight factors accumulate and inhibit nervous tissue transketolase. This biochemical defect-uncorrectable by thiamine but reversible by dialysis-may interfere with the metabolism of myelin-supporting cells, and/or of the axonal metabolism of medullated structures, and may thus contribute to the degeneration of myelinated nerves seen with uremic neuropathy.

Adolescent↗
PubMedDate not supplied

Mesangial cells and their adhesive properties.

Glomerular mesangial cells play a central role in maintaining structure and function of the glomerular capillary ultrafiltration apparatus. Under physiological and pathological conditions, mesangial cells regulate amount and composition of the surrounding extracellular matrix. Conversely, components of the embedding matrix affect the mesangial cell phenotype. These interactions are mediated via specific cell surface receptors, the best studied group of which is the beta1 integrin family. The beta1 integrins play a role in mesangial cell adhesion, migration, survival and proliferation. Expression and abundance of integrins in healthy and diseased glomeruli and their functions and mediation of signals are discussed in this review. Other factors modulating mesangial cell-matrix interactions, such as antiadhesive proteins, cytokines, disintegrins and nitric oxide, are also considered. The available evidence from in vitro and in vivo studies indicates that receptor-mediated interactions between mesangial cells and the normal or abnormal extracellular matrix regulate the mesangial cell phenotype and thus contribute to normal maintenance of the glomerulus and to remodeling and repair of the glomerular capillary tuft in response to injury.

Animals↗
PubMedDate not supplied

P2U-purinergic receptor activation mediates inhibition of cAMP accumulation in cultured renal mesangial cells.

Extracellular ATP has been reported to exert mitogenic and contractile effects on cultured renal mesangial cells (MCs). Since it is possible that these actions involve changes in the cAMP second messenger system, we examined the effect of extracellular nucleotides on the accumulation of cAMP in rat MCs. ATP, UTP and adenosine 5'-0-(3-thio)triphosphate (ATP gamma S) (100 microM) had no significant effects on baseline cAMP levels, but inhibited forskolin-stimulated accumulation of cAMP by 21-75% in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Maximal inhibitory effects were observed at 100 microM of ATP gamma S with a threshold dose of 1 microM. ATP gamma S, ATP and UTP were the most potent inhibitors indicating stimulation of the P2u receptor. The P2x agonists adenosine 5'-(alpha, beta-methylene) triphosphate and adenosine 5'-(beta, gamma-methylene) triphosphate, and the P2y agonist 2-methylthio-ATP did not affect cAMP accumulation. Treatment with the P2 receptor antagonist suramin (200 microM) reduced the inhibition by 58%. The inhibitory effects of the nucleotides were significantly attenuated by preincubation with pertussis toxin (10-100 ng/ml). Inhibition of phospholipase C and protein kinase C did not prevent the inhibitory effect of the nucleotides. Inhibitors of forskolin-stimulated cAMP accumulation had different effects on DNA synthesis in cultured MCs as measured by 3H-thymidine uptake at 48 h: ATP, ATP gamma S and the inhibitor of adenylyl cyclase, SQ 22536, stimulated DNA synthesis in MCs, while UTP showed no significant mitogenic effect. Agents which increased baseline levels of intracellular cAMP (forskolin, IBMX, dibutyryl-cAMP) significantly diminished DNA synthesis in MCs. The results indicate that the P2u-purinergic receptor mediates inhibition of forskolin-induced cAMP accumulation which is likely due to inhibition of adenylyl cyclase. This effect appears to be partially mediated by PTX-sensitive G proteins. While the increase in cAMP accumulation is anti-mitogenic, inhibition of cAMP accumulation by P2u receptors is not correlated with MC growth control. Thus, additional mechanisms other than inhibition of cAMP accumulation by P2u receptors are likely to be involved in the mitogenesis of extracellular ATP.

Adenosine Triphosphate↗
PubMedDate not supplied

Regulatory mechanism in glomerular mesangial cell proliferation.

Glomerular mesangial cells have a central function in maintaining structure and function of the glomerular capillary ultrafiltration apparatus. Regardless of the type of glomerular injury, imbalances in the control of mesangial cell replication appear to play a key role in the pathogenesis of progressive renal failure. The available evidence from in vitro and in vivo studies indicates that such regulatory mechanisms include specific soluble and non-soluble extracellular factors and a complex array of receptor-mediated signals which control cell proliferation, survival and apoptosis. This review summarizes results from recent investigations concerning regulation of cell cycle progression in mesangial cells. In addition to results from cell culture studies, descriptive findings on expression and regulation of cell cycle-regulatory proteins and their potential role for altered mesangial cell behaviour in glomerular disease are considered. We believe that better understanding of processes which regulate mesangial cell replication could lead to novel diagnostic as well as therapeutic strategies and, thus, help control better proliferative glomerulonephritis.

Apoptosis↗
PubMedDate not supplied

Effects of a calcium entry blocker on blood pressure and renal function during angiotensin-induced hypertension.

The effects of the calcium entry blocker nitrendipine on blood pressure (BP) and renal hemodynamics were studied in rats with angiotensin II (ANG II)-induced hypertension. The ANG II was infused subcutaneously by implanted osmotic minipumps for 14 to 16 days. There was a progressive rise in BP in ANG II-infused rats to levels 58 mm Hg above basal by Day 10, whereas control rats with sham pumps remained normotensive. Nitrendipine or vehicle was administered by gavage to groups of control and hypertensive rats for 5 days, and clearance experiments were performed with the rats under anesthesia on the last day. The prolonged infusion of ANG II increased the renal vascular resistance and reduced the glomerular filtration rate and renal Na+ excretion. At a dose of 3 mg/100 g body weight, nitrendipine had no consistent effects on BP or renal function of control rats. By contrast, in rats with ANG II-induced hypertension, nitrendipine normalized both the BP and the changes in renal vascular resistance and glomerular filtration rate. Despite the fall in BP, nitrendipine caused a marked diuresis and natriuresis. Moreover, nitrendipine increased Na+ excretion of conscious, ANG II-hypertensive rats but not of controls. Thus, nitrendipine appears to be highly effective in reversing ANG II-induced hypertension and Na+ retention. These findings also indicate that the hypertension, renal vasoconstriction, and Na+ retention accompanying prolonged ANG II infusions may be mediated by calcium-dependent mechanisms.

Angiotensin II↗