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Biomedical subjects

W N Suki

Publications and source records attributed to W N Suki.

At least 37 records · Page 2Linked to original sources
PubMed1997

Plasma membrane calcium ATPase isoform expression in cultured rat mesangial cells.

The maintenance of intracellular ionized calcium (iCa2+) in the submicromolar range is important for mesangial cell (MC) function, and, as in most mammalian cells, plasma membrane Ca(2+)-ATPases (PMCA) play an important role in the homeostatic process. Molecular studies have demonstrated four PMCA isoforms, each with multiple splice variants. The present study examines the expression of PMCA isoforms and calmodulin-binding region splice variants in cultured MC from Sprague-Dawley rats and from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats before and after the onset of hypertension in SHR. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses, we have demonstrated PMCA1, -3, and -4, but not PMCA2, to be present in MC from these rat strains. Splice variant analysis revealed PMCA1a and -1b, PMCA3a, -3b, and -3c, and PMCA4a and -4b to be expressed in MC from all three strains. The relative quantities of PMCA1 and PMCA4 mRNA were not different in age-matched SHR vs. WKY rats, correlating with similar iCa2+ measurements. The expression of all three isoforms declined with age in SHR and WKY.

Alternative Splicing↗
PubMed1997

Use of diuretics in chronic renal failure.

Patients with chronic renal failure retain Na+ and H2O, and they retain K- and acid. This disordered homeostasis results in hypertension, edema, hyperkalemia and acidosis. Diuretics may be used to favorably modify these disturbances. However, because of the limited filtered load of water and electrolytes, and the low renal blood flow, measures need to be taken to maximize the response to diuretics. These measures include: (a) the use of the most bioavailable drug, torasemide, when using the oral route; (b) the use of the drug with the least hepatic elimination, furosemide, when using the intravenous route; (c) the use of combinations of loop- and distal tubule-acting diuretics; (d) the use of the maximum effective diuretic dose; and (e) the use of repeated doses or constant infusion. In benefiting hypertension, vascular congestion and hyperkalemia diuretics appear to exert their effects not only on the kidneys but also on extrarenal sites, such as the vascular tree and the gastrointestinal tract. The use of diuretics, however, is not without complications, which include: intravascular volume depletion and azotemia, ototoxicity (when using loop-acting diuretics), hyperlipidemia, acute pancreatitis, hyperkalemia (when using K(+)-sparing agents), and acidosis (when using carbonic anhydrase inhibitors).

Diuretics↗
PubMed1996

Cell apoptosis and proliferation in experimental chronic obstructive uropathy.

Cell proliferation and apoptosis in kidneys with chronic obstructive uropathy (COU) have not been adequately studied. Whether these fundamental cellular processes play any role in the pathogenesis and evolution of COU remains undetermined. Sprague-Dawley rats with COU induced by unilateral ureteral ligation were sacrificed at postoperative days 1, 6, 9, 15, 34, 43, 60, 75, and 90, and were compared with control, sham-operated rats sacrificed at days 0, 15, 43, and 90. The kidneys with ureteral ligation, the contralateral kidneys, and the control kidneys were submitted to in situ end-labeling of fragmented DNAs for the detection of apoptotic cells, and to immunostaining with many monoclonal antibodies directed against the nuclear antigens associated with cell proliferation for the detection of proliferating cells. Additional rats with COU were also submitted to BrdU labeling to detect proliferating cells. The tubular, interstitial, and glomerular cells showing either apoptosis or proliferation were separately quantitated and the obtained data were correlated with dry kidney weight, tubular diameter, glomerular surface area and interstitial volume. Apoptotic tubular cells in kidney with COU increased rapidly, reaching 30-fold that of control at day 25, which was followed by an equally rapid decrease to the control level. During the same period, both the dry kidney weight and the mean tubular diameter decreased markedly. These data suggest that apoptosis may play a significant role in tubular atrophy and renal weight loss. The rapid increase in tubular cell apoptosis was immediately preceded by a 37% gain in the dry kidney weight over the control; just before that increase, there was also an approximate 60-fold increase in the proliferation rate of tubular cells detected by immunostaining for proliferating nuclear antigen or by BrdU labeling. The significance of this intriguing temporal relationship of tubular cell apoptosis and proliferation remains to be elucidated, but it may have pathogenetic implications. In contrast to the rise and fall of the frequency of tubular cell apoptosis and proliferation, the frequency of interstitial cell apoptosis and proliferation displayed continuous increase toward the end of the experiment, with a roughly parallel increase in the interstitial damage. Apoptosis and proliferation of glomerular cells in kidneys with COU did not show any significant changes throughout the experiment. In conclusion, the obtained data suggest that tubular cell apoptosis may be pathogenetically related to the tubular atrophy and renal tissue loss in COU, and that proliferation and apoptosis of interstitial cells may play a role in the observed interstitial changes in this model. This study should provide the impetus for further exploration of the mechanisms of cell death and cell proliferation as a novel venue for understanding the pathogenesis of COU.

Animals↗
PubMed1996

Regulation of body fluid compartments during short-term spaceflight.

The fluid and electrolyte regulation experiment with seven subjects was designed to describe body fluid, renal, and fluid regulatory hormone responses during the Spacelab Life Sciences-1 (9 days) and -2 (14 days) missions. Total body water did not change significantly. Plasma volume (PV; P < 0.05) and extracellular fluid volume (ECFV; P < 0.10) decreased 21 h after launch, remaining below preflight levels until after landing. Fluid intake decreased during weightlessness, and glomerular filtration rate (GFR) increased in the first 2 days and on day 8 (P < 0.05). Urinary antidiuretic hormone (ADH) excretion increased (P < 0.05) and fluid excretion decreased early in flight (P < 0.10). Plasma renin activity (PRA; P < 0.10) and aldosterone (P < 0.05) decreased in the first few hours after launch; PRA increased 1 wk later (P < 0.05). During flight, plasma atrial natriuretic peptide concentrations were consistently lower than preflight means, and urinary cortisol excretion was usually greater than preflight levels. Acceleration at launch and landing probably caused increases in ADH and cortisol excretion, and a shift of fluid from the extracellular to the intracellular compartment would account for reductions in ECFV. Increased permeability of capillary membranes may be the most important mechanism causing spaceflight-induced PV reduction, which is probably maintained by increased GFR and other mechanisms. If the Gauer-Henry reflex operates during spaceflight, it must be completed within the first 21 h of flight and be succeeded by establishment of a reduced PV set point.

Adult↗
PubMed1996

Tenascin is an ubiquitous extracellular matrix protein of human renal interstitium in normal and pathologic conditions.

Tenascin, a large oligomeric glycoprotein, is a recent addition to a list of increasing extracellular matrix proteins. Previous studies have documented the strong expression of tenascin in embryonic kidney and in both normal and abnormal mature glomeruli implicating an important role of this extracellular matrix protein in nephrogenesis and glomerular scarring. Whether tenascin plays any role in interstitial fibrosis, a common final pathway of tubulointerstitial nephritis, is no known; on the other hand, a detailed knowledge of the structural components of interstitial fibrosis is essential for further studies on other fundamental aspects of this biologically and clinically important process. In this study, the expression of tenascin in the renal interstitium was immunohistochemically evaluated in 208 renal specimens during normal kidney (23 cases), acute tubular necrosis (8), acute tubulointerstitial nephritis (8), chronic primary tubulointerstitial nephritis (30), tubulointerstitial nephritis secondary to glomerular diseases of mild (46) and severe (55) degree, ischemic damage (24), and rejection (14). It was found that in normal kidney tenascin expression was limited to the medullary interstitium. In kidney with tubulointerstitial nephritis, tenascin was ubiquitously and constantly expressed in any areas with tubulointerstitial damage regardless of diagnosis, etiology, the cortical vs. medullary location of the lesions, stage of the fibrogenetic process, density of fibroblasts, or severity of interstitial inflammation in the affected areas. Indeed, strong tenascin expression was seen in areas where there was only interstitial edema or inflammation as judged by routine light microscopic preparations. In summary, this study systematically documents tenascin as a novel extracellular matrix protein selectively expressed in the medullary interstitium in normal kidney, and ubiquitously present in areas with interstitial fibrosis.

Antibody Specificity↗
PubMed1996

Renal abnormality of calcium handling in spontaneously hypertensive rats.

Hypercalciuria has been observed in human and experimental hypertension. The distal convoluted tubule (DCT) is the site of fine regulation for Ca2+ excretion. We assessed the cellular factors responsible for Ca2+ reabsorption in the DCT of spontaneously hypertensive rats (SHR). Vitamin D3 dependent Ca-binding protein 28k (CaBP28k), a factor involved in Ca2+ influx, and plasma membrane Ca ATPases (PMCA), a factor involved in Ca2+ efflux, were studied in hypertensive 16-week-old SHR and normotensive Wistar-Kyoto rats (WKY). mRNA levels for CaBP28k, PMCA 2 and PMCA 4 were not different in the two strains. However, CaBP28k protein was more abundant, and PMCA protein was less abundant in SHR than in WKY. PMCA antibody recognized only DCT in the two strains. In conclusion, decreased PMCA in DCT may be responsible for the hypercalciuria in SHR.

Animals↗
PubMed1996

Ca-ATPase and bone cell mineralization.

The plasma membrane Ca-ATPases play an important role in the regulation of intracellular Ca2+ ion concentration by pumping Ca2+ out of the cell into the extracellular fluid at the expense of ATP. These pumps potentially play an important role in the delivery of Ca2+ during mineralization of hard tissues such as bone. The properties of the plasma membrane Ca2+ pump are compared with those of the sarco(endo)plasmic reticulum and the factors regulating pump function are presented. The different gene products for the plasma membrane Ca-ATPases are described as well as their known functional significance. Particular attention is paid on the plasma membrane Ca2+ pumps present in mineralizing tissues and evidence supporting a role for these pumps in the transcellular delivery of Ca2+ during the process of mineralization is also presented.

Animals↗
PubMed1996

Plasma membrane and sarcoplasmic reticulum Ca-ATPase and smooth muscle.

Calcium ions (Ca2+) are involved in the regulation of many cellular activities. The Ca-ATPase(s) of the plasma membrane and of the endoplasmic reticulum play an important role in controlling the intracellular Ca2+ concentration. Therefore, it is not unexpected that these enzymes are modulated by different factors. The activity of the plasma membrane Ca-ATPase is modified by the amount of negatively charged phospholipids surrounding the enzyme. The regulation of the endoplasmic reticulum Ca-ATPase depends on the phosphorylation of phospholamban by cAMP- and cGMP-dependent protein kinase. These two different Ca2+ transport ATPases are present in both visceral and vascular smooth muscle, but tissue- and species-dependent differences in their relative amount have been observed. In this article we will review the characteristics of Ca-ATPases of the smooth muscle.

Animals↗
PubMed1995

Renal neoplasm in acquired cystic kidney disease.

The development of renal cell neoplasms ranging from adenoma to metastatic carcinoma is the most serious complication of acquired cystic kidney disease (ACKD). A comprehensive review of the pertinent literature shows that there is up to 50-fold increased risk of renal cell carcinoma in ACKD compared to the general population. The ACKD-associated renal cell carcinoma is seen predominantly in males, occurs approximately 20 years earlier than in the general population, and is frequently bilateral (9%) and multicentric (50%). Acquired cystic kidney disease-associated renal cell carcinoma is frequently asymptomatic (86%), but may be associated with bleeding, abrupt changes in hematocrit, fever, and flank pain or rarely with hypoglycemia, hypercalcemia, or metastases at presentation. Computed tomography seems to provide a better diagnostic yield than sonography or magnetic resonance imaging; nevertheless, large (up to 8 cm) tumors not visualized by any imaging techniques have been reported. It is generally agreed that there is a need for regular screening of symptomatic ACKD patients for early detection of renal cell carcinoma; however, whether screening is needed for asymptomatic patients remains controversial. Nephrectomy is indicated for tumors larger than 3 cm. Management for tumors smaller than 3 cm with persistent symptoms, such as back pain or hematuria, remains controversial, but nephrectomy may be recommended since many of these tumors turn out to be unequivocal renal cell carcinoma. Asymptomatic tumors smaller than 3 cm should be serially screened, and tumor enlargement may be an indication for nephrectomy. Acquired cystic kidney disease-associated renal cell carcinoma accounts for approximately 2% of deaths in renal transplant patients. A median length of survival of approximately 14 months and a 5-year survival rate of 35% are comparable to the same data for renal cell carcinoma in the general population. Successful renal transplant probably decreases the risk of renal cell carcinoma in ACKD patients, but this preliminary observation needs confirmation. The development of ACKD-associated renal carcinoma is a continuous process with evolving phenotypic expression, including damaged renal tubule, simple cyst, cyst with atypical lining, adenoma, and, finally, carcinoma. The pathogenesis of this continuous process is not entirely known, but growth factor-induced compensatory growth of tubular epithelium initiated by the changes of end-stage kidney disease, and probably perpetuated by activation of proto-oncogenes, seems to be the most significant factor.

Adult↗
PubMed1995

Anticardiolipin antibody in patients on maintenance hemodialysis and its association with recurrent arteriovenous graft thrombosis.

To investigate the relationship between dialysis access thrombosis (arteriovenous grafts [AVG] and arteriovenous fistulas [AVF]) and the presence of elevated concentration of immunoglobulin G-anticardiolipin antibody (IgG-ACA), we conducted a cross-sectional study of all patients, in a single dialysis facility, who had a minimum of 6 months of uninterrupted hemodialysis. Episodes of thrombosis of AVGs and AVFs in the preceding 30 months were documented and each patient's IgG-ACA titer was determined. Sixteen of 74 patients with AVGs (22%) had a raised titer of IgG-ACA compared with only one of 17 patients (6%) with AVFs. In the patients with AVGs the odds ratio for patients with raised IgG-ACA titer to have experienced two or more episodes of thrombosis, compared with none or only one episode, was 3.7 (95% confidence interval, 1.2 to 11.8; P < 0.04). No events of AVF thrombosis were encountered during the same period. We conclude that in end-stage renal disease patients undergoing hemodialysis, there is a greater prevalence of elevated IgG-ACA titer in patients with AVGs than in patients with AVFs, and this in turn is associated with increased odds of having had recurrent AVG thrombosis.

Adult↗
PubMed1995

Cell calcium and arterial blood pressure.

In hypertensive humans and animals, intracellular calcium (Ca2+) has been found to be elevated in several cell types, including platelets, red blood cells, and smooth muscle cells. The messenger role of calcium requires its maintenance within cells at very low (submicromolar) ionic concentrations. This transcellular gradient is maintained by the reversible complexing of calcium to specific proteins. Intracellular free calcium can increase through an enhanced influx, release from intracellular stores, or a reduced efflux of calcium from the cell. Calcium channels are found to be increased in activity in some studies of hypertensive animals, but not in others. Sequestration of calcium within the cell has also been implicated in the increased cytosolic calcium in hypertension. Plasma membrane adenosine triphosphatases (ATPases) play a significant role in calcium extrusion; and the activity of these pumps has been found to be decreased in several human and animal studies. A single cause of the cellular calcium alterations in hypertension is not completely clear.

Animals↗
PubMed1995

Differential expression of plasma membrane calcium pump mRNA isoforms in rat osteoblast-like cells.

This study was conducted to identify the plasma membrane Ca2+ transport ATPase (PMCA) mRNA isoforms expressed in rat osteoblast-like cells as PMCAs are likely to participate in calcium deposition in bone. We designed oligonucleotide primers for each PMCA isoform based on rat cDNA sequences in order to develop reverse transcription polymerase chain reaction (RT-PCR) assays. Rat kidney total RNA was used to validate the assays as we have shown that each isoform is present in kidney. When used in RT-PCR assays each primer pair gave rise to a single major product of the appropriate size. Southern blot analysis of the PCR products with oligonucleotide probes specific for each isoform revealed that each probe hybridized only to the expected product. Reamplification of purified PCR products with probe and antisense primers gave rise to products of appropriate size, further confirming the identity of the products. Using these primers we have identified the presence of transcripts for PMCA1, 2 and 4 in RNA from UMR-106 osteoblasts and PMCA1 in RNA from ROS 17/2.8 osteoblasts. We conclude that the two major rat cell lines used as models to study osteoblast function differentially express PMCA mRNA isoforms.

Animals↗
PubMed1994

Frequent hemodialysis graft thrombosis: association with antiphospholipid antibodies.

We present two cases of patients with systemic lupus erythematosus and end-stage renal disease. Both were on hemodialysis and had multiple arteriovenous graft thromboses associated with the presence of antiphospholipid antibodies. A review of patients with end-stage renal disease secondary to systemic lupus erythematosus reveals that all had borderline or frankly elevated antiphospholipid antibody titers, and four of the seven patients had multiple graft thromboses. Possible etiologic and pathophysiologic mechanisms are discussed.

Adult↗
PubMed1994

ATP inhibits the hydrosmotic effect of AVP in rabbit CCT: evidence for a nucleotide P2u receptor.

In rabbit renal cortical collecting tubule (CCT), perfused in vitro at 38 degrees C, ATP in concentrations of 10(-7) M and greater inhibits arginine vasopressin (AVP)-stimulated osmotic water permeability (Pf). The P1-purinergic receptor antagonist 8-phenyltheophylline did not attenuate the inhibitory action of ATP, and the poorly hydrolyzable ATP analogue, 5'-adenylylimidodiphosphate (AMP-PNP), mimicked the effect of ATP, arguing against an effect of ATP on a P1 receptor or the "P site." Purinergic receptor agonists inhibited AVP-stimulated Pf with the following rank order efficacy: ATP = ADP = UTP = AMP-PNP = alpha, beta-methylene-ATP > 2-methylthio-ATP >> AMP > adenosine, consistent with the pharmacology of a "nucleotide" receptor subtype. Pertussis toxin pretreatment attenuated the action of 10(-5) and 10(-6) MATP; however, 10(-4) MATP failed to inhibit the hydrosmotic action of forskolin or 8-bromoadenosine 3',5'-cyclic monophosphate. Pretreatment with the phosphodiesterase inhibitor RO20-1724 or indomethacin did not inhibit the action of ATP. Staurosporin and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester significantly attenuated the inhibition of Pf by lower concentrations of ATP. These data suggest that ATP activates nucleotide receptors on the CCT, mobilizing intracellular Ca2+, which inhibits the hydrosmotic action of AVP.

Adenosine Triphosphate↗
PubMed1994

Unusual presentation of glomerulocystic kidney disease in an adult patient.

A 38-year-old Latin-American man developed uremic syndrome without any evidence of previous kidney diseases or any other health problems. Ultrasound and CT scan confirmed normal size of the kidneys without evidence of urinary tract obstruction or renal parenchymal cysts. Kidney biopsy showed cystic dilatation of Bowman's space (glomerulocystic kidney disease). The patient was started on hemodialysis. Severe renal dysfunction and uremic symptoms are a rare initial manifestation of glomerulocystic kidney disease. This pathology should be considered in the differential diagnosis of patients with normal size kidney and chronic renal failure.

Adult↗