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Biomedical subjects

I Kurtz

Publications and source records attributed to I Kurtz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of pistachio nuts on serum lipid levels in patients with moderate hypercholesterolemia.

BACKGROUND: Elevated serum cholesterol levels play an important role in the development of coronary artery disease. Previous studies have suggested that nut consumption benefits lipid profile. Pistachio nuts are widely available, inexpensive and frequently consumed by the general population. OBJECTIVE: To determine whether substituting 20% of the daily caloric intake in the form of pistachio nuts will improve the lipid profiles of humans with primary, moderate hypercholesterolemia. DESIGN: Controlled, randomized crossover design. SETTING: Outpatient dietary modification, counseling and blood analysis. PATIENTS: Ten patients with moderate hypercholesterolemia. INTERVENTION: Three weeks of dietary modification with 20% caloric intake from pistachio nuts. MEASUREMENTS: Body weight, blood pressure, total cholesterol, LDL, HDL, and triglycerides were monitored. Lipid profiles were analyzed prior to, during and after dietary modification. RESULTS: After three weeks, there was a decrease in total cholesterol (p<0.04), an increase in HDL (p<0.09), a decrease in the total cholesterol/HDL ratio (p<0.01) and a decrease in the LDL/HDL ratio (p<0.02). Triglycerides and LDL levels decreased, but not significantly. Body weight and blood pressure remained constant throughout the study. CONCLUSIONS: Results suggest that eating pistachio nuts instead of other dietary fat calories can improve lipid profiles, thereby decreasing coronary risk. Further studies will be required to confirm these results and to determine the mechanism of this effect.

Adult↗
PubMed1999

NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase.

We have recently cloned and characterized a unique sodium bicarbonate cotransporter, NBC3, which unlike other members of the NBC family, is ethylisopropylamiloride (EIPA) inhibitable, DIDS insensitive, and electroneutral (A. Pushkin, N. Abuladze, I. Lee, D. Newman, J. Hwang, and I. Kurtz. J. Biol. Chem. 274: 16569-16575, 1999). In the present study, a specific polyclonal antipeptide COOH-terminal antibody, NBC3-C1, was generated and used to determine the pattern of NBC3 protein expression in rabbit kidney. A major band of approximately 200 kDa was detected on immunoblots of rabbit kidney. Immunocytochemistry of rabbit kidney frozen sections revealed specific staining of the apical membrane of intercalated cells in both the cortical and outer medullary collecting ducts. The pattern of NBC3 protein expression in the collecting duct was nearly identical to the same sections stained with an antibody against the vacuolar H+-ATPase 31-kDa subunit. In addition, the NBC3-C1 antibody coimmunoprecipitated the vacuolar H+-ATPase 31-kDa subunit. Functional studies in outer medullary collecting ducts (inner stripe) showed that type A intercalated cells have an apical Na+-dependent base transporter that is EIPA inhibitable and DIDS insensitive. The data suggest that NBC3 participates in H+/base transport in the collecting duct. The close association of NBC3 and the vacuolar H+-ATPase in type A intercalated cells suggests a potential structural/functional interaction between the two transporters.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter.

We report the cloning, sequence analysis, tissue distribution, functional expression, and chromosomal localization of the human pancreatic sodium bicarbonate cotransport protein (pancreatic NBC (pNBC)). The transporter was identified by searching the human expressed sequence tag data base. An I.M.A.G.E. clone W39298 was identified, and a polymerase chain reaction probe was generated to screen a human pancreas cDNA library. pNBC encodes a 1079-residue polypeptide that differs at the N terminus from the recently cloned human sodium bicarbonate cotransporter isolated from kidney (kNBC) (Burnham, C. E., Amlal, H., Wang, Z., Shull, G. E., and Soleimani, M. (1997) J. Biol. Chem. 272, 19111-19114). Northern blot analysis using a probe specific for the N terminus of pNBC revealed an approximately 7.7-kilobase transcript expressed predominantly in pancreas, with less expression in kidney, brain, liver, prostate, colon, stomach, thyroid, and spinal chord. In contrast, a probe to the unique 5' region of kNBC detected an approximately 7.6-kilobase transcript only in the kidney. In situ hybridization studies in pancreas revealed expression in the acini and ductal cells. The gene was mapped to chromosome 4q21 using fluorescent in situ hybridization. Expression of pNBC in Xenopus laevis oocytes induced sodium bicarbonate cotransport. These data demonstrate that pNBC encodes the sodium bicarbonate cotransporter in the mammalian pancreas. pNBC is also expressed at a lower level in several other organs, whereas kNBC is expressed uniquely in kidney.

Amino Acid Sequence↗
PubMed1998

Axial heterogeneity of sodium-bicarbonate cotransporter expression in the rabbit proximal tubule.

It is generally accepted that Na(HCO3)n cotransport is the most important mechanism mediating basolateral bicarbonate efflux in the early proximal tubule. The presence of basolateral Na(HCO3)n cotransport in the late proximal tubule (S3 segment) and in the juxtamedullary S1 and S2 segments has been controversial. The renal sodium-bicarbonate cotransporter (NBC) has been recently cloned from rat (M. F. Romero, M. A. Hediger, E. L. Boulpaep, and W. F. Boron. J. Am. Soc. Nephrol. 7: 1259, 1996), salamander (M. F. Romero, M. A. Hediger, E. L. Boulpaep, and W. F. Boron. Nature 387: 409-413, 1997), and human (C. E. Burnham, H. Amlal, Z. Wang, G. E. Shull, and M. Soleimani. J. Biol. Chem. 272: 19111-19114, 1997). The localization of NBC in the kidney is unknown. The present study was designed to localize NBC mRNA expression in the rabbit proximal tubule. In situ hybridization studies were combined with functional studies of basolateral Na(HCO3)n cotransport in superficial and juxtamedullary S1, S2, and S3 segments of the rabbit proximal tubule. The results demonstrate that NBC mRNA is localized predominantly to the cortex, with less expression in the outer medulla. NBC expression was not detected in the inner medulla. The highest level of NBC mRNA is in the S1 proximal tubule. NBC is expressed at a low levels in the S3 segment, with intermediate expression in the S2 segment. In bicarbonate-buffered solutions, the rate of base efflux mediated by Na(HCO3)n cotransport followed a similar pattern in superficial and juxtamedullary proximal tubule segments, i.e., S1 > S2 > S3. The juxtamedullary S1 segment had the greatest rate of basolateral Na(HCO3)n cotransport and the highest level of NBC expression in the proximal tubule.

Animals↗
PubMed1998

The N-terminal portion of parathyroid hormone-related protein mediates the inhibition of apical Na+/H+ exchange in opossum kidney cells.

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) can activate a common receptor in several different cell types. Both PTH and N-terminal PTHrP peptides have been shown to acutely inhibit the apical Na+/H+ exchanger in the renal proximal tubule. In this study, the ability of various PTHrP fragments to inhibit apical Na+/H+ exchange was investigated. In addition, the signal transduction events associated with PTHrP inhibition of apical Na+/H+ exchange in polarized OK-P cells were characterized. Both PTHrP-(1-34)NH2 and recombinant full-length PTHrP-(1-141) inhibited apical Na+/H+ exchange activity by approximately 50%. These changes occurred in close temporal association with significant (threefold) increases in cellular cAMP accumulation. PTHrP-(1-34)NH2 had no effect on intracellular Ca2+, inositol phosphate production, or protein kinase C activity. PTHrP peptides, including PTHrP-(38-64)NH2, PTHrP-(67-86)NH2, PTHrP-(102-107)NH2, and PTHrP-(107-139)NH2, which lack the PTH-like N terminus, had no effect on the antiporter activity or cAMP accumulation. The results demonstrate that the N-terminal portion of the PTHrP molecule is responsible for inhibition of the apical Na+/H+ antiporter in OK-P cells.

Animals↗
PubMed1998

Peripheral blood mononuclear cells express mutated NCCT mRNA in Gitelman's syndrome: evidence for abnormal thiazide-sensitive NaCl cotransport.

Genetic analysis has demonstrated complete linkage between the human thiazide-sensitive sodium chloride cotransporter gene (NCCT or TSC) and Gitelman's syndrome (GS). Several genomic NCCT mutations have been reported. This study was performed to determine whether peripheral blood mononuclear cells (PBMC) express NCCT mRNA and whether defective PBMC NaCl cotransport could be demonstrated in GS. PBMC were isolated from two brothers with GS, their parents, and healthy control subjects. Northern analysis revealed that NCCT mRNA is expressed in PBMC. The sequence of full-length NCCT cDNA amplified from normal PBMC was identical to human renal NCCT cDNA. Two different mutations were detected in the patients' NCCT cDNA (compound heterozygote). In cDNA derived from the patient's maternal allele, exon 24 was deleted, resulting in a premature stop codon (after amino acid 920). cDNA derived from the patient's paternal allele had an additional 119-bp insertion between exons 3 and 4, generating a premature stop codon (after amino acid 187). The patient's genomic DNA had a previously described 5' splice site mutation in intron 24, GGT --> GTT (maternal allele), and a new 3' splice site mutation in intron 3, CAG --> CAA (paternal allele), which resulted in the activation of a nearby cryptic splice site in intron 3. The latter mutation was not present in 300 normal chromosomes. To determine the functional significance of these findings, chlorothiazide-inhibitable 22Na uptake was measured in PBMC from control subjects, the parents, and the patients with GS in the presence of bumetanide. In control PBMC, chlorothiazide inhibited 22Na uptake by approximately 9%. PBMC from the two patients with GS failed to respond to chlorothiazide. These results demonstrate that PBMC can be used for mutational analysis of NCCT mRNA in patients with GS. Furthermore, functional evidence is provided that the underlying cause of GS is defective NCCT NaCl cotransport.

Adult↗
PubMed1996

Freedom through a single switch: coping and communicating with artificial ventilation.

Challenging clients often stretch the limits of the imagination in terms of developing creative technologies to allow access to computers, communication devices and environmental controls. This paper provides a description of an innovative system that enables clients with motor neurone disease/amyotrophic lateral sclerosis (MND/ALS), on full ventilatory support and virtually no movement, to communicate and manipulate their environments, through the use of a myoelectrically controlled switch.

Amyotrophic Lateral Sclerosis↗
PubMed1995

NH3 permeability of principal cells and intercalated cells measured by confocal fluorescence imaging.

The cortical collecting duct (CCD) is an important site for NH3 secretion in mammalian nephron. However, given the cellular heterogeneity of this epithelium, the transcellular sites for NH3 secretion are unknown. In the present study, a dual-excitation confocal microscope was designed and optimized to have sufficient temporal resolution to measure the permeability of ammonia (PNH3) across the basolateral and apical membrane of principal cells (PCs) and intercalated cells (ICs) in perfused rabbit CCDs. The rate of cellular NH3 influx was calculated from the time course of increase in intracellular pH (pHi), measured with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein after 20 mM NH4Cl was added to the bath or luminal perfusate. The time course of increase in pHi was calculated from 488/442 image pairs stored at a rate of 4 Hz. The apparent basolateral and apical PNH3 values of PCs were 36 +/- 5 and 113 +/- 11 microns/s, respectively. The values were 5.0 +/- 0.7 and 34 +/- 3 microns/s after membrane folding correction. The apparent basolateral and apical PNH3 values of ICs were 38 +/- 6 and 132 +/- 15 microns/s. Corrected for membrane folding, the values were 9.0 +/- 1.0 and 47 +/- 5 microns/s, respectively. The results demonstrate that the apical surface was more permeable than the basolateral surface in both cell types. In addition, ICs were more permeable to NH3 than PCs across both membranes. The transcellular PNH3 of PCs and ICs were 27.3 and 29.5 microns/s, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1994

Functional characterization of three intercalated cell subtypes in the rabbit outer cortical collecting duct.

The distribution of Na(+)-independent Cl(-)-HCO3- exchange was studied in individual intercalated cells from in vitro perfused rabbit outer CCDs using dual excitation laser scanning confocal microscopy by measuring the pHi response to sequential removal of Cl- from both sides of the tubule. Three patterns of intracellular pH (pHi) response were observed. 39% of intercalated cells had only apical Cl(-)-HCO3- exchange (beta cell), 4% had only basolateral Cl(-)-HCO3- exchange (alpha cell), and 57% had both apical and basolateral Cl(-)-HCO3- exchange (gamma cell). Valinomycin-high K+ voltage clamping had no effect on the pHi response of intercalated cells with bilateral Cl(-)-HCO3- exchange. Although the mean rates of dpHi/dt following apical Cl- removal were similar in beta cells compared to gamma cells, a wide range of apical rates was seen among individual beta and gamma intercalated cells. Neither the apical nor the basolateral Cl(-)-HCO3- exchanger in gamma cells was inhibited by 0.5 mM H2DIDS. Binding of apical peanut lectin was seen both in beta cells and in gamma cells. In 41% of CCDs with four to seven intercalated cells studied, all intercalated cells were of the same subtype. We conclude that the majority of intercalated cells from the rabbit outer CCD have both apical and basolateral Na(+)-independent Cl(-)-HCO3- exchangers (gamma cells), which are stilbene-insensitive. Intercalated cells with only basolateral Cl(-)-HCO3- exchange are very uncommon in the rabbit outer CCD. There is a tendency for all intercalated cells in a given rabbit outer CCD to be of the same subtype (either all beta cells or all gamma cells), suggesting the presence of CCD intertubule heterogeneity at the same cortical level. This finding may account for intertubule differences in transepithelial H(+)-base transport.

Animals↗
PubMed1994

Mechanism of apical and basolateral Na(+)-independent Cl-/base exchange in the rabbit superficial proximal straight tubule.

The present study was undertaken to determine the magnitude and mechanism of base transport via the apical and basolateral Na(+)-independent Cl-/base exchangers in rabbit isolated perfused superficial S2 proximal tubules. The results demonstrate that there is an apical Na(+)-independent Cl-/base exchanger on both membranes. HCO3- fails to stimulate apical Cl-/base exchange in contrast to the basolateral exchanger. Inhibition of endogenous HCO3- production does not alter the rate of apical Cl-/base exchange in Hepes-buffered solutions. Both exchangers are inhibited by H2DIDS and furosemide; however, the basolateral anion exchanger is more sensitive to these inhibitors. The results indicate that the apical and basolateral Cl-/base exchangers differ in their transport properties and are able to transport base equivalents in the absence of formate. The formate concentration in rabbit arterial serum is approximately 6 microM and in vitro tubule formate production is < 0.6 pmol/min per mm. Formate in the micromolar range stimulates Jv in a dose-dependent manner in the absence of a transepithelial Na+ and Cl- gradient and without a measurable effect on Cl(-)-induced equivalent base flux. Apical formic acid recycling cannot be an important component of any cell model, which accounts for formic acid stimulation of transcellular NaCl transport in the rabbit superficial S2 proximal tubule. We propose that transcellular NaCl transport in this nephron segment is mediated by an apical Na+/H+ exchanger in parallel with a Cl-/OH- exchanger and that the secreted H+ and OH- ions form H2O in the tubule lumen.

Animals↗
PubMed1992

Tumor necrosis factor stimulates Na+/H+ antiporter in human fibroblasts: dissociation between intracellular alkalinization and cytokine mRNA accumulation.

Several hormones and cytokines stimulate the cellular Na+/H+ antiporter and this stimulation may be a signal transduction mechanism to mediate gene expression. We find that tumor necrosis factor rapidly stimulates both the Na+/H+ antiporter and the accumulation of mRNA coding for granulocyte-macrophage colony-stimulating factor and interleukin-6 in fibroblasts. Further experiments show that these phenomena occur independent of each other.

Carrier Proteins↗
PubMed1992

Denervation inhibits early increase in Na(+)-H+ exchange after uninephrectomy but does not suppress hypertrophy.

Na(+)-H+ exchange in the rat proximal tubule luminal membrane increases approximately 30% within 15 min after the contralateral uninephrectomy. The present study was designed to test whether altered renal sympathetic nerve outflow to the remaining kidney is the underlying mechanism of increased antiport activity and whether suppression of Na(+)-H+ antiport activity by renal denervation inhibits renal hypertrophy in the remaining kidney after uninephrectomy. Sprague-Dawley rats were divided into four groups: 1) sham operated, 2) uninephrectomized, 3) uninephrectomized with prior denervation of the remaining kidney, and 4) contralateral renal denervation. Na(+)-H+ antiport activity (brush-border vesicles), Na(+)-K(+)-ATPase activity (basolateral vesicles), and kidney weight were measured days 1-7. On days 1 and 7, Na(+)-H+ antiport activity and Na(+)-K(+)-ATPase activities were significantly greater in uninephrectomized rats. Denervation of the remaining kidney before contralateral uninephrectomy prevented the stimulation of the antiporter and Na(+)-K(+)-ATPase activity, but failed to inhibit renal hypertrophy by day 7. In separate experiments, contralateral renal denervation alone without removal of the kidney stimulated the Na(+)-H+ antiporter and Na(+)-K(+)-ATPase activity. Kidney weight, however, remained unchanged. The results demonstrate a dissociation between the activation of the Na(+)-H+ antiporter and induction of renal hypertrophy in vivo.

Animals↗
PubMed1992

Stimulation of Na+/H+ exchange is not required for induction of hypertrophy of renal cells in vitro.

Hypertrophy of renal proximal tubular cells is associated with an early increase in Na+/H+ antiport activity both in vivo and in vitro. The purpose of the study presented here was to determine whether functioning Na+/H+ antiport activity is required for hypertrophy to occur. LLC-PK1 cells deficient in Na+/H+ antiport activity were prepared by the "proton-suicide" method. Mutant cells had 28 to 40% of the normal Na+/H+ antiport activity. The addition of 50 nM methylisobutylamiloride to these cells decreased the antiport activity to less than 5% of the control value. In the mutant cells, steady-state intracellular pH was normal as was the protein content. After exposure of the wild-type cells for 72 h to 10(-6) M insulin and 10(-9) M insulin-like growth factor 1, cell protein content increased significantly. The increase in protein content induced by these growth factors in the mutant cells did not differ significantly from the response of the wild-type cells. Lowering the Na+/H+ exchange further by the addition of methylisobutylamiloride (50 nM) to less than 5% of the control value did not blunt the hypertrophic response in the mutant cells. These studies indicate that hypertrophy can be induced in LLC-PK1 cells by growth factors when basal Na+/H+ antiport activity is reduced to low levels by selective mutation or by competitive inhibition. The results suggest that stimulation of the Na+/H+ antiporter is not an essential prerequisite for the induction of hypertrophy in renal cells.

Amiloride↗