Search PubMed⌕ Search

Biomedical subjects

Y H Lien

Publications and source records attributed to Y H Lien.

At least 19 recordsLinked to original sources
PubMed1997

Kinetics and osmoregulation of Na(+)-and Cl(-)-dependent betaine transporter in rat renal medulla.

Betaine is one of the major organic osmolytes that accumulate in the renal medulla in response to high extracellular tonicity. Recent studies in MDCK cells have shown that betaine is taken up by an Na(+)- and Cl(-)-dependent transporter located on the basolateral membrane. We demonstrate here the presence of Na(+)-Cl(-)-dependent betaine transporter(s) in tubule suspensions prepared from the rat outer and inner medulla. The betaine transport activity was two to three times higher in the inner medulla compared with the outer medulla. The removal of Na+ and Cl- reduced betaine uptake in the outer medullary tubules by 86% and 82%, respectively. The betaine uptake was decreased by 39% in hypotonic buffer (189 mosmol/ kgH2O) and increased by 82% in hypertonic buffer (545 mosmol/kgH2O), compared with isotonic buffer (308 mosmol/ kgH2O). Kinetic studies of Na(+)-dependent betaine uptake in the outer medullary tubules revealed both a low- and a high-affinity component as follows: low-affinity and high volume component with Michaelis constant (K(m)1) of 8.6 mM and maximal uptake rate (Vmax1) of 112 pmol.microgram protein-1.h-1; and a low-volume and high-affinity component with K(m)2 of 0.141 mM and Vmax2 of 10 pmol. microgram protein-1.h-1. To investigate whether the Na(+)-Cl(-)-dependent betaine transporter is regulated by tonicity in vivo, we quantitated its mRNA in rat renal cortex and outer and inner medulla using both canine and rat Na(+)-Cl(-)-dependent betaine transporter cDNA probes. A single band of 3.0 kb was seen in the Northern blots prepared from both outer and inner medulla, but not in the cortex. Water deprivation for 3 days increased the abundance of this mRNA in the outer and inner medulla by 140% and 170%, respectively, but did not affect its expression in the cortex. In conclusion, Na(+)-Cl(-)-dependent betaine transporter(s) is present in rat outer and inner medullary tubules, and betaine transporter mRNA abundance is regulated by the hydration state in vivo.

Animals↗
PubMed1997

Distribution of de novo synthesized betaine in rat kidney: role of renal synthesis on medullary betaine accumulation.

The trimethylamine glycine-betaine is accumulated to high concentrations in medullary cells of mammalian kidneys, whereas betaine synthesis from choline is predominant in the renal cortex. We investigated the contribution of renal betaine synthesis to medullary betaine accumulation. De novo synthesis of betaine in situ was accomplished by injecting [14C]choline into the renal artery of male Sprague-Dawley rats. [14C]betaine was measured in the renal cortex and medulla, as well as in serum and urine samples. Betaine concentration in the cortex decreased from 3.5 +/- 1.3 at 5 min to 0.4 +/- 0.2 nmol/mg protein at 60 min, but it increased from 1.4 +/- 0.1 to 2.5 +/- 0.6 nmol/mg protein in the medulla. Serum and total urine [14C]betaine increased from 2.7 +/- 1.3 and 0.9 +/- 0.1 nmol/ml at 5 min to 5.3 +/- 0.3 and 2.1 +/- 0.4 nmol/ml at 60 min, respectively. Concentrations of newly synthesized betaine were not decreased by the ligation of the hepatic artery and portal vein, suggesting that most [14C]betaine was synthesized in the kidney. Coinjection with 5 mM dimethylamino-ethanol, a choline oxidase inhibitor, and 100 mM cold betaine reduced medullary betaine accumulation by 80 and 76%, respectively. Water deprivation for 60 h increased both cortical and medullary [14C]betaine, whereas furosemide diuresis decreased the medullary [14C]betaine concentration. We concluded that betaine synthesized in the kidney can be accumulated in the medulla and that the medullary concentrations of newly synthesized betaine are closely related to the hydration state of the animal.

Animals↗
PubMed1996

Hemodialysis increases apparent diffusion coefficient of brain water in nephrectomized rats measured by isotropic diffusion-weighted magnetic resonance imaging.

The nature of brain edema in dialysis disequilibrium syndrome (DDS) was investigated by diffusion-weighted magnetic resonance imaging (DWI). DWI was performed on normal or bilaterally nephrectomized rats before, and immediately after, hemodialysis. Hemodialysis was performed with a custom-made dialyzer (surface area 150 cm2) against a bicarbonate-buffered bath for 90 min with or without 70 mM urea. Hemodialysis with non-urea bath decreased plasma urea by 21 mM, and plasma osmolality by 22 mosmol/kg H2O, and increased brain water content by 8.0% (all < 0.05), while hemodialysis with urea bath did not affect plasma urea, osmolality, or brain water content. Three sets of axial DWI images of the brain were obtained at different gradient weighing factors with an in-plane resolution of 0.39 mm2. The apparent diffusion coefficient (Dapp) of the brain water was not affected by bilateral nephrectomy, or by hemodialysis in normal rats. In nephrectomized rats, brain Dapp was significantly increased after dialysis with non-urea bath (1.15 +/- 0.08 vs 0.89 +/- 0.07 x 10(-9)m2/sec, P < 0.01). No significant changes of brain water Dapp could be observed after dialysis with urea bath. The increased Dapp associated with DDS indicates that brain extracellular water increases and/or intracellular water decreases after hemodialysis. Our results strongly suggest that the brain edema induced by hemodialysis in uremic rats is due to interstitial edema rather than cytotoxic edema. Furthermore, our results support a primary role for the "reverse urea effect" in the pathogenesis of brain edema in DDS.DWI may be a useful diagnostic tool for DDS in patients with end-stage renal disease.

Animals↗
PubMed1996

Low dose megestrol increases serum albumin in malnourished dialysis patients.

To evaluate the efficacy of low dose megestrol on malnourished dialysis patients we treated 16 dialysis patients with persistent hypoalbuminemia ( < 3.5 gm/dl for 2 consecutive months) and adequate dialysis at a dose of 20 mg orally twice daily. Twelve patients on peritoneal dialysis and 4 on hemodialysis were followed for 4.3 +/- 0.6 m (2-11 m). Within one month serum albumin rose from 2.7 +/- 0.1 to 3.0 +/- 0.2 gm/dl (p < 0.05) and remained elevated at the end of follow-up (3.1 +/- 0.2, p < 0.05 vs. pre-treatment levels). In the 12 responders (increase of albumin > 0.3 gm/dl), all of whom reported improved appetite, the maximal increase of serum albumin in 2 months was 0.8 +/- 0.1 gm/dl (range: 0.3-1.2). Four patients did not respond (change of albumin: -0.05 +/- 0.18, range: -0.6-0.2) because of encephalopathy, amyloidosis, depression or noncompliance. One patient stopped megestrol because of vaginal bleeding from uterine leiomyoma. Three patients died from causes unrelated to the megestrol. Our preliminary study suggests that low dose megestrol (40 mg per day) increases serum albumin levels in 75% of dialysis patients with malnutrition. It is well tolerated but may cause vaginal bleeding from uterine tumors.

Administration, Oral↗
PubMed1995

Modulation of intracellular Ca2+ by glucose in MDCK cells: role of endoplasmic reticulum Ca(2+)-ATPase.

Intracellular free calcium ([Ca2+]i) has multiple functional roles in renal epithelia, including mediating ligand- and volume-activated K+ and Cl- channels, modulating the permeability of apical membrane to Na+, and regulating tubuloglomerular feedback. We investigated glucose effects on intracellular pH (pHi) and [Ca2+]i in Madin-Darby canine kidney (MDCK) cells using fluorescent probes, SNARF-1 and fura 2, respectively. The addition of glucose decreased both pHi and [Ca2+]i in a dose-dependent fashion. Thapsigargin (TG) and cyclopiazonic acid (CPA), well-known endoplasmic reticulum (ER) Ca(2+)-adenosinetriphosphatase (Ca(2+)-ATPase) inhibitors, abolished the glucose-induced [Ca2+]i decrease. Without glucose, 1 microM TG induced a sustained elevation in [Ca2+]i, which increased further with glucose addition, whereas 15 microM CPA induced a transient increase in [Ca2+]i that was not affected by further addition of glucose. The sustained elevation in [Ca2+]i induced by TG was dependent on extracellular Ca2+. TG-induced [Ca2+]i increase was modulated by glucose, i.e., at higher glucose concentrations, TG induced a larger and more rapid rise in [Ca2+]i. We conclude that glucose has dual effects on [Ca2+]i regulation. Glucose alone reduces [Ca2+]i by activating ER-type Ca(2+)-ATPase, since this phenomenon is TG and CPA sensitive. In the presence of TG, glucose increases [Ca2+]i probably by increasing Ca2+ entry. Our data suggest a model in which TG activates capacitative Ca2+ entry by depletion of the ER Ca2+ pool. Glucose increases TG-induced [Ca2+]i elevation by further enhancing capacitative Ca2+ entry.

Animals↗
PubMed1995

Role of organic osmolytes in myelinolysis. A topographic study in rats after rapid correction of hyponatremia.

Organic osmolytes have been implicated in the pathogenesis of myelinolysis because some of them are accumulated slowly during correction of chronic hyponatremia. I investigated whether there was a topographic correlation between demyelinative lesions and the regional changes of organic osmolytes after rapid correction of chronic hyponatremia. In normal female Sprague-Dawley rats, concentrations of glutamate, glutamine, taurine, and betaine were highest in the cerebral cortex and decreased toward the brain stem. Conversely, glycine level was highest in the brainstem, and decreased toward the cortex. Myoinositol, glycerophosphorylcholine, glycerophosphorylethanolamine, and creatine were distributed more evenly. In chronic hyponatremic rats (plasma Na 110 +/- 4 meq/liter), organic osmolytes decreased globally with the total loss ranging from 13 (medulla) to 24 (cerebellum) mmol/kg H2O. After rapid correction with intraperitoneal injection of hypertonic saline, the recovery of the loss of organic osmolytes was 48% in the cerebral cortex, cerebellum, and medulla oblongata, 44% in pons, but only 17% in midbrain and 36% in striatum. Histopathology of the brain was examined in nine rats 2-7 d after correction of hyponatremia. Large demyelinative lesions were seen persistently in the midbrain and striatum, and smaller lesions in cerebrum, cerebellum, and pons were found less frequently. This is the first report of regional distribution of brain organic osmolytes. After rapid correction of chronic hyponatremia, a topographic correlation between demyelination lesions and delayed accumulation of organic osmolytes exists.

Animals↗
PubMed1995

Acute renal failure in membranous glomerulonephropathy: a result of superimposed crescentic glomerulonephritis.

A patient who presented with acute renal failure and anasarca secondary to crescentic glomerulonephritis superimposed on existing membranous glomerulonephropathy of 15 years' duration is described. The patient responded to an initial course of prednisone but failed to respond to a second course after relapse. The differential diagnosis of acute renal failure in the setting of nephrotic syndrome is discussed. Eighteen cases of crescentic glomerulonephritis superimposed on membranous glomerulonephropathy are reviewed. The clinical setting is heterogeneous with variable presentation and outcome. It appears that patients without antiglomerular basement membrane antibodies have a better prognosis than those who have antibodies. Patients with membranous glomerulonephropathy who develop unexplained acute renal failure should undergo early renal biopsy in order to rule out unexpected pathologic complications.

Acute Kidney Injury↗
PubMed1994

Scyllo-inositol depletion in hepatic encephalopathy.

Cerebral myo-inositol depletion is found in patients with hepatic encephalopathy and can be implicated in the pathogenesis of hepatic encephalopathy. We measured scyllo-inositol, a stereoisomer of myo-inositol, in brain extracts from patients dying in hepatic coma using HPLC and high resolution 1H MRS. The cerebral scyllo-inositol concentration, determined by both methods, in patients without hepatic encephalopathy was 0.41 +/- 0.11 mmol/kg wet weight. It decreased by 73% and 76%, respectively, as measured by HPLC and 1H MRS, in patients with hepatic encephalopathy. These findings indicate that myo-inositol depletion in patients with hepatic encephalopathy is not due to enhanced conversion of myo-inositol to scyllo-inositol or inhibition of myo-inositol transport by scyllo-inositol, but rather to the reduced biosynthesis or transport of both inositols.

Autopsy↗
PubMed1994

Bicarbonate dependency of betaine synthesis in cultured LLC-PK1 cells.

Betaine, one of the major renal organic osmolytes, is synthesized from choline by choline dehydrogenase (EC 1.1.99.1) and betaine-aldehyde dehydrogenase (EC 1.2.1.8) in the kidney. A recent in vitro study has shown that betaine synthesis by renal cortical homogenate is dependent on millimolar amounts of bicarbonate. The present study was aimed to investigate the bicarbonate dependency of betaine formation in cultured LLC-PK1 cells. The data show that betaine formation increases in accordance with a rise in extracellular bicarbonate levels. The measured quantities of [14C]betaine synthesis ranged from 13.4 +/- 1.5 (4.6 mM HCO3-) to 38.0 +/- 1.4 pmol.micrograms protein-1.h-1 (24 mM HCO3-). The carbonic anhydrase inhibitor acetazolamide, added to the incubation medium to block bicarbonate transport, reduced betaine synthesis from choline by 41-49%. We conclude that betaine synthesis in LLC-PK1 cells is dependent on extracellular bicarbonate levels and is reduced by the inhibition of carbonic anhydrase. Because betaine accumulates in renal medulla during antidiuresis, our observations suggest a possible link between acid-base homeostasis and concentration mechanisms in the kidney.

Acetazolamide↗
PubMed1993

Decrease in cerebral inositols in rats and humans.

Rats with portacaval shunts and humans with hepatic encephalopathy show severe myo-inositol depletion in the brain. The portacaval-shunted rat may therefore be a useful model for the investigation of neurochemical pathways containing myoinositol, which are modulated not only in hepatic encephalopathy but also in diabetes mellitus and Alzheimer's disease.

Animals↗
PubMed1993

Dimethyl methylphosphonate (DMMP): a 31P nuclear magnetic resonance spectroscopic probe of intracellular volume in mammalian cell cultures.

Dimethyl methylphosphonate (DMMP), when added to a suspension of erythrocytes, has been reported to have a lower frequency chemical shift inside of cells than outside. This work further investigates the same phenomenon in hollow-fiber bioreactor cultures of six mammalian cell lines and describes the application of DMMP as a measure of intra- versus extracellular volumes in mammalian cell cultures. No toxic effects of the DMMP were observed at the concentrations used here. The dependence of the shift of intracellular DMMP on intracellular protein content was shown to be similar for cultured mammalian and red blood cells. Also consistent with shifts in erythrocytes, an increase in the intracellular protein concentration due to a reduction in cultured cell volume increased the magnitude of the shift to lower frequency. Longitudinal relaxation (T1) values for intra- and extracellular DMMP were measured so that partially saturated DMMP peaks in 31P NMR spectra of mammalian cell cultures can be corrected to give the relative volumes of the intra- and extracellular compartments; this information provides a relative measure of culture growth. Intracellular volume measured by this method can also be used to quantify intracellular metabolites such as ATP during the growth of the culture. To explore the mechanism behind the intracellular shift, we have also addressed the three possible contributions to the chemical shift of DMMP: hydrogen-bonding interactions, magnetic susceptibility, and ionic strength. Data is presented which eliminates the latter two mechanisms and strongly supports the hypothesis that the observed intracellular shift is due to a reduction in hydrogen bonding between water and DMMP in the cytoplasm.

Animals↗
PubMed1993

Ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis.

Ciprofloxacin is known to cause acute interstitial nephritis. We report the first case of ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis. The patient presented with acute renal failure and skin lesions following a 14-day course of ciprofloxacin administered for cellulitis. The patient had symmetric, palm-sized, tender violaceous plaques on both axillae. The renal biopsy revealed granulomatous interstitial disease. A skin biopsy revealed an elastolytic process with histocytic infiltration and calcification. After discontinuing ciprofloxacin and starting a short course of steroid therapy, the skin lesion and renal function improved promptly. The nephritis relapsed after prednisone was discontinued and responded to a second course of steroid therapy. Ciprofloxacin, like penicillin, can cause granulomatous interstitial nephritis and elastolysis. A prolonged course of steroid therapy may be indicated in patients with ciprofloxacin-induced granulomatous interstitial nephritis to avoid early relapse.

Ciprofloxacin↗
PubMed1993

Association of cyclosporin A with acquired cystic kidney disease of the native kidneys in renal transplant recipients.

Acquired cystic kidney disease (ACKD) is a common complication in patients treated with long-term dialysis. Previous studies performed prior to the cyclosporin A (CsA) era indicate that successful renal transplantation causes regression of ACKD. Little has been published, however, on the occurrence of ACKD in CsA-treated transplant recipients. We conducted a prospective sonographic study in 33 renal transplant recipients and 32 dialysis patients to evaluate the effect of CsA on ACKD in transplant recipients. Transplant recipients had a lower prevalence (39% vs. 56% in dialysis patients) and severity (smaller kidneys and lower cyst grades) of ACKD when compared with dialysis patients. Renal cell carcinoma was found in two dialysis patients. Using multiple regression analysis, we found that the use of CsA was significantly correlated with the presence of ACKD in transplant recipients (57% in CsA-treated vs. 8% in non-CsA-treated patients). We conclude that renal transplantation reduces the prevalence and severity of ACKD in the native kidneys; however, among transplant patients, CsA administration is associated with a greater prevalence of ACKD.

Adult↗
PubMed1993

Characterization of organic osmolytes in avian renal medulla: a nonurea osmotic gradient system.

We measured the organic osmolytes present in the renal cortex and medullary cones of adult female domestic fowl before and after 48 h of water deprivation. Urine osmolality increased from 198 +/- 82 to 569 +/- 42 mosmol/kgH2O after water deprivation. In water-deprived birds, the major organic osmolytes, myoinositol, betaine, and taurine, in the medullary cones increased by 40, 100, and 24%, respectively, compared with control birds. No sorbitol was detected, and glycerophosphorylcholine (GPC) content was not affected by water deprivation. In the renal cortex, only betaine content increased significantly (4.8 +/- 0.6 vs. 3.1 +/- 0.3 mmol/kg wet wt) after water deprivation. In this study, we demonstrated that birds, like mammals, accumulate organic osmolytes in response to the increased interstitial osmolality that occurs during antidiuresis. Because urea is nearly absent in the avian medullary interstitium, our observation that GPC is not osmoregulated in the avian kidney supports the idea that GPC is the "counteracting osmolyte" for urea in the mammalian kidney. Furthermore, the organic osmolytes present in avian medullary cones are remarkably similar to those of the mammalian outer medulla. This similarity may be relevant to the morphological analogy of the two regions.

Animals↗
PubMed1993

Effect of intradialytic parenteral nutrition on quality of life in hemodialysis patients.

The purpose of this study was to determine the effect of intradialytic parenteral nutrition (IDPN) on the quality of life of malnourished patients with end-stage renal disease on high-efficiency and high-flux hemodialysis therapy. Patients, who met the Medicare eligibility requirements for IDPN, were asked to fill out and extensive questionnaire covering several measures of quality of life prior to initiating and again after completing four months of IDPN therapy. Although the IDPN improved serum albumin levels significantly, aside from improved sleep patterns, no significant improvements in quality of life could be demonstrated. The mortality rate of these enrolled patients was as high as 28% within 4 months. We concluded that the limited amount of nutrition delivered over the course of a short dialysis session may not be enough to appreciably change the lives of our malnourished patients.

Female↗
PubMed1992

Glucose and glucose analogs modulate collagen metabolism.

Patients with diabetes often develop complications involving collagen-containing connective tissues. Previous in vitro studies have demonstrated that glucose inhibits collagen fibril formation and subsequent cross-linking. Collagen with diminished cross-linking is more susceptible to collagenolytic degradation. This may underlie the decreased collagen levels. To test this hypothesis, D-glucose and its two analogs, L-glucose and 2-deoxy-D-glucose, were used in chick calvaria organ cultures to examine parameters of collagen metabolism. L-Glucose is not used by the cell and functions as an extracellular glucose-like molecule, while 2-deoxy-D-glucose inhibits normal D-glucose uptake by blockading the glucose transport mechanism. Each of these three sugars had the ability to inhibit collagen fibril formation. D-Glucose stimulated collagen synthesis; L-glucose had no effect; and deoxyglucose inhibited collagen synthesis. D-Glucose was able to reverse the inhibitory effect of deoxyglucose. D-Glucose did not change levels of degradation of newly synthesized collagen while both L-glucose and deoxyglucose stimulated collagen degradation. When glucose transport was inhibited by deoxyglucose, collagen degradation was further enhanced. We suggest that decreased collagen levels in the connective tissues of diabetics may result from a combination of inhibition of collagen fibril formation and subsequent cross-linking, as well as increased collagen degradation.

Animals↗
PubMed1991

Metastatic renal cell carcinoma associated with acquired cystic kidney disease 15 years after successful renal transplantation.

Renal cell carcinoma (RCC) is a relatively uncommon cancer in renal transplant patients. From 1968 to 1987, 101 cases of RCC of native kidneys have been reported to the Cincinnati Transplant Tumor Registry. We describe here a case of metastatic RCC associated with acquired cystic kidney disease (ACKD) 15 years after successful renal transplantation. The patient presented with a subcutaneous nodule, which led to discovery of a large primary tumor in the left kidney. ACKD was present in the atrophic right kidney. The reported cases of ACKD-associated RCC in renal transplant recipients were reviewed. Most of these cases are middle-aged men with a long posttransplant course, good graft function, and usage of azathioprine and prednisone as immunosuppressive agents. ACKD can develop or persist and progress to RCC many years after successful renal transplantation. Transplant patients with flank pain, hematuria, or other suspicious symptoms should have imaging studies of their native kidneys.

Adult↗