Biomedical subjects

H D Kim

Publications and source records attributed to H D Kim.

At least 73 records · Page 4Linked to original sources

PubMed1998

Brain abscess and necrotic or cystic brain tumor: discrimination with signal intensity on diffusion-weighted MR imaging.

OBJECTIVE: The purpose of this study was to determine the differences in signal intensity between brain abscesses and necrotic or cystic tumors on diffusion-weighted MR imaging. CONCLUSION: Five consecutive patients with proven brain abscesses and four patients with proven cystic or necrotic brain tumors were prospectively evaluated with diffusion-weighted imaging. On diffusion-weighted imaging, brain abscesses showed markedly hyperintense signal in all five patients, whereas necrotic or cystic brain tumors revealed hypointense signal in all four patients. Diffusion-weighted imaging may allow the differentiation of brain abscess from necrotic or cystic brain tumor.

Adolescent↗

PubMed1998

Evidence of protein kinase C translocation by ischemic preconditioning in global ischemia model.

We tested recent evidence that ischemic preconditioning (PC) involves in translocation of protein kinase C (PKC) from the cytosol to myocyte membrane. Isolated Langendorff-perfused rabbit hearts (n=96) were subjected to 60 or 45 min of ischemia (I) and 120 min of reperfusion (R) with or without PC (4 cycles of 5 min I and 5 min R; or single dose of 5 min I and 10 min R), respectively. Left ventricular function and infarct size (IS) were measured; myocardial cytosolic and membrane PKC activity were determined by 32P-gamma-ATP incorporation into PKC-specific peptide. PC enhanced improvement of functional recovery and reduced IS (26.9+/-1.4% versus 15.3+/-1.9%, p<0.01, in 60 min of I; 18.3+/-2.6% versus 8.6+/-2.5%, p<0.05, in 45 min of I); cytosolic PKC activity decreased 74% of total activity (p<0.05) both in 60 and 45 min of I; membrane PKC activity increased (1.7-fold of baseline, p<0.01, in 60 min of I; 1.8-fold, p<0.01, in 45 min of I; 1.5-fold, p<0.05, in 60 of min I and 120 min of R). From these results, it is concluded that translocation of PKC from the cytosol to myocyte membranes is an important mechanism responsible for PC effect.

Animals↗

PubMed1998

In vivo single-voxel proton MR spectroscopy in intracranial cystic masses.

PURPOSE: Our objective was to evaluate the proton MR spectroscopic pattern of the cystic contents of various intracranial masses and to report characteristic spectral patterns that may be helpful in the differential diagnosis of these lesions. METHODS: We evaluated 40 proton MR spectra obtained from cystic contents of various intracranial cystic masses in 39 patients, including gliomas (n = 14), metastases (n = 3), abscesses (n = 8), cysticercosis (n = 4), epidermoids (n = 3), and others (n = 7). Proton MR spectroscopy was performed on a 1.5-T MR unit using a point-resolved spectroscopic sequence with a 2 x 2 x 2 cm3 volume of interest. Assignment of the resonance peaks was based on previous studies. RESULTS: Adequate proton MR spectroscopic data were obtained in 35 cases (88%). In most gliomas and metastases, only a lactate resonance was observed. There was a trend toward a higher lactate peak in high-grade gliomas. A few tumors, including malignant gliomas and metastases, showed lipid signal combined with lactate signal. In abscesses, there were various combinations of lactate, acetate, succinate, amino acids (including valine, alanine, and/or leucine), and/or unassigned resonances. In cysticercosis, resonances of lactate, succinate, alanine, acetate, and/or unassigned resonances were observed. Three epidermoid cysts showed only lactate signal. There were no identifiable resonances from the arachnoid and porencephalic cysts. CONCLUSION: Only lactate is commonly observed in a variety of intracranial cystic masses, except for abscess and cysticercosis, in which resonances of acetate, succinate, amino acids, and/or unassigned metabolites can be seen in addition to a lactate peak.

Adult↗

PubMed1998

MR of hippocampal sclerosis: comparison of qualitative and quantitative assessments.

PURPOSE: Our goal was to compare the diagnostic accuracy of subjective visual assessment versus MR volumetry in evaluating hippocampal sclerosis and to determine whether MR volumetry is needed in the lateralization of this disease process. METHODS: MR imaging findings were studied retrospectively in 48 patients who underwent surgery for temporal lobe epilepsy and were compared with findings at MR volumetry on an Allegro workstation. Both visual assessment and volumetry were carried out in a blinded fashion with oblique coronal T1-weighted three-dimensional MP-RAGE images obtained on either 1.0-T or 1.5-T units. Normal right-left volumetric differences were recorded in 30 control subjects. The optimum cutoff threshold value for right-left volumetric differences in the sensitivity and specificity of volumetric measurement was obtained from receiver operating characteristic analysis. RESULTS: Sensitivity, specificity, positive and negative predictive values, and accuracy of visual assessment were 86%, 83%, 86%, 83%, and 85%, respectively. For MR volumetry, with the optimum cutoff threshold value of right-left difference at 0.3 cm3, sensitivity, specificity, positive and negative predictive values, and accuracy were 81%, 82%, 87%, 83%, and 85%, respectively. CONCLUSION: Visual assessment was slightly superior to or similar to MR volumetry in assessing unilateral hippocampal sclerosis. MR volumetry of the hippocampus may not be needed for the evaluation of most cases of suspected hippocampal sclerosis.

Adolescent↗

PubMed1997

Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, enhances LPS-induced NO production from murine peritoneal macrophages.

To elucidate the role of phosphatidylinositol-3-kinase (PI3K) during macrophage activation, we examined the effects of wortmannin, a specific inhibitor of PI3K, on the induction of nitric oxide (NO) synthesis and tumor necrosis factor-alpha (TNF-alpha) secretion from lipopolysaccharide (LPS)-stimulated macrophages. Wortmannin had no effects on NO synthesis and TNF-alpha secretion by itself. Wortmannin markedly potentiated the LPS-induced NO production in a dose-dependent manner. Western blot analysis demonstrated that significantly increased levels of iNOS protein were expressed in LPS-stimulated macrophages treated with wortmannin, compared to those without LPS. Furthermore, enhancement of TNF-alpha secretion was observed in the initiation stage for activation of LPS-stimulated macrophages treated with wortmannin. These results suggest that PI3K plays an important role in transducing the signal that is involved in LPS-induced macrophage activation.

Androstadienes↗

PubMed1997

Cyclic AMP analogue as a triggering signal for the induction of nitric oxide synthesis in murine peritoneal macrophages.

To understand the role of cAMP during macrophage activation, we investigated the effects of various cAMP analogues in the induction of nitric oxide (NO) synthesis in murine peritoneal macrophages. Intracellular cAMP modulators such as N6,O2'-dibutyryl cyclic AMP (DB-cAMP), 8-bromo-cAMP, or 8-chloro-cAMP had no effect on NO synthesis by themselves, whereas cAMP analogues in combination with interferon-gamma (IFN-gamma) had a marked cooperative induction of NO synthesis in a dose-dependent manner. This increase in NO synthesis was reflected as an increased amount of inducible NO synthase mRNA, as determined by Northern blotting. To find the point in the signaling pathways of macrophage activation at which cAMP is involved, we carried out several of the following experiments. Although DB-cAMP showed synergistic action with rIFN-gamma to induce NO synthesis when the cells were treated with DB-cAMP after or with simultaneous treatment with rIFN-gamma, there is no synergistic induction of NO synthesis when the cells were treated with DB-cAMP 6 hr before treatment with rIFN-gamma. In addition, when phorbol 12-myristate 13-acetate (PMA), which is known to provide a triggering signal in the induction of NO synthesis in murine macrophages, was added to the cells 6 hr after the treatment with DB-cAMP, PMA showed no synergistic cooperation with DB-cAMP. On the other hand, DB-cAMP alone induced the release of NO to the incubation medium from bacillus Calmette-Guerin-infected peritoneal macrophages just as lipopolysaccharide (LPS) did. However, DB-cAMP, unlike LPS, decreased the secretion of tumor necrosis factor-alpha from IFN-gamma-treated macrophages. Based on the results obtained in this study, we suggest that cAMP analogue could give a "triggering" signal which might be different from one given by LPS in the production of NO by primed macrophages.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1997

A novel 90-kDa stress protein induced in fish cells by fish rhabdovirus infection.

A 90 kDa cellular protein in a fish cell, CHSE-214, showed increased expression by the infection of infectious hematopoietic necrosis virus (IHNV), heat shock, 2-mercaptoethanol, copper sulfate, and cadmium sulfate, and was detected in various kinds of cells such as human, rat, and mouse cells. The molecular mass of the 90 kDa protein was different from those of the hsp90 and grp94. In addition, all the anti-stress protein MAbs did not react with the 90 kDa protein. Finally, the subcellular distribution of the 90 kDa protein, determined by Western blots of subcellular fractions, was found to be mainly nuclear, both in normal and IHNV-infected CHSE-214 cells. The present results indicate that the 90 kDa protein is a kind of stress protein. However, based on its molecular mass, antigenic characteristics, and subcellular distribution, it is likely that this protein is a novel stress protein that has not been previously described in animal systems, especially in fish systems.

Animals↗

PubMed1997

Re-evaluation of optimal dose of contrast medium for vascular enhancement in CT of the head and neck.

Adequate contrast enhancement of major neck vessels is more important than that of a tumour itself in CT of most head and neck tumours because of differentiation from neck node metastases. Our purpose was to re-evaluate the dosage of contrast medium for adequate vascular enhancement in CT of the head and neck. In a blind prospective fashion, 60 patients with a variety of head and neck lesions were randomised into three equal groups receiving 0.75, 1.0, or 1.25 ml/kg of meglumine ioglycate, 300 mg/ml. Contrast medium was administered by injector at 2 ml/s. The scan time and interscan delay were each 1 s, and total scan time 50-180 s. The scan was started immediately after administration of two-thirds of the contrast medium. The degree of vascular enhancement was assessed visually and quantitatively. We visually scored the degree of vascular enhancement as excellent (4 points), good (3), fair (2) or poor (1). For quantitative study, after measuring the CT numbers of the common or internal carotid artery (CA), internal jugular vein (IJV) and adjacent muscle at three levels, were calculated mean vessel/muscle contrast ratios. The degree of enhancement of the CA and IJV tended to increase with dose of the contrast media, but no examination was rated as showing poor enhancement in any group. The mean visual assessment scores for 0.75, 1.0, and 1.25 ml/kg were 2.7, 2.9 and 3.1, respectively; the mean ICA/muscle contrast ratios were 1.58, 1.55 and 1.63, and those of IJV/ muscle 1.65, 1.59 and 1.59. There was no significant difference between visual and quantitative assessment in any group. The results suggest that 0.75 ml/kg of contrast medium appears sufficient for vascular opacification for head and neck lesions when the CT scan can be completed in about 120 s.

Adolescent↗

PubMed1997

Human osteoblast response in vitro to platelet-derived growth factor and transforming growth factor-beta delivered from controlled-release polymer rods.

The purpose of this work was (1) to develop extrudable ethylene-vinyl acetate (EVA) copolymer delivery systems capable of sustained release of bioactive proteins and (2) to determine the effect of platelet-derived growth factor (PDGF-BB) and/or transforming growth factor-beta2 (TGF-beta2) on human osteoblast proliferation and differentiation. Human osteoblasts were plated in vitro and proliferation and protein synthesis assayed at 48 and 96 h. EVA-PDGF rods releasing about 34 ng per ml PDGF per day produced a dramatic early increase in osteoblast proliferation and no effect on protein synthesis. EVA-TGF-beta2 rods releasing about 23 ng per ml per day increased protein synthesis but had no effect on proliferation. PDGF and TGF-beta2 together resulted in moderate increases in proliferation and a marked increase in protein synthesis. Morphologically, PDGF-treated cells became confluent as early as 48 h, while TGF-beta2-treated cells formed into nodules. This work shows that (1) it is possible to deliver physiological levels of bioactive proteins from an extrudable EVA delivery system, and (2) bone cell response is dependent on the sequence and timing of delivery. Controlled-release delivery systems which mimic injury-induced healing cascades may be useful in evaluating the role of various molecules in osseous repair.

Biocompatible Materials↗

PubMed1997

Sensitivity of a seizure activity detection computer in childhood video/electroencephalographic monitoring.

PURPOSE: Few data describe the sensitivity of a "Seizure Activity Detection Computer" (SzAC) in childhood video/EEG (VEEG) monitoring, especially for very young children. We examined the accuracy of SzAC in childhood VEEG monitoring in different pediatric age groups. METHODS: We visually analyzed VEEG monitoring samples for randomly designated subsets of 56 patients with childhood epilepsy, reviewing 335 visually detected electrographic seizures to analyze the sensitivity of SzAC for each age group as well as the electrographic characteristics affecting the sensitivity of automated computer-based seizure detection. RESULTS: SzAC was positive in 227 of 335 (67.8%) visually identified electrographic seizures in the entire study group. The SzAC sensitivity for infants (age 2 months to 2 years) was 59.7% (43 of 72 seizures); for young children (age 3-10 years), sensitivity 56.5% (91 of 161 seizures). In adolescents (age 11-18 years), SzAC was positive in 93 of 102 (91.2%) seizures--i.e., in a significantly greater number of seizures than in younger age groups. SzAC was significantly less sensitive in detecting electrographic seizures characterized as being of short duration or of low voltage. CONCLUSIONS: The overall sensitivity of SzAC in detecting childhood electrographic seizures was 67.8%. The sensitivity was significantly less in younger age groups as compared with that in children aged >11 years. Electrographic seizures of relatively short duration or low voltage were often missed by SzAC.

Adolescent↗

PubMed1997

Differential diagnosis of cervical lymphadenopathy: usefulness of color Doppler sonography.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of color Doppler sonography in differentiating benign from malignant cervical lymphadenopathy. MATERIALS AND METHODS: We used color Doppler sonography to evaluate 117 lymph nodes in 105 patients. The patients were pathologically and clinically confirmed to have benign reactive lymphadenitis (n = 28), tuberculosis (n = 17), lymphoma (n = 14), and metastasis (n = 46). The patterns of hilar vascularity, central nodal vascularity, and peripheral vascularity were assessed. The highest resistive index and pulsatility index in 116 lymph nodes were measured from spectral waveforms. Histologic findings of nodal vessels were analyzed in 14 nodes and compared with findings on color Doppler sonograms. RESULTS: Thirty-two (94%) of 34 nodes with benign reactive disease showed normal patterns of nodal vascularity; central hilar vascularity, radial symmetric central vascularity, and no peripheral vascularity. At least one of six abnormal patterns of vascularity (eccentric or absent hilar vascularity; deformed radial, aberrant multifocal, or absent central vascularity; and peripheral vascularity) was observed in 98% (65/66) of nodes with malignant disease and in all tuberculous nodes. We established cutoff values of 0.8 for the resistive index and 1.5 for the pulsatility index that were 100% specific for malignancy. However, sensitivities for these cutoff values were 47% and 55%, respectively. Also, histologic examinations showed that most flow signals in nodes with malignant disease represented arterioles or veins in the septa between tumor nests or near the capsule. CONCLUSION: Unlike nodes with benign reactive disease, 98% of nodes with malignant disease and 100% of tuberculous nodes showed abnormal patterns of nodal vascularity. Also, high values for the resistive and pulsatility indexes were highly specific for malignant lymphadenopathy. Color Doppler sonography combined with analysis of spectral waveforms was useful in differentiating benign from malignant cervical lymphadenopathy.

Adolescent↗

PubMed1997

Kikuchi disease: CT and MR findings.

Two cases of Kikuchi disease showed variable nodal enhancing features, including homogeneous enhancement and focal or extensive nodal necrosis on contrast-enhanced CT scans. At MR imaging, the area of central necrosis was isointense or hypointense on T1-weighted images and had a lower signal than nonnecrotic areas on T2-weighted images. The CT appearance of Kikuchi disease can be variable and can mimic not only lymphoma but various nodal diseases with nodal necrosis, including metastasis and tuberculosis.

Adult↗

PubMed1996

Glucose-regulated stresses cause decreased expression of cyclin D1 and hypophosphorylation of retinoblastoma protein in human cancer cells.

Glucose-regulated stress response of cancer cells occurs during the growth of solid tumors and is induced in culture by treatments with various agents, including 2-deoxyglucose, glucosamine, and calcium ionophore A23187. We previously reported that the three stressors commonly induced cell-cycle arrest in the G1 phase and resistance to antitumor drugs in human cancer A2780 and HT-29 cells. In this study, we investigated the mechanisms of stress-induced G1 arrest by determining the expression of cell-cycle-regulating proteins. Among G1 cyclins and cyclin-dependent kinases (cdk) examined, the expression levels of cyclin D1 preferentially decreased in the stressed cells. A time-course study showed that the decrease in cyclin D1 coincided with the appearance of hypophosphorylated retinoblastoma protein (pRb), which is the growth suppressive form. These findings suggest that the stress-induced G1 arrest is mediated through the down-regulation of cyclin D1-associated kinases (cdk4/6), pRb kinases during G1 phase. This was also supported by decreased cdk4 expression in stressed HT-29 cells. In addition, p21WAF1, a cdk inhibitor, was induced in the stressed cells, particularly A23187-treated cells. A23187, compared with the other stressors, caused extreme pRb hypophosphorylation, suggesting that p21WAf1 is involved in the regulation of pRb phosphorylation in the stressed cells. Our present findings could explain a molecular-based mechanism of a growth-arrested quiescent state and also resistance to chemotherapy of solid tumor cells.

Calcimycin↗

PubMed1996

Expression of intermediate filament desmin and vimentin in the human fetal heart.

BACKGROUND: The intermediate filament (IF) desmin provides support for contractile machinery in muscle cells, and vimentin plays an important role in maintaining the stability of mesenchymal cells and in signal transduction. However, development of IFs in heart tissue during intrauterine life in human is not well established. METHODS: In the present study, development of desmin and vimentin in human fetal hearts aged 9-28 weeks of gestation (n = 41) were investigated by immunohistochemistry with monoclonal antibodies against desmin and vimentin. Relative density of fluorescence of each sample was determined by densitometry. Left ventricle (LV) tissues from a 1-year-old child (n = 1) were examined by immunohistochemistry for postnatal comparison. Western blot analyses were done with only a few randomly selected LV tissues from fetuses of 9, 20, and 28 weeks gestation to assess trends of desmin and vimentin expression. RESULTS: By Western blot analyses, 53-kDa desmin and 54-kDa vimentin were present in all fetal heart tissues examined. Desmin intensity was progressively increased with increasing fetal age, whereas vimentin intensity decreased. Desmin was present only in cardiomyocytes. In the earlier period (10-14 weeks gestation), desmin was localized along the cardiomyocyte membrane and/or Z lines in regular intervals, and later (25-28 weeks gestation) it was structurally well integrated; however, its network was incomplete. Only cardiomyocytes from a 1-year-old child revealed highly developed and integrated desmin lattices. However, vimentin was present in the mesenchymal tissue including fibroblasts and surrounding blood vessels. In part, some cardiomyocytes showed a weakly positive reaction with monoclonal antibody against vimentin in 9-14 weeks gestation. Vimentin-positive areas, however, were progressively diminished with increasing fetal age. Vimentin was present only in the connective tissue and coverings of the 1-year-old child's heart. Relative density of fluorescence of desmin was increased with increasing fetal age, whereas that of vimentin decreased. CONCLUSIONS: These results indicate that there is a fetal age (or gestation)-dependent expression of IFs in human fetal heart: desmin increases with increasing fetal age, whereas vimentin decreases.

Blotting, Western↗

PubMed1996

Role of intracellular calcium as a priming signal for the induction of nitric oxide synthesis in murine peritoneal macrophages.

Because the role of intracellular Ca2+ in the two-signal process for the induction of nitric oxide (NO) synthesis is controversial, this study was undertaken to examine the role of Ca2+ in the transcriptional regulation of inducible NO synthase (iNOS) in murine peritoneal macrophages. Treatment of the cells with thapsigargin (TG) or 2,5-di-(t-butyl)-1,4-benzodihydroquinone (tBuBHQ), which are the specific and potent Ca(2+)-ATPase inhibitors of endoplasmic reticulum (ER), showed modest effects on tumoricidal function, whereas TG or tBuBHQ in combination with interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS) showed marked effects on tumoricidal function of the cells. The tumoricidal effects of the activated macrophages were correlated with the amount of NO synthesis, and totally abrogated by the use of NOS inhibitor, NG-monomethyl-L-arginine (NGMMA). The increases in NO synthesis was reflected as increased amounts of iNOS mRNA by Northern blotting. To confirm that iNOS induction was due to the changes in the intracellular Ca2+ level, the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular Ca2+ chelator, was used. Blocking the increase of cytosolic free Ca2+ significantly decreased the induction of NO synthesis. To demonstrate that intracellular Ca2+ acts as a 'priming' signal rather than a 'triggering' signal on the induction of NO synthesis by murine peritoneal macrophages, we designed several experiments. When the cells were treated with TG 6 hr after the treatment with IFN-gamma, there was no increase in NO synthesis. In addition, when the cells were treated with TG or LPS 6 hr after treatment with tBuBHQ, a synergistic increase on NO synthesis was shown only in the case of LPS. When phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, was added to the cells 6 hr after the treatment with TG, there was a marked co-operative induction of NO synthesis, even though PMA alone has no effect. Based on the results obtained in this study, we suggest that cytosolic Ca2+ might be enough for the expression of iNOS gene as a priming signal and PKC might be involved in the induction of NO synthesis as a triggering signal by post-transcriptional modification of iNOS mRNA or iNOS itself in the activated murine peritoneal macrophages.

Animals↗

PubMed1996

Ginsenoside-Rh1 and Rh2 inhibit the induction of nitric oxide synthesis in murine peritoneal macrophages.

The effects of ginsenoside-Rh1 and Rh2 in the induction of nitric oxide (NO) synthesis by IFN-gamma plus LPS were investigated using murine peritoneal macrophages. The NO production from rIFN gamma plus LPS-treated macrophages was markedly reduced by ginsenoside-Rh1 or Rh2 in a dose dependent manner, but had no inhibitory effects by ginsenoside-Rb1, Rc or Re. In addition, treatment of the cells with ginsenoside-Rh2 6 hr before the stimulation with IFN-gamma plus LPS showed more inhibitory effect than the treatment with ginsenoside-Rh2 6 hr after or simultaneously with the stimulation with IFN-gamma plus LPS in the NO production. Ginsenoside-Rh2 also effectively inhibited IFN-gamma induced NO production when the cells were treated with IFN-gamma 6 hr after the treatment with ginsenoside-Rh2. Our findings suggest that this phenomenon might be caused by inhibition of priming signal such as IFN-gamma for the synergistic induction of NO synthesis.

Animals↗

PubMed1996

Nutcracker syndrome: diagnosis with Doppler US.

PURPOSE: To assess diagnosis of the nutcracker (renal vein entrapment) syndrome with Doppler ultrasonography (US). MATERIALS AND METHODS: Doppler US findings in 16 patients with the nutcracker syndrome and in 18 healthy control subjects were compared. The anteroposterior (AP) diameter and peak velocity (PV) were measured at the hilar portion of the left renal vein (LRV) and at the LRV between the aorta and the superior mesenteric artery. RESULTS: The mean AP diameters of the LRV were 10.0 mm +/- 2.0 (standard deviation) and 1.9 mm +/- 1.0 (ratio, 5.0 +/- 2.3) in the patient group and 7.2 mm +/- 1.8 and 2.3 mm +/- 0.6 (ratio, 3.3 +/- 1.1) in the control group. The PVs at the two locations were 14.2 cm/sec +/- 2.5 and 110.7 cm/sec +/- 35.8 (ratio, 7.9 +/- 2.7) in the patient group and 18.6 cm/sec +/- 3.7 and 50.9 cm/sec +/- 27.9 (ratio, 2.8 +/- 1.5) in the control group. Differences in AP diameter and PV were statistically significant between the two groups (P < .01). CONCLUSION: Doppler US of the LRV with measurement of the AP diameter and PV may be useful in diagnosing the nutcracker syndrome.

Adolescent↗

PubMed1996

Potentiation of regulatory volume decrease by P2U purinoceptors in HSG-PA cells.

HSG-PA human salivary gland duct cells exhibit progressively increased regulatory volume decrease (RVD) in response to decreased medium osmolarity. The P2U purinoceptor agonist UTP causes a potentiation of RVD, the extent of which is most pronounced in 220 mosM medium and is least apparent in 180 mosM medium. We examined the underlying mechanisms for this effect. Exposure of HSG-PA cells to UTP promotes Ca2+ mobilization, hyperpolarization, and net K+ efflux, suggesting the participation of Ca(2+)-activated K+ channels in RVD. To delineate the anion counterpart of K+ movement during RVD, cell swelling in the presence of gramicidin, which abolishes the membrane potential, was measured. In response to a sudden dilution in hypotonic media, gramicidin-treated cells swelled immediately, followed by a "secondary swelling" in 180 but not in 220 mosM medium. The results suggest that in 180 mosM cells perform spontaneous RVD mediated by increased anion conductance. In 220 mosM medium in which RVD is minimal, the increase in anion conductance is marginal. In our model of RVD in which cells were challenged by UTP, the ensuing hyperpolarization provides the driving force for net Cl- efflux, which is confirmed by tracer flux studies during purinoceptor-activated RVD. Thus RVD, which has long been regarded as a self-sufficient cellular program, appears to be subject to extracellular control in HSG-PA cells through receptor-mediated processes.

Biological Transport↗