Biomedical subjects

Y Yu

Publications and source records attributed to Y Yu.

At least 109 records · Page 6Linked to original sources

PubMed2001

IFN-gamma gene therapy by intrasplenic hepatocyte transplantation: a novel strategy for reversing hepatic fibrosis in Schistosoma japonicum-infected mice.

Liver-targeted gene therapy using hepatocyte as recipient cells has recently been documented to be effective in treatment of numerous hepatic diseases, such as metabolic diseases and liver carcinoma. IFN-gamma elicits antipreliferative and antifibrogenic activity in a variety of mesenchymal cells, including hepatic satellite cells. To investigate the antifibrogenic response of liver gene therapy mediated by intrasplenic transplantation of gene-modified hepatocytes, normal mouse liver cell line BNL CL.2 cells were transfected with murine IFN-gamma gene (BNL.IFN-gamma) in vitro, and transplanted intrasplenically into Schistosoma japonicum-infected mice. The amounts and distribution of IFN-gamma (which inhibits collagen synthesis), TGF-beta (which stimulates collagen synthesis) and extracellular matrix, including type I and III collagen, were detected. In mice infected with S. japonicum and then treated with BNL.IFN-gamma, an increase of IFN-gamma and decrease of TGF-beta1 were detected at 20 weeks postinfection compared to untreated S. japonicum-infected mice. Immunohistochemical analysis showed that S. japonicum infection induced a marked increase of type I and III collagen synthesis. Whereas, 4 weeks after treatment with BNL.IFN-gamma, net synthesis rates of type I and III collagen were markedly decreased in the liver of infected mice. In addition, a decreased expression of TGF-beta1 and its receptor TGF-betaRII in the liver of BNL.IFN-gamma-treated mice was also observed. Moreover, the decrease in TGF-beta1 and TGF-betaRII protein approximately paralleled the decrease in their mRNA expression, which was detected by RNA dot blotting. The data indicate that intrasplenic transplantation of IFN-gamma gene-modified hepatocyte can be a candidate approach to treat hepatic fibrosis.

Animals↗

PubMed2001

Pressure-exploration of the 33-kDa protein from the spinach photosystem II particle.

The 33-kDa protein isolated from the spinach photosystem II particle is an ideal model to explore high-pressure protein-unfolding. The protein has a very low free energy as previously reported by chemical unfolding studies, suggesting that it must be easy to modulate its unfolding transition by rather mild pressure. Moreover, the protein molecule consists of only one tryptophan residue (Trp241) and eight tyrosine residues, which can be conveniently used to probe the protein conformation and structural changes under pressure using either fluorescence spectroscopy or fourth derivative UV absorbance spectroscopy. The different experimental methods used in the present study indicate that at 20 degrees C and pH 6, the 33-kDa protein shows a reversible two-state unfolding transition from atmospheric pressure to about 180 MPa. This value is much lower than those found for the unfolding of most proteins studied so far. The unfolding transition induces a large red shift of the maximum fluorescence emission of 34 nm (from 316 nm to 350 nm). The change in standard free energy (DeltaGo) and in volume (DeltaV) for the transition at pH 6.0 and 20 degrees C are -14.6 kJ.mol-1 and -120 mL.mol-1, respectively, in which the DeltaGo value is consistent with that obtained by chemical denaturation. We found that pressure-induced protein unfolding is promoted by elevated temperatures, which seem largely attributed to the decrease in the absolute value of DeltaGo (only a minor variation was observed for the DeltaV value). However, the promotion of the unfolding by alkaline pH seems mainly related to the increase in DeltaV without any significant changes in DeltaGo. It was also found that NaCl significantly protects the protein from pressure-induced unfolding. In the presence of 1 M NaCl, the pressure needed to induce the half-unfold of the protein is shifted to a higher value (shift of 75 MPa) in comparison with that observed without NaCl. Interestingly, in the presence of NaCl, the value of DeltaV is significantly reduced whilst that of DeltaGo remains as before. The unfolding-refolding kinetics of the protein has also been studied by pressure-jump, in which it was revealed that both reactions are a two-state transition process with a relatively slow relaxation time of about 102 s.

Anilino Naphthalenesulfonates↗

PubMed2001

Saikosaponin v-1 from roots of Bupleurum chinense DC.

Three triterpenoidal saponins, saikosaponin v-1(1), 6"-O-acetyl-saikosaponin b2 (2) and 6"-O-acetyl-saikosaponin d(3) were isolated from the roots of the title plant and the structures were identified on the basis of spectral analysis. Saikosaponin v-1 is a new compound, which was identified as 3beta,16alpha,23,28-tetrahydroxy-olean-11,13(18)-dien-30-oic acid-3-O-beta-D-glucopyranosyl-(1-->3)-beta-D-fucopyranosyl-30-O-xylitol ester.

Adjuvants, Immunologic↗

PubMed2001

Improved binding of a bivalent single-chain immunotoxin results in increased efficacy for in vivo T-cell depletion.

Anti-CD3 immunotoxins exhibit considerable promise for the induction of transplantation tolerance in pre-clinical large animal models. Recently an anti-human anti-CD3epsilon single-chain immunotoxin based on truncated diphtheria toxin has been described that can be expressed in CHO cells that have been mutated to diphtheria toxin resistance. After the two toxin glycosylation sites were removed, the bioactivity of the expressed immunotoxin was nearly equal to that of the chemically conjugated immunotoxin. This immunotoxin, A-dmDT390-sFv, contains diphtheria toxin to residue 390 at the N-terminus followed by VL and VH domains of antibody UCHT1 linked by a (G(4)S)(3) spacer (sFv). Surprisingly, we now report that this immunotoxin is severely compromised in its binding affinity toward CD3(+) cells as compared with the intact parental UCHT1 antibody, the UCHT1 Fab fragment or the engineered UCHT1 sFv domain alone. Binding was increased 7-fold by adding an additional identical sFv domain to the immunotoxin generating a divalent construct, A-dmDT390-bisFv (G(4)S). In vitro potency increased 10-fold over the chemically conjugated immunotoxin, UCHT1-CRM9 and the monovalent A-dmDT390-sFv. The in vivo potency of the genetically engineered immunotoxins was assayed in the transgenic heterozygote mouse, tgepsilon 600, in which the T-cells express human CD3epsilon as well as murine CD3epsilon. T-cell depletion in the spleen and lymph node observed with the divalent construct was increased 9- and 34-fold, respectively, compared with the monovalent construct. The additional sFv domain appears partially to compensate for steric hindrance of immunotoxin binding due to the large N-terminal toxin domain.

Animals↗

PubMed2001

Effect of recombinant bactericidal/permeability-increasing protein on endotoxin translocation and lipopolysaccharide-binding protein/CD14 expression in rats after thermal injury.

OBJECTIVE: To investigate the potential mechanisms underlying the in vivo effect of recombinant bactericidal/permeability-increasing protein (rBPI21) on endogenous bacteria or endotoxin translocation and lipopolysaccharide-binding protein/CD14 expression secondary to thermal injury. DESIGN: Prospective, randomized, controlled animal study. SETTING: College hospital animal research laboratory. SUBJECTS: Thirty-six male Wistar rats weighing 250-300 g. INTERVENTIONS: The rats were anesthetized, and a 35% total body surface area full-thickness burn was created. Animals were randomized to receive treatment with either rBPI21 or the control protein (albumin). rBPI21 (2 mg/kg body wt, BPI group) or a protein control preparation (burn group) in the same dose was administered in an intravenous bolus at 30 mins and 4 hrs after thermal injury. All animals were killed at 12 and 24 hrs postburn (six to ten rats for each interval). In addition, eight rats were taken as normal controls. MEASUREMENT AND MAIN RESULTS: Our data showed that treatment with rBPI21 was effective in preventing endotoxin translocation secondary to severe burns. Meanwhile, tissue lipopolysaccharide-binding protein, CD14, and tumor necrosis factor-alpha mRNA expression in various organs were inhibited markedly by rBPI21 secondary to acute insults (p <.05-.01). Furthermore, significant reduction in serum aminoleucine transferase concentrations and elevation in intestinal diamine oxidase activities in the rBPI21-treated group were found compared with controls (p <.05-.01). CONCLUSIONS: These findings indicate that endotoxin accumulated in local sites after thermal injury can markedly up-regulate lipopolysaccharide-binding protein/CD14 and tumor necrosis factor-alpha mRNA expression in various organs. Meanwhile, up-regulation of lipopolysaccharide-binding protein/CD14 expression would be the major molecular mechanism of increasing sensitivity to endogenous endotoxin response after burns. Early treatment with rBPI21may be effective in attenuating multiple organ damage resulting from gut-origin endotoxin translocation. This might be associated with the down-regulation effects of tissue lipopolysaccharide-binding protein and CD14 gene expression by the use of rBPI21.

Acute-Phase Proteins↗

PubMed2001

Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs.

Fetal liver intriguingly consists of hepatic parenchymal cells and hematopoietic stem/progenitor cells. Human fetal liver aged 22 wk of gestation (HFL22w) corresponds to the turning point between immigration and emigration of the hematopoietic system. To gain further molecular insight into its developmental and functional characteristics, HFL22w was studied by generating expressed sequence tags (ESTs) and by analyzing the compiled expression profiles of liver at different developmental stages. A total of 13,077 ESTs were sequenced from a 3'-directed cDNA library of HFL22w, and classified as follows: 5819 (44.5%) matched to known genes; 5460 (41.8%) exhibited no significant homology to known genes; and the remaining 1798 (13.7%) were genomic sequences of unknown function, mitochondrial genomic sequences, or repetitive sequences. Integration of ESTs of known human genes generated a profile including 1660 genes that could be divided into 15 gene categories according to their functions. Genes related to general housekeeping, ESTs associated with hematopoiesis, and liver-specific genes were highly expressed. Genes for signal transduction and those associated with diseases, abnormalities, or transcription regulation were also noticeably active. By comparing the expression profiles, we identified six gene groups that were associated with different developmental stages of human fetal liver, tumorigenesis, different physiological functions of Itoh cells against the other types of hepatic cells, and fetal hematopoiesis. The gene expression profile therefore reflected the unique functional characteristics of HFL22w remarkably. Meanwhile, 110 full-length cDNAs of novel genes were cloned and sequenced. These novel genes might contribute to our understanding of the unique functional characteristics of the human fetal liver at 22 wk.

Cloning, Molecular↗

PubMed2001

Identification of the maize amyloplast stromal 112-kD protein as a plastidic starch phosphorylase.

Amyloplast is the site of starch synthesis in the storage tissue of maize (Zea mays). The amyloplast stroma contains an enriched group of proteins when compared with the whole endosperm. Proteins with molecular masses of 76 and 85 kD have been identified as starch synthase I and starch branching enzyme IIb, respectively. A 112-kD protein was isolated from the stromal fraction by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subjected to tryptic digestion and amino acid sequence analysis. Three peptide sequences showed high identity to plastidic forms of starch phosphorylase (SP) from sweet potato, potato, and spinach. SP activity was identified in the amyloplast stromal fraction and was enriched 4-fold when compared with the activity in the whole endosperm fraction. Native and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses showed that SP activity was associated with the amyloplast stromal 112-kD protein. In addition, antibodies raised against the potato plastidic SP recognized the amyloplast stromal 112-kD protein. The amyloplast stromal 112-kD SP was expressed in whole endosperm isolated from maize harvested 9 to 24 d after pollination. Results of affinity electrophoresis and enzyme kinetic analyses showed that the amyloplast stromal 112-kD SP preferred amylopectin over glycogen as a substrate in the synthetic reaction. The maize shrunken-4 mutant had reduced SP activity due to a decrease of the amyloplast stromal 112-kD enzyme.

Amino Acid Sequence↗

PubMed2001

Real-time US versus CT determination of pubic arch interference for brachytherapy.

PURPOSE: Part 1, to determine whether transrectal ultrasonography (US) enables accurate determination of pubic arch interference (PAI) for prostate brachytherapy (PBT); part 2, to compare the accuracy of transrectal US with that of computed tomography (CT) for PAI determination; and part 3, to determine the cost savings of PAI determination with transrectal US versus that with CT. MATERIALS AND METHODS: Part 1: The pubic arch was identified intraoperatively with transrectal US and compared with attempted needle passage (14 patients). Part 2: Planning CT with the patient supine was compared with planning transrectal US with patients in the dorsal lithotomy position (nine patients). Part 3: Cost savings were calculated for PAI determination with transrectal US versus that with CT (32 patients per group). RESULTS: Part 1: Transrectal US accurately showed the pubic arch relative to the prostate. Part 2: CT resulted in PAI overestimation by 11.8 mm. Part 3: Cost savings with transrectal US were $1,465 per patient. CONCLUSION: Transrectal US PAI determination is easily performed, intraoperatively useful, and accurate. CT can result in PAI overestimation. Reducing direct CT costs and the indirect costs of unnecessary hormonal therapy for false-positive PAI will reduce expense and improve patient care. Transrectal US should replace CT for PAI determination.

Aged↗

PubMed2001

Cloning of a novel EGFR-related peptide: a putative negative regulator of EGFR.

Although epidermal growth factor receptor (EGFR) plays a key role in regulating cell proliferation, differentiation, and transformation in many tissues, little is known about the factor(s) that may modulate its function. We have isolated a cDNA clone from the rat gastroduodenal mucosa whose full length revealed 1,958 bp that contained 227 bp of 5'-untranslated region (UTR) and an open-reading frame encoding 479 amino acids, followed by 290 bp of 3'-UTR. It showed ~85% nucleotide homology to the external domain of the rat EGFR. We refer to the product of the newly isolated cDNA as EGFR-related protein (ERRP). In Northern blot analysis with poly(A)(+) RNA from different rat tissues, ERRP cDNA hybridized to several mRNA transcripts with the strongest reaction noted with a transcript of approximately 2 kb. Maximal expression of the 2-kb mRNA transcript was observed in the small intestine, followed by colon, liver, gastric mucosa, and other tissues. Transfection of ERRP cDNA into a colon cancer cell line, HCT116, resulted in a marked reduction in proliferation in monolayer and colony formation in soft agar compared with the vector-transfected controls. In another colon cancer cell line, Caco-2, with a tetracycline-regulated promoter system, induction of ERRP expression in the absence of doxycycline was associated with a marked reduction in EGFR activation and proliferation. We conclude that the ERRP cDNA may represent a new member of the EGFR gene family and that ERRP plays a role in regulating cell proliferation by modulating the function of EGFR.

5' Untranslated Regions↗

PubMed2001

Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells.

Cell shrinkage is an incipient hallmark of apoptosis in a variety of cell types. The apoptotic volume decrease has been demonstrated to attribute, in part, to K+ efflux; blockade of plasmalemmal K+ channels inhibits the apoptotic volume decrease and attenuates apoptosis. Using combined approaches of gene transfection, single-cell PCR, patch clamp, and fluorescence microscopy, we examined whether overexpression of Bcl-2, an anti-apoptotic oncoprotein, inhibits apoptosis in pulmonary artery smooth muscle cells (PASMC) by diminishing the activity of voltage-gated K+ (Kv) channels. A human bcl-2 gene was infected into primary cultured rat PASMC using an adenoviral vector. Overexpression of Bcl-2 significantly decreased the amplitude and current density of Kv currents (I(Kv)). In contrast, the apoptosis inducer staurosporine (ST) enhanced I(Kv). In bcl-2-infected cells, however, the ST-induced increase in I(Kv) was completely abolished, and the ST-induced apoptosis was significantly inhibited compared with cells infected with an empty adenovirus (-bcl-2). Blockade of Kv channels in control cells (-bcl-2) by 4-aminopyridine also inhibited the ST-induced increase in I(Kv) and apoptosis. Furthermore, overexpression of Bcl-2 accelerated the inactivation of I(Kv) and downregulated the mRNA expression of the pore-forming Kv channel alpha-subunits (Kv1.1, Kv1.5, and Kv2.1). These results suggest that inhibition of Kv channel activity may serve as an additional mechanism involved in the Bcl-2-mediated anti-apoptotic effect on vascular smooth muscle cells.

4-Aminopyridine↗

PubMed2001

Chronic hypoxia decreases K(V) channel expression and function in pulmonary artery myocytes.

Activity of voltage-gated K+ (KV) channels regulates membrane potential (E(m)) and cytosolic free Ca2+ concentration ([Ca2+](cyt)). A rise in ([Ca2+](cyt))in pulmonary artery (PA) smooth muscle cells (SMCs) triggers pulmonary vasoconstriction and stimulates PASMC proliferation. Chronic hypoxia (PO(2) 30-35 mmHg for 60-72 h) decreased mRNA expression of KV channel alpha-subunits (Kv1.1, Kv1.5, Kv2.1, Kv4.3, and Kv9.3) in PASMCs but not in mesenteric artery (MA) SMCs. Consistently, chronic hypoxia attenuated protein expression of Kv1.1, Kv1.5, and Kv2.1; reduced KV current [I(KV)]; caused E(m) depolarization; and increased ([Ca2+](cyt)) in PASMCs but negligibly affected KV channel expression, increased I(KV), and induced hyperpolarization in MASMCs. These results demonstrate that chronic hypoxia selectively downregulates KV channel expression, reduces I(KV), and induces E(m) depolarization in PASMCs. The subsequent rise in ([Ca2+](cyt)) plays a critical role in the development of pulmonary vasoconstriction and medial hypertrophy. The divergent effects of hypoxia on KV channel alpha-subunit mRNA expression in PASMCs and MASMCs may result from different mechanisms involved in the regulation of KV channel gene expression.

Animals↗

PubMed2001

Capacitative Ca(2+) entry in agonist-induced pulmonary vasoconstriction.

Agonist-induced increases in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary artery (PA) smooth muscle cells (SMCs) consist of a transient Ca(2+) release from intracellular stores followed by a sustained Ca(2+) influx. Depletion of intracellular Ca(2+) stores triggers capacitative Ca(2+) entry (CCE), which contributes to the sustained increase in [Ca(2+)](cyt) and the refilling of Ca(2+) into the stores. In isolated PAs superfused with Ca(2+)-free solution, phenylephrine induced a transient contraction, apparently by a rise in [Ca(2+)](cyt) due to Ca(2+) release from the intracellular stores. The transient contraction lasted for 3-4 min until the Ca(2+) store was depleted. Restoration of extracellular Ca(2+) in the presence of phentolamine produced a contraction potentially due to a rise in [Ca(2+)](cyt) via CCE. The store-operated Ca(2+) channel blocker Ni(2+) reduced the store depletion-activated Ca(2+) currents, decreased CCE, and inhibited the CCE-mediated contraction. In single PASMCs, we identified, using RT-PCR, five transient receptor potential gene transcripts. These results suggest that CCE, potentially through transient receptor potential-encoded Ca(2+) channels, plays an important role in agonist-mediated PA contraction.

Animals↗

PubMed2001

Analysis of the afferent limb of the vesicovascular reflex using neurotoxins, resiniferatoxin and capsaicin.

The afferent limb of the vesicovascular reflex (VV-R) evoked by distension or contraction of the urinary bladder (UB) was studied in urethane-anesthetized female rats by examining the changes in VV-R after administration of C-fiber afferent neurotoxins [capsaicin and resiniferatoxin (RTX)]. Systemic arterial blood pressure increased parallel (5.1 to 53.7 mmHg) with graded increases in UB pressure (20 to 80 cm H(2)O) or during UB contractions. The arterial pressor response to UB distension was significantly reduced (60-85%) by acute or chronic (4 days earlier) intravesical administration of RTX (100-1,000 nM) or by capsaicin (125 mg/kg sc) pretreatment (4 days earlier). Chronic neurotoxin treatments also increased the volume threshold (>100%) for eliciting micturition in anesthetized rats but did not change voiding pressure. Acute RTX treatment (10-50 nM) did not alter the arterial pressor response during reflex UB contractions, whereas higher concentrations of RTX (100-1,000 nM) blocked reflex bladder contractions. It is concluded that VV-R is triggered primarily by distension- and contraction-sensitive C-fiber afferents located, respectively, near the luminal surface and deeper in the muscle layers of the bladder.

Administration, Intravesical↗

PubMed2001

Anorexic effect of K+ channel blockade in mesenteric arterial smooth muscle and intestinal epithelial cells.

Activity of voltage-gated K+ (Kv) channels controls membrane potential (E(m)). Membrane depolarization due to blockade of K+ channels in mesenteric artery smooth muscle cells (MASMC) should increase cytoplasmic free Ca2+ concentration ([Ca2+]cyt) and cause vasoconstriction, which may subsequently reduce the mesenteric blood flow and inhibit the transportation of absorbed nutrients to the liver and adipose tissue. In this study, we characterized and compared the electrophysiological properties and molecular identities of Kv channels and examined the role of Kv channel function in regulating E(m) in MASMC and intestinal epithelial cells (IEC). MASMC and IEC functionally expressed multiple Kv channel alpha- and beta-subunits (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv2.1, Kv4.3, and Kv9.3, as well as Kvbeta1.1, Kvbeta2.1, and Kvbeta3), but only MASMC expressed voltage-dependent Ca2+ channels. The current density and the activation and inactivation kinetics of whole cell Kv currents were similar in MASMC and IEC. Extracellular application of 4-aminopyridine (4-AP), a Kv-channel blocker, reduced whole cell Kv currents and caused E(m) depolarization in both MASMC and IEC. The 4-AP-induced E(m) depolarization increased [Ca2+]cyt in MASMC and caused mesenteric vasoconstriction. Furthermore, ingestion of 4-AP significantly reduced the weight gain in rats. These results suggest that MASMC and IEC express multiple Kv channel alpha- and beta-subunits. The function of these Kv channels plays an important role in controlling E(m). The membrane depolarization-mediated increase in [Ca2+]cyt in MASMC and mesenteric vasoconstriction may inhibit transportation of absorbed nutrients via mesenteric circulation and limit weight gain.

4-Aminopyridine↗

PubMed2001

Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease.

BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. METHODS: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3 +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(-) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.

Adult↗

PubMed2001

Clonality and altered behavior of endothelial cells from hemangiomas.

Hemangioma, the most common tumor of infancy, is a benign vascular neoplasm of unknown etiology. We show, for the first time to our knowledge, that endothelial cells from proliferating hemangioma are clonal, and we demonstrate that these hemangioma-derived cells differ from normal endothelial cells in their rates of proliferation and migration in vitro. Furthermore, migration of hemangioma endothelial cells is stimulated by the angiogenesis inhibitor endostatin, unlike the inhibition seen with normal endothelial cells. We conclude that hemangiomas constitute clonal expansions of endothelial cells. This is consistent with the possibility that these tumors are caused by somatic mutations in one or more genes regulating endothelial cell proliferation.

Alleles↗

PubMed2001

Comparison of discharge rates and drug costs for patients with schizophrenia treated with risperidone or olanzapine.

This study compared the discharge rates and drug costs of 789 patients with schizophrenia or schizoaffective disorder who began pharmacotherapy with olanzapine or risperidone between July 1997 and June 1998. Discharge rates 30 days after the start of treatment were 45 percent for the patients treated with risperidone and 32 percent for those treated with olanzapine (p=.001). Daily drug costs during the same period were $6.42 for risperidone and $12.29 for olanzapine (p<.001). For risperidone, lower dosages were associated with higher hospital discharge rates, whereas no significant association was observed for olanzapine. These data suggest that among inpatients with schizophrenia or schizoaffective disorder, use of risperidone results in a higher discharge rate and a lower drug cost than use of olanzapine.

Antipsychotic Agents↗

PubMed2001

Inhibition of K(+) channel activity in human pulmonary artery smooth muscle cells by serum from patients with pulmonary hypertension secondary to congenital heart disease.

Activity of K(+) channels regulates cytosolic free Ca(2+) concentration by controlling membrane potential. A rise in cytosolic free Ca(2+) concentration in pulmonary artery smooth muscle cells (PASMC) triggers pulmonary vasoconstriction and stimulates PASMC proliferation. Whether serum from children with pulmonary hypertension (PH) secondary to congenital cardiopulmonary diseases contains a factor(s) that inhibits K(+) channel function in PASMC was investigated using patch clamp techniques. PASMC isolated from normal subjects were cultured in media containing 5% serum from normotensive (NPH) or PH patients. Cell growth rate and the currents through voltage-gated K(+) channels were determined and compared between the cells treated with serum from NPH and PH patients. In the absence of growth factors, incubation of PASMC in media containing NPH serum for 48 h increased cell numbers by 2.5-fold, whereas incubation of the cells in media containing PH serum increased cell numbers by 4.5-fold (p < 0.001). Amplitude of whole-cell voltage-gated K(+) currents in NPH serum-treated cells (1119 +/- 222 pA at +80 mV, n = 43) was 3.5-fold greater than in PH serum-treated cells (323 +/- 34 pA, n = 43, p < 0.001). Consistently, membrane potential was much more depolarized in PASMC treated with PH serum (-28 +/- 2 mV, n = 29) than cells treated with NPH-serum (-47 +/- 2 mV, n = 28; p < 0.001). These results suggest that a circulating mitogenic agonist, which induces membrane depolarization by inhibiting voltage-gated K(+) channel activity in PASMC, may be produced or up-regulated in pediatric patients with secondary PH.

Blood↗