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Biomedical subjects

S Horie

Publications and source records attributed to S Horie.

At least 127 records · Page 7Linked to original sources
PubMed1993

Inhibition of gastric acid secretion in vivo and in vitro by an inhibitor of Cl(-)-HCO3- exchanger, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid.

The mode of action of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of the Cl(-)-HCO3- exchanger, on gastric acid secretion has been studied in vitro and in vivo. In the mouse isolated whole stomach preparation, DIDS (100 microM-1 mM) inhibited gastric acid secretion induced by histamine or bethanechol in a concentration-dependent fashion. On the other hand, DIDS, at a concentration enough to reduce the stimulated acid secretion, did not inhibit basal acid secretion in the resting preparation. In the perfused stomach of urethane-anesthetized rats, DIDS (1-10 mg/kg i.v.) inhibited gastric acid secretion stimulated by histamine, bethanechol or tetragastrin, whereas DIDS did not inhibit basal acid secretion. In pylorus-ligated rats, DIDS (3-30 mg/kg) administered intraduodenally also inhibited gastric acid output as well as gastric juice volume when administered immediately after ligation. When injected 6 h before ligation, DIDS inhibited the gastric acid secretion. However, this potency was weak in comparison with that observed when DIDS was administered immediately after ligation. These results demonstrate that DIDS can inhibit stimulated gastric acid secretion in vitro and in vivo, probably through its inhibitory effect on the Cl(-)-HCO3- exchanger.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Participation of calpain I activation in the ATP release reaction of platelets stimulated with thrombin.

Proteolytic activation of calpain (calcium-dependent neutral protease) I in thrombin-stimulated platelets was determined by following the production of the 76- and 78-kDa forms from the 80-kDa subunit of calpain I as measured by immunoblotting using monospecific antibody to human calpain I, and the correlation between the extents of calpain I activation and ATP release was investigated. When platelets were stimulated with thrombin in the range from 0.01 to 0.5 U/ml, the maximal 60% activation of calpain I was achieved within 15 s after the stimulation, and ATP release began after the maximal activation had been reached. The extent of ATP release decreased in parallel with the decrease in activation ratio of calpain I on treatment of platelets with EGTA or EST, a membrane-permeable inhibitor of calpain. Although pretreatment of platelets with EST did not affect the thrombin-dependent elevation of the cytosolic Ca2+ concentration, both the inhibition of calpain I activation and the reduction of ATP release were observed as a function of EST concentration. These results suggest that calpain I participates in one of the processes leading to the ATP release reaction of platelets stimulated with thrombin.

Adenosine Triphosphate↗
PubMed1992

Effects of drugs acting on Cl(-)-HCO3- and Na(+)-H+ exchangers on acid secretion in the rat gastric mucosa sheet preparation.

The effects of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of the Cl(-)-HCO3- exchanger, and amiloride, an inhibitor of the Na(+)-H+ exchanger, on gastric acid secretion under basal conditions and after stimulation with bethanechol or dibutyryl cyclic AMP were studied in rat gastric mucosa sheet preparation. DIDS inhibited bethanechol-induced acid secretion in a dose-dependent manner, but amiloride had no effect. The stimulation of acid secretion by dibutyryl cyclic AMP plus 3-isobutyl-1-methylxanthine was also inhibited by DIDs, but not by amiloride. DIDS did not reduce basal acid secretion, and neither did amiloride. These results suggest that the Cl(-)-HCO3-exchanger in the basolateral membrane of the parietal cell plays an important role in stimulated gastric acid secretion and that the Na(+)-H+ exchanger is less important. In addition, these data show that DIDS inhibits stimulated gastric acid secretion irrespective of the secretagogue, but not basal gastric acid secretion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Retinoic acid counteracts both the downregulation of thrombomodulin and the induction of tissue factor in cultured human endothelial cells exposed to tumor necrosis factor.

Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) shift the hemostatic balance of endothelial cell surfaces in favor of prothrombotic properties by downregulating thrombomodulin (TM) and inducing tissue factor (TF) expression. We investigated the effects of retinoic acid (RA) on the prothrombotic properties of cultured umbilical vein endothelial cells exposed to TNF-alpha. The approximate 50% downregulation of TM antigen and cofactor activity induced by TNF-alpha (10 U/mL for 24 hours) was completely prevented when the cells were coincubated with both TNF-alpha and 10 mumol/L RA. In accordance with changes in cell surface TM antigen levels, the 70% decrease in TM messenger RNA (mRNA) induced by TNF-alpha was also prevented by 10 mumol/L RA. TNF-alpha induced TF activity of lysed cells (100-fold greater than untreated controls), an effect prevented when the cells were coincubated with both the TNF-alpha and 10 mumol/L RA. The 34-fold increase in TF mRNA levels induced by TNF-alpha (10 U/mL for 3 hours) was only two-fold in the presence of both TNF-alpha and RA. The effects of RA on the regulation of TM and TF expression in the cells exposed to TNF-alpha was dose-dependent from 0.01 to 10 mumol/L RA. The present results suggest that RA may affect on the mRNA level to alter TM and TF expression, effectively counteracting expression of prothrombotic properties of endothelial cells induced by inflammatory cytokines such as TNF-alpha.

Cells, Cultured↗
PubMed1992

Procalpain I in cytoplasm is translocated onto plasma and granule membranes during platelet stimulation with thrombin and then activated on the membranes.

Thrombin stimulation of platelets resulted in changes in the subcellular localization of calpain I, with a concomitant alteration of its molecular weight as measured by immunoblotting. Calpain I in resting platelets was distributed as procalpain I, an 80 kDa form which does not exhibit the enzyme activity, and 83% of the total antigen was localized in the cytosol fraction. When platelets were stimulated with thrombin, the total content of calpain I antigen was not significantly changed as compared with that of the resting platelets, though a decrease in the cytosolic distribution of 80 kDa form (from 83% to 47% of the total antigen) was observed with concomitant appearance of the active 76 kDa and intermediate 78 kDa forms of calpain I and increase in the 80 kDa form in the granule and membrane fractions. These results indicated that calpain I was translocated from the cytosol to both the plasma and granule membranes as procalpain I and then activated on the membranes during platelet stimulation with thrombin.

Blood Platelets↗
PubMed1992

Role of protein kinase C and transcription factor AP-1 in the acid-induced increase in Na/H antiporter activity.

Chronic incubation of cultured renal tubular epithelial cells in acid medium causes an increase in Na/H antiporter activity that persists after removal from acid, is dependent on protein synthesis, and is associated with an increase in Na/H antiporter mRNA. Chronic activation of protein kinase C has similar effects in these cells. The present studies examined the role of protein kinase C in the effect of acid incubation. Incubation of MCT cells in acid for 24 h caused a 50% increase in Na/H antiporter activity. This was prevented by inhibition of protein kinase C, either with sphingosine or by protein kinase C downregulation. Pertussis toxin pretreatment did not prevent the increase in antiporter activity. Acid incubation caused an increase in transcription factor AP-1 activity, as shown by an increase in expression from a reporter gene containing six tandem AP-1 binding sites. This was associated with transient increases in c-fos and c-jun mRNAs. This response is typical of that for gene activation by protein kinase C. These studies demonstrate that acid activation of the Na/H antiporter requires protein kinase C and is associated with c-fos and c-jun expression and increased AP-1 activity.

Animals↗
PubMed1992

Biosynthesis of glycerolipid precursors in rat liver peroxisomes and their transport and conversion to phosphatidate in the endoplasmic reticulum.

The transport of glycerolipid intermediates, viz. palmitoyl dihydroxyacetone phosphate (DHAP) and lysophosphatidate from peroxisomes and their conversion to phosphatidate in endoplasmic reticulum (microsomes) were studied in cell-free systems. The lipids were biosynthesized from [32P]DHAP, palmitoyl-CoA, and freshly made rat liver peroxisomes and microsomes in the presence or absence of Mg2+, NADPH, and bovine serum albumin (BSA). After incubation, the soluble fraction and the membranes were separated, and the distribution of radioactive lipids in these fractions were determined. The results showed that palmitoyl-DHAP and lysophosphatidate were recovered in the supernatant when BSA was present or when BSA was absent, but Mg2+ was removed after incubation by chelation with EDTA (or ATP). At low optimum palmitoyl-CoA concentration or when palmitoyl-CoA was generated in peroxisomes, and in the absence of BSA, the biosynthesized keto ether and ester lipids and lysophosphatidate were similarly present in the supernatant. Phosphatidate, however, was always localized in the membranes. Further fractionation showed that phosphatidate was associated with the microsomes. The critical micellar concentrations of palmitoyl-DHAP and 1-palmitoyl-rac-glycerol 3-phosphate, under the incubation conditions used, were determined to be 58 and 70 microM, respectively. These results suggest that at physiological concentrations the biosynthesized lysolipids are water soluble, and therefore, a carrier protein is unnecessary for their transport. These lipids freely diffuse from peroxisomes to endoplasmic reticulum where they are converted to membrane-bound phosphatidate.

Acyltransferases↗
PubMed1992

Changes in plasma thrombomodulin antigen in rabbit developing endotoxin-induced disseminated intravascular coagulation and the effect of heparin.

Soluble thrombomodulin (TM) antigen level was 1.64 +/- 0.64 microgram/ml (n = 18, mean +/- S.D.) in plasma of normal male rabbits as measured by enzyme immunoassay, and the antigen consisted of subspecies of 94, 83 and 51 kd. When disseminated intravascular coagulation (DIC) was induced by intravenous infusion of endotoxin into rabbits, the TM antigen level in plasma was elevated to about 1.5 times of the control value, and an increase in the 83 kd subspecies as well as the appearance of new subspecies of 76 and 48 kd was observed concomitantly with disappearance of the 94 kd subspecies in plasma. Elevation of the antigen level and disappearance of the 94 kd subspecies caused by infusion of endotoxin were reduced by simultaneous infusion of heparin. Addition of leukocytes stimulated with endotoxin plus FMLP to cultured endothelial cells induced release of TM antigen to the medium accompanying cell injury as measured by 51Cr release, which was prevented by treatment with heparin. It was suggested that the increase in plasma TM antigen level in parallel with the generation of DIC reflected endothelial injury of rabbits, and that the elevation of TM antigen and the endothelial cell injury were prevented by heparin treatment.

Animals↗
PubMed1992

Retinoic acid stimulates expression of thrombomodulin, a cell surface anticoagulant glycoprotein, on human endothelial cells. Differences between up-regulation of thrombomodulin by retinoic acid and cyclic AMP.

Thrombomodulin (TM) is a surface protein on endothelial cells, and represents one of the most valuable regulatory factors in the anticoagulant system. In this paper, we demonstrate that retinoic acid (RA) causes an increase in TM antigen on human umbilical vein endothelial cells (HUVECs) in vitro. The effect of RA on the surface TM level of HUVECs was dose-dependent in the range from 0.01 to 10 microM-RA. Antigen levels began to increase 3 h after addition of 10 microM-RA, and plateaued at a maximum level of approx. 2.5 times that of the untreated control at 24 h. TM levels remained at a maximum for a further 12 h, and then gradually decreased. The effects of RA on cell surface TM activity and antigen levels were parallel in all experiments. TM expression was also increased by treatment with 10 microM-retinal or 10 microM-retinol for 24 h, though the increases were approx. 70% and 30% respectively of that produced by 10 microM-RA. Pretreatment of HUVECs with cycloheximide inhibited the effect of RA. When HUVECs were incubated with both 10 microM-RA and 5 mM-8-bromo cyclic AMP (or 1 mM-3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor), the increase in TM antigen was greater than that observed with either compound alone. Northern blot analysis showed that treatment of HUVECs with 8-bromo cyclic AMP, RA or RA plus 8-bromo cyclic AMP increased TM mRNA levels by 2.2-, 4.5- and 5.5-fold respectively compared with the untreated control. Furthermore, no significant difference in cellular cyclic AMP levels was observed between RA-treated and control cells. These results indicate that the expression of TM is not only controlled by the intracellular cyclic AMP level but is also affected by RA, and suggest that RA-induced up-regulation of TM on HUVECs is independent of cyclic AMP regulation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Effects of hirsutine, an antihypertensive indole alkaloid from Uncaria rhynchophylla, on intracellular calcium in rat thoracic aorta.

The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla (MIQ.) Jackson, on cytosolic Ca2+ level ([Ca2+]cyt) were studied by using fura-2-Ca2+ fluorescence in smooth muscle of the isolated rat aorta. Noradrenaline and high K+ solution produced a sustained increase in [Ca2+]cyt. Application of hirsutine after the increases in [Ca2+]cyt induced by noradrenaline and high K+ notably decreased [Ca2+]cyt, suggesting that hirsutine inhibits Ca2+ influx mainly through a voltage-dependent Ca2+ channel. Furthermore, the effect of hirsutine on intracellular Ca2+ store was studied by using contractile responses to caffeine under the Ca(2+)-free nutrient condition in the rat aorta. When hirsutine was added at 30 microM before caffeine treatment, the agent slightly but significantly reduced the caffeine-induced contraction. When added during Ca2+ loading, hirsutine definitely augmented the contractile response to caffeine. These results suggest that hirsutine inhibits Ca2+ release from the Ca2+ store and increases Ca2+ uptake into the Ca2+ store, leading to a reduction of intracellular Ca2+ level. It is concluded that hirsutine reduces intracellular Ca2+ level through its effect on the Ca2+ store as well as through its effect on the voltage-dependent Ca2+ channel.

Alkaloids↗
PubMed1992

Mouse and rat strain variations in sensitivity to N-nitroso-diethylamine, hereditary transmission of the trait and the effect of 3-tert-butyl-4-hydroxyanisole on sensitivity.

1. Strain variations among male mice were studied in terms of the number of days of survival with chronic administration of N-nitroso-diethylamine (NDEA). Four inbred strains, two F1 progenies and one F2 progeny were tested. 2. BALB/c mice survived for the longest period, whereas C3H mice survived for the shortest time. Results of examinations of BALB/c-C3H-F1, -F2 and C57BL-CBA-F1 mice revealed that the hereditary trait could be adequately explained by postulating two loci of genes or gene clusters that regulate the sensitivity to NDEA. 3. Simultaneous chronic administration of 3-tert-butyl-4-hydroxyanisole (BHA) could prolong the survival period. 4. Preliminary histopathological examinations of the liver tissues revealed that the lesion at the time of death of the mice varied considerably depending on the strain and the length of survival. Evidence for hereditary transmission of the characteristics of histopathological changes, including development of liver hemangiosarcoma, is presented. 5. The strain variations among male and female rats were also studied in terms of the number of days of survival with chronic administration of NDEA. Five strains and one F1 progeny were tested. 6. From these and previous observations, the possible biochemical factors determining sensitivity to NDEA were discussed.

Animals↗
PubMed1992

Long-term activation of protein kinase c causes chronic Na/H antiporter stimulation in cultured proximal tubule cells.

To examine the role of protein kinase C as a chronic regulator of proximal tubule Na/H antiporter activity, the effect of phorbol 12-myristate 13-acetate (PMA) on the Na/H antiporter was studied in cultured proximal tubule cells. Short-term activation of protein kinase C by 5 min exposure to PMA caused an acute increase in Na/H antiporter activity that was not prevented by cycloheximide or actinomycin D and did not persist 24 h later. Long-term activation of protein kinase C by 2 h exposure to PMA caused a dose-dependent increase in Na/H antiporter activity 24 h later. This latter effect was due to protein kinase C activation in that it was inhibited by sphingosine and was not seen with 4 alpha-PMA, an inactive analogue. The chronic effect of PMA was inhibited by 10 nM actinomycin D or 7 microM cycloheximide. Proximal tubule cells exposed to PMA for 2 h demonstrated a two- to threefold increase in Na/H antiporter mRNA (mRNANa/H) abundance 4 h later. In conclusion, short-term activation of protein kinase C leads to a transient increase in Na/H antiporter activity that is independent of transcription and translation, whereas long-term activation of protein kinase C causes a persistent increase in antiporter activity that is dependent on transcription and translation and is associated with increased mRNANa/H abundance. This latter effect may mediate increased Na/H antiporter activity in a number of chronic conditions.

Animals↗
PubMed1992

Induction of stress proteins in cultured myogenic cells. Molecular signals for the activation of heat shock transcription factor during ischemia.

Expression of major stress proteins is induced rapidly in ischemic tissues, a response that may protect cells from ischemic injury. We have shown previously that transcriptional induction of heat-shock protein 70 by hypoxia results from activation of DNA binding of a preexisting, but inactive, pool of heat shock factor (HSF). To determine the intracellular signals generated in hypoxic or ischemic cells that trigger HSF activation, we examined the effects of glucose deprivation and the metabolic inhibitor rotenone on DNA-binding activity of HSF in cultured C2 myogenic cells grown under normoxic conditions. Whole-cell extracts were examined in gel mobility shift assays using a 39-bp synthetic oligonucleotide containing a consensus heat-shock element as probe. ATP pools were determined by high-pressure liquid chromatography and intracellular pH (pHi) was measured using a fluorescent indicator. Glucose deprivation alone reduced the cellular ATP pool to 50% of control levels but failed to activate HSF. However, 2 x 10(-4) M rotenone induced DNA binding of HSF within 30 min, in association with a fall in ATP to 30% of control levels, and a fall in pHi from 7.3 to 6.9. Maneuvers (sodium propionate and amiloride) that lowered pHi to 6.7 without ATP depletion failed to activate HSF. Conversely, in studies that lowered ATP stores at normal pH (high K+/nigericin) we found induction of HSF-DNA binding activity. Our data indicate that the effects of ATP depletion alone are sufficient to induce the DNA binding of HSF when oxidative metabolism is impaired, and are consistent with a model proposed recently for transcriptional regulation of stress protein genes during ischemia.

Acidosis↗
PubMed1992

[A case report of laparoscopic adrenalectomy].

Laparoscopic left adrenalectomy was performed on a 47 years old male patient with primary aldosteronism. Subcutaneous steel traction method was utilized in addition to intraperitoneal CO2 insufflation method. The combined use of steel traction method reduced CO2 insufflation pressure below 12 mmHg and might reduce possibility of CO2-related complications. A left adrenal gland was approached by a resection of phrenic colic ligament and a traction of a transverse and descending colon. Laparoscopic adrenalectomy has distinct advantages over open adrenalectomy in terms of avoidance of skin and muscle incision and rib resection, and early convalescence. This less invasive method might prevail in near future.

Adrenal Gland Neoplasms↗
PubMed1992

[Laparoscopic nephrectomy. Animal experiment and clinical application].

Laparoscopic nephrectomy was carried out on 6 sows in order to develop the procedures of clinical laparoscopic nephrectomy and the equipment necessary for this operation. Based on the animal experiments, it was shown that (1) retroperitoneal approach was difficult due to narrow space. (2) there must be at least 5 cm distance between each trocar and 4 or 5 trocar 1 cm in diameter were basically required. (3) The procedure consisted of incision and dissection of the peritoneum around the kidney, cutting and ligation of the ureter, dissection along the medial side of the ureter to approach the renal pedicle and clipping and cutting of the renal vessels. (4) The equipment required for this surgery must be functionally equivalent to those used in the open surgery. (5) In addition, the specifically designed equipment, such as a morcellator and an instrument to ligate renal vessels are necessary. The first clinical case of laparoscopic nephrectomy was a 34 years old man with a right non-functioning hydronephrosis due to ureteropelvic junction stricture. The surgery was successfully performed with a 110 ml blood loss. It took 7 and half hours because of abundant peri-renal fatty tissue and large extra-renal pelvis. The convalescence was uneventful. Laparoscopic nephrectomy can be applied on selected cases and the development of equipment will make the surgery more popular.

Animals↗