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Biomedical subjects

S Horikawa

Publications and source records attributed to S Horikawa.

At least 37 records · Page 2Linked to original sources

MRI of enlarged endolymphatic sacs in the large vestibular aqueduct syndrome.

We studied ten inner ears of five patients with a bilateral large vestibular aqueduct syndrome, using CT and MRI. Although the large vestibular aqueduct varied in size, a markedly dilated endolymphatic sac extending to the sigmoid sinus was demonstrated bilaterally on MRI in all patients. The cause of hearing loss in this syndrome is unclear. However, it is suggested that reflux of the protein-rich, hyperosmolar endolymph from the enlarged endolymphatic sac (EES) into the cochlea through a widely patent endolymphatic duct may damage the neuroepithelium. CT density and spin-echo MRI signal intensity of the endolymph in EES were markedly higher than those of CSF in eight inner ears of four patients. Increased density and high signal may indicate protein-rich, hyperosmolar endolymph. In some patients with sensorineural hearing loss and EES, the vestibular aqueduct may not appear dilated on CT. MRI is therefore necessary for correct diagnosis of this syndrome, which should more correctly be termed "large endolymphatic duct and sac syndrome". Prominent EES may predict poor prognosis in this syndrome.

Adolescent↗

The repetitive activation of extracellular signal-regulated kinase is required for renal regeneration in rat.

In this study, we investigated the activation of p42 extracellular signal-regulated kinase (ERK2) during renal regeneration after HgCl2-induced acute renal failure (ARF) in rat. ERK2 activation was observed at 5 and 29 hr after HgCl2 injection, respectively. The tyrosine phosphorylation of hepatocyte growth factor receptor (c-MET) occurred between 2.5 and 5 hr after the treatment. On the other hand, the phosphorylation of epidermal growth factor receptor (EGFR) was transiently observed at 29 hr after the injection. The peak of ornithine decarboxylase activity as a marker of G1 phase was at 10 hr, and subsequently the labeling index of proliferating cell nuclear antigen as a marker of S phase increased at 53 hr. These results indicate that the repetitive activation of ERK2 related to the phosphorylation of c-MET and EGFR is required for the renal regeneration in HgCl2-induced ARF of rat.

Acute Kidney Injury↗

Both positive and negative portal venous and hepatic arterial glucose gradients stimulate hepatic glucose uptake after the same amount of glucose is infused into the splanchnic bed in conscious dogs.

We studied the effects of both positive and negative portal venous and hepatic arterial glucose gradients on hepatic glucose uptake after the same amount of glucose was administered into the portal vein and/or hepatic artery. Studies were performed on eight unrestrained conscious dogs with catheters in the portal vein, hepatic vein, gastroduodenal artery, superior mesenteric vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Glucose was infused as follows: protocol 1, 55.6 micromol/kg/min into the portal vein for the first 90 minutes; protocol 2, 27.8 micromol/kg/min into both the portal vein and hepatic artery for the next 90 minutes; and protocol 3, 55.6 micromol/kg/min into the hepatic artery for the last 90 minutes. The portal venous and hepatic arterial plasma glucose gradient was 2.1+/-0.3, -3.0+/-0.5, and -7.1+/-0.6 mmol/L, the rate of hepatic glucose uptake divided by the administered glucose load was 46%+/-11%, 42%+/-10%, and 57%+/-8%, net hepatic glucose uptake was 25.4+/-5.9, 23.5+/-5.6, and 31.6+/-4.6 micromol/kg/min; and the fractional hepatic extraction of glucose was 10.7%+/-2.2%, 11.6%+/-2.5%, and 15.0%+/-2.1%, respectively (mean+/-SEM of three points at 60, 75, and 90 minutes in each protocol). The rate of hepatic glucose uptake divided by the administered glucose load, net hepatic glucose uptake, and fractional hepatic extraction of glucose did not change significantly despite the various portal venous and hepatic arterial glucose gradients. We also studied the effect of the same amount of intraportal glucose infusion for 240 minutes on net hepatic glucose uptake. From 60 to 240 minutes, net hepatic glucose uptake did not change significantly. In conclusion, the liver took up a large amount of glucose administered into the portal vein and/or hepatic artery, regardless of positive or negative portal venous and hepatic arterial glucose gradients. Augmentation of hepatic glucose uptake is not dependent on the signal of the positive or negative portal venous and hepatic arterial glucose gradient.

Animals↗

Structure of the rat methionine adenosyltransferase 2A gene and its promoter.

In this study, to understand the regulation of methionine adenosyltransferase (MAT) gene expression, we isolated the rat MAT2A gene encoding MAT alpha2, the catalytic subunit of non-hepatic-type enzyme MAT II and characterized its structural organization and 5'-flanking region. The gene spans approximately 7 kbp and consists of nine exons interrupted by eight introns. The transcription initiation site, as demonstrated by primer extension analysis, is located 123 bp upstream of the translation start codon. Comparison of the structural organization of the rat MAT2A gene to that of the mouse MAT1A gene encoding MAT alpha1, the subunit of liver-type enzymes MAT I and III, shows that the exon structure of two genes is very similar and the insertion sites of all corresponding introns are identical. A canonical TATA box and a GC box, the potential Sp1-binding site, are found 32 bp and 70 bp upstream of the transcription initiation site, respectively. The 5'-flanking region also contains potential recognition sites for various transcription factors including AP-1, AP-2 and NF-IL6 (C/EBPbeta), and a large G+C-rich domain with the characteristics of a CpG island. The 5'-flanking sequence of the rat MAT2A gene has no significant similarity with those of the MAT1A genes. Transient transfection experiments using a luciferase reporter gene showed that the first 820-bp sequence of the 5'-flanking region directed high levels of luciferase activity in cultured rat kidney fibroblast (NRK-49F) and hepatocellular carcinoma (FAA-HTC1) cells, but not in primary rat hepatocytes. Deletion analysis suggested that the first 343 bp of the 5'-flanking region contained cell-type-specific promoter elements of this gene.

Animals↗

Effects of vitamin E deficiency and glutathione depletion on stress protein heme oxygenase 1 mRNA expression in rat liver and kidney.

Heme oxygenase 1 (HO-1) is a stress protein and has been suggested to provide defense mechanisms against agents that may induce oxidative injury. Vitamin E (VE) is considered to function as an important cellular antioxidant. Rats were fed a VE-deficient (0E) or a VE-sufficient (10E) diet for 6 weeks and then were intraperitoneally administered buthionine sulfoximine (BSO), a glutathione (GSH)-depleting reagent. Whereas HO-1 mRNA levels were undetectable in untreated 0E and 10E rat livers, BSO administration induced HO-1 mRNA expression in both 0E and 10E rat livers. High levels of HO-1 mRNA expression were observed in particular in BSO-treated 0E rat livers. The time-course of changes in HO-1 mRNA expression in 0E rat liver after BSO administration showed that HO-1 mRNA expression was transiently induced at 2.5 hr after BSO treatment, the earliest time examined. In addition, to determine whether VE deficiency and GSH depletion affect the expression of HO-1 mRNA in other tissues, we also examined the time-course of HO-1 mRNA expression in BSO-treated 0E rat kidney. The expression pattern of HO-1 mRNA in the kidney was very similar to that in the liver, and the peak was also observed at about 2.5 hr after BSO administration. Interestingly, histologic assessment of liver and kidney showed that VE deficiency and GSH depletion induced injury in the kidney, but not in the liver.

Animals↗

Regulation and immunohistochemical analysis of stress protein heme oxygenase-1 in rat kidney with myoglobinuric acute renal failure.

Intramuscular injection of hypertonic glycerol solution to rats results in acute renal injury. In this model, the proximal tubules are characteristically damaged. After glycerol injection renal glutathione (GSH) levels drastically decreased. On the other hand, stress protein heme oxygenase-1 (HO-1) was induced. When N-acetyl cysteine was administered to rats before 1 h glycerol injection, renal function was obviously improved. In this condition, the renal GSH content were sustained in the normal levels and HO-1 protein levels were decreased compared with those of glycerol-treated rats. Induction of HO-1 was accompanied by reduced renal GSH content. In addition, to investigate whether the location of HO-1 protein induced by glycerol injection is restricted to injured region or not in the kidney, we determined the localization of HO-1 protein using immunohistochemical staining. HO-1 protein was identified in the epithelia of the distal tubules, Henle's loop and collecting ducts, but not in the injured proximal tubules.

Acetylcysteine↗

Differential expression of S-adenosylmethionine synthetase isozymes in different cell types of rat liver.

Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, liver-type and nonhepatic-type enzymes, which are the products of two different genes. It is known that the liver-type isozyme is only expressed in adult liver. Whereas, the nonhepatic-type isozyme is widely distributed in various tissues. In addition to the liver-type isozyme, a minor amount of the nonhepatic-type isozyme is also detected in adult liver. To investigate the distribution of these two isozymes in the liver in detail, the localization of these two isozymes was examined in each cell type of liver using a combination of cell fractionation technique and Western blot analysis. In the parenchymal cells, the liver-type isozyme protein was predominantly expressed, and a small amount of the nonhepatic-type isozyme protein was also detected. On the other hand, in the stellate cells the nonhepatic-type isozyme protein was exclusively or only expressed. Interestingly, a large amount of both isozymes were present in endothelial and Kupffer cell fraction. Using both antibodies to anti-rat nonhepatic-type and liver-type isozymes, respectively, immunohistochemical analysis clearly confirmed these results. In addition, in cultured hepatocellular carcinoma cells (FAA-HTC1), the nonhepatic-type isozyme protein only was detected, and the liver-type isozyme protein completely disappeared. This result indicates that the changes in the isozyme expression is regulated within the parenchymal cells. Administration of hepatotoxic drug carbon tetrachloride (CCl4) to rats resulted in about 40% to 50% reduction of enzyme activity in parenchymal cells and stellate cells compared with those of control rats. However, enzyme activity in endothelial and Kupffer cell fraction was not changed.

Animals↗

Surgical management of Mycobacterium avium complex disease.

Between July 1991 and October 1996, eight patients with Mycobacterium avium complex (MAC) underwent pulmonary resection in our department. There was equal distribution of men women. The length of the preoperative period averaged 8.1 months (range: 1 to 30 months). Surgical resection was complete, consisting of lobectomy in 4 patients, lobectomy with partial resection in 2, segmentectomy in 1, and segmentectomy with partial resection in 1. There were no major complications postoperatively. No patients had positive sputum culture with MAC just after operation; however, one patient had positive sputum culture 6 months after operation. Our results show the good outcome of resectional surgery for MAC in properly selected patients, who should be operated as early as possible.

Female↗

Molecular cloning of rat p38 mitogen-activated protein kinase and it's osmotic regulation in rat kidney.

Rat p38 mitogen-activated protein (MAP) kinase cDNA was isolated from rat kidney cDNA library using a PCR cloning strategy. The deduced amino acid sequence consists of 360 amino acids and shares 95.3% similarity with human p38 MAP kinase. The message for rat p38 MAP kinase was about 3.4 kilobases and was highly expressed in the kidney. In water-deprived rat kidneys, the steady-state levels of p38 MAP kinase mRNA increased about 2.7-fold as compared with those of control rats. This result suggests that p38 MAP kinase may play an important role in the osmoregulation in the kidney.

Amino Acid Sequence↗

Immunohistochemical analysis of heme oxygenase-I in rat liver after ischemia.

Total hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct. After 15 min hepatic ischemia, we examined a time course of the changes in the steady-state levels of heme oxygenase-1 (HO-1) mRNA and protein in the livers. The levels of HO-1 mRNA was transiently induced and peaked at 4 h after the start of reperfusion. In addition, a pattern of the time course of HO-1 protein levels was similar to that of HO-1 mRNA levels. Immunohistochemical analysis clearly showed that the localization of HO-1 protein induced by hepatic ischemia was restricted to the hepatocytes in the pericentral vein.

Animals↗

Bioactive constituents of Chinese natural medicines. IV. Rhodiolae radix. (2).: On the histamine release inhibitors from the underground part of Rhodiola sacra (Prain ex Hamet) S. H. Fu (Crassulaceae): chemical structures of rhodiocyanoside D and sacranosides A and B.

The methanolic extract of the underground part of Rhodiola sacra (PRAIN ex HAMET) S. H. Fu was found to show inhibitory activity on the histamine release from rat peritoneal exudate cells induced by an antigen-antibody reaction. From the methanolic extract with the inhibitory activity on histamine release, a new cyanoglycoside called rhodiocyanoside D and two new monoterpene glycosides called sacranosides A and B were isolated, together with eight known compounds, rhodiocyanoside A, heterodendrin, lotaustralin, rhodioloside, 2-phenylethyl alpha-L-arabinopyranosyl(1-->6)-beta-D-glucopyranoside, 2-methyl-3-buten-2-yl beta-D-glucopyranoside, kenposide A, and rhodiooctanoside. The structures of new compounds were determined on the basis of chemical and physicochemical evidence, which included the synthesis of sacranoside A from (-)-myrtenol. All major chemical constituents from R. sacra inhibited the histamine release and, among them, lotaustralin and rhodiooctanoside were found to show potent inhibitory activity.

Animals↗

Interleukin-2 induces gamma-S-adenosyl-L-methionine synthetase gene expression during T-lymphocyte activation.

The regulation of expression of the gamma-S-adenosyl-L-methionine (AdoMet) synthetase gene was investigated in T-cells during G0/G1 transition, as well as throughout the G1 phase. Stimulation of G0 T-lymphocytes with concanavalin A induces AdoMet synthetase gene expression, starting 8 h after stimulation. Interleukin-2 (IL-2) stimulates the induction of this gene expression and AdoMet synthetase activity in G1 lymphoblasts, in part by an increase in the transcription rate of the gene. Phorbol esters, which also stimulate the proliferation of G1 lymphoblasts, show a similar kinetics of AdoMet synthetase mRNA induction. In contrast, the mRNA levels of the S-adenosyl-L-homocysteine hydrolase, another enzyme of the methionine cycle, remain unchanged upon IL-2 or phorbol 12,13-dibutyrate treatment. Dexamethasone and 8Br-cAMP, both inhibitors of lymphocyte proliferation, are able to block the expression of the AdoMet synthetase gene and, consequently, AdoMet synthetase activity. Together these findings indicate that the AdoMet synthetase gene is subject to cell-cycle regulation in T-lymphocytes.

8-Bromo Cyclic Adenosine Monophosphate↗

Expression of S-adenosylmethionine synthetase isozyme genes in regenerating rat liver after partial hepatectomy.

Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, liver-type and non-hepatic-type enzymes. To investigate the possible role of AdoMet synthetase in proliferating cells, we have examined the expression of these two isozyme genes in regenerating rat liver after partial hepatectomy using Northern blot analysis. In normal adult rat liver the non-hepatic-type isozyme mRNA was not detectable, however, when partial hepatectomy was performed, there was an obvious appearance of the non-hepatic-type enzyme mRNA after operation. The levels of non-hepatic-type isozyme mRNA was peaked at 4h and maintained the level at least till 8 h after operation, then decreased. In addition, the liver-type AdoMet synthetase gene expression was also induced by partial hepatectomy with similar time course. These results indicate that these two AdoMet synthetase isozymes may play an important role during the prereplicative phase which precedes DNA synthesis.

Animals↗

Molecular cloning and characterization of a novel truncated from (ClC-2 beta) of ClC-2 alpha (ClC-2G) in rabbit heart.

Two cDNAs encoding rabbit heart Cl- channels (rabClC-2 beta and rabClC-2 alpha) were isolated by a PCR cloning strategy. RabClC-2 beta is a novel cDNA consisting of 2998 bp and encoding the 822-amino acid protein, while rabClC-2 alpha is identical to previously reported ClC-2G. RabClC-2 beta is 68 amino acids truncated from NH2-terminus of rabClC-2 alpha, but all 13 putative hydrophobic domains are conserved in rabClC-2 beta. Although rabClC-2 alpha was suggested to be activated by extracellular hypotonicity, expression of rabClC-2 beta in Xenopus oocytes induced large Cl- currents even in the absence of extracellular hypotonicity. Induction of external hypotonicity did not further increase the amplitude of membrane currents. On the other hand, as similar to rabClC-2 alpha, rabClC-2 beta current was augmented by PKA activation. Thus, different RNA processing of the same gene appears to provide two highly homologous PKA-activated Cl- channels with or without responsiveness to cell swelling in rabbit heart.

Amino Acid Sequence↗

[Intrapleural bleomycin for management of malignant pleural effusions].

We studied the efficacy of intrapleural administration of bleomycin for the management of malignant pleural effusions of non-small cell lung cancer in 24 cases. Bleomycin 60 mg was administered into the pleural space after tube drainage. If the effusion continued, one additional dose was given. The efficacy was seen in 18 cases (75%). The main adverse drug reaction was transient fever among others. There was little toxicity and no cases of pulmonary fibrosis. Intrapleural administration of bleomycin is useful in management of malignant pleural effusions.

Aged↗

Expression of deoxyuridine triphosphatase during liver regeneration in rat.

Deoxyuridine triphosphatase (dUTPase) activity increases concomitantly with DNA replication in the course of liver regeneration in rat. We confirmed in this report using Western blot analysis and Northern blot hybridization that the increase of dUTPase activity was derived from expression of the gene. The content of dUTPase protein quantitatively coincided with the activity, they reached to the maximum at about 24 h after partial hepatectomy. We also detected a transcript (1.0 kb) presumed to be a rat spleen dUTPase mRNA by the human dUTPase cDNA probe. This transcript appeared in the liver after a lag of about 16 h, reached to the maximum at 24 h, and could be detected until 48 h after partial hepatectomy. The increase of this transcript nearly coincided with the changes of dUTPase activity and the quantity of enzyme protein. These results indicated that the expression of dUTPase gene is related to the DNA replication.

Animals↗