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Biomedical subjects

S Hata

Publications and source records attributed to S Hata.

At least 73 records · Page 4Linked to original sources
PubMed1998

Leukoencephalopathy induced by chemotherapy with tegafur, a 5-fluorouracil derivative.

We report an autopsy case of a 64 year-old Japanese man diagnosed as having leukoencephalopathy caused by tegafur, a 5-fluorouracil derivative, and review seven previous cases, mostly reported in Japan. In the present case, tegafur had been orally administered for the shortest period of 3 weeks in pre- and postoperative cancer chemotherapy. He died 2 years later after having made a slight recovery from a prolonged akinetic mute state. Unlike similar cases previously reported, the degeneration of the white matter was most prominent in the temporal lobes. Histologically, the severely involved white matter showed nearly complete myelin and axonal loss with a proliferation of hypertrophic astrocytes. In the less severely involved areas, such as in the frontal white matter where myelin was relatively well preserved, numerous activated microglial cells and a small number of T lymphocytes were identified immunohistochemically. The cerebral cortex, cerebellum and brain stem were well preserved, which is consistent with the previous reports. Literature review revealed that the histopathological features of the lesions reported in human cases are quite different from those reported in animal experiments.

Antimetabolites, Antineoplastic↗
PubMed1998

Ascidian phenoloxidase: its release from hemocytes, isolation, characterization and physiological roles.

Hemocytes of the solitary ascidian Halocynthia roretzi released phenoloxidase in response to sheep red blood cells and yeast cells but not to latex beads. Phenoloxidase was also released from the hemocytes by treatments with zymosan and lipopolysaccharides but not with beta 1-3 glucan. EDTA scarcely inhibited the activity of phenoloxidase but inhibited the release of the enzyme. Phenoloxidase was purified from H. roretzi hemocytes by SP-Sephadex chromatography and Sephadex G-100 gel filtration. The molecular weight of the purified enzyme was estimated to be 62,000. Phenoloxidase activity was strongly inhibited by diethyldithiocarbamate, phenylthiourea and reducing agents. H. roretzi phenoloxidase was characterized as a metalloenzyme that required copper ions for the expression of full activity. The phenoloxidase showed antibacterial activity in the presence of L-(3,4-dihydroxy)-phenylalanine and H. roretzi plasma. Thus, it can be concluded that phenoloxidase released from H. roretzi hemocytes functions as a humoral factor in the defense system of H. roretzi.

Animals↗
PubMed1998

Expression of a soybean nodule-enhanced phosphoenolpyruvate carboxylase gene that shows striking similarity to another gene for a house-keeping isoform.

Three different cDNAs for phosphoenolpyruvate carboxylase (PEPC) were isolated from soybean root nodules. The full-length cDNA of the most abundant isoform (GmPEPC7) was very similar to another one (GmPEPC15), the nucleotide sequence of which is identical to that of a reported clone (gmppc1) (Vazquez-Tello, A., Whittier, R.F., Kawasaki, T., Sugimoto, T., Kawamura, Y. and Shibata, D. (1993) Plant Physiol. 103, 1025-1026). In the coding region, the newly isolated GmPEPC7 and the previously reported were gmppc1 99% and 98% identical at the amino acid and nucleotide levels, respectively. In contrast, they exhibited only 39% identity in the 3' non-coding region, indicating that they are encoded by distinct genes. Northern blot analysis with 3' non-coding regions as isoform-specific probes showed that GmPEPC7 is nodule-enhanced whereas GmPEPC15 (gmppc1) is expressed in most soybean tissues. The third clone (GmPEPC4) was much less homologous to the above two clones and thus was not further characterized. It was also shown by in situ hybridization that the nodule-enhanced isoform is expressed in all cell types in nodules, including in Bradyrhizobium-infected and uninfected cells and cortical cells. A relatively strong hybridization signal was detected in the vascular bundle pericycle. Southern blot analysis indicated that there are only two PEPC genes exhibiting a high degree of similarity in the soybean genome, one for the nodule-enhanced GmPEPC7 and the other for the constitutively expressed gmppc1. A phylogenetic tree based on the amino acid sequences of soybean PEPCs and nodule-enhanced PEPCs of alfalfa and pea suggested that the soybean nodule-enhanced isoform evolved from the housekeeping PEPC gene after the ureid-translocating and amide-translocating legumes diverged from each other.

Base Sequence↗
PubMed1998

The treatment of neuroleptic malignant syndrome using dantrolene sodium.

The use of dantrolene sodium (DS) in the treatment of neuroleptic malignant syndrome (NMS) was studied from the data of 21 cases of NMS, which satisfied the diagnostic criteria of Pope et al. The mean dosage of DS was 0.97+/-0.52 mg/kg per day and the mean duration of treatment was 8.3+/-5.3 days. It was confirmed that the mean duration of treatment with DS tended to be longer in the cases involving disturbance of consciousness. However, there were no significant differences in the duration of treatment or the mean daily dosage, in the cases without disturbance of consciousness regardless of any other complications and symptoms. Also, there were no significant differences in the mean duration of treatment using DS and the mean dosage of DS between five cases that were considered to be 'typical' and 16 cases that were considered to be 'incomplete'. In addition, the prognoses of these cases were good such that not even one death occurred. In 13 cases, the treatment of psychiatric symptoms with thioridazine was started without recurrence of NMS.

Adolescent↗
PubMed1998

Pirfenidone improves renal function and fibrosis in the post-obstructed kidney.

BACKGROUND: Pirfenidone (PFD) is a novel anti-fibrotic agent that can prevent and even reverse extracellular matrix accumulation in several organs, as shown by experimental and clinical studies. Unilateral ureteral obstruction (UUO) is a well-characterized model of experimental renal disease culminating in tubulointerstitial fibrosis. METHODS: UUO or sham-operated rats were administered PFD (500 mg/kg/day) in their food for 21 days to examine the effect on collagen production. The renal function was measured in the kidney after release of obstruction which had been maintained for one week to examine the effects of PFD on restoration after renal dysfunction. RESULTS: The collagen content detected by hydroxyproline progressively increased in kidney with UUO for 21 days. These increases were significantly suppressed by administration of PFD. PFD had no effect on collagen production in sham-operated rats. Expression of mRNA for type IV and I collagen and matrix metalloproteinase-2 in the cortex increased with UUO, but was inhibited by PFD treatment. The levels of cortical transforming growth factor-beta (TGF-beta) mRNA progressively rose with UUO for 21 days, but this increase also could be suppressed by PFD. Inulin clearance of the obstructed kidney was markedly depressed and remained low at five weeks after release. A progressive increase in hydroxyproline content was also observed in the post-obstructed kidney despite the release of obstruction. Administration of PFD following the release not only attenuated collagen accumulation, but also induced recovery of the impaired renal function. CONCLUSIONS: These results demonstrate that PFD can attenuate both renal fibrosis and renal damage in this model, and suggest that PFD can be clinically useful for preventing progressive, irreversible renal failure.

Administration, Oral↗
PubMed1998

Cloning, expression, and characterization of a root-form phosphoenolpyruvate carboxylase from Zea mays: comparison with the C4-form enzyme.

A full-length cDNA for maize root-form phosphoenolpyruvate carboxylase (PEPC) was isolated. In the coding region, the root-form PEPC showed 76 and 77% identity with the C4- and C3-form PEPCs of maize, respectively, at the nucleotide level. At the amino acid level, the root-form was 81 and 85% identical to the C4- and C3-form PEPCs, respectively. The entire coding region was inserted into a pET32a expression vector so that it was expressed under the control of T7 promoter. The purified recombinant root-form PEPC had a Vmax value of about 28 mumol min-1 (mg protein)-1 at pH 8.0. The K(m) values of root-form PEPC for PEP and Mg2+ were one-tenth or less of those of C4-form PEPC when assayed at either pH 7.3 or 8.0, while the value for HCO3- was about one-half of that of C4-form PEPC at pH 8.0. Glucose 6-phosphate and glycine had little effect on the root-form PEPC at pH 7.3; they caused two-fold activation of the C4-form PEPC. The Ki (L-malate) values at pH 7.3 were 0.12 and 0.43 mM for the root- and C4-form PEPCs, respectively. Comparison of hydropathy profiles among the maize PEPC isoforms suggested that several stretches of amino acid sequences may contribute in some way to their characteristic kinetic properties. The root-form PEPC was phosphorylated by both mammalian cAMP-dependent protein kinase and maize leaf protein kinase, and the phosphorylated enzyme was less sensitive to L-malate.

Amino Acid Sequence↗
PubMed1998

Endothelin-1 enhances nitric oxide-induced cell death in cultured vascular smooth-muscle cells.

Increased expression of endothelin-1 (ET-1) immunoreactivity is demonstrated in the active atherosclerotic plaque. Here we show that both ETA and ETB receptors are expressed in rat vascular smooth-muscle cells (VSMCs). ET-1 binding to ETB receptors enhances nitric oxide-induced cell death in VSMCs. These findings suggest that ET-1 may participate in the mechanism of cell death (apoptosis) in the plaque through activation of ETB-mediated pathways and that a selective ETB receptor antagonist could be useful in preventing acute plaque alterations, such as plaque rupture.

Amino Acid Sequence↗
PubMed1998

Oligodendroglioma with signet-ring cell morphology: a case report with an immunohistochemical and ultrastructural study.

A case of oligodendroglioma with signet-ring cell (SRC) morphology arising in the right thalamic region in a 12-year-old boy is described. Histopathologically, the tumor was a composite neoplasm consisting of typical oligodendroglioma and anaplastic components with aggregates of SRC. Immunohistochemically the SRC were negative for glial fibrillary acidic protein (GFAP) but surrounded by GFAP-positive anaplastic cells with high-grade nuclear features. Typical oligodendrogliomatous components were negative for GFAP. The Ki-67 labeling index evaluated with MIB-1 antibody was 1.3% in the SRC component, 9.2% in the GFAP-positive anaplastic cell component, and 0.8% in the typical oligodendrogliomatous component. Ultrastructurally, the cytoplasm of the SRC was filled with irregularly and widely dilated cisternae of rough endoplasmic reticulum containing granular material. Intermediate filaments and a small number of other organelles were distributed in the perinuclear and peripheral areas. Both the SRC and anaplastic cells had slender cytoplasmic processes, although those of the SRC were short and few in number. These findings are distinct from those of SRC hitherto described in oligodendrogliomas to date, and suggest that there is a morphological heterogeneity in SRC rarely seen in oligodendrogliomas and that some examples of SRC are related to the anaplastic cells with astrocytic features in their origin.

Antigens, Nuclear↗
PubMed1998

Potential contribution of endothelin to renal abnormalities in glycerol-induced acute renal failure in rats.

We studied the possible participation of endothelin-1 (ET-1) in the pathogenesis of renal damage in glycerol-induced acute renal failure (ARF). Cortical mRNA expression of ET-1 increased, peaking at 10 hr postinjury, but this did not occur in the medulla, plasma concentration and urinary excretion of ET-1 also increased in this model. There was no change in ETA receptor mRNA, whereas the ETB receptor tended to be down-regulated in the kidney after glycerol administration. In situ hybridization study demonstrated that elevated expression of prepro ET-1 was predominantly localized in cells in the proximal tubules of the nephritic kidney. The administration (30-3 mg/kg) of S-0139, (+)-disodium 27-[(E)-3-[2-[(E)-3-carboxylatoacryloylamino]-5-hydroxyphenl ]acrylayl oxy]-3-oxoolean-12-en-28-oate, an ETA selective antagonist, after initiation of insult offered dose-dependent prevention against ARF, demonstrating preventing of renal function impairment and mortality. These findings indicate that ET-1 participates in the pathogenesis of acute tubular injury in glycerol-induced ARF and that ETA antagonist may be useful in the treatment of some types of human ARF.

Acute Kidney Injury↗
PubMed1998

[Immunohistochemical study of p53, p27 and PCNA expression in esophageal cancer].

We evaluated the clinical significance of p53, p27 and PCNA expressions in esophageal squamous cell carcinomas. Operative specimens obtained from 70 patients with esophageal squamous cell carcinomas were investigated by staining with antibodies against p53, p27 and PCNA. The correlations among p53, p27 and PCNA expression, clinicopathologic factors and prognosis were studied. The expression of p53 was observed in 55.7%, and it did not correlate to histologic classification, growth pattern, and lymphatic invasion. The expression of p27 was observed in 48.6%, and it correlated to lymph node metastasis. The PCNA positive index (PCNA-PI) was high in the p27 negative cases. The p53 positive and p27 negative group revealed the worst survival rate among groups. Therefore, the p27 positive case, often associated with well differentiated carcinoma, tends to have a slower tumor-growth rate and better prognosis. It is suggested that immunohistochemical assessment on the p53 and p27 expressions would be useful to the recognize the malignant potential and differentiation of squamous cell carcinoma of the esophagus.

Aged↗
PubMed1998

[Good response in case of hepatocellular carcinoma; a case report of interdisciplinary local therapy].

A 47-year-old male patient with chronic hepatitis had a high AFP level during the follow-up period. Abdominal CT revealed at S5, which led to a diagnosis of hepatocellular carcinoma. In August 1992, partial resection of S5 was performed, and ethanol was injected into the tumor at S2. In July 1993, recurrent tumors were observed at S5 and S3. PEIT was performed for each lesion. In December 1994, multiple recurrence was observed and 4 mg SMANCS was injected through the proper hepatic artery. In July 1995, another 4 mg of SMANCS was injected into the tumors. In June 1996, only a 20 mm lesion at S5 remained while the other lesions disappeared. Under general anesthesia, the patient underwent percutaneous microwave tumor coagulation. In December 1997, the AFP level was normal, and imaging revealed disappearance of the recurrent tumor. Selection of local therapy for hepatocellular carcinoma achieved long survival in our case considering the QOL and frequent therapy administration.

Antineoplastic Agents↗
PubMed1998

Role of virus-induced apoptosis in a host defense mechanism against virus infection.

Many animal viruses are known to induce apoptosis in infected cells. This virus-induced apoptosis has been often described as a mechanism of host defense against virus infection, based on the finding that mutants of an insect virus with the ability to induce extensive apoptosis in some cells cannot grow in the same cells. In animal virus infection, we have shown that (1) viruses can somehow overcome this defense mechanism and that (2) virus multiplication in the apoptotic cells is not as completely suppressed as in the insect virus infection. These results suggest that, in the case of animal viruses, the virus-induced apoptosis does not play the same role in the host defense system as in insect cells. However, by examining the virus infection under the conditions comparable to the infection in vivo, we demonstrated the defensive role of apoptosis in animal virus infection.

Animals↗
PubMed1997

Regulatory phosphorylation of plant phosphoenolpyruvate carboxylase: role of a conserved basic residue upstream of the phosphorylation site.

In order to mimic regulatory phosphorylation of the Ser-15 of maize C4-form phosphoenolpyruvate carboxylase (PEPC), we replaced Ser-15 and Lys-12 with Asp (S15D) and Asn (K12N), respectively, by site-directed mutagenesis. Although both mutant enzymes were catalytically as active as the wild-type PEPC, they showed much less sensitivity to malate, an allosteric inhibitor, similarly to the phosphorylated wild-type PEPC. A maize protein kinase of 30 kDa which is known to be specific to PEPC (PEPC-PK), phosphorylated K12N as well as the wild-type PEPC but not S15D. The phosphorylation of K12N further diminished the sensitivity to malate. Thus, a positive charge of the conserved Lys-12 is not required for the recognition by PEPC-PK but contributes to the intrinsic sensitivity to malate inhibition.

Asparagine↗
PubMed1997

Determination of simvastatin and its active metabolite in human plasma by column-switching high-performance liquid chromatography with fluorescence detection after derivatization with 1-bromoacetylpyrene.

By using a fluorescent derivatization and column-switching technique, a highly sensitive and selective high-performance liquid chromatographic (HPLC) method has been developed for the determination of simvastatin (I, beta-hydroxy-delta-lactone form) and its active hydrolyzed metabolite (II, beta,delta-dihydroxy acid form of I) in human plasma. A plasma sample spiked with internal standards was applied to a C8 solid-phase extraction column. Compounds I and II were separately extracted from plasma into two fractions. Compound I in one of the fractions was hydrolyzed to II. A fluorescent derivative was prepared by esterification of II with 1-bromoacetylpyrene in the presence of 18-crown-6 for both fractions. The pyrenacyl ester of II thus obtained was purified on a phenylboronic acid (PBA) solid-phase extraction column, and was measured by column-switching HPLC with fluorescence detection. The calibration curves for both I and II were linear in the concentration range of 0.1-10 ng/ml. The intra-day coefficients of variation were less than 11.0%, and the accuracies were between 91.7% and 117% within the concentration range for both analytes. The limits of quantification (LOQ) for both analytes were set to 0.1 ng/ml. This assay method has adequate sensitivity and selectivity to measure the concentrations of I and II in human plasma from clinical studies.

Anticholesteremic Agents↗
PubMed1997

cDNA cloning and prokaryotic expression of maize calcium-dependent protein kinases.

Using degenerate oligonucleotide primers corresponding to conserved regions of the calcium-dependent protein kinase (CDPK) family, we carried out a polymerase chain reaction and obtained four distinct partial-length cDNAs from a maize leaf library. We then used these clones as probes for conventional screening and isolated 19 longer clones from another cDNA library of maize seedlings. These clones were classified into four groups based on their DNA cross-hybridization. Two full-length cDNAs, designated as ZmCDPK9 and ZmCDPK7, were sequenced and characterized. The predicted protein of each clone was a typical CDPK with eleven canonical subdomains of protein kinases, and four EF-hand calcium-binding motifs in its N-terminal and C-terminal halves, respectively. The catalytic and regulatory domains were linked by a well-conserved junction domain. The N-terminus of the protein also contained a consensus sequence for an N-myristoylation signal. Northern blot analysis showed that the transcription level of each gene was higher in roots and etiolated leaves than in green leaves. To confirm the calcium dependency of the maize enzymes, the entire coding region of ZmCDPK9 was subcloned into an expression vector so that it was in frame with the vector-encoded peptide tags. A cell-free extract of Escherichia coli transformed with the recombinant plasmid exhibited calcium-dependent phosphorylation activity, using casein as a substrate.

Amino Acid Sequence↗
PubMed1997

Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells.

Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by AII, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2-induced enhancement of DNA synthesis induced by AII. These findings suggest that autocrine HB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC.

Angiotensin II↗
PubMed1997

Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus.

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to the effects of lard, olive oil, safflower oil, or distilled water as the control on the development of insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous non-insulin-dependent diabetes mellitus (NIDDM) with obesity. After 17 or 18 weeks of treatment, the glucose infusion rate (GIR) in the euglycemic insulin-glucose clamp test only showed a significant increase in EPA-E-treated rats compared with control rats given distilled water alone as the vehicle. The GIR in EPA-E-treated animals was approximately three times greater than in the controls. This is the first report to display the influence of various fatty acids on the development of insulin resistance in OLETF rats. We demonstrated that EPA-E prevents the onset of insulin resistance, whereas olive oil and safflower oil have no effect and lard exacerbates insulin resistance. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase of the C18:2, C20:5, and C22:5 components in EPA-E-treated rats and, conversely, a significant decrease in C20:4. In addition, EPA-E-treated rats showed a significant increase in GLUT4 mRNA in skeletal muscle when compared with control rats. Our results indicate that the beneficial effect of EPA-E on insulin resistance in OLETF rats is likely to be dependent on modification of the phospholipid components of the skeletal muscle membrane. These findings suggest that dietary fatty acids may play a key role in the development of insulin resistance in patients with NIDDM.

Animals↗