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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 577 records · Page 32Linked to original sources
PubMed1998

[A case of renal cell carcinoma in a nonfunctioning kidney caused by staghorn calculus].

A 62-year-old man was referred to our clinic with a chief complaint of gross hematuria. He had bilateral renal staghorn calculi at the age of 50 years and had undergone left nephrolithotomy. However, no treatment had been given to the right staghorn calculi associated with nonfunctioning kidney. Imaging diagnosis demonstrated no mass lesions in the bilateral kidneys. Right nephrectomy revealed renal cell carcinoma, tubular type, mixed subtype, G2, INF-beta with lymph node metastasis to the renal hilum. Cancer cells infiltrated diffusely throughout the entire renal parenchyma. He died of progressive metastases 15 months postoperatively.

Carcinoma, Renal Cell↗
PubMed1998

[Neoadjuvant intraarterial chemotherapy for ten cases of inflammatory breast cancer by Seldinger's methods].

The conventional methods (CM) of intraarterial (IA) chemotherapy for inflammatory breast cancer were catheterizations from superior epigastric and brachial artery under general anesthesia. Since 1997, we selected the Seldinger's methods (SM) for ten cases of the disease to control local effects and simplify the technique. Complications of the SM were slight, and side effects were equal to those with CM. The postoperative pathological findings of the SM showed the direct effects of chemotherapy to tumor cells (degenerative and necrotic changes) as compared with the embolism-like effects of CM. But the overall histological effects of chemotherapy by SM were almost equal to those for CM. The strong points of the SM were as follows: 1) More selective IA chemotherapy is available, 2) one can find the passage of the aim vessels and no trouble related to catheter, 3) general anesthesia is not necessary, and the techniques are simple, 4) the wounds are not remarkable. The disadvantages are as follows: 1) Patients must rest the day of IA chemotherapy, 2) in 20% of the procedures, one can not search the vessels, and 3) in 4 cases complications of stiffness of Mj or Mn pectral muscles were found. In future, we expect more effective results by dose escalation or combination chemotherapy.

Adenocarcinoma↗
PubMed1998

[Microwave tissue coagulation therapy with mini-laparotomy for hepatocellular carcinoma].

Recently microwave tissue coagulation therapy (MCT) has been established as a therapeutic procedure for hepatocellular carcinoma (HCC). The route of approach to penetrate the tumor is two-fold: By the percutaneous route (PMCT) or by conventional laparotomy. PMCT has the advantage of less invasive therapy, however, it is not applicable to a tumor that cannot be detected by ultrasonography. Therefore, we tried MCT with mini-laparotomy. The patient was a 57-year old man with HCC located in the S6 subsegment. The operation was performed at the semi-right side up position, and laparotomy was done by skin incision of 12 cm in the right hypochondral area. MCT was performed about 30 times, with an output of 60 watts for 45 seconds at a time. Abdominal CT image showed a low-density area of 7 x 4 cm on the 18th postoperative day. Slight damage to the liver and no obvious complications were observed. We concluded that a much wider range-coagulation than PMCT was able to be obtained by MCT with mini-laparotomy, and postoperative quality of life was better than MCT with conventional laparotomy.

Carcinoma, Hepatocellular↗
PubMed1998

Expression of matrix metalloproteinase-7 and tissue inhibitor of metalloproteinase-1 in human prostate.

PURPOSE: Matrix metalloproteinase-7 (MMP-7), one of the extracellular matrix-degrading metalloproteinases, plays an important role in carcinoma invasion and metastasis. Tissue inhibitor metalloproteinase-1 (TIMP-1), one of the inhibitors of MMP-7, regulates extracellular matrix turnover. MATERIALS AND METHODS: Gene expression levels of MMP-7 and TIMP-1 were examined in 20 prostate carcinomas after hormonal therapy and 12 benign prostate hyperplasias (BPH) by Northern blot analysis. Enzymatic activities of MMP-7 were examined in 7 prostate carcinomas and 1 BPH in the above prostate tissues by the method of caseinolytic zymography. These data were compared with the clinicopathological features. RESULTS: There were significant correlations between levels of MMP-7 mRNA or the ratio of MMP-7 mRNA/TIMP-1 mRNA and pathological stage (p <0.01), lymph node metastasis (p <0.05), histological differentiation (p <0.05), vascular invasion (p <0.05), and lymphatic invasion (p <0.05). Levels of MMP-7 mRNA and the ratio of MMP-7 mRNA/TIMP-1 mRNA were significantly increased in prostate carcinomas from patients with high levels of serum prostate specific antigen (PSA) (>10 ng./ml.) after hormonal therapy (p <0.05). The activation ratio of pro MMP-7 was elevated in the cases with advanced prostate carcinoma compared with those of organ-confined prostate carcinoma and BPH. CONCLUSION: These results suggest that MMP-7 may play an important role for invasion and metastasis in prostate carcinomas, and the balance between MMP-7 and TIMP-1 expression may relate to an invasive ability of prostate carcinomas.

Aged↗
PubMed1998

Effects of dietary calcium restriction on vascular constriction and relaxation of the rat isolated aorta.

The blood pressure of the rat is influenced by the dietary restriction of calcium. Since the vasomotor activities may be affected by calcium restriction, we measured vasoconstriction as well as endothelium-dependent and endothelium-independent relaxation responses in isolated aortic rings of the Wistar rat. Compared with the control rat fed a normal diet (1.04% calcium), the femur mineral density was significantly reduced in the rat fed the low-calcium (< 0.01%) diet for one month (LC1M) or for three months (LC3M). Although neither LC1M nor LC3M changed Cmax (the maximum constriction induced by phenylephrine) in aortic rings without endothelium, LC3M, but not LC1M, significantly increased CD50 (the dose of phenylephrine inducing 50% of Cmax). On the other hand, the low-calcium diet did not change Cmax and CD50 in rings with intact endothelium. Thel low-calcium diet showed no significant change in the vasorelaxation responses to acetylcholine (Ach) or sodium nitroprusside (SNP). Cyclic GMP production stimulated by Ach or SNP was not affected by calcium restriction. These results suggest that an insufficient calcium supply for three months, attenuates alpha-adrenoceptor-mediated vasoconstriction in the normotensive rat but vasorelaxation responses to Ach or SNP are not affected.

Acetylcholine↗
PubMed1998

[Methods of evaluating SPECT images: the usefulness of the Matsuda's method by the Patlak plot method in children].

Single photon emission computed tomography (SPECT) is a tool to study cerebral blood flow (CBF) kinetics. There are three methods of evaluating SPECT images: visual, semi-quantitative (evaluation of the radioactivity ratio of the cerebral region to the cerebellum [R/CE] or to the thalamus [R/TH]) and quantitative (Matsuda's method by Patlak plot method using 99m Tc-hexamethylpropylene amine oxime radionuclide angiography). We evaluated SPECT images by the quantitative method in 14 patients with neurological disorders and examined the correlation of the results to those obtained by the semi-quantitative method. There was no significant correlation between the R/CE or R/TH ratio and regional CBF except two regions. The evaluation by the semi-quantitative method may have been inappropriate, probably because the cerebellar or thalamic blood flow was not constant in each case. Evaluation by the quantitative method, on the other hand, seemed to be useful not only for the comparison of CBF among normal subjects, but also in the demonstration of progressive changes of CBF in the same case. The Matsuda's method by the Patlak plot method is suitable for examination of children, since it dose not require aortic blood sampling.

Adolescent↗
PubMed1997

Impaired parallel fiber-->Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor delta2 subunit.

The glutamate receptor delta2 subunit (GluRdelta2) is specifically expressed in cerebellar Purkinje cells (PCs) from early developmental stages and is selectively localized at dendritic spines forming synapses with parallel fibers (PFs). Targeted disruption of the GluRdelta2 gene leads to a significant reduction of PF-->PC synapses. To address its role in the synaptogenesis, the morphology and electrophysiology of PF-->PC synapses were comparatively examined in developing GluRdelta2 mutant and wild-type cerebella. PCs in GluRdelta2 mutant mice were normally produced, migrated, and formed spines, as did those in wild-type mice. At the end of the first postnatal week, 74-78% of PC spines in both mice formed immature synapses, which were characterized by small synaptic contact, few synaptic vesicles, and incomplete surrounding by astroglial processes, eliciting little electrophysiological response. During the second and third postnatal weeks when spines and terminals are actively generated, the percentage of PC spines forming synapses attained 98-99% in wild type but remained as low as 55-60% in mutants, and the rest were unattached to any nerve terminals. As a result, the number of PF synapses per single-mutant PCs was reduced to nearly a half-level of wild-type PCs. Parallelly, PF stimulation less effectively elicited EPSCs in mutant PCs than in wild-type PCs during and after the second postnatal week. These results suggest that the GluRdelta2 is involved in the stabilization and strengthening of synaptic connectivity between PFs and PCs, leading to the association of all PC spines with PF terminals to form functionally mature synapses.

Animals↗
PubMed1997

Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galphaq.

Mice lacking the alpha-subunit of the heterotrimeric guanine nucleotide binding protein Gq (Galphaq) are viable but suffer from ataxia with typical signs of motor discoordination. The anatomy of the cerebellum is not overtly disturbed, and excitatory synaptic transmission from parallel fibers to cerebellar Purkinje cells (PCs) and from climbing fibers (CFs) to PCs is functional. However, about 40% of adult Galphaq mutant PCs remain multiply innervated by CFs because of a defect in regression of supernumerary CFs in the third postnatal week. Evidence is provided suggesting that Galphaq is part of a signaling pathway that is involved in the elimination of multiple CF innervation during this period.

Age Factors↗
PubMed1997

Antiarrhythmic effects of cariporide, a novel Na+-H+ exchange inhibitor, on reperfusion ventricular arrhythmias in rat hearts.

Cariporide (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate: HOE642) is a novel Na+-H+ exchange subtype 1 inhibitor and has antiarrhythmic effects on ischemia/reperfusion arrhythmias without apparent cardiovascular effects in dogs and rats when given before coronary occlusion. The aim of this study was to determine the minimum effective dose and to examine the dose related effects of cariporide when it was administered before and during coronary occlusion as well as simultaneously with reperfusion. In the pre-treatment group, cariporide dose-dependently reduced the ventricular tachycardia duration from 140 to 36 (P < 0.01), 59 (P < 0.05) and 23 s (P < 0.01) with 0.03, 0.1 and 1 mg/kg, respectively, and reduced the incidence of reperfusion-induced ventricular tachycardia from 100 to 50 and 58% (P < 0.01), ventricular fibrillation from 83 to 8 and 0% (P < 0.01), and mortality from 75 to 8 and 8% (P < 0.01) with 0.1 and 1 mg/kg, respectively. In the post-treatment group, cariporide dose-dependently reduced the ventricular tachycardia duration from 92 to 37, 40, 42 (P < 0.05) and 24 s (P < 0.01) with 0.03, 0.1, 0.3 and 1 mg/kg, respectively, and the incidence of ventricular tachycardia from 100 to 53% (P < 0.01) by 1 mg/kg, and ventricular fibrillation from 87 to 33, 7 and 7% (P < 0.01), and the mortality from 73 to 27 (P < 0.05), 0 and 7% (P < 0.01) with 0.1, 0.3 and 1 mg/kg, respectively. In the group with simultaneous injection, both doses of cariporide (1 and 3 mg/kg) reduced the incidence of ventricular fibrillation from 83 to 42% (P < 0.05). The heart rate, blood pressure and QT interval did not change after drug treatment.

Animals↗
PubMed1997

cDNA cloning and chromosomal mapping of genes encoding novel protein kinases termed PKU-alpha and PKU-beta, which have nuclear localization signal.

We have cloned cDNAs for novel serine/threonine protein kinases (PK), termed PKU-alpha and PKU-beta, by screening a bacteriophage expression library for kinase activity. Sequence analysis of PKU-alpha and PKU-beta genes revealed that their open reading frames (ORF) were 2151 and 2361 nucleotides (nt) encoding polypeptides of 717 and 787 amino acid (aa) residues, respectively. The deduced aa sequences of PKU-alpha and PKU-beta contained typical serine/threonine PK domains at the C-terminal region and were 86% identical to each other, indicating that they belong to the same PK family. Northern analysis reveals that they are expressed in nearly all human tissues and in cultured cells. The genes for PKU-alpha and PKU-beta were mapped to chromosome 17q23 and 8p12-p22, respectively, by fluorescence in situ hybridization. The proteins encoded by both cDNAs contain a putative nuclear localization signal (NLS) in their N-terminal region. These signals are likely to function in nuclear localization. Glutathione S-transferase (GST)-fusions to regions of PKU-alpha and beta containing the NLS were efficiently localized to the nucleus. In addition, PKU-beta transiently expressed in COS-1 cells was predominantly nuclear. PKU-alpha and PKU-beta differ: a consensus sequence for a nt binding motif is present near the NLS of PKU-beta. These results suggest that PKU-alpha and beta may phosphorylate serine and/or threonine residues on similar proteins, but their activities are regulated through distinct interactions with a nuclear component.

Amino Acid Sequence↗
PubMed1997

Cloning and chromosomal mapping of human casein kinase I gamma 2 (CSNK1G2).

A clone of immature cDNA for human casein kinase I gamma 2 (CSNK1G2) was isolated by screening the human testis cDNA library with a PCR-amplified probe (about 400 bp) representing the kinase domain of rat casein kinase I gamma 2 (CKI gamma 2). Comparison of the entire sequence with that of rat CKI gamma 2 showed that the cDNA contained the complete coding sequence of CKI gamma 2 as well as an intron-like sequence of 1006 bp, part of which was homologous to the Alu sequence. To obtain an insertion-free CSNK1G2 cDNA, PCR cloning was performed based on the above sequence. The amplified 1687-bp fragment was subcloned and sequenced. The predicted amino acid sequence consisted of 416 residues, 94% of which were identical to that of the rat homologue. Although there are two Src homology 3 (SH3) domain-binding motifs (Pro-X-X-Pro consensus), Pro-Lys-Val-Pro and Pro-Ser-Glu-Pro in the C-terminal region of rat CKI gamma 2, only the latter was conserved in the human counterpart. This finding suggests that the latter motif is important for binding to the signal transduction adaptor protein Nck (NCK). The human CSNK1G2 gene was mapped to chromosome 19p13.3 by fluorescence in situ hybridization and PCR analysis of the human/rodent hybrid cell panel.

Amino Acid Sequence↗
PubMed1997

Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia.

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis through binding to the cytokine receptor c-Mpl (the product of the c-mpl proto-oncogene). In an effort to determine the pathophysiological role of TPO-c-Mpl system in essential thrombocythemia (ET), we have examined the levels of serum TPO and the expression and function of platelet c-Mpl in 17 patients with ET. In spite of extreme thrombocytosis, serum TPO levels were slightly elevated or within normal range in most, if not all, patients with ET (mean +/- SD, 1.31 +/- 1.64 fmol/mL), as compared with normal subjects (0.76 +/- 0.21 fmol/mL). Flow cytometric and Western blot analyses revealed that the expression of platelet c-Mpl was strikingly reduced in all patients with ET. Furthermore, the expression of platelet c-mpl mRNA was found to be significantly decreased in the ET patients tested. In contrast, almost identical levels of GPIIb/IIIa protein and mRNA were expressed in platelets from ET patients and normal controls. In addition to expression level, activation state of platelet c-Mpl was investigated in ET patients. Immunoblotting with anti-phosphotyrosine antibody showed that no aberrant protein-tyrosine phosphorylation was observed in platelets of ET patients before treatment with TPO, and the levels of TPO-induced protein-tyrosine phosphorylation, including c-Mpl-tyrosyl phosphorylation, roughly paralleled those of c-Mpl expression, suggesting that c-Mpl-mediated signaling pathway was not constitutively activated in platelets of ET patients. These results suggested that the TPO-c-Mpl system may not be directly linked to pathogenesis of ET, and that gene(s) mutated in ET may be important in regulating the levels of c-mpl gene expression in addition to the growth and differentiation of multipotential hematopoietic stem cells.

Adolescent↗
PubMed1997

The addition of mitogen-activated protein kinase and p34cdc2 kinase substrate peptides inhibits the flagellar motility of demembranated fowl spermatozoa.

The motility of demembranated fowl spermatozoa was vigorous at 30 degrees C, but decreased markedly following the addition of mitogen-activated protein (MAP) kinase or p34cdc2 kinase substrate peptide. Dephosphorylation of approximately 116, 86 and 79-kDa proteins of demembranated spermatozoa was observed after the addition of MAP kinase or p34cdc2 kinase substrate peptide. The activities of MAP kinase and histone H1 kinase of spermatozoa, estimated by measuring the phosphorylation of myelin basic protein and histone H1 as substrates, were 1.22 and 0.29 pmol/min/ mg protein, respectively. Both enzymatic activities of spermatozoa were lower than those of chick brain, but higher than those of chick liver. These results suggest that the phosphorylation of axonemal and/or accessory cytoskeletal proteins mediated by MAP kinase and p34cdc2 kinase may be involved in the regulation of flagellar movement of fowl spermatozoa.

Animals↗
PubMed1997

Abnormal expression of mouse mast cell protease 5 gene in cultured mast cells derived from mutant mi/mi mice.

Mast cells contain a lot of mast cell-specific proteases. We have reported that the expression of mouse mast cell protease 6 (MMCP-6) is remarkably reduced in both cultured mast cells (CMCs) and skin mast cells of mi/mi mutant mice. In the present study, we found that the expression of MMCP-5 was reduced in CMCs but not in skin mast cells of mi/mi mice, and we compared the regulation mechanisms of MMCP-5 with those of MMCP-6. The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). The consensus sequence recognized and bound by bHLH-Zip transcription factors is CANNTG. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-5 gene in mi/mi CMCs, indicating the involvement of +-MITF in transactivation of the MMCP-5 gene. Although +-MITF directly bound CANNTG motifs in the promoter region of the MMCP-6 gene and transactivated it, the binding of +-MITF to the CAGTTG motif in the promoter region of the MMCP-5 gene was not detectable. The +-MITF appeared to regulate the transactivation of the MMCP-5 gene indirectly. Moreover, addition of stem cell factor to the medium normalized the expression of the MMCP-5 but not of the MMCP-6 gene in mi/mi CMCs. Despite the significant reduction of both MMCP-5 and MMCP-6 expressions in mi/mi CMCs, their regulation mechanisms appeared to be different.

Animals↗
PubMed1997

Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene.

Thyrotropin-releasing hormone (TRH) is a brain hypothalamic hormone that regulates thyrotropin (TSH) secretion from the anterior pituitary and is ubiquitously distributed throughout the brain and other tissues including pancreas. To facilitate studies into the role of endogenous TRH, we have used homologous recombination to generate mice that lack TRH. These TRH-/- mice are viable, fertile, and exhibit normal development. However, they showed obvious hypothyroidism with characteristic elevation of serum TSH level and diminished TSH biological activity. Their anterior pituitaries exhibited an apparent decrease in TSH immunopositive cells that was not due to hypothyroidism. Furthermore, this decrease could be reversed by TRH, but not thyroid hormone replacement, suggesting a direct involvement of TRH in the regulation of thyrotrophs. The TRH-/- mice also exhibited hyperglycemia, which was accompanied by impaired insulin secretion in response to glucose. These findings indicate that TRH-/- mice provide a model of exploiting tertiary hypothyroidism, and that TRH gene abnormalities cause disturbance of insulin secretion resulting in marked hyperglycemia.

Animals↗