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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 469 records · Page 26Linked to original sources
PubMed1999

[Combined multimodal therapy for osteosarcoma--neoadjuvant chemotherapy].

Until the 1970s, the survival rate of osteosarcoma patients was less than 20%. By the 1990s, this had improved to 60% to 70%, and limb-sparing procedures have replaced amputation in many patients thanks to effective combination therapy. Neoadjuvant chemotherapy has become an accepted practice in the majority of institutions using protocols which include MTX, ADR, BCD and CDDP as the most active agents against this disease. Newer agents, particularly IFM and ETP, are increasingly incorporated into complex regimens. While several studies have reported multivariate analyses to identify prognostic factors, the histologic response to preoperative chemotherapy remains the most important prognostic factor. Pulmonary metastases are the primary cause of death in patients with osteosarcoma. Although current treatment regimens allow effective salvage therapy for the patients with pulmonary metastases, the actuarial survival rate is 30%. A more effective systemic treatment for those patients is needed. The current management of osteosarcoma is critically reviewed and a treatment strategy is proposed for discussion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Clinical results of cord blood transplantation].

Nearly 1000 cases have received cord blood transplantation in the world since the first successful transplantation by Gluckman. 79 cases have been reported to the Ministry of Health in Japan. Results of sibling transplantation have been good and the survival rates are as good as those in bone marrow transplantation. On the other hands, results of unrelated transplantation seem to be poor due to lower engraftment rate and higher transplant-related mortality. Number of attempts in adults is increasing, but the initial results do not look so good, probably because many transplants were done at the advanced stages, specially in adults. Further analysis and follow-up are needed for more accurate evaluation of this treatment modality.

Adult↗
PubMed1999

Modulation by endogenous nitric oxide of acid secretion induced by gastric distention in rats: enhancement by nitric oxide synthase inhibitor.

The mechanism underlying acid hypersecretion induced by gastric distention was investigated in rats, especially in relation to endogenous nitric oxide (NO). Under urethane anesthesia, rat stomach was distended by instillation of saline (1-10 ml) through the acute fistula that was provided through a pylorus. Gastric samples were collected every 1 h, and the acid secretion was measured by titration with 100 mM NaOH. Gastric acid secretion was increased by distention, and the degree of stimulation was dependent on the volume of saline instillation; a maximal response occurred with 6-ml instillation, which maintained the intraluminal pressure of about 20 cm H(2)O. The increased acid secretory response induced by distention was completely blocked by omeprazole and significantly mitigated by vagotomy, sensory deafferentation, atropine, or famotidine but markedly enhanced by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). On the other hand, the enhanced acid response in the presence of L-NAME occurred in an L-arginine-sensitive manner and was almost totally abolished by vagotomy and sensory deafferentation as well as by atropine. Gastric distention increased the release of NO metabolites and histamine into the gastric lumen. The NO metabolite release in the distended stomach was significantly decreased by vagotomy or L-NAME, whereas the histamine output was decreased by vagotomy but increased by L-NAME in an L-arginine-sensitive manner, respectively. These results suggest that 1) gastric distention increases acid secretion, initially through the perception by sensory neurons of the mechanical stimulation and mainly through the efferent vagocholinergic pathway, with the process being modified by endogenous NO, and 2) this molecule, released in a vagal-dependent manner, exerts a negative influence on acid secretion, at least in part by suppressing histamine release from the histamine-containing cells.

Animals↗
PubMed1999

11p15 translocations involving the NUP98 gene in childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome.

In a survey of childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) in Japan, we found 11p15 translocations in 5 (6%) of 81 children with t-AML/MDS. t(11;17)(p15;q21), t(11;12)(p15;q13), t(7;11)(p15;p15), inv(11)(p15q22), and add(11)(p15) were each found in one patient. Southern blotting and/or RT-PCR analyses revealed rearrangements of the NUP98 gene in tumor samples of all five patients. Rearrangements of DDX10 were detected in t-AML/MDS cells with inv(11), and rearrangements of HOXA9 were detected in t-AML cells with t(7;11). The 17q21 breakpoint of t(11;17) and the 12q13 breakpoint of t(11;12)(p15;q13) coincided with the loci of the HOXB and HOXC gene families, respectively. Therefore, it is reasonable to speculate that one of the HOXB genes and one of the HOXC genes were fused to NUP98 by t(11;17) and t(11;12), respectively, in t-AML/MDS cells. We propose that NUP98 may be a target gene for t-AML/MDS, and that t-AML/MDS with a fusion of NUP98 and HOX or DDX10 genes may be more frequent in children than in patients of other age groups.

Acute Disease↗
PubMed1999

[The clinico-pathological findings of the patients grouped as respiratory motor paralysis preceded type of ALS].

We reported five autopsied patients grouped as respiratory motor paralysis preceded type of ALS (R-ALS) classified as one clinical type of ALS from the patients living beyond respiratory failure reported in the previous paper, in which ALS the ontogenetically new motor functions in the "first motor system" proposed by Holstege involved first. The neuropathological changes of five patients were not limited in the degeneration of conventional "motor system" such as corticospinal tract and spinal and cranial motoneurons, but extended into the realm of "non-motor system", which could show the anterolateral myelin pallor in spinal cord by myelin staining, and detect the fibrillary gliosis of the anterior commissural area, the spinal grey matter of intemediate zone and anterior horn in all patients, and of medullary reticular formation in three one by Holzer staining. These pathological lesions could be included in the "first motor system". Considered from this study of the clinico-pathological findings of R-ALS based on "a new view of ALS", which respiratory failure in ALS is not terminus in ALS and total course of ALS might be TLS, it might be concluded that the clinico-pathologically involved initial lesions of ALS might be in the "first motor system", and include not only degenerations of "motor system", but also those of "non-motor system", which is the basically pathological lesions in ALS. Furthermore, the hitherto clinico-pathological ALS findings, which respiratory failure in ALS is terminus in ALS, could be included in this group, and showed as a part of ALS discussed from this study. Total clinico-pathological on ALS from the initial ones (R-type) to the advanced ones (TLS) including ALS-dementia should be considered further based on "the second and the third motor systems in addition to the first one".

Adult↗
PubMed1999

FGF-FGFR signaling in vertebrate organogenesis.

Fibroblast growth factor and FGF receptor (FGFR) system play significant roles in many biological events including pattern formation in many tissues during vertebrate embryogenesis at early stages. The functions of each of FGFs and their receptors have recently been revealed by a variety of approaches among species. We have recently generated FGF10-deficient mice by gene targeting. This KO mice had complete truncation of the fore-and hindlimbs and with no lung. Analyses of the embryos and marker gene expression showed that FGF10 triggers sequential events, which are essential for formations of limb and lung. Focusing on FGF10 function, the FGF-FGFR system is discussed.

Animals↗
PubMed1999

[Gene structure and transcriptional regulation of vitamin A, D binding proteins and nuclear receptors].

Vitamin A and D play an important role in many biological processes including cell differentiation, proliferation and bone metabolism. These effects are believed to be mediated by specific nuclear receptors such as retinoic acid receptors (RARs) or vitamin D receptor (VDR), that regulate the transcription of a particular set of target genes. Hetero-dimers of RAR or VDR to retinoid X receptors (RXRs) bind target enhancer elements in their gene promoters. The target enhancer elements are referred as RA response elements (RAREs) or vitamin D response elements (VDREs), and composed of two hexamer core motife. DNA-bound RAR/VDR control transcription in a ligand-binding dependent way in co-operation with a multiprotein complex containing RNA polymerase II and a series of auxiliary factors, TFIIA, B, D, E, F and H. During process of ligand-induced transactivation by nuclear receptors, nuclear coactivators interacting with the AF-2 including ligand binding domain (LBD) seems to be involved. Several transcriptional coactivators and corepressors have been recently identified, and their function is currently under investigation.

Genes, Regulator↗
PubMed1999

Dual action of nitric oxide in pathogenesis of indomethacin-induced small intestinal ulceration in rats.

We investigated the pathogenic role of nitric oxide (NO) in indomethacin-induced intestinal ulceration in rats. Nonfasting animals responded to a single administration of indomethacin (10 mg/kg, s.c.), resulting in multiple hemorrhagic lesions in the small intestine, mostly the jejunum and ileum. The damage was first observed 6 hr after indomethacin, the severity increasing progressively with time up to 24 hr later, accompanied with the gene expression of inducible NO synthase (iNOS) and the increase of nitrite and nitrate (NOx) contents in the mucosa. The ocurrence of damage was significantly prevented when iNOS induction was inhibited by dexamethasone given either once 0.5 hr before or twice 0.5 hr before and 6 hr after indomethacin. Likewise, aminoguanidine (a relatively selective iNOS inhibitor) reduced the severity of damage, irrespective whether given twice or as a single injection 6 hr after indomethacin. By contrast, the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) exhibited a biphasic effect, depending on the time of administration; the pre-administration worsened the damage, while the later administration reduced the severity of these lesions, yet both responses occureed in a L-arginine-sensitive manner. Pre-administration of L-NAME, but not aminoguanidine, significantly decreased NOx production in the intestinal mucosa of normal rats, while the increase of NOx production following indomethacin was significantly suppressed by the later administration of aminoguanidine as well as L-NAME. These results suggest that NO exerts a dual action in the pathogenesis of indomethacin-induced intestinal ulceration; NO generated by cNOS is protective against indomethacin, by maintaining the integrity of intestinal mucosa, while NO derived by iNOS plays a key pathogenic role in the ulcerogenic process.

Animals↗
PubMed1999

[A case of transitional cell carcinoma of the bladder in a juvenile patient].

A case of transitional cell carcinoma of the bladder in a 18-year-old female is presented. Cystoscopic examination revealed a papillary tumor on the left lateral wall. Histopathology of the excised tumor showed transitional cell carcinoma, G1 > 2, pT1a. Recurrence has not been observed for about 1 year, after intravesical pirarubicin therapy.

Administration, Intravesical↗
PubMed1999

The impact of HLA-A matching in corneal transplantation.

Previously, we have reported the results of our retrospective study on the effect of HLA class II allele matching on the outcome of corneal transplant. Here, we demonstrate our findings of the study for HLA class I allele matching in the same study subjects. Eighty transplant recipients were typed for HLA-A, and 79 transplant recipients were typed for HLA-B alleles, by PCR-SSOP. The association between HLA class I allele matching and 1-year rejection-free graft survival was evaluated. When a total of 79 transplant recipients were subdivided into groups with matching (one to four alleles matched) and without matching (no allele matched) for HLA class I (HLA-A and -B), a significantly higher rate of 1-year rejection-free graft survival was detected in transplant recipients with matching, compared with those without matching (p=0.0258). We have found that matching for at least one HLA class I allele was more beneficial especially in high-risk transplant recipients (p=0.0076). Also, an analysis of matching for each locus separately, detected that, HLA-A matching was significantly associated with a higher rate of 1-year rejection-free graft survival. Transplant recipients with HLA-A matching (one or two-alleles matched) had significantly higher rejection-free graft survival compared with those without matching (no allele matched), when high- and low-risk groups were analyzed together (p=0.0099). Furthermore, matching for HLA-A allele was significantly beneficial compared with no matching in high-risk transplant recipients (p=0.0154). Nevertheless, no significant effect of HLA-B matching was detected. We conclude that HLA class I, especially HLA-A matching has a beneficial effect for corneal transplant outcome.

Alleles↗
PubMed1999

[Clinical statistics at the urological clinic of Sanjukai Hospital--statistics on new outpatients over the last five years].

We herein report the clinical statistics on new outpatients over five years from 1994 at our hospital. The average number of new outpatients per year was 8,534.4 (8,366-8,658) and there was only a slight variation in the number over the last five years. The male to female ratio was 1.61:1. Twenty-one percent of the outpatients were referred to us by other sources. The representative operations on outpatients were circumcision, vasectomy, resection of condylomas and resection of caruncles. A statistical study was made on new outpatients according to the international classification of disease. There were 197.0 (2.3%) malignant urogenital tumors per year. There was a tendency for sexually transmitted diseases to increase over the last five years. In males, the major diseases were upper urinary tract stones (23-27%), benign prostatic hypertrophy (19-26%) and prostatitis (15-24%). In females, they were cystitis (57-59%), upper urinary tract stones (17-18%) and neurogenic bladder (3-4%). We conclude that our hospital plays a major role as a private urological hospital.

Adult↗
PubMed1998

Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1.

Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.

Amyotrophic Lateral Sclerosis↗
PubMed1998

cDNA cloning and functional analysis of p28 (Nas6p) and p40.5 (Nas7p), two novel regulatory subunits of the 26S proteasome.

We employed cDNA cloning to deduce the complete primary structures of p28 and p40.5, two novel subunits of PA700 (also called 19S complex), a 700 kDa multisubunit regulatory complex of the human 26S proteasome. These polypeptides consisted of 226 and 376 amino acids with calculated molecular masses of 24428 Da and 42945 Da, and isoelectric points of 5. 68 and 5.46, respectively. Intriguingly, p28 contained five conserved motifs known as 'ankyrin repeats', implying that this subunit may contribute to interaction of the 26S proteasome with other protein(s). Computer-assisted homology analysis revealed high sequence similarities of p28 and p40.5 with yeast proteins, termed Nas6p and Nas7p (non-ATPase subunits 6 and 7), respectively, whose functions are as yet unknown. Disruption of these yeast genes, NAS6 and NAS7, had no effect on cell viability, indicating that neither of the two subunits is essential for proliferation of yeast cells. However, the NAS7, but not NAS6, disruptant cells caused high sensitivity to heat stress, being unable to proliferate at 37 degreesC.

Adenosine Triphosphatases↗
PubMed1998

The promoter of the human 25-hydroxyvitamin D3 1 alpha-hydroxylase gene confers positive and negative responsiveness to PTH, calcitonin, and 1 alpha,25(OH)2D3.

25-Hydroxyvitamin D3 1 alpha-hydroxylase (1 alpha-hydroxylase) catalyzes hydroxylation, mainly in the kidney, of 25-hydroxyvitamin D3 [25(OH)D3] into 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonal form of vitamin D, acting as a key enzyme of vitamin D biosynthesis. Reflecting its biological significance, this enzymatic activity is differentially regulated by several factors involving calcium homeostasis, though the molecular mechanism is poorly understood. In our recent study (K. Takeyama, et al., 1997), we cloned the cDNA of mouse 1 alpha-hydroxylase, and this led us to investigate the regulation of gene expression and the function of the promoter of this gene. Here we report the isolation of the 5' flanking region of the human 1 alpha-hydroxylase gene and the identification of the human 1 alpha-hydroxylase promoter by a primer extension assay. We found that in the identified promoter, a positively regulatory region to parathyroid hormone (PTH) and calcitonin and a negatively regulatory region to 1 alpha,25(OH)2D3 are located around -4 and -0.5 kb, respectively. Thus, we provide direct evidence that the positive and negative regulation of 1 alpha-hydroxylase gene expression by hormones takes place at transcriptional levels through two distinct promoter regions.

Animals↗
PubMed1998

A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with dual antiemetic and gastroprokinetic activities.

A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with a medium perhydroazacycle ring in the amine moiety were prepared, and their antiemetic and gastroprokinetic activities were evaluated. Among them, N-(1-ethylhexahydroazepin-3-yl)-, N-(1-ethyloctahydroazocin-3-yl)- and N-(1-ethyloctahydroazonin-3-yl)-6-methoxy-1H-benzotriazole-5-carbo xamides (24, 36, 37) showed a potent antiemetic activity (inhibition of apomorphine-induced emesis in dogs) along with gastroprokinetic activity (gastric emptying in rats).

Animals↗