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Biomedical subjects

Y Nishi

Publications and source records attributed to Y Nishi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Growth inhibition of CD20-positive B lymphoma cell lines by IDEC-C2B8 anti-CD20 monoclonal antibody.

Treatment with IDEC-C2B8 (C2B8), the chimeric anti-CD20 antibody, was shown in a phase I-II study to be very effective for the treatment of low-grade B-cell lymphoma, in contrast to the results of most previous immunotherapies with monoclonal antibodies. In a study designed to elucidate the reason for this efficacy, two cell lines derived from lymphomas with BCL2 gene rearrangement (SU-DHL-4 and SU-DHL-6) showed remarkable growth inhibition and cell-death, and two other cell lines derived from a diffuse lymphoma (RC-K8) and a mantle cell lymphoma (SP-49) showed moderate growth inhibition, but neither a CD20 weakly positive cell line (NALL-1) nor a negative cell line (MOLT-4) showed any growth inhibition. An examination of the intensity of cell-surface CD20 expression showed no correlation between intensity and degree of growth inhibition among the four cell lines showing growth inhibition. Morphological examination revealed condensed and fragmented nuclei and budding of the plasma membrane, both characteristic of apoptosis, with some cells in these cell lines showing growth inhibition by C2B8. Such apoptosis was also confirmed by flow cytometric analysis, suggesting that, at least in part, apoptosis plays a role in this growth inhibition. This growth-inhibitory mechanism may thus account for the effectiveness of C2B8 antibody therapy.

Animals↗
PubMed1998

MRI of cervical intervertebral discs in asymptomatic subjects.

We studied degenerative changes in the cervical intervertebral discs of 497 asymptomatic subjects by MRI and evaluated disc degeneration by loss of signal intensity, posterior and anterior disc protrusion, narrowing of the disc space and foraminal stenosis. In each subject, five disc levels from C2-C3 to C6-C7 were evaluated. The frequency of all degenerative findings increased linearly with age. Disc degeneration was the most common observation, being present in 17% of discs of men and 12% of those of women in their twenties, and 86% and 89% of discs of both men and women over 60 years of age. We found significant differences in frequency between genders for posterior disc protrusion and foraminal stenosis. The former, with demonstrable compression of the spinal cord, was observed in 7.6% of subjects, mostly over 50 years of age. Our results should be taken into account when interpreting the MRI findings in patients with symptomatic disorders of the cervical spine.

Adolescent↗
PubMed1998

Registration system for growth hormone (GH) treatment with standardized immunoreactive GH values in Japan.

The Foundation for Growth Science has been controlling the use of GH by its registration system, which includes a scoring system for the eligibility for GH treatment according to the diagnostic criteria for GH deficiency (GHD) established by the Study Group for Hypothalamo-pituitary Disorder of the Ministry of Health and Welfare. Until 1995, 28,876 patients with GHD (19,432 boys and 9,444 girls) had been registered as eligible for GH treatment. The number of patients registered in a year increased gradually till 1990 due to the unlimited hGH supply by recombinant techniques and the change in the criteria for GH treatment and the number registered became stable after 1990. The frequency of GH-treated patients is calculated to be 55.2/100,000 persons (72.2/100,000 in boys and 37.1/100,000 in girls) in patients born between 1960 and 1990. The highest frequency was 148.4/100,000 persons (191.7/ 100,000 boys and 103.7/100,000 girls) in 1981, when 2,278 patients (1,508 boys and 770 girls) were born. Eligibility for GH treatment is assessed according to the scoring system which is basically dependent on peak GH values in provocation tests so that standardization of GH values measured with the various commercial GH kits is required to avoid inequality of patients' access to the treatment. In samples obtained by GRF test in 10 normal volunteers, hGH was measured with seven human GH (hGH) kits at a laboratory center. Since the RIA value has been used historically for the diagnosis of GHD, the mean of two RIA measurements was selected as the basis for the standardization procedure and the linear regression formula was used for each hGH kit. After the freely available supply of hGH obtained by recombinant DNA techniques, the role of the Foundation for Growth Science has changed to avoid hGH abuse. Even with this regulation, the frequency of registered patients may indicate a tendency to GH overuse.

Child↗
PubMed1998

Long-term outcome in triple-vessel coronary artery disease in medically treated Japanese patients.

The long-term outcome in 198 patients with triple-vessel disease (TVD) treated medically was investigated. The patients, who underwent coronary angiography between September 1973 and February 1984, had significant (75% or more) stenotic lesions in all three major coronary arteries. The mean follow-up period was 8.4 years. The 5- and 10-year survival rates were 80.7% and 64.2%, respectively. Cardiac death occurred in 73 patients (36.9%) and nonfatal cardiac events developed in 60 patients (30.9%) during follow-up. When cardiac death and nonfatal myocardial infarction (MI) were defined as cardiac events, the annual attrition rate was 4.7%. There was no difference in survival with regard to the presence or absence of MI, the site of infarction, or the presence of total occlusion. In the AP group, however, the survival rate decreased as the number of totally-occluded arteries increased. In the MI group, the survival rate was not altered by the number of totally-occluded arteries, but was affected by the ejection fraction (EF). The 5-year survival rate was better in patients with good left ventricular function (EF > or = 60%) than in those with impaired left ventricular function (EF < 60%), although the 10-year survival rate was similarly low in both groups. Revascularization such as PTCA or CABG might improve the long-term outcome in patients with TVD.

Angina Pectoris↗
PubMed1998

KQT2, a new putative potassium channel family produced by alternative splicing. Isolation, genomic structure, and alternative splicing of the putative potassium channels.

Potassium (K+) channels are critical for a variety of cell functions, including modulation of action potentials, determination of the testing membrane potential, and development of memory and learning. Eleven mouse cDNA clones homologous to the new human putative K+ channel (designated HNSPC, which we recently reported) were isolated from the brain cDNA libraries. All these proteins coded by the isolated cDNAs were identical from the N-terminal to the sixth transmembrane domain, but exhibited differences in the sequence and length of the C-terminal cytoplasmic region. Analyses of the mouse genomic DNAs showed that these clones originated from a single gene located on mouse chromosome 2H3-4, which proved that these clones were generated by alternative RNA splicing. Since all isoforms showed significant structural identity with KVLQT1 (64% identity in the transmembrane domains), which is known to associate with IsK, they were designated mKQT2.1-mKQT2.11. Northern blot analysis indicated that the mRNAs of the mKQT2 isoforms were exclusively expressed in the brain. In the mouse cerebellum region, the localized expression of these clones in the Purkinje cell layer and Golgi cells was shown by in situ hybridization analysis. These transcripts were also detected in the mouse embryonic developmental stage (11th, 15th and 17th day); and in particular, the mRNAs for shorter forms (mKQT2.9, mKQT2.10 or mKQT2.11) were abundantly found on the 11th day after gestation. Although these mKQT2 isoforms had the characteristic structure of voltage-gated K+ channels, functional expression of K+ currents were not detected in Xenopus oocytes.

Alternative Splicing↗
PubMed1998

[Relationship between evolution of ischemic heart disease and changes in lipid profile].

The relationship between the evolution of ischemic heart disease and changes in lipid profile was investigated in 115 of 11,875 patients underwent coronary angiography (CAG). The 115 patients had no significant stenosis on initial CAG and underwent repeat CAG for several reasons. Changes in lipid profile and other coronary risk factors were compared in 30 patients who developed ischemic cardiac events (Group E) and 85 patients who did not (Group NE). Ischemic cardiac events were defined as ischemic chest symptoms with ST-T changes or appearance of significant angiographic stenosis. At initial CAG, smoking was significantly more common in Group E (23.3% vs 4.7%, p < 0.01) and high-density lipoprotein cholesterol was significantly lower in Group E (42 +/- 11 vs 48 +/- 15 mg/dl, p < 0.05). At repeat CAG, smoking continued to be significantly more common in Group E (26.7% vs 10.6%, p < 0.05), and serum cholesterol (219 +/- 36 vs 193 +/- 34 mg/dl, p < 0.01) and low-density lipoprotein cholesterol (141 +/- 33 vs 115 +/- 29 mg/dl, p < 0.01) were also significantly higher in Group E. Multivariate analysis revealed only the increase of serum cholesterol at repeat CAG was a significant factor in the evolution of coronary artery disease (p = 0.026). Two patients from Group E died of cardiac causes within 1 year after repeat CAG but no patients in Group NE died (6.7% vs 0%, p < 0.05). Increased serum cholesterol level is related to the evolution of ischemic heart disease and cardiac death.

Cholesterol↗
PubMed1997

Spatial patterns of Ca2+ signals define intracellular distribution of a signaling by Ca2+/Calmodulin-dependent protein kinase II.

Ca2+ plays a central role in cell signaling, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of Ca2+ actions. The spatial distribution of intracellular Ca2+ signaling is not homogenous, rather it is dynamically organized, and it has been speculated that spatial patterns of Ca2+ signals may function as a form of cellular information transmitted to downstream molecules. To address this issue, we studied the intracellular distributions of the signalings by CaMKII and Ca2+ in the same astrocytes. The former was visualized by monitoring site-specific phosphorylation of a cytoskeletal protein vimentin, using site- and phosphorylation-specific antibodies, while the latter was examined by fura-2-based Ca2+ microscopy. Local Ca2+ signals induced vimentin phosphorylation by CaMKII localized in the same area. On the other hand, Ca2+ waves in astrocytes induced global phosphorylation of vimentin by CaMKII. A small population of vimentin filaments highly phosphorylated by CaMKII underwent structural alteration into short filaments at electron microscopic level. These results indicate that CaMKII transmits spatial patterns of Ca2+ signals to vimentin as cellular information. The possibility is discussed that spatial patterns of vimentin phosphorylation may be important for intracellular organization of vimentin filament networks.

Actin Cytoskeleton↗
PubMed1997

Isolation of a cDNA encoding a widely expressed novel zinc finger protein with the LeR and KRAB-A domains.

We have isolated a human cDNA clone representing a novel human gene. The predicted 683-amino-acid protein, designated FPM315, contains nine C2H2-type zinc finger motifs and two regions homologous to the LeR domain, a finger-associated structural domain, and the A element of the Kruppel-associated box (KRAB) domain involved in transcriptional repression. The FPM315 mRNAs were expressed in all human tissues so far examined. A cross-species genomic hybridization indicates that the FPM315 gene is highly conserved among eukaryotes. These data suggest that FPM315 might play an important role in basic cellular processes.

Amino Acid Sequence↗
PubMed1997

Phosphorylation of glial fibrillary acidic protein at the same sites by cleavage furrow kinase and Rho-associated kinase.

Site- and phosphorylation state-specific antibodies are useful to analyze spatiotemporal distribution of site-specific phosphorylation of target proteins in vivo. Using several polyclonal and monoclonal antibodies that can specifically recognize four phosphorylated sites on glial fibrillary acidic protein (GFAP), we have previously reported that Thr-7, Ser-13, and Ser-34 on this intermediate filament protein are phosphorylated at the cleavage furrow during cytokinesis. This observation suggests that there exists a protein kinase named cleavage furrow kinase specifically activated at metaphase-anaphase transition (Matsuoka, Y., Nishizawa, K., Yano, T., Shibata, M., Ando, S., Takahashi, T., and Inagaki, M. (1992) EMBO J. 11, 2895-2902; Sekimata, M., Tsujimura, K., Tanaka, J., Takeuchi, Y., Inagaki, N., and Inagaki, M. (1996) J. Cell Biol. 132, 635-641). Here we report that GFAP is phosphorylated specifically at Thr-7, Ser-13, and Ser-34 by Rho-associated kinase (Rho-kinase), which binds to the small GTPase Rho in its GTP-bound active form. The kinase activity of Rho-kinase toward GFAP is dramatically stimulated by guanosine 5'-(3-O-thio)-triphosphate-bound RhoA. Furthermore, the phosphorylation of GFAP by Rho-kinase results in a nearly complete inhibition of its filament formation in vitro. The possibility that Rho-kinase is a candidate for cleavage furrow kinase is discussed.

Antibodies↗
PubMed1997

Isolation and characterization of cDNA encoding mouse RNA polymerase II subunit RPB14.

By means of the yeast two-hybrid system using the 40-kDa subunit of mouse RNA polymerase I, mRPA40, as the bait, we isolated a mouse cDNA which encoded a protein with significant homology in amino acid sequence to the 12.5-kDa subunit of Saccharomyces cerevisiae RNA polymerase II, B12.5 (RPB11). Specific antibody raised against the recombinant protein that was derived from the cDNA reacted with a 14-kDa polypeptide in highly purified mammalian RNA polymerase II and did not react with any subunit of RNA polymerase I or III. Moreover, the antibody co-immunoprecipitated the largest subunit of mouse RNA polymerase II. These results provide biochemical evidence that the cDNA isolated, named mRPB14, encodes a specific subunit of RNA polymerase II, and indicate that the subunit organization of the enzyme is conserved between yeast and mouse. A possible role of the alpha-motif [Dequard-Chablat, M., Riva, M., Carles, C. and Sentenac, A., J. Biol. Chem. 266 (1991) 15300-15307] in the protein-protein interaction between mRPA40 and mRPB14 is also discussed.

Amino Acid Sequence↗
PubMed1997

Long-term follow-up study of anterior decompression and fusion for thoracic myelopathy resulting from ossification of the posterior longitudinal ligament.

STUDY DESIGN: This was a retrospective study of the results of anterior decompression and fusion in patients with thoracic myelopathy secondary to ossification of the posterior longitudinal ligament with a minimum follow-up time of 5 years. OBJECTIVES: To clarify the effectiveness and limits of anterior decompression and fusion for thoracic ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Posterior decompression for the surgical management of thoracic ossification of the posterior longitudinal ligament has had an uncertain success record. Anterior decompression and fusion have been considered the treatment of choice however, there are few reports describing the long-term results. METHODS: The participants in this investigation were 33 patients whose cases were followed for an average period of 8 years and 2 months. The factors that were investigated included changes in the Japanese Orthopedic Association score and in recovery rates, postoperative complications, and radiographic findings of bone union and progression of ossification of the posterior longitudinal ligament within the area of anterior decompression. RESULTS: Although the recovery rates were relatively stable from 1-5 years after surgery, the rates declined thereafter. The average recovery rate at the final follow-up visit was 53.2%. Postoperative complications included three cases of deterioration of thoracic myelopathy and four cases of extrapleural cerebrospinal fluid leakage. Except for the one case of deterioration of thoracic myelopathy, the remainder of the complications were transient. CONCLUSIONS: Anterior decompression and fusion is an effective surgical procedure for thoracic ossification of the posterior longitudinal ligament with good, stable, long-term results; when thoracic ossification of the posterior longitudinal ligament was extensive or coincident with ossification of the intraspinal ligament, however, the results were not as predictable.

Adult↗
PubMed1997

Open coring-out (function-preserving) technique for low fistulas.

PURPOSE: Fistula operations can be very destructive to the anal sphincters; functional abnormalities occur easily after such surgery (even with an internal spincterotomy, minor incontinence occurs), hence, function-preserving operations are best. A low fistula goes through the thin sphincter muscle layer, making it more difficult to preserve than a deeper fistula. In 1984, we developed a technique to treat long string-type low fistulas showing heavy inflammation and induration from the internal opening to the primary focus, namely, the infected intersphincteric anal gland. This report shows the main surgical techniques used. TECHNICAL METHOD: For the fistula procedure, we developed an "open coring-out" technique in which the whole fistula is pulled out, making the inside and outside clearly visible. The portion from the internal opening to the primary focus is easily opened (fistulotomy), and the primary focus is excised by coring-out (fistulectomy). For the repair procedure, the sphincter muscle edges are fixed to the underlying tissues with two kinds of sutures. The cored portion is provided with adequate drainage and two sutures that narrow and prevent pocket formation. RESULTS: Since 1984, 319 of 5,055 patients with low fistulas have been treated using this technique, and 52 patients required postoperative treatment; delayed healing occurred in 48 patients; recurrence occurred in 4 patients. Of patients responding to our survey, 16 (6.4 percent) reported postoperative complaints. Delayed healing has always been a major problem. Because the repair procedure inhibits pocket formation and allows for adequate drainage of the cored portion, cases of delayed healing have been reduced to approximately 7 percent in the last four years. CONCLUSION: This technique, which is continually being improved and evaluated, is simple, has a low risk of infection, preserves functions, and prevents deformity of the anal verge and perineum.

Anal Canal↗
PubMed1997

Myelopathy secondary to ossification of the posterior longitudinal ligament of the thoracic spine treated by anterior decompression and bony fusion.

We examined the utility of anterior decompression and bony fusion via the extrapleural approach in the treatment of thoracic myelopathy secondary to ossification of the posterior longitudinal ligament (OPLL). Patient outcome and complications were analyzed in 48 patients treated with this procedure, with a follow-up of at least 2 years. The Japanese Orthopaedic Association score was used to evaluate the severity of the thoracic myelopathy, and the recovery rate was used to evaluate the surgical outcome. The outcome, postoperative complications, radiographic evaluations of bony union, and progression of OPLL within the area of anterior decompression were examined. The T3 vertebral body was the highest level to which anterior decompression was applied. The average follow-up period was 57 months with a recovery rate of 56.7% which stabilized 1 year after operation. However, the surgical outcome was less favorable in patients with long-standing myelopathy, extensive OPLL, or thoracic OPLL with coexisting intraspinal ligament ossification. Four patients experienced deterioration of their myelopathy, and seven patients had the postoperative complication of extraspinal leakage of cerebrospinal fluid. The myelopathy was transient in all but one patient. Radiographic studies showed that bony union was achieved and restenosis of the spinal canal due to progression of OPLL within the area of decompression did not occur. We conclude that anterior decompression and bony fusion using the extrapleural approach provides a good outcome and is useful in treating mid- and lower thoracic OPLL when performed carefully at an early stage of disease.

Adult↗
PubMed1997

Trial of duplication procedure for complete dentures by CAD/CAM.

The purpose of this study was to duplicate the shapes of complete dentures by using a computer-aided design/manufacturing (CAD/CAM) system. The shapes of the complete dentures of an edentulous patient were measured using a non-contact type shape measurement system and morphological data at the interval of 0.25 mm were obtained in the X-axis and Y-axis directions. Measurement was performed from the occlusal surface and mucosal surface sides. Based on the three-dimensional morphological data, cutter paths for cutting were generated. For cutting, the three-step method consisting of rough cutting, finish cutting, and partial finish cutting was used and for duplicating the dentures the modelling wax was cut using a computerized numerical control (CNC) processor and ball-end mills with diameters of 6 mm and 1 mm. The method for the controlling of three axes (X, Y, and Z) of CNC machine was used, and cutting was performed only from two directions. Although further improvements are needed in the measurement and cutting in acute slope areas, the duplication of complete dentures appears to be possible using the CAD/CAM system.

Analog-Digital Conversion↗
PubMed1997

Dominant mutations of Drosophila MAP kinase kinase and their activities in Drosophila and yeast MAP kinase cascades.

Eight alleles of Dsor1 encoding a Drosophila homologue of mitogen-activated protein (MAP) kinase kinase were obtained as dominant suppressors of the MAP kinase kinase kinase D raf. These Dsor1 alleles themselves showed no obvious phenotypic consequences nor any effect on the viability of the flies, although they were highly sensitive to upstream signals and strongly interacted with gain-of-function mutations of upstream factors. They suppressed mutations for receptor tyrosine kinases (RTKs); torso (tor), sevenless (sev) and to a lesser extent Drosophila EGF receptor (DER). Furthermore, the Dsor1 alleles showed no significant interaction with gain-of-function mutations of DER. The observed difference in activity of the Dsor1 alleles among the RTK pathways suggests Dsor1 is one of the components of the pathway that regulates signal specificity. Expression of Dsor1 in budding yeast demonstrated that Dsor1 can activate yeast MAP kinase homologues if a proper activator of Dsor1 is coexpressed. Nucleotide sequencing of the Dsor1 mutant genes revealed that most of the mutations are associated with amino acid changes at highly conserved residues in the kinase domain. The results suggest that they function as suppressors due to increased reactivity to upstream factors.

Alleles↗
PubMed1997

No genetic mutation in type II 3 beta-hydroxysteroid dehydrogenase gene in patients with biochemical evidence of enzyme deficiency.

Nonclassic or the mild form of 3 beta-hydroxysteroid dehydrogenase (NC3 beta-HSD) deficiency is an entity which is identified with typical features of premature pubarche, hirsutism, or oligomenorrhea. In this study, type II 3 beta-HSD gene from 4 girls who were diagnosed as NC3 beta-HSD deficient, base on the adrenal steroidogenic responses to ACTH, was analyzed to determine whether NC3 beta-HSD deficiency was an allelic variant of classical 3 beta-HSD deficiency by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). We could not detect any alterations of type II 3 beta-HSD gene from these patients. Our result strongly suggests that unlike classical 3 beta-HSD deficiency, NC3 beta-HSD deficiency may be secondary adrenal biosynthetic defects, rather than dual inherited deficiencies.

Adolescent↗