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Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 19 recordsLinked to original sources

A novel saccharide structure, Xyl 1----3 Gal 1----(SO3-)3,4 Fuc----, is present in acrosome reaction-inducing substance of the starfish, Asterias amurensis.

The jelly coat of echinoderm eggs contains a glycoconjugate, acrosome reaction-inducing substance (ARIS), that is essential for triggering the acrosome reaction in homologous spermatozoa. In the starfish, Asterias amurensis, ARIS is a sulfated glycoprotein of an apparent molecular size of greater than 10(7). Since its biological activity is dependent mostly on its sugar moiety, oligosaccharides liberated by hydrolysis with 10 mM H2SO4 for 60 min at 100 degrees C from pronase digests of ARIS (P-ARIS) were chemically analyzed. The main oligosaccharide purified by high-performance anion-exchange chromatography was determined to be Xyl1----3Gal1----(SO3-)3,4Fuc by compositional analysis and FAB mass spectrometry. This structure indicates that ARIS possesses a novel saccharide chain having sulfated fucose as an internal residue.

Acrosome

Analysis of the 5' flanking region of the rat proliferating cell nuclear antigen (PCNA) gene.

The proliferating cell nuclear antigen (PCNA), highly conserved among eukaryotes, is an auxiliary factor for DNA polymerase delta. In this report we sequenced 1560 nucleotides (nt) of the 5' flanking region of the rat PCNA gene and located the transcription initiation site. The sequence contains 1435 nt upstream of the cap site and promotes transcription of a linked heterologous reporter gene in rat, mouse and human cells. Transient expression assays using a series of 5' deletion mutants revealed that 240 nt of the upstream sequence are sufficient for full promoter activity. Three GC boxes and several other binding sites of transcription factors were observed, but neither a TATA nor a CCAAT sequence was found in this region. The results also suggested the existence of a negative regulatory element(s) between -968 and -691. Cotransfection with early region 1 (E1) genes of human adenoviruses activated the expression of the reporter gene, suggesting that an E1-responsive element is located at the proximal promoter region within 81 nt upstream of the transcription initiation site.

3T3 Cells

Multiple intracellular signaling pathways of the neuropeptide substance P receptor.

The rat substance P (SP) receptor cDNA has been transfected into cultured rat KNRK cells, and a stable cell line expressing functional SP receptors established. Upon stimulation with SP, these cells responded by simultaneously activating two signaling pathways: the mobilization of intracellular Ca2+ and the raising of cyclic adenosine triphosphate (cAMP) levels. Both Ca2+ and cAMP responses were elicited in a similar dose-dependent manner with half maximal concentrations of approximately 5 x 10(-10) M. Following ionomycin treatment SP-dependent Ca2+ responses were abolished, whereas cAMP responses were preserved. Forskolin eliminated the SP-dependent cAMP elevation, however, the SP-induced Ca2+ mobilization remained unchanged. Furthermore, treatment with phorbol esters had no significant effect on either of the two SP-induced responses. Thus it appears that the SP receptor is capable of independently activating Ca2+ mobilization and cAMP pathways. These results may provide new insights for further understanding the diverse activities of SP in various systems in vitro and in vivo.

Animals

Preoperative serum immunosuppressive acidic protein (IAP) test for the prognosis of gastric cancer: a statistical study of the threshold level and evaluation of the effect of the biological response modifier PSK.

The prognostic value of immunosuppressive acidic protein (IAP), which is known to suppress various immune responses in cancer patients, was studied in a prospective randomized trial of advanced gastric cancer patients, designed to evaluate the effect of PSK, a kind of biological response modifier with protein-bound polysaccharides. Preoperative serum IAP levels were determined in 228 patients who received radical gastric resection and tests conducted in one laboratory by the single radial immunodiffusion (SRID) method. All patients were followed up for 24 months or more. There was an overall significant difference in disease-free survival time in favour of the PSK-treated group compared with the control group. Preoperative IAP values were strongly associated with disease-free survival time. The statistical analysis to define an appropriate cut-off level for IAP was performed using Cox's proportional hazards model. The most significant difference was observed at the threshold value of 580 micrograms/ml, the hazard ratio being 2.13 with a 95% confidence interval [1.17, 3.88] (P = 0.013). Patients in the PSK-treated group with a preoperative IAP of lower than 580 micrograms/ml showed improved disease-free survival (P = 0.029), however, no significant difference was seen between the two groups when the preoperative IAP exceeded the threshold level. From these results, 580 micrograms/ml is postulated to be the most appropriate threshold value for predicting the prognosis of advanced gastric cancer patients, and it is suggested that PSK would be most effective in patients whose preoperative IAP level is lower than the threshold level.

Biomarkers, Tumor

Isolation and characterization of cDNA clones encoding cdc2 homologues from Oryza sativa: a functional homologue and cognate variants.

Using probes obtained by PCR amplification, we have isolated two cognate rice cDNAs (cdc2Os-1 and cdc2Os-2) encoding structural homologues of the cdc2+/CDC28 (cdc2) protein kinase from a cDNA library prepared from cultured rice cells. Comparison of the deduced amino acid sequences of cdc2Os-1 and cdc2Os-2 showed that they are 83% identical. They are 62% identical to CDC28 of Saccharomyces cerevisiae and much more similar to the yeast and mammalian p34cdc2 kinases than to rice R2, a cdc2-related kinase isolated previously by screening the same rice cDNA library with a different oligonucleotide probe. Southern blot analysis indicated that the three rice clones (cdc2Os-1, cdc2Os-2 and R2) are derived from distinct genes and are each found in a single copy per rice haploid genome. RNA blot analysis revealed that these genes are expressed in proliferating rice cells and in young rice seedlings. cdc2Os-1 could complement a temperature-sensitive yeast mutant of cdc28. However, despite the similarity in structure, both cdc2Os-2 and R2 were unable to complement the same mutant. Thus, the present results demonstrate the presence of structurally related, but functionally distinct cognates of the cdc2 cell cycle kinase in rice.

Amino Acid Sequence

The 4th study of prophylactic intravesical chemotherapy with adriamycin in the treatment of superficial bladder cancer: the experience of the Japanese Urological Cancer Research Group for Adriamycin.

A multicentric randomised trial was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancers. A total of 443 patients (number of evaluable patients, 284) were registered from July 1987 to December 1989 and randomised into 3 groups. Group A received 21 intravesical instillations of Adriamycin (ADM) at 20 mg/40 ml physiological saline for 2 years after undergoing transurethral resection (TUR); group B was given the same dose as group A but received 6 intravesical instillations for 2 weeks before undergoing TUR; and group C served as a control and underwent TUR only. Better prophylactic effects were obtained in group A. The overall non-recurrence rates calculated for groups A and B differed significantly (P less than 0.05) on day 240, and those determined for groups A and C were also significantly different (P less than 0.01) on day 480. No benefit was obtained using intravesical instillation prior to TUR (group B). The major side effects encountered were pollakisuria and miction pain, which occurred in 32% of the patients in group A and in 52% of those in group B.

Administration, Intravesical

Long-term results of intravesical chemoprophylaxis of superficial bladder cancer: experience of the Japanese Urological Cancer Research Group for Adriamycin.

Long-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, randomized, controlled trial conducted on primary tumors treated with a long-term instillation regimen that involved control versus intravesical instillations of Adriamycin or mitomycin C given once a week for the first 2 weeks, once every other week for 14 weeks, once a month for 8 months, and once every 3 months for 1 year, for a total of 21 instillations in 2 years. An analysis of the prophylactic effects of such treatment on bladder tumors after TUR has previously been performed, and the results have been published elsewhere. The present study represents a follow-up of the above trial. Of the 671 cases previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were eligible to be followed for tumor progression and survival. A detailed comparison of the background factors between these 158 patients and the other 513 cases revealed no statistically significant difference. Thus, the 158 evaluable cases might reasonably be considered to represent all patients enrolled in the second study, and the results were thought to be reasonable enough to reflect the long-term efficacy of the long-term instillation regimen adopted in this study. The median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of the disease stage and/or grade occurred in 43 of 127 patients who received prophylactic instillations and in 12 of 31 control cases. No significant difference in the incidence of tumor progression was found between the treatment and the control groups. In addition, no difference in survival was observed between the treatment group and the control group. Survival was also compared between patients who showed tumor progression and those who did not. All patients whose tumors did not progress survived, whereas the 7-year survival of those exhibiting tumor progression was less than 90%.

Actuarial Analysis

Intravesical instillation of adriamycin in the presence or absence of verapamil for the treatment of superficial bladder cancer: preliminary report of a collaborative study.

A case-controlled collaborative study on the intravesical administration of Adriamycin in the presence or absence of verapamil, a calcium-channel blocker, as chemotherapy of superficial bladder cancer was carried out at two universities, Okayama and Kagoshima, and their affiliated hospitals. Although little is known about the expression of P-glycoprotein in superficial bladder cancer, it may be a cause of multidrug resistance (MDR). Verapamil was used as an inhibitor of P-glycoprotein. Arm A consisted of Adriamycin given at 50 mg/50 ml saline, and arm B constituted Adriamycin given at 50 mg/40 ml saline plus 5 ampules (10 ml) of injectable verapamil. The drugs were instilled into the bladder for 3 consecutive days in each of 3 consecutive weeks for a total of 9 instillations. No significant difference in antitumor effects was observed between arm A and arm B. Recurrent tumors responded better than did primary tumors to both arm-A and arm-B treatments (P = 0.012). In both treatment arms, significant differences (P = 0.031) in the response rate were found between tumors with diameters of less than 1 cm and those measuring 1-3 cm in diameter. Although the number of evaluable patients was limited, recurrent subjects who had previously received Adriamycin instillations responded in both treatment arms.

Administration, Intravesical

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of lipiodol-transcatheter arterial embolization with and without adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial comparing the use of lipiodol-transcatheter arterial embolization (L-TAE) in the presence versus the absence of Adriamycin (ADR) for the treatment of hepatocellular carcinoma was conducted from August 1988 through September 1989. In all, 125 Japanese hospitals participated in this study and 289 patients were entered in the trial. The patients were randomly allocated into group A (L-TAE) or group B (L-TAE + ADR) by telephone registration. There was no significant difference in background factors between group A and group B. Additional treatment, including repeated TAE or hepatic resection, was given to 189 patients. Among the four endpoints analyzed, the rate of tumor reduction and lipiodol accumulation in the tumor did not significantly differ between the two groups. The 3-year survival values for groups A and B were 33.6% and 34.9%, respectively; the difference was not significant. The serum alpha-fetoprotein level, however, decreased to a significantly greater extent in the group that received ADR than in the group that did not (P < 0.05). This result suggests that ADR has some favorable additional effect in L-TAE for the treatment of hepatocellular carcinoma.

Adult

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of L-TAE with Farmorubicin and L-TAE with adriamycin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized clinical trial comparing L-TAE with Farmorubicin (FARM) and L-TAE with Adriamycin (ADR) in the treatment of hepatocellular carcinoma was conducted from October 1989 through December 1990. In all, 192 hospitals participated in this study and 117 patients were entered. The patients were randomly allocated to group A (L-TAE+FARM) or group B (L-TAE+ADR). There was no significant intergroup difference in background factors. Additional treatment consisting of repeated TAE or surgery was given to 66 patients. Four factors were analyzed in this study: the percentage of reduction in tumor size, the change in the AFP level, lipiodol accumulation, and survival. None of these factors differed significantly between the two groups. The final evaluation of this study will be based on differences in survival after a long-term follow-up. Toxic effects manifested less frequently in group A than in group B, and the decrease in the platelet count in the peripheral blood was significantly lower in group A than in group B. These results suggest that FARM exerts a more favorable effect than does ADR in the treatment of hepatocellular carcinoma.

Adult

The reversed Müller-Lyer illusion and figure-ground organization theory.

When the shaft is shortened and reaches neither of the vertices of the two pairs of wings, a reversed Müller-Lyer illusion is observed: a shaft between inward-pointing wings appears to be longer than a shaft between the outward-pointing wings. In this paper it is examined whether this illusion can be explained in terms of figure-ground organization. A circle was used as the focal area, instead of a shaft or a pair of dots, so that the figure-ground character could be seen more definitely in this focal area. The apparent size of the focal circle was measured under different conditions with three variables (enclosure, wings direction, and depth). The focal circle appeared to be largest in the condition where the circle should appear most readily as a hole, ie in the single, wings-in, space condition. The circle appeared to be smallest in the condition where the circle should appear most readily as a disc, ie in the separate, wings-out, object condition. This is consistent with an explanation of the usual, as well as the reversed, Müller-Lyer illusion in terms of figure-ground organization theory.

Adult

Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma.

Inflammation of the airway wall and airway hyperresponsiveness are consistent features of chronic asthma. We investigated how damage of the bronchial epithelium is related to airway hyperresponsiveness and how bronchial infiltration of eosinophils and lymphocytes is related to bronchial epithelial damage. We examined the biopsy specimens of bronchial mucosa taken from 19 patients with chronic asthma by electron microscopy. We also measured the incidence of opening of epithelial tight junctions, the widening of intercellular spaces in the epithelium, and the density of infiltrated eosinophils and lymphocytes in bronchial mucosa. Airway responsiveness was accessed by measuring PC20-acetylcholine (PC20-ACh). The inflammatory cells in the airway mucosa were counted by electron microscopy. Lymphocytes were most abundant, being 54.5% of the cells counted; eosinophils were 22.1%, neutrophils were 4.9%, and mast cells were 4.6%. A significant correlation was noted between the density of eosinophils and that of lymphocytes infiltrated in the airway mucosa (r = 0.80, p less than 0.01), suggesting that T cells may potentiate eosinophil infiltration. With increased density of eosinophils infiltrated in bronchial mucosa, both the incidence of opening of tight junctions of epithelial ciliary cells and the degree of widening of intercellular spaces in epithelium increased significantly (r = 0.51, p less than 0.05; r = 0.52, p less than 0.05), suggesting that eosinophils are related to damage of the bronchial epithelium. No correlation was observed between the density of lymphocyte infiltration and the degree of epithelial damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Anti-LFA-1 antibody treatment of a patient with steroid-resistant severe graft-versus-host disease.

For treatment of steroid-resistant severe graft-versus-host disease, a murine monoclonal antibody (25.3) against the alpha chain (CD11a) of the lymphocyte function-associated antigen 1 (LFA-1) was infused into a patient with posthepatitic aplastic anemia who had undergone allogeneic bone marrow transplantation. The monoclonal antibody infusion was well tolerated and resulted in appreciable improvement in symptoms of gastrointestinal illness such as diarrhea and abdominal pain, suggesting that this antibody may be useful for controlling severe acute graft-versus-host disease.

Anemia, Aplastic

Mass screening for neuroblastoma in Miyagi Prefecture.

In Japan, aiming at early and preclinical detection of neuroblastoma in infancy a mass screening program for the tumor has been implemented nationwide using urinary tests for catecholamine metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA) (Sawada 1990; Sawada et al. 1991). In this report, the results obtained from the screening program in Miyagi Prefecture for the last 6 years are described. The detection rate of neuroblastoma by mass screening was 1:8,377 among 125,652 infants tested in Miyagi Prefecture. All but one patients survived after removal of the primary tumor and none or minimal chemotherapy.

Biomarkers, Tumor

Allogeneic bone marrow transplantation for malignant hematologic disorders in children.

In the present study we carried out allogeneic bone marrow transplantation (BMT) in 14 leukemia children with high risk prognostic factors. Six patients with acute nonlymphocytic leukemia (ANLL), four with acute lymphocytic leukemia (ALL), two with chronic myelogenous leukemia (CML), and two with myelodysplastic syndrome (MDS). Among these patients, six with ANLL, two with ALL, one with CML and one with MDS were alive in complete remission 8 to 58 months post-BMT. Four patients died of relapse (one with ALL, and one with MDS), and chronic GVHD (one with ALL and one with CML). In six patients recombinant granulocyte colony stimulating factor (rG-CSF) was used to shorten the period of granulocytopenia. The mean time of recovery to granulocyte count of 500/mm3 was 13.2 days in the rG-CSF+ group, being 15.9 days faster than that in the rG-CSF- group. In light of these results, allogeneic BMT is shown to be a choice of treatment for leukemia children with high risk prognostic factors and rG-CSF may be an effective reagent to prevent infectious episodes in BMT.

Adolescent