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Biomedical subjects

A Tsunoda

Publications and source records attributed to A Tsunoda.

At least 19 recordsLinked to original sources

Total metabolic flow of glycosphingolipid biosynthesis is regulated by UDP-GlcNAc:lactosylceramide beta 1-->3N-acetylglucosaminyltransferase and CMP-NeuAc:lactosylceramide alpha 2-->3 sialyltransferase in human hematopoietic cell line HL-60 during differentiation.

We have previously reported that ganglioside GM3 was remarkably increased during monocytoid differentiation of human myelogenous leukemia cell line HL-60 cells and that neolacto series gangliosides (NeuAc-nLc) were enriched during granulocytoid differentiation. In addition, HL-60 was differentiated into monocytic lineage by exogenous GM3 and into granulocytoid by NeuAc-nLc. In the present report, the enzymatic bases of glycosphingolipid biosynthesis in HL-60 during differentiation induced by 12-O-tetradecanoylphorbol-13-acetate and all-trans-retinoic acid were investigated. The following results were of particular interest. (i) Lactosylceramide alpha 2-->3 sialyltransferase (GM3 synthase) was remarkably up-regulated during monocyte differentiation, while the GM3 synthase level did not change in granulocytic differentiation. (ii) By contrast, lactosylceramide beta 1-->3N-acetylglucosaminyltransferase (Lc3Cer synthase) was down-regulated during monocytic differentiation, while the activity of Lc3Cer synthase was found to increase in granulocytic differentiation. (iii) The activities of four downstream glycosyltransferases (for synthesis of NeuAc-nLc) were found to increase or to remain unchanged during monocytic and granulocytic differentiation. These results strongly suggested the following. The dramatic GM3 increase and the decrease of NeuAc-nLc during monocytic differentiation are the consequences of the up-regulation of GM3 synthase and the down-regulation of Lc3Cer synthase, although the downstream enzymes are ready to catalyze their enzyme reactions. The notable increase of NeuAc-nLc and the relative decrease of GM3 during granulocytic differentiation are the results of the unchanged level of GM3 synthase and the up-regulation of Lc3Cer synthase together with the activation of the downstream glycosyltransferases. These results suggest that these two key upstream glycosyltransferases, GM3 synthase and Lc3Cer synthase, play critical roles in regulating the glycosphingolipid biosynthesis in HL-60 cells during differentiation. This switching mechanism of these two glycosyltransferases, together with our previous findings, might be one of the most important parts of the determining system of differentiation direction in human myeloid cells into monocytic or granulocytic lineages.

Antibodies, Monoclonal

Transforming growth factor-beta inhibits phosphorylation of the retinoblastoma susceptibility gene product in human monocytic leukemia cell line JOSK-I.

Proliferation of the human monocytic leukemia cell line JOSK-I is inhibited by transforming growth factor-beta (TGF-beta). Growth inhibition by TGF-beta was not due to either a toxic effect or to induction of differentiation. TGF-beta induced a cell cycle arrest at late G1 phase and was not found to be inhibitory to JOSK-I cells in S phase or G2/M. This G1 cell cycle arrest was associated with an accumulation of the unphosphorylated form of the retinoblastoma susceptibility gene product (Rb) in good correlation with inhibition of DNA synthesis. In contrast to the effects of TGF-beta, two other agents which induced a G1 arrest of JOSK-I cells had a different effect on Rb. Aphidicolin blocked cells at G1/S but could not reduce Rb phosphorylation as great as that seen with TGF-beta. 12-O-Tetradecanoylphorbol-13-acetate, an inducer of differentiation, did reduce Rb phosphorylation, but not until 72 h, when differentiation had already occurred. The identities of the Rb kinases are unknown, but recent evidence suggests that the cdc2 gene product could participate in Rb phosphorylation. Although cdc2 mRNA and total protein levels were not affected, TGF-beta inhibited the rate of translation and kinase activity of cdc2 in JOSK-I cells. These results suggest that growth inhibition of hematopoietic cells by TGF-beta is linked to suppression of Rb phosphorylation to retain Rb in an unphosphorylated, growth-inhibitory state. The suppression of Rb phosphorylation is suggested to be mediated through inhibition of cdc2 kinase activity by TGF-beta.

Aphidicolin

Reduced growth rate of dimethylhydrazine-induced colon tumors in rats.

alpha-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including breast, urinary bladder, and colon. This study was designed to determine whether DFMO treatment can inhibit tumor growth on chemical-induced colon cancer in rats. Effectiveness of DFMO in combination with mitomycin C (MMC) was also evaluated. Forty-two Sprague-Dawley rats received dimethylhydrazine (20 mg/kg) s.c. once weekly for 20 wk to induce colon cancer. Then a double-contrast barium enema was performed, and colon tumors were detected. The animals were divided into four groups that were subjected to the following treatment: none; DFMO alone; MMC alone; and a combination of DFMO plus MMC. After 5 wk of treatment, the barium enema was repeated. For the evaluation of treatment efficacy, tumor doubling time was adopted. The mean tumor doubling time in the control group was 20.7 +/- 9.1 days (SD). "Response" was judged as effective when tumor doubling time in treatment groups was more than 38.9 days, calculated from the mean + 2 SDs in the control group. Response rates in the DFMO, MMC, and DFMO plus MMC groups were 40.0%, 10.0%, and 82.3%, respectively. DFMO was a more effective inhibitor of tumor growth than MMC, and DFMO in combination with MMC resulted in a synergic diminution of tumor growth. The double-contrast barium enema is useful to observe sequential tumor growth and may be appropriate for the evaluation of new treatment on experimental colon cancer in rats.

Animals

[Jugular bulb position in the cranial base and its relation to cranial venous system].

Target CT images of 147 patients and digital subtraction angiography (DSA) images of 15 patients were examined to assess the relation between jugular bulb position and intracranial veins. First, relation of jugular bulb position to venous volume was examined from CT. The height of the jugular bulb was measured from the lower margin of the tympanic annulus to the apex of the jugular bulb by counting CT slices individually on the both side. The heights of the right and left jugular bulbs were 4.0 +/- 3.9 mm and 2.0 +/- 3.9 mm respectively, indicating that the right jugular bulb was higher than the left, consistent with previous reports. The depth of the sigmoid sinus sulcus, which may reflect the venous volume, was measured on the slice showing the internal auditory canal. The right side was 6.7 +/- 2.2 mm deep, while the left side was 5.3 +/- 2.0 mm in depth. These measurement also showed that the height of jugular bulb and depth of the sulcus of the sigmoid sinus were closely related. The jugular bulb was higher on the side with the deeper sigmoid sinus sulcus (correlation coefficient r = 0.73). Frontal head and neck angiography were performed after bolus injection of contrast medium. Angiographic images were modified and examined by means of a digital subtraction process. A result from angiography was consistent with the measurement of CT. The side with greater venous flow has the higher jugular bulb. And such difference in right and left venous flows was observed at and pproximately to the transverse sinuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography, Digital Subtraction

Prospective randomized trial comparing anal function after hand sewn ileoanal anastomosis with mucosectomy versus stapled ileoanal anastomosis without mucosectomy in restorative proctocolectomy.

A prospective randomized trial was performed to compare complications and function after hand sewn ileoanal anastomosis with mucosectomy (group A) with stapled ileoanal anastomosis without mucosectomy (group B) during restorative proctocolectomy. Thirty-two age- and sex-matched consecutive patients under the care of one surgeon were randomized. The median duration of anal dilatation while making the anastomosis was 19 min (range 14-33 min) and 1 min (range 0-39 min) in groups A and B respectively (P less than 0.005). The median level of the anastomosis was at the dentate line (range 0-0.5 cm) in group A and 2 cm above the dentate line (range 0.2-4.0 cm) in group B (P less than 0.005). Seven patients in group A and 11 in group B had at least one postoperative complication (n.s.). One patient in group A and four in group B developed an anastomotic stricture requiring dilatation (n.s.). One patient in group B had the reservoir removed. Function was assessed at a median of 11 months (range 7-15 months) after ileostomy closure in 14 patients in group A, and at a median of 12 months (range 5-17 months) in 14 patients in group B. Median frequency of defaecation per 24 h was 4 in both groups (group A, range 2-7; group B, range 2-10). Night evacuation (greater than once per week) occurred in seven patients in each group. All patients in both groups could delay the desire to defaecate by more than 30 min. Eleven patients in group A and 12 in group B had normal continence. Evidence to date favours a full mucosectomy. Function is not vitiated by this technique and surgical removal of the disease is more complete.

Adult

Radioimmune assay of sialyltransferase and N-acetylgalactosaminyltransferase activities using specific antibodies on a 96-well filtration plate of a multiscreen assay system.

A new assay method for glycosphingolipid glycosyl-transferase activities was developed using a 96-well filtration plate of a MultiScreen assay system. An acceptor glycosphingolipid and a donor radioactive nucleotide sugar were incubated with an enzyme source in a well of the filtration plate. After incubation, both identification and quantification of the reaction product were carried out simultaneously using a specific antibody for the product which was trapped on a filtration membrane of the plate as a complex with Staphylococcus aureus protein A (IgGSorb). This assay method was used for determining the activity of cytidine 5'-monophosphate-N-acetylneuraminic acid:Lcn4Cer alpha 2----6sialyltransferase and uridine 5'-diphosphate-N-acetyl galactosamine:GM3 N-acetylgalactosaminyltransferase. In addition to the simple and rapid identification and quantification of the product, this method proved to be as reliable and sensitive as the previously published assay procedures. Furthermore, this assay method can be used with a high concentration of detergent which should not be used in the other procedures described previously using enzyme-linked immunosorbent assay methods on a 96-well multiplate even if the enzyme reaction might require a certain percentage of the detergent concentration.

Animals

[Increased polyamine levels of normal-appearing mucosa and cancers in DMH induced cancer-bearing colon in rats].

Polyamine levels (putrescine, spermidine, spermine) in normal-appearing colonic mucosa of DMH administrated rats were measured in order to assess their importance as markers of precancerous changes. Mean putrescine, spermidine and spermine levels of normal-appearing mucosa were more than three times mean putrescine, more than twice mean spermidine and more than 1.5 times mean spermine levels of normal colonic mucosa. Mean polyamine levels of colon cancers were higher than those of normal-appearing mucosa but only spermidine level was significantly different between them. The mucosal polyamine levels may be a good biochemical marker to detect precancerous changes. There was no correlation between the polyamine levels and the growth rate of the colon cancers.

Animals

[Raised polyamines in erythrocytes of DMH administrated rats with colonic cancers and those relationship to tumor volume].

The objective of this study was to assess, in a controlled experimental system, whether the concentrations of polyamines (Pa) in urine or erythrocytes increase during the process of colon carcinogenesis in rats, and whether such changes reflect tumor volume. Colon carcinoma was induced in Sprague-Dawley rats by subcutaneous injection of 1, -2 dimethylhydrazine (DMH). 24-hour urine and blood samples were collected and analysed for their Pa consent, with high pressure liquid chromatographic method. The levels of any Pa derivatives in either urine or erythrocytes at 32 weeks after the administration of DMH were not significantly high compared with the control group at the same week. However, certain increases of Pa in erythrocytes were observed in the levels of putrescine (1.3 times), spermidine (1.3 times), and spermine (1.5 times) respectively compared with the control group and there were high positive correlations between tumor volume and the levels of each Pa derivatives. On the ground of the results, Pa in erythrocytes seems to be the sensitive parameter for tumor volume compared with Pa in urine.

1,2-Dimethylhydrazine

Incidence of dysplasia in the anorectal mucosa in patients having restorative proctocolectomy.

The incidence of dysplasia in the mucosal strippings from the anorectal stump was studied in 132 patients treated by restorative proctocolectomy with ileal reservoir for ulcerative colitis and familial adenomatosis. The anorectal mucosa was stripped from the level of division of the gut tube to the dentate line. Of 118 patients with ulcerative colitis, 12 (10.2 per cent) had dysplasia in some part of the large bowel. Mucosal strippings were examined histologically in 118 cases, of which only three (2.5 per cent) showed dysplasia. There was a correlation between dysplasia and the presence of carcinoma and the duration of the disease in the operative specimen of colon and rectum and also in the anorectal mucosal specimen although the number of patients with carcinoma (eight cases) in this analysis was small. All 14 patients with familial adenomatous polyposis showed large bowel mucosal dysplasia in the operative specimen which was severe in six cases. Anorectal mucosal strippings were examined in these patients and 12 showed dysplasia which was severe in three.

Adenomatous Polyposis Coli

Decrease in childhood neuroblastoma death in Japan.

Death statistics cards under 15 years of age submitted between 1979 and 1987 and coded as malignant neoplasms of organs or sites, in which neuroblastoma might affect, were inspected. A total of 1,037 cases of neuroblastoma death were identified. Total number of neuroblastoma deaths among those under 15 years of age ranged between 118 and 145 from 1979 to 1984. However, after 1985 the number of deaths showed a declining tendency, down to 89 in both 1985 and 1986 and totalling only 93 in 1987. This declining tendency was mostly-seen among children between 1 to 4 years of age. In this age group, the rate of death in 1987 was about one half of that in 1979; In the other age groups no declining tendency of neuroblastoma death was found. The reason for the decrease in neuroblastoma death among children in Japan may be a result of widespread mass-screening for neuroblastoma. However, further study is necessary before any final conclusions can be drawn.

Adolescent

Surgical treatment of reflux stricture of the esophagus.

Ten children, aged 7 months to 15 years, with peptic esophageal stricture, were treated surgically. In four of the children, the stricture had occurred after esophageal anastomosis. Peptic stricture was diagnosed by esophagography, pH monitoring, manometry, and esophagoscopy. Barrett's esophagus was found in two children. Nine children underwent transabdominal Nissen fundoplication initially. In the first child of this series, a tight anastomotic stricture had been excised 2 weeks before fundoplication. Seven children became complaint-free within 2 or 3 months after fundoplication without any dilatation, and two children with anastomotic stricture improved after 1 or 2 postoperative dilatations. The condition of one boy, with a 6-year history of tight stricture, did not improve with repeat Nissen and subsequent dilatations. Histological examination showed proliferation of smooth muscle cells in the submucosa. A conservative surgical approach is effective for the management of peptic esophageal stricture in children, and direct surgical intervention for stricture should be attempted only in cases of stricture resistant to antireflux surgery with a long history of reflux.

Adolescent

Effect of sympathectomy on capillaries of the cochlear lateral wall.

The right superior cervical ganglia of 11 cats were removed. After intravenous injection of horseradish peroxidase, both sides of the cochleas were infused with 2% glutaraldehyde and the lateral wall of the cochlea was then microdissected. As control group, both sides of the cochleas of 4 cats were extracted while the superior cervical ganglia remained intact. The samples were incubated after a modified Graham-Karnovsky method and observed by light microscopy. The diameters of the capillaries of the stria vascularis and spiral ligaments were measured. In 8 cats (73%), the diameters of the capillaries of the stria vascularis on the side on which sympathectomy was performed were significantly greater than those on the opposite side. There was no statistical difference between the diameters of the capillaries of the spiral ligament on either the sympathectomized side or the intact side, except in 2 cats. In the control group (in which the superior cervical ganglia were left intact), no statistical difference was found as regards the diameters of the stria vascularis capillaries on either the left or right side. In summary, sympathectomy affected only the capillaries of the stria vascularis and not those of the spiral ligament.

Animals

Mass screening for neuroblastoma in Japan. Committee of the Neuroblastoma Mass Screening Study of the Japanese Society of Pediatric Oncology.

The present status of NB mass screening in Japan, which is the first national trial in the world, is presented. This program was conducted in cooperation with infants' mothers, local health centers, screening centers and hospitals. Three hundred and thirty-seven cases detected by the program, from the start in Kyoto in 1974 to the end of 1989, are analyzed. As many cases were detected at early stages, 97% of them were expected to be cured. Several clinical, technical and programmatic problems are also discussed.

Child

[Growth rate of experimental colonic cancer in rats].

Colonic cancers were induced in rats by subcutaneous injection of 1,2-Dimethylhydrazine. Tumor growth patterns were estimated by means of a double contrast barium enema technique. Tumor growth was almost exponential and the average doubling time was 20 +/- 5 (m +/- S.D.) days, at which time three different types of tumor growth patterns: Constant type, decreasing type and reaccelerating type, were noted. Serial double contrast barium enema technique appeared to be an useful method of studying in vivo primary colonic cancer growth patterns in rats.

1,2-Dimethylhydrazine

Serum anti-PT and anti-FHA antibody levels, and agglutinin titers after administration of acellular pertussis vaccines.

Simultaneous evaluation of acellular pertussis vaccines from three manufacturers (Takeda, Biken, and Chiba) was performed. After receiving two doses of acellular pertussis vaccine in the form of DPT (diphtheria pertussis tetanus), both infants and children showed high serum anti-PT (pertussis toxin) and anti-FHA (filamentous hemagglutinin) antibody levels. These levels were equivalent to those observed in children in the convalescent stage of natural pertussis infection. Children who received 2 doses of Biken vaccine showed higher anti-PT and anti-FHA antibody levels than those who received Takeda or Chiba vaccine. Elevation of agglutinin titers was observed in children who received either Takeda or Chiba vaccine.

Antibodies, Bacterial

[Studies on respiratory infections in the field of primary care (I). Correlation between viral infection and secondary bacterial infection in patients visiting a doctor in private practice].

We attempted to find out whether there is a correlation between viral infection and secondary bacterial infection on the basis of the analysis of the results of the culture of virus and bacteria in the same specimen from the throat swabs of 95 patients who had an acute upper respiratory inflammation when they visited a doctor in private practice in Sendai city during the epidemic caused by influenza virus. Viral culture was performed by a microplate-method devised originally by Numazaki. The influenza virus was recovered from 56 cases (59%) consisting of 43 cases of type A (Hong-Kong) and 13 cases of type B. From 73 cases, (77%), 79 strains of possibly pathogenic bacteria were recovered, consisting of 43 strains of H. influenzae, 18 strains of S. aureus, seven strains of S. pneumoniae, four strains each of C. freundii and S. liquefaciens and one strain each of beta-haemolytic Streptococcus and B. catarrhalis. The incidence of positive culture of both virus and possibly pathogenic bacteria was high already at the early stage (2-3 days) of the disease. We found no correlation between the type of virus and the species of the microbial isolates. There was no difference in the incidence of positive bacterial culture in relation to age group. We suggest that a secondary bacterial infection occurs already at the early stage of the disease after viral infection because the incidence of positive culture of possibly pathogenic bacteria was high at the above stage.

Adolescent