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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 1,099 records · Page 61Linked to original sources
PubMedDate not supplied

Effects of tumor necrosis factor alpha on replication of varicella-zoster virus.

Replication of varicella-zoster virus (VZV) and expression of VZV nuclear antigen are inhibited in human embryonic lung fibroblast (HEL) cells pretreated with recombinant tumor necrosis factor (TNF) alpha for 24 h. This antiviral activity is completely blocked by the addition of monoclonal antibodies against TNF. TNF acts synergistically with interferons alpha and gamma. When TNF is added to HEL cells after VZV adsorption, virus replication is still inhibited. When VZV-infected HEL cells are co-cultured with HEL cells which have been pretreated with TNF or grown in the presence of TNF, spread of VZV from VZV-infected HEL cells to uninfected cells is unaffected. No interferon is detected in the supernatants or cell lysates of HEL cells cultured with TNF and antibodies to alpha-, beta- and gamma-interferon have no effect on the antiviral action of TNF.

Antibodies, Monoclonal↗
PubMedDate not supplied

A Japanese case of infantile sialic acid storage disease.

We report a 4-year-old Japanese girl with infantile sialic acid storage disease. She presented with failure to thrive, coarse facial features, hepatosplenomegaly, severe mental retardation and spastic quadriplegia. Electron microscopic examination of cultured skin fibroblasts revealed multiple vacuoles and inclusion material representing distended lysosomes, thus suggesting a lysosomal storage disorder. A high concentration of free sialic acid was present in the urine and cultured fibroblasts, but bound sialic acid was not increased. The activity of a variety of lysosomal enzymes was not diminished. The MRI findings included brain atrophy and a diffuse high signal in the cerebral white matter and low signal in the basal ganglia on T2-weighted images. To our knowledge, this is the first case of infantile sialic acid storage disease described in a non-Caucasian family.

Atrophy↗
PubMedDate not supplied

A child case of CD34+, CD33-, HLA-DR-, CD7+, CD56+ stem cell leukemia with thymic involvement.

It has been reported that the CD56+/CD7+/CD3- phenotype of natural killer (NK) cells develop from the CD34+/HLA-DR- bone marrow (BM) mononuclear cell population in long-term BM culture (LTBMC). An HLA-DR-/CD33+/CD56+/CD16- myeloid/natural killer cell acute leukemia has been described. We report here a 7-year-old boy who developed stem cell acute leukemia with superior vena cava syndrome secondary to thymic involvement. Surface marker analyses revealed that the leukemia cells showed CD34+/HLA-DR-/CD33-/CD7+/CD56+ phenotype. When stimulated with phorbol ester in vitro the leukemic cells morphologically differentiated to myeloid cells developing CD13, CD15 and CD56 antigens. Our results suggest that CD34+/HLA-DR-/CD7+/CD56+ stem cell leukemia may arise from transformation of a pluripotent precursor cell, which could differentiate to both myeloid and NK cell lineages.

Antigens, CD↗
PubMedDate not supplied

[Clinical testing of intra-articularly injected glycosaminoglycan polysulfate in gonarthrosis ( a controlled multicenter double-blind study)].

In order to evaluate the clinical efficacy of glycosaminoglycan polysulfate (GAGPS) in osteoarthrosis of the knee, a double blind comparative study was carried out at 26 orthopaedic clinics throughout Japan. A total of 120 patients was divided into two groups; one group was treated with 1 mg GAGPS (control group) and the other with 50 mg GAGPS (drug group). Five or more injections (average: 9.3) were given at about weekly intervals (average: 8.2 days). The score derived from the knee scoring scale improved significantly in both groups, either after the 5th and the 10th injections. The score that had improved after the 10th injection in drug group was statistically superior compared to the control (p less than 0.05), however, the difference in the two groups after the 5th injection did not reach a level of any statistical significance. Doctors' assessment of the usefulness of the drug based on the balance of effects and side effects was obtained in 71.2% and 41.1% in drug group and control group, respectively. The difference was statistically significant (p less than 0.01). In conclusion, the authors confirmed that the intraarticular injections of 50 mg GAGPS were useful for osteoarthrosis of the knee although the clinical symptoms were improved only gradually following the injections.

Clinical Trials as Topic↗
PubMedDate not supplied

c-erbB-2 and c-erbA-1 (ear-1) gene amplification and c-erbB-2 protein expression in Japanese breast cancers: their relationship to the histology and other disease parameters.

We studied c-erbB-2 and c-erbA-1 (ear-1) gene amplification, and c-erbB-2 protein expression in 123 primary Japanese breast cancers. c-erbB-2 amplification was found in 19 of the 123 tumors (15%), and c-erbA-1 was coamplified in 7 of the 19. The presence or absence of c-erbB-2 amplification correlated with the grade of cellular atypism (P = 0.008), or that of mitotic index (P = 0.002), but not with the histologic types. The tumor size (P = 0.04) and the lymph node status (P = 0.06) were associated, but the patients' age, the TNM stage, or the presence or absence of estrogen or progesterone receptors was not associated, with c-erbB-2 amplification. There were no differences in the histologic type, cellular atypism, mitotic index, and other disease parameters between tumors with c-erbB-2 amplification only and those with coamplification of c-erbB-2 and c-erbA-1. Paraffin sections from all 19 tumors with c-erbB-2 amplification, and those from only one of 104 tumors without the amplification were positively stained with polyclonal anti-c-erbB-2 protein antibody. Since the correlation between the amplification and the protein expression was excellent, such immunohistochemical studies may be substituted for the time-consuming DNA studies using Southern blotting.

Adult↗
PubMedDate not supplied

Rearrangement, amplification and overexpression of c-Ha Ras gene in premalignant lesion of Turcot's syndrome.

Ras gene family (c-Ha, Ki, N ras) and c-myc proto-oncogenes were analyzed in seven colonic and three gastric adenomatous polyps obtained from a patient with Turcot's syndrome. The rearrangement and amplification as well as overexpression of c-Ha ras gene in one colonic adenomatous polyp were determined. The amplified c-Ha ras gene in this polyp revealed larger fragments of BamHI, PstI and SacI than those in the normal colonic mucosa from the same patient. But, such abnormalities were not observed in other polyps. No abnormalities of c-Ki ras, c-N ras or c-myc gene were observed in any polyps. These results suggest that the alternations of c-Ha ras gene in this patient may not be responsible for the adenomatous change, but may be related to the transition from adenoma to carcinoma of the colon.

Adenoma↗
PubMedDate not supplied

Functional significance of adhesion molecules in Fas-dependent apoptotic cell death induced by interleukin-2-activated T cells.

We investigated the functional significance of the adhesion molecules CD2 and lymphocyte function-associated antigen-1 (LFA-1: CD11a/CD18) in Fas-Fas ligand (FasL) death pathway. Interleukin-2-activated T cells expressed a large amount of FasL protein and could efficiently kill a Fas-sensitive leukemic cell line, MML-1. The major part (over 80%) of MML-1 cell death was Fas-dependent. Antibodies to CD2 and CD11a/CD18 completely inhibited MML-1 target cell lysis, whereas effector to target cell binding was partially reduced or not affected at all. These results suggest that effector/target interaction via CD2/CD58 and LFA-1/CD54 systems would be essential for triggering target cell death. More interestingly, there is the discordance in the ability of anti-CD2, and particularly anti-LFA-1 antibodies, to block Fas-dependent cell death versus effector to target conjugate formation. This suggests some non-adhesive role for CD2 and LFA-1 in induction of Fas-dependent cell death. Although these antibodies were capable of inhibiting T cell proliferative response, there was no significant reduction of FasL or granzyme B expression. Thus, the signaling pathway for growth inhibition via CD2 and LFA-1 could not be linked to signaling for FasL and granzyme B expression.

Antibodies, Monoclonal↗
PubMedDate not supplied

CD3-mediated T cell activation is inhibited by anti-CD44 monoclonal antibodies directed to the hyaluronan-binding region.

The CD44 molecule has been shown to play a role in T cell adhesion and activation. We have investigated the ability of five anti-CD44 monoclonal antibodies (MoAb) including 15C6, 18A3, BU75 (Ancell), J173 (Immunotech), and L178 (Becton Dickinson) to regulate T cell activation. Three MoAb: 15C6, BU75, and J173 were found to selectively inhibit DNA synthesis, interleukin-2 (IL-2) receptor expression, and G1-->S transition of the cell cycle in T cells stimulated with anti-CD3 MoAb. None of anti-CD44 MoAb had influence on T cell proliferation induced by IL-2 or phorbol 12-myristate 13-acetate plus ionomycin. Inhibition of the CD3 pathway by anti-CD44 MoAb occurred by binding of MoAb directly to T cells without the involvement of monocytes or Fc receptors. In addition, the inhibitory anti-CD44 MoAb clearly suppressed intracellular calcium mobilization in T cells stimulated with anti-CD3 MoAb. Interestingly, the ability of anti-CD44 MoAb to inhibit T cell activation was well correlated with their capability to block the binding of hyaluronan (HA) to CD44 molecules. These results suggest that anti-CD44 MoAb directed to HA-binding site could selectively inhibit CD3-mediated T cell activation. Furthermore, CD44-mediated inhibitory signals would be linked to the blocking of early CD3-mediated signal transduction.

Animals↗
PubMedDate not supplied

Treatment of chemotherapy-induced neutropenia in children with subcutaneously administered recombinant human granulocyte colony-stimulating factor.

Fifty-six children with various malignancies were treated subcutaneously with recombinant human granulocyte colony-stimulating factor (rhG-CSF, KRN 8601) for neutropenia induced by cancer chemotherapy. Patients received the first chemotherapy without rhG-CSF (control course). In the second course, rhG-CSF was given once daily, starting 3 days after completion of identical chemotherapy (day 3) and continuing until day 12. At day 12, the white blood counts and neutrophil counts were found to be 6.8 and 30 times higher in the rhG-CSF course than in the control course (P = .0001) Nadirs of white blood counts and neutrophils were significantly elevated in the rhG-CSF course (P = .003 and .0001, respectively). rhG-CSF administration shortened the neutropenic period in the majority of patients. Children tolerated the rhG-CSF administration well and we have hereby confirmed that rhG-CSF administration is useful for proceeding with chemotherapy in children with cancer.

Adolescent↗
PubMedDate not supplied

Transient encephalopathy following a single exposure of high-dose methotrexate in a child with acute lymphoblastic leukemia.

An episode of transient encephalopathy after the first course of intravenous high-dose methotrexate (HD-MTX; 1000 mg/m2) was observed in a 4-year-old girl with acute lymphoblastic leukemia. The neurological abnormalities took place 5 days after HD-MTX therapy. She experienced complex partial seizure and left hemiparesis, which resolved spontaneously in 5 days. Cranial computed tomographic scan and magnetic resonance imaging showed multiple low-density lesions in bilateral hemispheres. It is well appreciated that neurotoxicity from MTX follows prolonged exposures, often accompanying or following radiation therapy. To our knowledge, however, there have been no reports that such neurological complications developed following a single exposure of HD-MTX in patients with ALL. Follow-up electroencephalograms showed that she had periodic lateralized epileptiform discharges (PLEDS), suggesting functional deafferentation of cortical neurons following HD-MTX. Moreover, the serum and CSF MTX levels following a second low-dose course and her clinical course suggested that she had presumably central nervous system leukemia at the time of HD-MTX therapy, which might have been related to neurological complications. The pathogenesis of MTX-induced neurotoxicity is discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Ataxia telangiectasia associated with B-cell lymphoma: the effect of a half-dose of the drugs administered according to the acute lymphoblastic leukemia standard risk protocol.

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by cerebellar ataxia, oculocutaneous telangiectasia, and variable degrees of humoral and cellular immunodeficiency. Affected individuals are known to exhibit a high incidence of lymphoma and leukemia. Because of increased chemosensitivity, the treatment of A-T patients with malignancies requires extremely careful planning and caution with respect to the use of chemotherapy. The authors report on a 12-year-old boy with A-T who developed B-cell lymphoma. He received a half-dose of the drugs administered according to the acute lymphoblastic leukemia (ALL) protocol issued by our children's cancer study group (9104 Standard Risk Protocol, Tokai Pediatric Oncology Study Group). As a result, he continues to be in complete remission and free of treatment complications 32 months after the diagnosis of B-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Piroxicam suppositories in the treatment of osteoarthritis of the knee joint.

The subjects were 231 patients aged 16 to 75 years with osteoarthritis of the knee joint. Each patient received 20 mg of piroxicam daily as a suppository administered before sleep; 75% of the patients were treated for 14 days or longer. Overall treatment outcome was excellent in 34% according to physicians' ratings and in 36% according to the patients' self-ratings, good in 39% and 41%, fair in 22% and 17%, and unimproved in 5% and 7%, respectively. Side effects were reported by 3% of the patients. It is concluded that treatment of osteoarthritis with piroxicam suppositories is safe and effective.

Adult↗
PubMedDate not supplied

Methylthiopropylamine, a potent inhibitor of spermidine synthase and its antiproliferative effect on human lymphoid leukemia Molt 4B cells.

The catalytic activity of spermidine synthase isolated from rat ventral prostate was significantly inhibited by methylthiopropylamine (MTPA). Spermine synthase was almost insensitive to this inhibitor. Inhibition of spermidine synthase by MTPA was competitive with respect to a substrate putrescine (Ki, 3.3 = 10(-7) M), but not competitive with another substrate decarboxylated S-adenosylmethionine (dec AdoMet). MTPA inhibited the growth of human lymphoid leukemia Molt 4B cells. The spermidine content in the inhibitor-treated cells was dose-dependently depressed, whereas the putrescine content was increased concomitantly. In these spermidine depleted and growth retarded Molt 4B cells, the synthesis of protein, but not of DNA or RNA, was found to be significantly diminished.

Animals↗
PubMedDate not supplied

Treatment of acute non-lymphocytic leukemia in Saitama Cancer Center.

Forty patients with previously untreated acute nonlymphocytic leukemia (ANLL) were treated at Saitama Cancer Center between February 1979 and November 1983. Their median age was 43 years (range: 14 to 68 years), 13 patients (32.5%) being 55 years old or older. Twenty-three patients had Auer bodies. Complete remission was achieved in 75.0% of the patients (30/40) with the first line therapy, and in 6 of 7 patients in the second line therapy. Thus, the overall remission rate was 90.0%. The median duration of remission was 14 months and 39% of the patients showed no relapse within 3 years. The median survival for all patients was 26 months and the actuarial 3-year survival rate was 41%. The better results in this series were thought to be due to intensive post-induction reinforcement therapy.

Aclarubicin↗
PubMedDate not supplied

Effect of hypoxia on bronchial reactivity in dogs.

The effect of hypoxia on bronchial reactivity was studied in six anesthetized dogs. Bronchial reactivity was obtained by inhalation of histamine aerosol in stepwise incremental concentrations during fixed tidal volume breathing. Two kinds of hypoxia were induced by inspiration of nitrogen until the end-tidal oxygen concentration (FETO2) reached 15% (mild) and 10% (severe hypoxia). Pulmonary resistance (RL) was measured by the 3 HZ forced oscillation technique in the open chest condition. Before histamine challenge, hypoxia did not increase RL in any of the dogs with mild hypoxia (FETO2 15%) and increased it in one dog with severe hypoxia (FETO2 10%). There was synergy between hypoxia and inhaled histamine in all dogs with both mild and severe hypoxia. The magnitude of synergy was significantly higher in severe than in mild hypoxia (p less than 0.05). With vagi cut, hypoxia did not increase RL compared with normoxia at any histamine concentration. It is suggested that hypoxia enhanced bronchial reactivity through the vagal nerves.

Aerosols↗