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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 649 records · Page 36Linked to original sources

Angioimmunoblastic lymphadenopathy and related disorders: a retrospective look in search of definitions.

The recent report of an immunoblastic lymphadenopathy (IBL)-like T cell lymphoma has rekindled questions about the nature, reactive or neoplastic, of IBL, angioimmunoblastic lymphadenopathy (AIL), and lymphogranulomatosis X (LgX) and blurred the criteria for their diagnosis. We looked in the literature and our own data for a categorization of AIL (IBL, LgX) and related disorders, needed for future prospective studies. Specific differences in the original histologic definitions and discordant immunophenotypic data may warrant the separate consideration of AIL, IBL and LgX and their subdivision into predominantly T cell or B cell lesions. DNA hybridization and cytogenetic studies of the processes sharing histologic features of AIL (IBL, LgX) demonstrate a continuum of disorders from purely reactive to frankly malignant, which may be categorized as follows: (1) those without evidence of clonality by any of three parameters (immunophenotypic, immunogenotypic, and cytogenetic), for which only the term AIL (IBL, LgX) might be reserved; (2) those with evidence of clonality by all parameters, or AIL (IBL, LgX)-like lymphomas; and (3) those that, due to any discordance among the three parameters, do not fit into either of the above categories, and for which the term AIL (IBL, LgX)-like dysplasias is proposed. This intermediate group seems to be composed of unstable lymphoproliferative conditions, in which a predominant component of normal cells coexists with clonal population(s) that may either disappear with time or selectively proliferate and develop into frank lymphoma.

Humans↗

[A case of bilateral testicular germ cell tumor].

A case of bilateral successive tumor of germ cell origin is reported. A 29-year-old man visited our clinic with a complaint of swelling of right scrotal contents 18 months after initial left orchiectomy for a seminoma. The right orchiectomy was performed and its histological finding was also seminoma. Between 1965-1987 we treated 55 patients with testicular germ cell tumors. Two of them suffered a second germ cell tumor. One of them who had different histology of teratocarcinoma on left side and seminoma on right side had been reported previously. Herein, we report the second case and review the literature.

Adult↗

[Pharmacokinetic and clinical studies on sulbactam/ampicillin in the pediatric field].

The new antibiotic, sulbactam/ampicillin (SBT/ABPC) was administered to 25 children. The results obtained are summarized as follows. 1. In 5 cases of children administered with SBT/ABPC (30 mg/kg) by intravenous drip infusion for 30 minutes, the mean values of T 1/2 (beta) were 0.94 hour (SBT) and 0.86 hour (ABPC) and the mean 6.5 hour urinary excretion rates were 64.2% and 42.9%, respectively. 2. The antibiotic was administered to a total of 25 patients with bronchopneumonia, pneumonia, bronchitis, cervical lymphadenitis, tonsillitis, streptococcal infection, urinary tract infection, felon, periappendicular abscess, sepsis or purulent meningitis. Response to the treatment were excellent in 17 cases, good in 7, fair in 1, and poor in none. The efficacy rate was 96%. From our results, this drug appears to be particularly effective against bronchopneumonia, bronchitis and urinary tract infection. 3. Eruption occurred in 1 of 25 patients and elevation of eosinophil, GOT/GPT, platelet in 3 and descent of WBC in 1 were observed, but these were transient. These results showed that SBT/ABPC is a drug which can be safely used in the pediatric field as well as for adults.

Age Factors↗

[High-dose cytosine arabinoside treatment of leukemia with special reference to the optimal number of doses].

A high dose of cytosine arabinoside (ara-C) was given to 51 patients during consolidation therapy or with refractory or relapsed acute leukemia. Ara-C was administered as a 3-hour infusion at a dose ranging from 2 to 3 g/m2 every 12 hours, diluted in 500 ml of 5% dextrose in water for 2 to 6 days. Complete remission was attained in 3 (25%) of 12 evaluable patients. Two with blast crisis of chronic myelogenous leukemia of these did not obtain complete remission. Death due to marrow aplasia occurred in five patients, and two of these had relatively good performance status and were given a dose of 3.0 g/m2 x 8 or 12 of ara-C. At a dose of 3.0 g/m2 x 6, the mean duration of granulocytes of less than 100/mm3 was 6.7 days. This duration seemed to be manageable myelosuppression. Therefore, 3.0 g/m2 x 6 was thought to be an adequate dose. Seizure occurred in one patient, and conjunctivitis was seen in another. In conclusion, from the manageable myelosuppression observed, administration of 3.0 g/m2 x 6 of ara-C seemed to be an adequate dose.

Adolescent↗

Effects of the novel anti-ulcer agent 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine on experimental ulcers and gastric secretion in rats.

The effects of 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285) on various experimentally induced ulcers and gastric acid secretion were investigated in rats. HWA 285 (10-50 mg/kg, p.o.) inhibited restraint and water-immersion-induced stress, ulcers, indometacin- and absolute ethanol-induced gastric ulcers and mepirizole-induced duodenal ulcers in rats in a dose-dependent manner. HWA 285 (10-25 mg/kg i.d.) had inhibitory effects on acetylsalicylic acid-induced ulcers. The healing of acetic acid-induced chronic ulcers was significantly accelerated by HWA 285 (25 mg/kg p.o.) when it was given twice daily for 7 consecutive days. When given orally (twice a day, 11 doses in total) before the induction of gastric ulcers by stress, cimetidine at 100 mg/kg aggravated the ulcers, whereas, HWA 285 at 25 mg/kg had not such an effect. In conscious pylorus-ligated rats, HWA 285 (10-100 mg/kg i.p.) showed a dose-dependent inhibition on basal and desglugastrin- and 2-deoxy-D-glucose (2-DG)-stimulated gastric acid secretion. In stomach-lumen perfused rats, HWA 285 (30 mg/kg i.v.) inhibited 2-DG-stimulated gastric acid secretion but not carbachol-stimulated gastric acid secretion. These results suggest that the anti-ulcer effects of HWA 285 are produced by cytoprotective and central anti-secretory activity without peripheral anti-cholinergic properties. Whether the central anti-secretory effects of HWA 285 play thereby the key role, have to be clarified in further investigation.

Acetates↗

[A case of repeated hematomyelia caused by cavernous hemangioma in the spinal cord].

A case is reported of repeated hematomyelia caused by cavernous hemangioma in the spinal cord. A 47-year-old woman first noticed a sudden onset of numbness in her thigh and then it gradually disappeared. Four months after the onset, she began to experience weakness and numbness in both of her legs, and difficulty in voiding and defecating. She recovered gradually for several months, but felt numbness in both legs. Myelography showed swelling at Th5 level. T2-weighted MRI showed a reticulated core of mixed intensity with rims of decreased intensity. During the subsequent operation, a dark brown lesion was detected at Th5 level, which consisted of multicystic cavities with old hematoma. But there were no abnormal vessels, or active bleeding. This lesion was almost completely removed and was diagnosed as cavernous hemangioma.

Female↗

[Arterial switch operation for simple transposition of the great arteries in infancy].

Five infants (22-42 days of life) underwent arterial switch operation for simple transposition of the great arteries under deep hypothermic cardio-pulmonary bypass. Three babies required prostaglandin E1 infusion to keep ductus arteriosus opened widely before surgery. Balloon atrioseptostomy was necessary in 0-10 days of life in all babies because of poor condition. Left to right ventricular peak pressure ratio ranged from 0.75 to 0.86, preoperatively. Four of the five survived the operation, and one died of coronary insufficiency because of kinking of the implanted coronary artery. Hypothermic circulatory arrest was used in three (38-41 minutes). Aortic cross clamp time was 70-100 minutes, and cold crystalloid cardioplegia was given only one time just after aortic clamp in 3 babies. Single dose of cardioplegia protected left ventricular muscle well in babies with transposition of the great arteries as same as multiple dose method used in those with ventricular septal defect.

Humans↗

[Laboratory and clinical investigations of cefodizime in infectious diseases in childhood].

In this study, cefodizime (CDZM, THR-221) was administered to 34 children with infections and the efficacy was evaluated in 30 patients. The efficacy rate was 90.0% and CDZM was proved to be a highly effective antibiotic for infectious diseases in childhood. We also demonstrated that CDZM had strong antibacterial activities against both Gram-positive and Gram-negative bacteria. No severe toxicity related to intravenous injection of CDZM was observed in our 34 cases.

Age Factors↗

2-Mercaptoethylamine, a competitive inhibitor of spermidine synthase in mammalian cells.

Spermidine synthase from rat ventral prostate was inhibited by 2-mercaptoethylamine (MEA). Inhibition of spermidine synthase by MEA was competitive with respect to one of the substrates putrescine, but not competitive with respect to the other substrate decarboxylated S-adenosylmethionine. MEA markedly depressed spermidine and spermine contents in human erythroid leukemia K562 cells, suggesting that these changes resulted from the inhibitory effect of MEA on spermidine synthase in situ.

Animals↗

In vivo antitumor activity of multiple injections of recombinant interleukin 2, alone and in combination with three different types of recombinant interferon, on various syngeneic murine tumors.

We have used several transplantable experimental murine tumors to evaluate the potentiation of antitumor activity by a combination of human recombinant interleukin 2 (rHIL2) and recombinant interferons (rIFNs). The combination of rHIL2 and either human hybrid recombinant alpha-interferon A/D (rIFN-alpha A/D) or mouse recombinant beta-interferon (rIFN-beta) induced the s.c. adenocarcinoma 755, which had been established for 8 days, to regress, although rHIL2 or the rIFNs alone hardly inhibited the tumor's growth. Eight injections of the rHIL2-rIFN-alpha A/D combination cured 38% of the tumor-bearing mice. The rHIL2-rIFN-beta combination achieved a complete cure only when given in more than 13 injections. The administration of rHIL2 and mouse recombinant gamma-interferon (rIFN-gamma) markedly inhibited tumor growth of the s.c. established adenocarcinoma 755, but did not cure any of the mice. Other tumors, B16-F10 melanoma, and colon tumors 38 and 26 responded almost as well to a rHIL2-rIFN-alpha A/D or -beta combination, but not to a rHIL2-rIFN-gamma combination. The growth of Lewis lung carcinoma was inhibited to a lesser extent by all combinations, for which there were no long-term survivors. The combination therapy of rHIL2 and rIFN-beta produced a marked regression of the tumor in beige mice which have low natural killer activity, suggesting the activated natural killer cells not to be responsible for the therapeutic effect. And T-cell immunity may be important in the regression of s.c. established tumors, because of the lesser potentiation of antitumor activity in athymic mice. These results demonstrate that combination therapies of rHIL2 and rIFN-alpha A/D or -beta can function synergistically in the various s.c. established murine tumor systems and give further evidence in support of their clinical potential.

Animals↗

Comparative study of the antitumor effect of two types of murine recombinant interferons, (beta) and (gamma), against B16-F10 melanoma.

A comparative study of the antitumor effect of murine recombinant interferon(beta) less than Mu-rIFN(beta) greater than and murine recombinant interferon(gamma) less than Mu-rIFN(gamma) greater on B16-F10 melanoma was conducted. Administration of Mu-rIFN(gamma) i.p. into C57BL/6 mice on days 1 to 7 produced a higher suppressive effect than Mu-rIFN(beta) both on the growth of s.c. implanted tumor and on the formation of artificial pulmonary metastasis. Pharmacokinetic study of Mu-rIFN(gamma) demonstrated that high plasma levels were retained for a long time. In clonogenic assay, Mu-rIFN(gamma) at 1000 units/ml showed about 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN(beta) hardly inhibited the colonies, even at 1000 units/ml. Augmentation of natural killer (NK) cytotoxicity was much greater with Mu-rIFN(beta) than Mu-rIFN(gamma), whereas Mu-rIFN(gamma) enhanced the cytotoxicity of peritoneal macrophages more strongly than Mu-rIFN(beta). Injection of Mu-rIFN(gamma) i.p. 1 day before tumor challenge also inhibited the formation of pulmonary metastasis of B16-F10 melanoma. However, pretreatment of mice with carrageenan significantly suppressed the inhibitory effect of Mu-rIFN(gamma). From these results, it is suggested that the inhibitory effect of Mu-rIFN(gamma) on the tumor growth and metastases of B16-F10 melanoma is mediated partly by direct antitumor effect and partly by the activation of macrophages, and that the augmentation of NK activity contributes mainly to the antitumor effect of Mu-rIFN(beta).

Animals↗

Cytogenetic effect of carboplatin on human lymphocytes.

Carboplatin, a second generation cisplatin analogue, was tested for induction of sister chromatid exchange (SCE) as well as chromosomal aberrations in human lymphocytes in vitro and in vivo. A dose-dependent effect was observed for increased frequency of metaphases with SCE (r = 0.984, P less than 0.001) as well as chromosomal aberrations (r = 0.994, P less than 0.001), primarily chromatid gap or break, in vitro. SCE induction by carboplatin was less than that by cisplatin at the same concentration. When patients were treated with a single dose of carboplatin at a dose of 450 mg/m2, the frequency of SCE and chromatid type aberrations increased significantly. However, even when considering dose and peak plasma concentration in patients receiving carboplatin, it appears that the ability of carboplatin to induce SCE and chromosomal aberrations is weaker than that of cisplatin. SCE frequencies induced by carboplatin decreased with time going by, and in one patient who was tested 5 weeks after treatment, SCE frequency showed a decrease to the pretreatment level. It thus appears that carboplatin has an improved therapeutic index over the parent compound, cisplatin, because of its less mutagenic or carcinogenic hazard, in addition to the largely reduced incidence of untoward effects.

Aged↗

Antitumor effect of methylglyoxal bis(3-aminopropylamidinohydrazone), a new inhibitor of S-adenosylmethionine and ornithine decarboxylases, on human erythroid leukemia K562 cells.

Methylglyoxal bis(3-aminopropylamidinohydrazone (MGBA) inhibited S-adenosylmethionine decarboxylase (AdoMetDC) activity competitively with S-adenosylmethionine (AdoMet), showing a Ki value of 2.60 x 10(-5) M. It also inhibited ornithine decarboxylase competitively with ornithine, showing a Ki value of 3.80 x 10(-5) M. MGBA inhibited the growth of human erythroid leukemia K562 cells. Putrescine, spermidine, and spermine concentrations in MGBA-treated cells were depressed to 19%, 36%, and 66% of the values of control cells, respectively.

Adenosylmethionine Decarboxylase↗

Immunohistochemical study of nodular hyperplastic parathyroid glands in patients with secondary hyperparathyroidism.

Thirty-seven nodular hyperplastic parathyroid glands obtained by subtotal parathyroidectomy from 11 haemodialysed patients with secondary hyperparathyroidism were examined both pathologically and immunohistochemically. Four consecutive sections of the largest section-surface of each gland were subject to 4 different stains (haematoxyline-eosin, Grimelius, and the immunohistochemical stains for parathyroid hormone and chromogranin A) for comparison of each nodule. It was found that the major part of each nodule consisted of a single cell type with a single pattern of cells. These reacted uniformly to each stain. The mechanism involved in the storage and secretion of the secretory granule appeared to be regulated at the nodule and not at the cell level. The results suggest that the nodules may come from a monoclonal proliferation of a single parathyroid cell. Our present light microscopic immunohistochemical study, failed to demonstrate completely identical immunoreactive positivity of each nodule or each parathyroid cell to PTH. Chromogranin A or secretory protein-I did not indicate the coexistence of PTH and SP-I in the same secretory granule, which was in good agreement with the electron microscopic immunocytochemical study of Arps using bovine parathyroid glands. Our present study, however, provides good evidence that chromogranin A positivity is demonstrable in the human parathyroid gland outside the adrenal medulla and sympathetic nerves.

Humans↗

Trisomy 11 in chronic myelomonocytic leukemia: report of two cases and review of the literature.

Two cases of chronic myelomonocytic leukemia (CMMoL) with trisomy 11 as the sole chromosome abnormality are reported. A simple trisomy 11 also has been reported in 11 patients with myeloproliferative disorders, including CMMoL and acute nonlymphocytic leukemia (ANLL) in the literature. From data on these 13 patients, leukemia with trisomy 11 may be characterized by a nonlymphoid origin and myelomonocytic features. Patients with this abnormality were mostly elderly, and often had a preleukemic phase and a short survival. We propose that trisomy 11 and nonlymphocytic leukemia with myelomonocytic features may be a new association in human neoplasia.

Aged↗

Sequence-dependent antitumor effect of VP-16 and 1-beta-D-arabinofuranosylcytosine in L1210 ascites tumor.

The sequence-dependence of the antitumor effect of etoposide (VP-16) and 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated against the L1210 ascites tumor in BDF1 mice. Treatment with VP16 (7.5 or 15 mg/kg) and ara-C (25 or 500 mg/kg) was administered intraperitoneally on days 1, 4 and 7 after tumor inoculation. Six hour pretreatment with 15 mg/kg VP16 followed by 500 mg/kg ara-C yielded a 100% cure rate, but only a 20% cure rate was obtained with the reverse sequence. Simultaneous administration of 15 mg/kg of VP-16 and 500 mg/kg ara-C interacted synergistically, producing a 70% cure rate. In contrast with the results obtained with VP-16 and 500 mg/kg ara-C, simultaneous administration of 25 mg/kg ara-C neither antagonized nor potentiated the antitumor effect of VP-16. Twenty-five mg/kg ara-C was too low to produce any antitumor effect with VP-16 in simultaneous administration. At every dose investigated, pretreatment with VP-16 followed by ara-C was the most effective antitumor schedule in L1210 leukemia. This sequence of drug administration did not cause greater toxicity as measured by weight loss or toxic death.

Animals↗