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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 613 records · Page 34Linked to original sources
PubMed1989

Effect of scopolamine and HP 029, a cholinesterase inhibitor, on long-term potentiation in hippocampal slices of the guinea pig.

The effect of scopolamine and a cholinesterase inhibitor on long-term potentiation (LTP) of population spikes was studied in a guinea pig hippocampal slice preparation. After brief application of each drug (10 min), LTP in CA1 and CA3 was induced by tetanus stimulation delivered to commissural/associational fibers and mossy fibers, respectively. Scopolamine at concentration of 10 microM had no effect on LTP in CA1 but significantly suppressed LTP in CA3. The cholinesterase inhibitor, 9-amino-1,2,3,4-tetrahydroacridine-1-ol maleate (HP 029) at concentration of 10 microM significantly enhanced LTP both in CA1 and CA3. These results suggest that the cholinergic system is involved in producing LTP in CA3. Another mechanism of the effect of HP 029 on LTP in CA1 is discussed.

Action Potentials↗
PubMed1989

A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis.

We report a novel chromosome translocation--t(2;5)(p23;q35) or its variant, t(2;5;13)(p23;q35;q12)--in 3 patients with peripheral T-cell lymphoma. All 3 were female children who had peripheral lymphadenopathy without organomegaly and underwent complete remission with or without chemotherapy. Their tumors were characterized histologically by predominant large cells, at times showing phagocytosis, and immunologically by peripheral T-cell phenotype and expression of Ki-1 antigen and epithelial membrane antigen (EMA). Since the same translocation has been reported in the literature in 4 patients with malignant histiocytosis (MH), and our patients had histologic features suggestive of that disease, it is likely that many tumors previously interpreted as MH are actually phagocytic large T-cell lymphoma carrying this translocation.

Antigens, Differentiation↗
PubMed1989

Phase I study of combination therapy with interleukin 2 and beta-interferon in patients with advanced malignancy.

Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and beta-interferon (IFN-beta) on mouse tumors and previous results of a phase I study of rIL-2, a phase I study of combination therapy with human rIL-2 and IFN-beta was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-beta by 2-h i.v. infusion for 5 days each week for 4 weeks. The common side-effects were fever, malaise, chills, appetite loss, and diarrhea. Leukocytosis and eosinophilia were observed in 56% and 69% of the patients, respectively. Transient leukopenia and thrombocytopenia were also observed in some patients. Dose-limiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-beta were 1.1 x 10(6) U/m2/day for rIL-2 and 6.0 x 10(6) IU/m2/day for IFN-beta. No patients achieved complete and partial response to therapy in this study. One patient with pulmonary metastasis from pharyngeal cancer showed a minor response. Natural killer (NK) and lymphokine-activated killer (LAK) activities increased during the 5 days of treatment and decreased during the 2-day intermission. The percentage of IL-2 receptor-positive cells increased markedly until Day 12, and gradually decreased thereafter. The percentage of OKT 4-positive cells and the OKT 4/OKT 8 ratio increased. In contrast, the percentage of Leu 7- or Leu 11-positive cells decreased over the 4-week treatment. A phase II study of this combination therapy is ongoing against head and neck cancer, and renal cell carcinoma.

Adult↗
PubMed1989

Synergistic interaction between etoposide and 1-beta-D-arabinofuranosylcytosine.

The sequence-dependency of the antitumor effect of etoposide (VP-16) and 1-beta-D-arabinofuranosylcytosine (ara-C) and its mechanisms were investigated in L1210 ascites tumor. Treatment with VP-16 (15 mg/kg) and ara-C (25 mg/kg) was administered intraperitoneally on days 1, 4, and 7 after tumor inoculation. Three-hour pretreatment with VP-16 followed by ara-C produced 70% of cure rate, but only 20% of cure rate was obtained with the reverse sequence. Simultaneous administration led to the worst therapeutic result. To clarify this sequence-dependent interaction of the both drugs, the effect of VP-16 on incorporation of ara-C into DNA was investigated in vivo. On day 3 after intraperitoneal transplantation of 1 x 10(6) L1210 cells, 15 mg/kg of VP-16 and 1 microCi of (3H)ara-C was administered intraperitoneally with or without time interval. The effect of VP-16 on ara-C incorporation was also strikingly schedule-dependent and compatible with the schedule dependency of the antitumor effect. At 1 hr after injection of ara-C, simultaneous administration of 15 mg/kg of VP-16 reduced ara-C incorporation by 67% of ara-C injection alone. But in sharp contrast to simultaneous-administration, 3 hour preadministration of VP-16 increased ara-C incorporation up to 247%. From 1 to 6 hour after intraperitoneal administration of 15 mg/kg of VP-16, the sedimentation rate of L1210 DNA was increasing on alkaline sucrose gradients. This repairing period from VP-16 induced DNA damage might be the vulnerable time to ara-C through an increase in ara-C incorporation into DNA.

Animals↗
PubMed1989

Discontinuing therapy in childhood acute lymphoblastic leukemia treated with a chemoimmunotherapy protocol.

We examined the results of discontinuing therapy in Japanese children with acute lymphoblastic leukemia. Of the 209 patients in the chemoimmunotherapy study, 120 (57.4%) had all chemotherapy stopped after 3 years of complete remission, and 72 (34.4%) reached the point of discontinuing immunotherapy after 5 years of complete remission. Of the 120 children removed from chemotherapy, 14 (11.7%) have relapsed, mainly in the extramedullary sites (5: testis, 5: bone marrow, 3: central nervous system, 1: bone); relapses occurred 1-23 months after cessation of chemotherapy (median 11 months). Boys had higher post-chemotherapy relapse rate than girls (0.21 versus 0.08, P less than 0.05). None of the 72 children removed from immunotherapy have yet relapsed. Long-term remission and possibly cure can be expected in approximately one-half of newly diagnosed Japanese patients. Although the active immunotherapy had no beneficial effect on the overall outcome for leukemic children, it could be of benefit to the elimination of bone marrow relapses after cessation of chemotherapy.

Antineoplastic Agents↗
PubMed1989

Significance of transcatheter chemoembolization combined with surgical resection for hepatocellular carcinomas.

In order to improve the survival rate after liver resection for hepatocellular carcinoma (HCC), 71 HCC patients were treated with transcatheter chemoembolization (TCE). In the present study, we analyzed the effects of TCE on the patients' survival rates, as well as on the liver specimens resected in a histopathological study, comparing those not treated with TCE (n = 21). The overall survival rates, including hospital mortality, for 1 year, 3 years and 5 years were 81%, 72% and 54% respectively. However, no differences were observed in the survival rates between the TCE and the non-TCE groups. A histopathological study demonstrated that TCE was quite effective on the main tumor but not on intrahepatic metastasis or on tumor thrombus in the portal vein. However, we found that most of the intrahepatic metastatic lesions were necrotized in 8 of the 30 cases with these lesions. The histopathological study proved that these particular cases had some abnormalities in the portal blood supply. All but one of them are currently alive 3-48 months after resection, although the prognosis of the patients who had intrahepatic metastasis or a tumor thrombus in the portal vein was extremely poor. Preoperative TCE may, therefore, be thought of as a useful modality when it is effective in killing intrahepatic metastases. To control the lesions, portal vein embolization may be a promising technique in the future.

Aged↗
PubMed1989

Hepatocellular carcinoma in adenomatous hyperplasia of the liver.

A hepatocellular carcinoma (HCC) measuring 0.2 cm in diameter was found in the center of an adenomatous hyperplasia (AH) measuring 1.7 cm in diameter in a cirrhotic liver. The liver cells of the AH showed a marked fatty change and contained many Mallory bodies. The AH and HCC were studied in relation to liver cell dysplasia in 108 surgically resected livers. The AH was mainly associated with fully developed cirrhosis in 5 (71%) of the 7 cases. The liver cell dysplasia, however was accompanied largely by fibrosis and early-stage incomplete septal cirrhosis in 10 (67%) of the 15 cases. As far as the active inflammatory change was concerned, a fairly active inflammation was found in only 3 (20%) of the 15 livers with liver cell dysplasia, but in 4 (57%) of the 7 livers with AH.

Adenoma↗
PubMed1989

Combination of pipemidic acid, colistin sodium methanesulfonate and nystatin may be less effective than nystatin alone for prevention of infection during chemotherapy-induced granulocytopenia in acute leukemia.

Pipemidic acid (PPA) and colistin sodium methanesulfonate (CLM) may selectively suppress aerobic gram-negative bacilli. Twenty-nine patients with acute leukemia were randomized after each course of consolidation chemotherapy to receive a single agent of nystatin (NYS) (34 courses) versus a combination of NYS, PPA and CLM (36 courses). The duration of fever over 39 degrees C was longer with the three drug combination (4.6 +/- 5.1 days) than with NYS alone (1.8 +/- 1.8 days) (P less than 0.01). Four cases of pneumonia occurred and four patients including one having pneumonia died of infection with the three drug combination, while no pneumonia or death occurred with NYS alone (P = 0.06 and P = 0.06, respectively). The combination of NYS, PPA and CLM may be less effective than NYS alone for the prevention of infection in acute leukemia patients with chemotherapy-associated granulocytopenia.

Acute Disease↗
PubMed1989

Increased sensitivity to 1-beta-D-arabinofuranosylcytosine in P388 murine leukemic cells resistant to etoposide.

A variant P388 murine leukemic cell resistant to 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidine)-beta-D-gl ucopyranoside (etoposide) (VP-16-213) was cloned. The variant P388/VP-16 cell line was 159-fold resistant to VP-16. We found that this variant P388/VP-16 cell line showed collateral drug sensitivity to 1-beta-D-arabinofuranosylcytosine(Ara-C), determined by comparing the 50% inhibitory concentrations in 48-h growth inhibition assay. To clarify the mechanism of this increased sensitivity to Ara-C, we quantified the deoxyribonucleoside triphosphate pools and 1-beta-D-arabinofuranosylcytosine triphosphate(Ara-CTP) using high-performance liquid chromatography in the parent and drug-resistant sublines of P388 cells. The analysis of deoxyribonucleoside triphosphate pools revealed that the pyrimidine triphosphate pools were significantly decreased in the P388/VP-16 cell line and the Ara-CTP concentration of two variant cell lines were not significantly different. The Ara-CTP/dCTP ratio was significantly increased in P388/VP-16 cells. These data suggest that the inhibition of the dCTP de-novo pathway and the preservation of the dCTP salvage pathway in P388/VP-16 cells might correlate with the increased sensitivity to Ara-C.

Animals↗
PubMed1989

Nucleotide sequence of capsid protein gene of porcine parvovirus.

Approximately 90% of the genome of porcine parvovirus was cloned into bacterial cells. The nucleotide sequence of the genome from 33 map units (MU) to 95 MU was determined and shown to include the entire gene encoding the capsid proteins. The predicted amino acid sequences of the capsid proteins showed extensive homology to those of other autonomous parvoviruses.

Amino Acid Sequence↗
PubMed1989

Erythema multiforme in children: unusual clinical features with seasonal occurrence.

Eighty-six cases of erythema multiforme (EM) were studied based on the distribution of skin lesions. Twenty-nine patients had distinct facial skin lesions as well as lesions on the extremities (Group A) and 57 patients had skin lesions only on the extremities (Group B). Patients in Group A were younger than those in Group B; the average ages being 7.5 and 25.2 years, respectively. In Group A, the disease occurred mainly in winter, while, in Group B, it began most frequently in summer. Preceding ulcerated pernio was seen in 11 patients of Group A, but only one of Group B. Histopathologically, both groups are compatible with a diagnosis of EM, although the seasonal occurrence of facial involvement in Group A may suggest a specific etiological relationship to cold.

Adolescent↗
PubMed1989

Establishment and characterization of a small round cell sarcoma cell line, SCCH-196, with t(11;22)(q24;q12).

A cell line designated SCCH-196 was established from an extraskeletal small round cell sarcoma developed in a 16-year-old Japanese girl. The cells grew as a monolayer, and have been continuously propagated by serial subcultures during the past 26 months. Cells from the primary tumor and those from the SCCH-196 cell line at passage 10 both showed the same karyotype, 51,XX, +8, +20, +21, t(11;22)(q24;q12), +i(1q), +i(1q). Histologically the primary tumor was difficult to classify as either Ewing's sarcoma (ES) or peripheral neuroepithelioma (NE). Neuron-specific enolase-positive cells in the primary tumor and the occurrence in the upper extremity were in favor of NE, while positive reaction of SCCH-196 cells to an ES-specific monoclonal antibody 5C11 suggested a diagnosis of ES. The SCCH-196 cell line may be useful for basic studies on differentiation of neuroectodermal tumors, and for future cloning of still unidentified genes which may be located at the breakpoints of the 11;22 translocation.

Adolescent↗
PubMed1989

Studies of expression of the DQ beta promoter and its 5' deletion derivatives in normal and mutant human B cell lines.

A series of 5' deletion test plasmids harboring promoter sequences of the HLA-DQ beta gene fused to the bacterial chloramphenicol acetyl transferase (CAT) gene were constructed. Transient CAT expression from these constructs in several types of cells was employed to examine the role of the promoter sequence in the regulation of DQ beta gene expression. The DQ beta constructs drove CAT expression in Raji cells (human Burkitt lymphoma cells) to at least 25-fold or 50-fold higher levels than in Hela cells (human cervical carcinoma cells) or Jurkat cells (human T-leukemia cells), respectively. A short promoter sequence of -160 bp containing the conserved X and Y sequences was sufficient for expression in Raji cells, and deletion to -106 bp which interrupted the X sequence abolished the expression. Sequences further upstream to -160 bp as far as -2500 bp which included an Ig-like octamer appeared to have no effect on expression in Raji cells. Thus, the promoter up to -160 bp has all of the sequences required for B cell specific expression of CAT in this assay. CAT expression from the 5' deletion constructs introduced into RJ2.2.5 and 6.1.6 cells (class II-negative mutant B cells lines) was also examined. None of the 5' deletion constructs, including that with -160 bp of promoter, showed CAT expression in these cells, suggesting that a transcriptional factor(s) required for the activity of the DQ beta promoter was missing in these cells. Moreover, the -160 to -66 bp sequence (including the X and Y elements), which functions as a B cell specific enhancer, was inactive in the mutant cells. Thus, the missing factor(s) are required for the enhancer function of this fragment.

B-Lymphocytes↗
PubMed1989

Insulin secretion in childhood obesity.

In 132 severely obese children (72 boys and 60 girls) who underwent institutional therapy, oral glucose tolerance tests were carried out on admission, and these children were divided into groups with normal and high insulin levels, in terms of the sigma IRI values obtained, on the basis of the reference value + 2SD calculated by Maruhama et al. From these children, those who had diabetes mellitus (DM) and those in whom DM was suspected were distinguished according to the diagnostic criteria of USPHS (Drash et al). The insulin levels were normal in 58 children and high in 64. Ten children were found to have DM, and 19 were suspected to have DM. Metabolism of the glucose load occurred at both normal and high insulin levels in some children. There was also a group of children in whom glucose metabolism was incomplete at high insulin levels and a group of children in whom glucose metabolism was not possible even at high insulin levels, showing an obvious DM reaction. These findings suggest that there is a difference in the sensitivity of the insulin receptors in these children. Age, severe obesity and a family history of DM were considered to be risk factors for DM. Although there was a moderate, positive correlation between sigma IRI and the obesity index and between sigma IRI and age, it seems that the level of insulin secretion varies considerably in obese children.

Adolescent↗
PubMed1989

Asymmetric synthesis of 2-substituted-3-aminocarbonyl propionic acid.

An asymmetric synthetic route to 2-substituted-3-aminocarbonyl propionic acid, which is the significant component of low-molecular-weight renin inhibitors, is described. The key step of this synthesis is diastereoselective alkylation by using chiral oxazolidinone and benzyl bromoacetate.

Chemical Phenomena↗
PubMed1989

[Studies on the relationship between therapeutic schedule and antitumor effect of etoposide and cytosine arabinoside in murine L1210 leukemia].

The sequence dependency of the antitumor effect of etoposide and ara-C was investigated against the L1210 ascites tumor in BDF1 mice. Etoposide (7.5 mg/kg or 15 mg/kg) and ara-C (25 mg/kg or 500 mg/kg) were administered intraperitoneally on days 1, 4 and 7 after inoculation of L1210 with or without time interval of 3 or 6 h. Antitumor effect was decided for cure rate and post inoculation survival time of the mice died of tumor. Six hours pretreatment with 15 mg/kg of etoposide followed by 500 mg/kg of ara-C yielded 100% of cure rate, but only 20% of cure rate was obtained with the reverse sequence. Simultaneous administration of etoposide and ara-C produced 70% of cure rate. At every dosage examined, pretreatment with etoposide given 6 hr before ara-C was the most effective antitumor schedule in L1210 leukemia.

Animals↗