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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 415 records · Page 23Linked to original sources

The mechanical behavior and morphological structure of callus in experimental callotasis.

Experimental callotasis was made in rabbit femurs. In order to compare mechanical behaviors and morphological structure of callus in callotasis, mechanical tests and histological examination were performed. Twenty Japanese white male rabbits were used. The right femurs were osteotomized at the level of the midshaft with a rotary cutter and fixed with a mini-model external fixator. After a 5-day waiting period, bone lengthening was started at the rate of 0.25 mm two times a day. Animals were divided into four groups. Group 1 and Group 2 were continual distraction group, Group 3 and Group 4 discontinued distraction group. The viscoelastic property was demonstrated in continual distraction group irrespective of distraction period, we thought the central undifferentiated connective tissue in callus was mainly responsible for the mechanical behavior. On the other hand, in discontinued distraction group, viscoelastic property shifted to elastic property corresponding to the rest period, we thought this change of mechanical behavior was histologically owing to the replacement of undifferentiated connective tissue by cartilage and the partial union of bone in callus.

Animals↗

Clinical significance of chromosome abnormalities in childhood acute lymphoblastic leukemia in Japan.

Of 240 Japanese children with acute lymphoblastic leukemia (ALL) treated between 1983 and 1990, 75 (31%) had normal diploidy, 47 (20%) hyperdiploidy with more than 50 chromosomes, 18 (8%) hyperdiploidy with 47-50 chromosomes, 77 (32%) pseudodiploidy, 22 (9%) hypodiploidy and one hypotetraploidy in the leukemic cells. Event-free survival (EFS) +/- standard error (SE) at 4 years was 74 +/- 7% in patients with hyperdiploidy > 50, 68 +/- 6% in those with normal diploidy, 55 +/- 13% in those with hyperdiploidy 47-50, 54 +/- 11% in those with hypodiploidy, and 22 +/- 5% in those with pseudodiploidy (log-rank, p < 0.0001). Seventy-four patients with translocation and 166 patients without translocation had EFS +/- SE of 26 +/- 6% and 64 +/- 4%, respectively, at 4 years (p < 0.0001). The overall prognosis of our patients was comparable to that of the patients mainly treated in the late 1970s and reported by the Sixth International Workshop on Chromosomes in Leukemia, but was much poorer than that of the patients more recently treated and reported from some American institutions. These findings may possibly reflect less appropriate chemotherapy having been applied to Japanese children with ALL.

Adolescent↗

[Increased levels of circulating hyaluronate in the sera of patients with rheumatoid arthritis with special reference to joint destruction].

We sought to assess whether serum levels of hyaluronate (HA) in patients with rheumatoid arthritis (RA) are elevated and correlated with grade of joint destruction and with laboratory data. Circulating HA levels were determined by protein binding assay of serum from 236 patients and 19 healthy controls. The greatest elevations of HA were seen in RA patients (350.7 +/- 689.5 ng/ml) than controls (33.7 +/- 24.2 ng/ml). Their levels showed only weak correlation values of CRP in laboratory data. Although HA levels of sera in stage III and IV in Steinbrocker's classification revealed significantly higher on average than ones in stage I and II (p < 0.01), there were many cases with low HA levels even in stage III and IV. Comparing HA levels between the cases with progressive and non-progressive type of hip or knee joint destruction within a year, the former (1143.6 +/- 1746.0 ng/ml median 480.1 ng/ml) presented significantly higher HA levels than the latter (245.3 +/- 255.8 ng/ml median 140.0 ng/ml) (p < 0.01). Further, one of 7 cases followed by 4 years with extremely high levels of HA showed progression of joint destruction from grade III to IV in Larsen Grade in bilateral knee joints during these times, though there were no significant correlations between HA levels and laboratory data. From above results, levels of circulating HA in the sera of patients with RA correspond to the joint destruction, not to a result of one.

Aged↗

[Phase I/II study of a combination regimen composed of cisplatin, carboplatin and etoposide against small cell lung cancer].

Phase I/II study of combination regimen composed of cisplatin (CDDP), carboplatin (CBDCA) and etoposide (VP-16) [CPVP] was conducted for small cell lung cancer. The dose level of VP-16 was fixed at 100 mg/m2, while the dosages of CDDP and CBDCA administered at each of the 4 steps were 50/200, 60/200, 60/250 and 70/250 mg/m2, respectively. Nine patients were allocated to each step dose group. Toxicities were evaluated in the first 2 courses to determine the maximum tolerated dose (MTD). As a result, step 3 dosages proved to be MTD, and the dose limiting factor (DLF) was hematotoxicity, but gastro-intestinal toxicity was tolerated. The response (CR+PR) was found in 21 out of 23 patients with evaluable lesions (91%). In the 22 patients who had not received pretreatment, median survival time (M ST) was 16.4 months. These results suggest that the recommended dose is step 2, and that the CPVP regimen is both more tolerable and more effective than the standard regimen. The CPVP regimen warrants further study in phase III trials.

Aged↗

[Laboratory and clinical study on combined effects of fosfomycin plus sulbactam/cefoperazone for mixed infections of MRSA and Pseudomonas aeruginosa].

Pseudomonas aeruginosa has been a major bacterial partner when MRSA (Methicillin-resistant Staphylococcus aureus) is isolated clinically. Hence, we studied the in vitro combined effect of fosfomycin (FOM) plus sulbactam/cefoperazone (SBT/CPZ) against mixed infections of MRSA and P. aeruginosa. The combined effect of FOM plus SBT/CPZ was observed through an FIC index using the checkerboard method, log reduction of colony counts on the time killing curve, and morphological changes observed using scanning electron micrography. Under serum concentration at 3 hours after administration in consider of pharmacokinetics, the combination effect was also evaluated. Furthermore, we evaluated a time-lag combination therapy in which FOM is administered 60 minutes before SBT/CPZ administration for mixed infections. Synergistic effects of FOM plus SBT/CPZ were clearly observed against mixed infections of MRSA and P. aeruginosa. Log reduction of colony counts on the time killing curve seemed to be an appropriate indicator in the evaluation of synergistic effects.

Aged↗

[A case report of left ventricular-right atrial communication with tricuspid regurgitation due to infective endocarditis].

A case of 58-year-old man with a left ventricular-right atrial communication with tricuspid regurgitation due to infective endocarditis was reported. Surgical treatment was performed following intensive chemotherapy. The communication was found in the center of a vegetation on the septal leaflet. Closure of the communication and replacement of the tricuspid valve were done successfully. His postoperative course was uneventful.

Endocarditis, Bacterial↗

[Study on clinical effects of tosufloxacin (TFLX) and the long-term low dose therapy for the prophylaxis of recurrent urinary tract infection].

Forty five patients with complicated urinary tract infections were treated with tosufloxacin (TFLX) in the initial antibacterial treatment. Excellent and moderate responses were obtained in 39 patients (86.7%). No side effects were seen. Clinical efficacy and safety of long-term preventive administration of TFLX (150mg, a day) were also examined in 39 patients who showed an excellent or a moderate response in the initial treatment. The period of the administration ranged from 28 to 112 days (average; 55 days). The rate of preventing recurrence of urinary tract infection was 92.3% on the last day of treatment. These findings suggested that TFLX was useful not only in treating the patients with complicated urinary tract infections but also in preventing recurrence of urinary tract infection.

Adult↗

[Experience of fluconazole granules and injection in pediatric patients].

Fluconazole (FLCZ) is an antifungal agent of triazole class and has been proven to be effective against deep-seated mycosis caused by Candida spp., Aspergillus spp. and Cryptococcus spp. This time, as we had an opportunity to use fluconazole granules, a new dosage form of the agent, we investigated its efficacy and safety in children with deep-seated mycosis together with the efficacy of the injectable form of the agent. FLCZ was administered to 6 patients with fungal infections for treatment and 5 compromised hosts with a high risk of fungal infections for evaluation of its prophylactic effect. The patients enrolled in the study were 11 in total, of whom 6 patients were evaluated for efficacy: fungal phlegmon in 2, esophageal candidiasis in 2, fungal bronchitis in 1 and oral mycosis in 1. Causative fungi for those infections were Candida albicans in 4 patients, Aspergillus, fumigatus in 1 and Aspergillus flavus in 1. The clinical efficacies were excellent in 3 patients and good in 3. The mycological efficacies were rated as eradicated in 5 patients and reduced in 1. In 5 patients to whom FLCZ was given prophylactically, development of neither fungal infection nor unknown fever was noted. No side effects nor clinical laboratory abnormalities were observed during treatment with either granules or injection, indicative of its safety in children.

Administration, Oral↗

[Planned combination therapy of coronary artery bypass and PTCA in ischemic heart disease].

Concomitant planned therapy consisting of a coronary artery bypass operation and percutaneous transluminal coronary angioplasty (PTCA) was attempted to shorten the period of cardiac arrest and make operations safer in patients undergoing emergency coronary artery bypass operations or coronary artery bypass operations in cases of significantly reduced left ventricle function or small perfusion lesions. The bypass operation was performed to treat only the main lesion and PTCA was undertaken 1-2 months later for coronary revascularization to treat secondary lesions. Finally, complete coronary revascularization was achieved. This concomitant method was performed on three cases. In all of these cases, two grafts were made and 1-2 lesions were dilated by PTCA. It was suggested that planned concomitant coronary artery bypass operations and PTCA provide a safer method of treatment in certain selected cases.

Angioplasty, Balloon, Coronary↗

Novel internal promoter/enhancer of HTLV-I for Tax expression.

The transcription initiation signals in retroviruses lie within the long terminal repeat (LTR) sequences. We have found a new transcriptional promoter in a central portion of the genome of human T-cell leukaemia virus type I (HTLV-I). The transcription start site is located just upstream to the ATG codon of the transcriptional trans-activator molecule, tax protein (Tax). The internal promoter may provide a new insight into gene expression of HTLV-I. The mechanism of leukaemogenesis by the defective HTLV-I is also discussed. Furthermore, we have identified two repeats of a novel enhancer sequence AGTTCT, which are located around the initiation site. We call the sequence HIRE (HTLV-I Internal Regulatory Element).

Animals↗

Cloning and expression of the chicken c-kit proto-oncogene.

The Kit protein is a cell-surface tyrosine kinase receptor encoded by the c-kit proto-oncogene. cDNA clones encoding chicken Kit were isolated from a chicken brain cDNA library, and the nucleotide (nt) sequence of a cDNA clone containing the entire protein-coding region was determined. The deduced amino acid (aa) sequence of chicken Kit shows 63% identity to mouse Kit, and suggests that chicken Kit shares common structural and functional features with mouse Kit. RNA blot analysis indicated that the expression pattern of the chicken c-kit transcript in chicken organs was similar to that of mouse c-kit in mice, suggesting that chicken Kit has biological roles analogous to those of mouse Kit.

Amino Acid Sequence↗

Sequence of a cDNA encoding chicken stem cell factor.

Stem cell factor (SCF) is a polypeptide growth factor and the ligand for the c-kit proto-oncogene product. We cloned a chicken cDNA encoding a protein homologous to the mouse and human SCFs. The deduced amino acid (aa) sequence shows 53 and 52% identity to the mouse and human SCFs, respectively.

Amino Acid Sequence↗

The 8;21 chromosome translocation in acute myeloid leukemia is always detectable by molecular analysis using AML1.

The AML1 gene was rearranged in leukemic cells with t(8;21)(q22;q22) or its variant, complex t(8;V;21) translocations from 33 acute myeloid leukemia (AML) patients. The AML1 rearrangement was also detected in three AML patients without t(8;21); two had a normal diploid karyotype, and one had a karyotype of 45,X, - X. The AML1 rearrangement in the t(8;21) breakpoint cluster region was not detected in leukemic cells with cytogenetic abnormalities other than t(8;21), or with normal diploidy obtained from 23 AML patients. Because leukemic cells of the five patients with complex t(8;V;21) translocations had a der(8)t(8;21) chromosome with a break in band 8q22 in common, the juxtaposition of the 5' side of AML1 to a predicted counterpart gene located in the breakpoint region of 8q22 may be an essential step in the leukemogenesis of AML with t(8;21). Our findings show that the 8;21 translocation, its variants, and the masked t(8;21) may all be detectable by the Southern hybridization method using the AML1 probes.

Adolescent↗

An experimental recurrence model for malignant fibrous histiocytoma induced by 4-hydroxyaminoquinoline 1-oxide in the rat.

To clarify the relationship between local recurrence of mesenchymal tumors and their malignant potentiality, we made an experimental recurrence model for malignant fibrous histiocytoma (MFH) induced by 4-hydroxyaminoquinoline 1-oxide in the rat by repeated excisional operations. By the repeated excision, the number of recurrent tumors increased, and the doubling time of tumor growth was shortened. The mean doubling time of primary tumors was 6.6 days, that of the first locally recurrent tumors was 4.3 days, and that of the second locally recurrent tumors was 3.3 days. However, mitotic count and 5-bromo-2-deoxyuridine (BrdU) labeling index did not change. This study proved experimentally that MFH shows more rapid growth through repeated local recurrences, and this experimental model may provide a better understanding of the local recurrence of MFH.

4-Hydroxyaminoquinoline-1-oxide↗

Ten-year survey of the intellectual deficits in children with acute lymphoblastic leukemia receiving chemoimmunotherapy.

Effects of chemoimmunotherapy, including cranial irradiation for central nervous system (CNS)-directed therapy, on children with acute lymphoblastic leukemia (ALL) were investigated. Fifty-five children with ALL in continuous complete remission (> 5 yr) and without evidence of current or past CNS diseases were evaluated in this retrospective study. Using standard measures of intelligence (IQ), we repeatedly (1-4 times/person; mean 2.1 times) evaluated IQ in the cohort of patients for the mean follow-up time of 9.7 yr, ranging from 5.4 to 15.8 yr. Fifty-five patients received the total number of 118 IQ testings and 40 patients received them more than twice. Patients were examined periodically at intervals of 1.4 to 10.0 yr (mean 4.8 yr) following diagnosis. Most of the published studies dealt with single IQ testing, and long-term follow-ups were not enough to assess the consequent IQ change. This report confirms and extends the previous findings: decreased IQ was related to age at diagnosis and irradiation (< 5 yr of age at diagnosis), irradiation-examination interval, and female sex. Further long-term follow-up study will be needed in these groups, since their IQs are still on the decline even after 10 yr of diagnosis.

Adolescent↗

Increase of interleukin 2 receptor and CD45RO antigen on lymphocytes cultured with human cytomegalovirus.

To determine the expression of interleukin 2 receptor (IL-2R) and the change of CD45RA and CD45RO antigen on lymphocytes in response to human cytomegalovirus (HCMV), peripheral blood mononuclear cells (PBMC) were cultured with HCMV antigen, and the expression of IL-2R and of CD45RA and CD45RO antigens on lymphocytes was analyzed by flow cytometry. The expression of IL-2R alpha (p55) and -beta (p75) was significantly increased on T cells obtained from CMV-seropositive donors following culture with the CMV antigen. An increased expression of IL-2R alpha and -beta was observed on both CD4+ and CD8+ cells, but the percentage of cells that expressed IL-2R was higher in CD4+ cells. The percentage of CD45RA+ cells was decreased and the percentage of CD45RO+ cells, especially of CD4+CD45RO+ cells, was increased when cultured with the CMV antigen. These observations suggest that switching of CD45RA+ cells to CD45RO+ cells occurred following stimulation with the CMV antigen. The expression of IL-2R and the activation of memory T cells are important to the recovery from and the protection against CMV infection.

Adult↗

Cytotoxic activity of rev protein of human immunodeficiency virus type 1 by nucleolar dysfunction.

The rev protein (Rev) of the human immunodeficiency virus type 1 (HIV-1) is known as a post-transcriptional regulator of viral gene expression. It is located in the cell nucleolus. Transiently expressed Rev caused nucleolar ballooning and deformity with aberrant accumulation of rRNAs, and de novo synthesis of rRNAs decreased dramatically in these cells. However, similarly expressed rex protein (Rex) of the human T-cell leukemia virus type I, which is a functional homologue to Rev, did not affect nucleolar structure and function. Rev expression resulted in cell death with nucleolar destruction in an inducible cell line. Analysis of Rev mutants revealed that both the nucleolar targeting signal of Rev and the multimerization domain are prerequisites to the nucleolar disintegration by Rev. Human T-cells acutely infected with HIV-1 contained nucleoli which were deformed and filled with Rev, but chronically infected cells had intact nucleoli. Involvement of Rev in cytopathic effects in HIV-1 infection is discussed.

Base Sequence↗