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Biomedical subjects

S Minami

Publications and source records attributed to S Minami.

At least 73 records · Page 4Linked to original sources

Multicenter prospective study of interferon-alpha and conventional chemotherapy versus bone marrow transplantation for newly diagnosed patients with chronic myelogenous leukemia. Kouseisho Leukemia Study Group.

We compared interferon-alpha (IFN-alpha therapy with bone marrow transplantation (BMT) after initial conventional chemotherapy in patients with chronic myelogenous leukemia (CML) in a multicenter prospective study. Ninety patients with Philadelphia chromosome-positive CML in chronic phase were enrolled between 1991 and 1994. Sixty-six of 89 evaluable patients received IFN-alpha after conventional chemotherapy with hydroxyurea or busulfan (IFN-alpha group). Twenty-three patients received allogeneic BMT (BMT group). Fifteen of them received transplants from HLA-identical family donors and 8 from HLA-matched unrelated donors. Forty-seven of 66 patients (71%) in the IFN-alpha group and 17 of 23 patients (74%) in the BMT group achieved complete hematologic response, and 12% in the IFN-alpha group and 13% in the BMT group achieved partial hematologic response. Complete cytogenetic response was induced in 5 (8%), partial cytogenetic response in 8 (12%), and minor cytogenetic response in 12 (18%) in the IFN-alpha group. At a median follow-up of 54 months (range, 30-76 months), in the IFN-alpha group, the predicted 6-year survival rate was 54.5% and the predicted 6-year rate of those remaining in chronic phase was 45.7%. Compared with patients with no cytogenetic response, the patients with some cytogenetic response after IFN-alpha treatment had significantly superior survival and duration of the chronic phase even after correction for the time to response using landmark analysis (P < .05). In the BMT group, the predicted 5-year survival rate was 93.3% for family-donor BMT and 21.9% for unrelated-donor BMT Acute graft-versus-host disease of grade III or IV was observed in 1 of 15 patients who received family-donor BMT and 3 of 8 patients who received unrelated donor BMT. Prior treatment with conventional cytotoxic drugs induced early hematologic response and did not reduce the effect of IFN-alpha on CML. Unrelated-donor transplantation should be offered to some patients according to patient age, HLA-matching status, time from diagnosis to BMT, and risk factors.

Adolescent↗

Effective and safe interferon treatment for Japanese patients with chronic myelogenous leukemia relapse after bone marrow transplantation. The Nagoya Blood and Marrow Transplantation Group.

The purpose of this study was to assess the efficacy and safety of interferon (IFN) treatment in patients with a relapse of chronic myelogenous leukemia (CML) after bone marrow transplantation in Japan. Accordingly, we retrospectively analyzed the results obtained from 8 patients treated with IFN by the Nagoya Blood and Marrow Transplantation Group. One of 3 patients with hematologic relapse and all 5 patients with cytogenetic relapse achieved complete cytogenetic response (CCR). The median time to achieve CCR was 8 months (range, 3-16 months). One patient relapsed 9 months after starting IFN and died of blast crisis. CCR was maintained for a median duration of 47 months (range, 9-79 months) in the remaining 5 patients. The median duration of survival of these 5 patients after starting IFN was 58 months (range, 12-89 months). At the time of this report, 2 patients who did not attain CCR have survived for 81 months and 142 months after starting IFN, respectively. During IFN treatment, 1 patient showed a transient deterioration of chronic graft-versus-host disease, and no treatment-related deaths were observed. These results suggest that treatment with IFN for CML patients who relapse after bone marrow transplantation is effective and safe. A prospective study to compare IFN with donor lymphocyte infusion is necessary to establish the optimal strategy for the treatment of CML patients who relapse after bone marrow transplantation.

Adult↗

[Nephrotoxicity of piperacillin combined with furosemide in rats].

Nephrotoxicity of piperacillin (PIPC) was evaluated in rats after combined administration with furosemide. After intravenous administration of PIPC (1600 mg/kg), the rats showed no change in urinalysis, biochemical analysis of plasma and histopathological analysis. The rats receiving furosemide (100 mg/kg) showed elevation of urinary NAG, BUN and creatinine concentrations, and showed slight degeneration of the renal proximal tubules. The rats receiving PIPC (1600 mg/kg) and furosemide (100 mg/kg) showed elevation of BUN and creatinine concentrations, and showed slight degeneration of the proximal tubules. These changes were comparable to those in rats receiving furosemide alone. The rats receiving cephaloridine (1600 mg/kg) showed elevation of urinary protein, BUN and creatinine concentrations, and showed moderate degeneration and necrosis of the proximal tubules. The nephrotoxicity was enhanced by combination with furosemide. In conclusion, no enhanced effect of nephrotoxicity was observed by combination of PIPC with furosemide.

Animals↗

[Improvement in quality of life with vinorelbine as a single agent in two patients with recurrent lung cancer].

Two patients with lung cancer that recurred after surgery and chemotherapy were administered vinorelbine (20 mg/m2) as a single agent on days 1 and 8 every 4 weeks. Patient 1 had recurrences in both lung lobes and metastases in the bone and liver after surgery, while patient 2 had a recurrence in the left lung lobe and metastases in the brain and liver after prior chemotherapy. In both patients, vinorelbine treatment improved several clinical indicators of cancer symptomatology including serum LDH, levels of other clinical blood tests, as well as a subjective assessment of the quality of life (QOL). Both patients were discharged from the hospital and subsequently treated on an outpatient basis. Because recurrent lung cancer patients generally have a poor performance status, chemotherapy for these patients is thought to worsen the QOL and increase hospital stays. The present report suggests that vinorelbine, as a single agent, might improve the QOL and make it possible to treat recurrent lung cancer patients on an outpatient basis.

Adenocarcinoma↗

Prolactin secretion in response to prolactin-releasing peptide and the expression of the prolactin-releasing peptide gene in the medulla oblongata are estrogen dependent in rats.

Prolactin-releasing peptide (PrRP), recently isolated from bovine hypothalamus as an endogenous ligand to a seven transmembrane-domain orphan receptor, is a candidate specific prolactin-releasing factor. The prolactin-releasing activity of the peptide and the expression of the PrRP gene were examined in vivo in relation to estrogen status. Plasma prolactin levels increased significantly with a peak at 5 min after the administration of 50 microg/kg PrRP in female rats in estrus under urethane anesthesia as compared with those in vehicle-treated control rats, but not in female rats in diestrus or proestrus or in male rats. In ovariectomized rats treated with supraphysiological concentration of estrogen, a dose-dependent increase of prolactin secretion in response to 2-50 microg/kg PrRP was observed. However, the peak values induced by 50 microg/kg PrRP were much less than those induced by 2 microg/kg thyrotropin-releasing hormone (TRH). PrRP mRNA levels in the medulla oblongata were decreased by ovariectomy and increased by estrogen treatment. The data indicate that estrogen is prerequisite to the stimulatory effect of PrRP on the secretion of prolactin and to the increase of PrRP mRNA levels in the medulla oblongata. The weak in vivo potency of PrRP on prolactin secretion relative to TRH suggests that PrRP differs from the classical hypophysiotropic hypothalamic releasing hormones.

Animals↗

Effect of insulin-like growth factor-I on growth hormone-releasing factor receptor expression in primary rat anterior pituitary cell culture.

We examined the effect of insulin-like growth factor-I (IGF-I) on GH-releasing factor (GRF) receptor expression in the primary rat anterior pituitary cell culture. The levels of GRF receptor mRNA were dose-dependently reduced by IGF-I treatment for 24 h. To clarify whether altered levels of GRF receptor mRNA contribute to GRF receptor concentrations, we examined the GH response to GRF in vitro. There was no difference in basal GH secretion between control and IGF-I pretreated cells, while GRF-stimulated GH secretion in cells pretreated with IGF-I for 24 h was significantly lower than that in control cells. Moreover, specific [125I] Tyr10-human GRF binding to pituitary cells was reduced significantly by IGF-I treatment. These results suggest that IGF-I acts directly on the pituitary and participates in the regulation of GRF receptor expression.

Animals↗

Massive outbreak of Escherichia coli O157:H7 infection in schoolchildren in Sakai City, Japan, associated with consumption of white radish sprouts.

In July 1996, an outbreak of Escherichia coli O157:H7 infection occurred among schoolchildren in Sakai City, Osaka, Japan. This outbreak developed in 13 North-East District and 34 Middle-South District elementary schools in the city. All children hospitalized on July 17-19 had presented on July 8 (North-East District) and July 9 (Middle-South District). School lunches served on July 1 and 8 in the North-East District and on July 1, 4, 8, and 9 in the Middle-South District were proposed by a food consumption study to be associated with infection. White radish sprouts from a single farm were the only uncooked food common to the most highly implicated meals on the involved days in two school districts (sweet and sour chicken with lettuce on July 8 in the North-East District and chilled Japanese noodles on July 9 in the Middle-South District). Two incidents of E. coli O157:H7 in neighboring areas were also related to white radish sprouts from the farm. The pulse-field gel electrophoresis patterns of isolates from patients in these two districts and the neighboring areas were identical. Thus, it was concluded that the cause of the outbreak was the white radish sprouts shipped on July 7-9 from one particular farm.

Child↗

The ubiquitous transcription factor NF-Y positively regulates the transcription of human p27Kip1 through a CCAAT box located in the 5-upstream region of the p27Kip1 gene.

Abnormally low levels of the cyclin-dependent kinase inhibitor p27Kip1 are found frequently in human carcinomas, and these levels correlate directly with both histological aggressiveness and patient mortality. p27Kip1 is haplo-insufficient for tumor suppression. Thus, p27Kip1 may be a useful molecule for the development of cancer therapies. To know the possible mechanisms underlying transcriptional control, we previously cloned the promoter region of human p27Kip1 gene. We report here the characterization of the 5'-regulatory region of the human p27Kip1 gene. Promoter analysis using 5'-deletion mutants revealed that a 39-bp region between -549 and -511 was required for maximal promoter activity. Point mutation analysis revealed that a CCAAT box within this region was essential for promoter activity. Gel shift assays and cotransfection experiments using a dominant negative form of the NF-Y transcription factor showed that NF-Y directly regulates p27Kip1 transcription through this CCAAT box. This finding might provide a clue to approach the mechanism of tumorigenesis.

Base Sequence↗

Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia.

Internal tandem duplication of the FLT3 gene and point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). However, their prognostic importance is unclear. In this study, their prognostic significance was analyzed in 201 newly diagnosed patients with de novo AML except acute promyelocytic leukemia. Three patients had mutations in both genes, 43 had only the FLT3 gene mutation, 25 had only the N-RAS gene mutation, and 130 had neither. These mutations seemed to occur independently. Both mutations were related to high peripheral white blood cell counts, and the FLT3 gene mutation was infrequently observed in the French-American-British (FAB)-M2 type. AML cases with wild FLT3/mutant N-RAS had a lower complete remission (CR) rate than those with wild FLT3/wild N-RAS, whereas the presence of mutant FLT3 did not affect the CR rate. Univariate analysis showed that unfavorable prognostic factors for overall survival were age 60 years or older (P =.0002), cytogenetic data (P =.002), FAB types other than M2 (P =.002), leukocytosis over 100 +/- 10(9)/L (P =.003), and the FLT3 gene mutation (P =.004). However, the N-RAS gene mutation was only a marginal prognostic factor (P =.06). For the subjects under 60 years old, multivariate analysis showed that the FLT3 gene mutation was the strongest prognostic factor (P =.008) for overall survival. The FLT3 gene mutation, whose presence is detectable only by genomic polymerase chain reaction amplification and gel electrophoresis, might serve as an important molecular marker to predict the prognosis of patients with AML.

Acute Disease↗

Cellular localization of prolactin-releasing peptide messenger RNA in the rat brain.

Prolactin-releasing peptide (PrRP), a novel peptide identified as the endogenous ligand for an orphan receptor isolated from the pituitary, is a potent stimulator of prolactin release. To get a clue of the functional roles of the peptide, we performed in situ hybridization histochemistry for PrRP mRNA to define the cellular localization of PrRP-producing cells in the brain of the cycling adult female rat during diestrus. The PrRP mRNA-containing cells were located in the caudal part of the dorsomedial nucleus of the hypothalamus. In the brainstem, the cells were found in the caudal part of the solitary tract nucleus and in the caudal ventrolateral medulla (ventrolateral intermediate reticular field). Specific signals for PrRP mRNA were not detected in other brain regions. Although PrRP is a candidate for being a hypophysiotropic specific releasing factor, the discrete distribution of PrRP in the extrahypothalamic area suggests that the peptide has other physiological functions in the central nervous system.

Animals↗

Veterinary practice with chitin and chitosan.

Dramatic effects of chitin and chitosan on wound healing were demonstrated in field cases of many small animals (dogs and cats), food animals (338 cows) and 142 zoo animals. In comparison with conventional therapy with irrigation and antibiotic administration to wound, new treatment with chitin and chitosan permitted a substantial decrease in treatment frequency with minimum scar formation.

Animals↗

Immunohistochemical localization of inhibin and activin subunits in human epithelial ovarian tumors.

OBJECTIVE: Our purpose was to examine the cellular localization of inhibin and activin subunits in human epithelial ovarian tumors. STUDY DESIGN: We examined the immunohistochemical localization of the alpha, betaA, and betaB subunits of inhibin in human mucinous and serous ovarian tumors including adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. RESULTS: Immunostaining specific for the alpha, betaA, and betaB subunits of inhibin was observed in the tumor cells of the mucinous adenoma and the cystic tumor with borderline malignancy. We observed negative immunostaining specific for the alpha subunit and positive staining specific for the betaA and betaB subunits in the tumor cells of the mucinous adenocarcinoma. We did not observe any staining for the alpha subunit of inhibin in the serous tumors including benign adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. However, positive staining results for the betaA and betaB subunits were observed in the serous tumor cells. CONCLUSION: Our results suggest that inhibins and activins might be secreted by the mucinous adenoma and the cystic tumor with borderline malignancy and that activins might be secreted by the mucinous adenocarcinoma and the serous tumors including benign adenoma, cystic tumor with borderline malignancy, and adenocarcinoma.

Activins↗

Molecular structure of canine LINE-1 elements in canine transmissible venereal tumor.

We determined the 4251-bp sequence of open reading frame 2 (ORF2) of canine LINE-1 retroposon that encodes 1275 amino acids. The truncated LINE-1 inserts associated with transmissible venereal tumor (TVT) of dogs contained the 1378-bp LINE-1 insert (TVT-LINE) flanked by 10-bp direct repeats upstream to c-myc gene. The TVT-LINE elements were composed of 416 bp inverse sequences homologous to the complementary strand of the LINE-1, a 5-bp deletion and 962-bp sequences homologous to the 3' region of the LINE-1.

Animals↗

A new preconditioning regimen with melphalan, busulphan and total body irradiation followed by low-dose immunosuppressant in allogeneic haemopoietic stem cell transplantation.

Twenty adult patients with high-risk leukaemia underwent allogeneic haemopoietic stem cell transplantation after melphalan, busulphan and total body irradiation followed by short-term methotrexate and low-dose cyclosporine or tacrolimus. Three patients developed veno-occlusive disease and no patient developed renal dysfunction. Seven patients experienced grade II-IV acute graft-versus-host disease (aGVHD) and five patients experienced grade III-IV. The 3-year probabilities of relapse and leukaemia-free survival were 22 +/- 11% (95% confidence interval) and 50 +/- 11%, respectively. These data suggest that this preconditioning regimen followed by a low-dose immunosuppressant provided a more anti-leukaemic effect without increased regimen-related toxicity and aGVHD.

Adult↗

Restricted expression of WT1 messenger ribonucleic acid in immature ovarian follicles: uniformity in mammalian and avian species and maintenance during reproductive senescence.

WT1 is a zinc finger protein with transcriptional repressor activity on several growth factor and growth factor receptor genes. In the ovary, a potential role for WT1 in the suppression of the development of immature follicles has been demonstrated. Here, gel retardation assays further showed that recombinant WT1 protein interacted with consensus DNA sequences in the inhibin-alpha gene promoter. We investigated the pattern of WT1 expression in a wide variety of species and also over the reproductive life span in rats. In chicken ovaries, Northern blot analysis revealed the presence of WT1 transcript in small healthy white follicles (1-5 mm in diameter) and its absence in small yellow (6-12 mm in diameter) or larger follicles (F1-F5). In pig and monkey ovaries, WT1 expression was limited to granulosa cells of preantral follicles, as shown by in situ hybridization analysis. In rats, Northern blot analyses demonstrated the presence of WT1 transcript in the ovaries of young (3-mo-old) and middle-aged (9-mo-old) rats on the proestrous day, with a decrease in old (12-mo-old) rats in persistent estrus. In situ hybridization analysis further suggested that the decrease in WT1 expression in aging ovaries was associated with fewer immature follicles. Thus, WT1 expression is restricted to immature follicles in diverse avian and mammalian species and over the reproductive life span in rats. These data demonstrated that WT1 is a marker for immature follicles and suggested a potential role of this transcriptional repressor in the slow growth of early follicles.

Animals↗

In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone.

The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against Chlamydia trachomatis, Mycoplasma pneumoniae, and Mycobacterium tuberculosis. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.025 to 6.25 microgram/ml. T-3811 was the most active agent against methicillin-resistant Staphylococcus aureus and streptococci, including penicillin-resistant Streptococcus pneumoniae (PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the family Enterobacteriaceae and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against Haemophilus influenzae, Moraxella catarrhalis, and Legionella sp., with MIC90s of 0.0125 to 0.1 microgram/ml. T-3811 showed a potent activity against anaerobic bacteria, such as Bacteroides fragilis and Clostridium difficile. T-3811 was the most active agent against C. trachomatis (MIC, 0.008 microgram/ml) and M. pneumoniae (MIC90, 0.0313 microgram/ml). The activity of T-3811 against M. tuberculosis (MIC90, 0.0625 microgram/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of S. aureus and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.

Administration, Oral↗

Role of permeability in the activities of beta-lactams against gram-negative bacteria which produce a group 3 beta-lactamase.

The production of a group 3 beta-lactamase permitted Escherichia coli to raise the MICs of ceftazidime, cefpirome, and meropenem greatly but those of imipenem and piperacillin only slightly. The ratios of maximum rate of hydrolysis to K(m) of ceftazidime, cefpirome, and piperacillin were lower than those of meropenem and imipenem for the group 3 beta-lactamase. The permeability coefficients for piperacillin and meropenem were higher than those for ceftazidime and cefpirome. Imipenem had the highest permeability coefficient.

Anti-Bacterial Agents↗

The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy.

In human ovaries, angiogenesis is known to be associated with the development of follicles and the formation of the corpus luteum (CL). A complex vascular network is formed within the thecal cell layer during follicular growth, and rapid neovascularization occurs toward the granulosa cell layer after ovulation. Vascular endothelial growth factor (VEGF) is a multifunctional cytokine, stimulating endothelial cell growth and enhancing microvascular permeability. A specific receptor for VEGF, fms-like tyrosine kinase (Flt-1), is expressed in vascular endothelial cells that mediates the action of VEGF. We examined the localization and expression of VEGF and Flt-1, using an immunohistochemical technique and RT-PCR analysis, in human follicles and corpora lutea during the normal menstrual cycle and early pregnancy. We measured concentrations of VEGF in extracts of human CL using an enzyme-linked immunosorbent assay during the luteal phase and early pregnancy. Immunostaining for VEGF was observed in granulosa cells from small antral follicles to preovulatory follicles. The staining was detected in thecal cells from medium-sized to preovulatory follicles. The intensity of the staining was gradually increased as a follicle grew. Flt-1 was localized in granulosa and thecal cells of preovulatory follicles as well as in endothelial cells. In the human CL, the intense staining for VEGF was observed in granulosa and thecal lutein cells, especially in the midluteal phase. The immunostaining for Flt-1 was faint in endothelial cells in the CL, whereas it was distinct in granulosa and thecal lutein cells. The concentrations of VEGF in lutein extracts were high in the early and midluteal phases and tended to decrease toward the late luteal phase. During early pregnancy, a measurable amount of VEGF was detected. RT-PCR analysis demonstrated that messenger ribonucleic acids encoding VEGF121, VEGF165, and Flt-1 were expressed in the CL. These results suggest that VEGF might have an autocrine role in the ovulatory process and luteal function as well as a paracrine role in angiogenesis.

Adult↗