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Biomedical subjects

M Kashimura

Publications and source records attributed to M Kashimura.

At least 37 records · Page 2Linked to original sources
PubMed1998

Concentration-dependent differential effects of N-acetyl-L-cysteine on the expression of HSP70 and metallothionein genes induced by cadmium in human amniotic cells.

Cadmium induces the expression of the 70 kDa heat shock protein (HSP70) and metallothionein (MT), both of which are considered to be associated with intracellular glutathione (GSH) metabolism in the cellular protection mechanism against cadmium-induced cellular injury. We determined the effects of N-acetyl-L-cysteine (NAC), which increases the intracellular GSH levels, on the induction of HSP70 and MT gene expression in a cultured cell line of human amniotic cells (WISH) exposed to CdCl2. The mRNA level of MT-II, a major isoform of MT genes, was more prominently increased than that of HSP70 when WISH cells were exposed to CdCl2 (5-15 microM, for 6 h). The treatment of WISH cells with 1.5 and 30 mM NAC for 2 h increased the intracellular GSH levels by 1.4- and 3.1-fold, respectively. Pretreatment of cells with 30 mM NAC significantly reduced both HSP70 and MT-II mRNA levels in the cells exposed to 50 microM CdCl2. This concentration of NAC also efficiently suppressed the cadmium-induced lethality. On the contrary, pretreatment with 1.5 mM NAC suppressed only the induction of HSP70 gene expression in the 50 microM CdCl2-treated cells, and did not inhibit the metal toxicity. However, this low concentration of NAC efficiently suppressed lipid peroxidation which was increased by 50 microM CdCl2. Furthermore, this low concentration of NAC also decreased the CdCl2-induced gene expression of HSP32 which represents a general response to oxidative stress. Taken together, NAC seems to have at least two concentration-dependent functions in WISH cells exposed to CdCl2; the low concentration of NAC can suppress the induction of HSP70 gene expression as well as the increase of lipid peroxidation via an antioxidant pathway, while the high concentration of NAC can suppress the induction of MT-II mRNA as well as cadmium-induced cell death. Our present data suggest that changes in intracellular redox status, as reflected by GSH concentration, have more important effects on the induction of HSP70 mRNA rather than that of MT-II mRNA in human amniotic cells exposed to cadmium.

Acetylcysteine↗
PubMed1997

Complete remission in three patients with acute myeloblastic leukemia by administration of G-CSF without antileukemic agents.

We describe 3 patients with acute myeloblastic leukemia (AML), who received rhG-CSF for infections such as pneumonia or for prophylaxis of infection, and who achieved complete remission. They had not received any antileukemic therapy before or during the administration of rhG-CSF. These findings suggest the possibility that complete remission can be brought about by G-CSF itself in some patients with AML.

Aged↗
PubMed1997

The significance of peritoneal cytology in uterine cervix and endometrial cancer.

OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to elucidate the prognostic value of peritoneal cytology in patients with uterine cervix and endometrial cancer. MATERIALS AND METHODS: The incidence of positive peritoneal cytology was investigated in 642 patients including 339 uterine cervix and 303 endometrial cancers. Survival was estimated by the Kaplan-Meier method in a subgroup of 116 stage II cervix and 199 stage I endometrial cancers, and multivariate analysis using Cox's proportional hazards model was used to identify an independent prognostic factor. RESULTS: The incidence of positive peritoneal cytology was found to be 9% in uterine cervix cancer and 15% in endometrial cancer. The incidence was higher in patients with some clinicopathologic status such as advanced stage, lymph node metastasis, ovarian metastasis, and deeper myometrial invasion. The 5-year survival rate for patients with positive or negative peritoneal cytology was 44 or 80% in stage II cervix cancers and 80 or 92% in clinical stage I endometrial cancers, respectively. Multivariate analysis revealed that independent prognostic determinants were pelvic and paraaortic lymph node metastasis and peritoneal cytology in stage II cervix cancer and peritoneal cytology in stage I endometrial cancer. Proper treatment protocol should be scheduled for patients with positive peritoneal cytology.

Endometrial Neoplasms↗
PubMed1997

A case of active acromegalic woman with a marked increase in serum insulin-like growth factor-1 levels after delivery.

Pregnancy in a woman with active acromegaly is very rare, because amenorrhea, due to hyperprolactinemia and disturbed pituitary gonadotropin secretion may cause infertility. We report a 28-year-old pregnant woman with untreated acromegaly, who was followed up from early pregnancy to delivery. Her pregnancy was uneventful, and she went into spontaneous labor at 38 weeks and delivered a normal infant. Her serum GH levels were further increased in late pregnancy, followed by decreased in postpartum periods, which may be associated with enlargement of pituitary adenoma during pregnancy. In contrast with serum GH, her serum insulin-like growth factor-1 (IGF-1) levels were dissociated with her serum GH levels during late pregnant and postpartum period. Her serum GH and IGF-1 levels in late pregnancy were different from the levels in pregnant women with acromegaly reported previously.

Acromegaly↗
PubMed1997

[Treatment of acute lymphoblastic leukemia of young adults (15-22 years of age): results of co-operative study with internal medicine and pediatrics].

Ten young adults (15-22 years of age) with acute lymphoblastic leukemia were treated with the protocol of internal medicine and pediatrics co-operative study group since 1989. All patients had complete remission within 5 weeks. Four of 6 patients of low risk group (less than 30,000/microliter of WBC count at diagnosis) and 1 of 4 patients of high risk group have continued the complete remission. Three patients relapsed in bone marrow (BM), and 2 patients in both BM and central nervous system (CNS). All patients could be treated without serious complications except for infection. We obtained the good results of treatment for the low risk group, but did not for the high risk group in this study. Little is known about acute lymphoblastic leukemia in young adults because these individuals are at the borderline age between internal medicine and pediatrics. Taken together with the psychologically distinct age of these patients, it is necessary to establish a closer relationship between internal medicine and pediatrics.

Adolescent↗
PubMed1997

[A study on sexual dysfunction in female patients with alcoholics].

Few investigations have been made concerning hormonal changes and dyspareunia in fertile aged women with alcoholics experiencing sexual dysfunction. Twenty-seven Japanese woman with alcoholics under 40 years of age excluded with liver cirrhosis were studied to describe alcohol drinking related to sexual dysfunction. Among 21 sexually active women, 20(95.2%) had both symptoms of dyspareunia and vaginal dryness, and only one had neither symptom. Most of patients have lower estradiol levels and 92.0% of patients have the moderately elevated prolactin levels. Eleven of them were having the second grade amenorrhea associated with hyperprolactinemia and hypergonadotropic hypogonadism and 14 were having the first grade amenorrhea. In this study alcoholic abuse women may have deeply related to the hyperprolactinemia, dyspareunia, amenorrhoea, vaginal dryness, ovarian dysfunction and fetal alcohol syndrome.

Adult↗
PubMed1996

Polyclonal B cell chronic lymphoproliferative disease with hairy cell morphology: a case report and clonal studies.

We describe a patient who has a chronic polyclonal B lymphocyte proliferation with a hairy-cell appearance. A 48-year-old Japanese woman with marked splenomegaly, systemic lymphadenopathy, and leukocytosis was referred to out hospital. Laboratory examination revealed marked polyclonal IgG hypergammaglobulinemia. Morphologic examination of the patient's peripheral blood, including May-Giemsa staining and scanning electron microscopy, showed a monotonous proliferation of hairy-appearing mature lymphocytes. An immunophenotypic study revealed an expansion of cells with mature B cell antigens positive for CD11c; however, light-chain restriction was not seen. The lack of both immuno-globulin heavy-chain and T cell receptor gene rearrangements by Southern blot analysis indicated the polyclonal nature of the proliferating B cells. This was confirmed further by a clonal analysis of the patient's lymphocytes using an X-chromosome-linked restriction fragment polymorphism within the X-linked phosphoglycerate kinase (PGK) gene. Since chronic B cell lymphoproliferation with a hairy cell appearance has not been described previously, this case might be extremely rare, and has important implication for the pathogenesis of mature B cell lymphoproliferative diseases, including hairy cell leukemia.

B-Lymphocytes↗
PubMed1996

Inhibition of nucleolar function and morphological change by adriamycin associated with heat shock protein 70 accumulation.

Adriamycin (ADR) has been considered to target mainly DNA metabolism in the nucleus. Recently, we observed the nuclear translocation of heat shock protein 70 (HSP70) after ADR treatment. We examined which intranuclear changes might be related to this alteration of HSP70 localization. We found considerable alternations in the nucleolar morphology and function in ADR-treated tumor cells, i.e., a ring-shaped segregation of granular components of almost all nucleoli and a dramatic reduction of nucleolar 45S ribosomal precursor RNA biosynthesis in HeLa cells exposed to 100 microM ADR for 2 h. Concomitantly with these changes, HSP70 was concentrated into the nucleoli, as in the case of heat shock treatment. These results indicate a novel anticancer effect of ADR via the suppression of cellular protein biosynthesis, in addition to its effect on DNA.

Antibiotics, Antineoplastic↗
PubMed1995

Possible correlation between DNA damage induced by hydrogen peroxide and translocation of heat shock 70 protein into the nucleus.

Oxygen radicals have been implicated as the causative agent in deleterious processes such as gene mutation, cellular transformation and cell death. Cellular response to DNA damage induced by hydrogen peroxide was examined in human amniotic cultured cells (WISH). The content of 8-hydroxydeoxyguanosine in nuclear DNA increased during the early period of exposure to hydrogen peroxide, that is, it peaked at 1 h in the cells treated with 1 mM hydrogen peroxide and then declined, but not to the control levels within 4 h. Interestingly, immunofluorescence staining of treated cells revealed that cytoplasmic hsp70 protein translocated transiently into the nucleus, which was most remarkable around 30 min after the addition of 1 mM hydrogen peroxide into the culture medium. On the other hand, the induction of hsp70 gene mRNA was not significant during the early period of treatment by 0.5 mM hydrogen peroxide and was occurred after 5 h. DNA damage induced by Adriamycin further supported the possible correlation between hydroxyl radical-mediated cleavage of DNA and nuclear translocation of hsp70 protein. These results suggest that preexisting hsp70 protein translocated into the nucleus to either protect chromatin DNA from further damage or to facilitate the repair of DNA damage in some unknown ways.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

[Bence Jones type multiple myeloma showing diffuse infiltration to the dura mater by myeloma cells].

A 62-year-old man with aleukemic Bence Jones type multiple myeloma who developed neurologic abnormalities is reported. After admission, consciousness disturbance appeared and a lumbar puncture obtained M-protein. Though brain CT showed no abnormal findings except a punched out lesion of the temporal bone, MRI disclosed remarkable enhancement of the dura mater. Meningeal involvement by myeloma cells without leukemic blood picture is very rare though it is common in other lymphoproliferative disorders such as acute lymphocyte leukemia and malignant lymphoma. We report a case of BJ type multiple myeloma with meningeal involvement due to diffuse infiltration to the dura mater and discuss a possible mechanism of meningeal involvement in this patient.

Bence Jones Protein↗
PubMed1995

The contraction of small arteries in the perimetrium by presurgical medication with the luteinizing hormone-releasing hormone agonist to patients with leiomyomas: an electron and immunoelectron microscopy.

The remarkable contraction of small arteries occurred in the perimetrium of the uteri with leiomyomas by a presurgical medication P6th the luteinizing hormone-releasing hormone (LHRH) agonist (buserelin). The contracted vessels showed a significant increase in number of the Weibel-Palade (WP) bodies which occasionally underwent the degranulation and the discharge in a manner of exocytosis. By immunoelectron microscopy, localizations of endothelin (ET)-1 immunoreactive gold particles on the WP bodies as well as on cisterns of the rough endoplasmic reticulum (rER) and Golgi apparatus were pronounced in the buserelin-medicated group when compared to the non-medicated one. These findings indicate that the increase of the WP bodies storing ET-1, of which synthesis in the rER-Golgi system enhances, predominantly occurred in the small arteries in the perimetrium by the buserelin-medication prior to the hysterectomy. ET-1, released into the subendothelial layer, seems to play an important role in the contraction of the vascular media in a manner of paracrine.

Adult↗
PubMed1994

Induction of heat shock 70 mRNA by cadmium is mediated by glutathione suppressive and non-suppressive triggers.

The induction mechanism of heat shock 70 (Hsp70) gene by cadmium was investigated. In human amniotic WISH cells, Hsp 70 was induced by cadmium in a dose- and time-dependent manner. Cadmium-induced Hsp70 mRNA levels were enhanced 3- to 4-fold after depletion of intracellular glutathione (GSH) by either diethylmaleate or buthionine sulfoximine. Under these conditions, hydrogen peroxide might increase in the absence of substrate for glutathione peroxidase. We found that exogenous hydrogen peroxide alone induced Hsp70 which was further enhanced significantly after GSH-depletion by diethylmaleate. On the other hand, treatment of cells by diethyldithiocarbamate, an inhibitor of superoxide dismutase, induced Hsp70 2-fold over the level of control. This induction was further stimulated by cadmium even in the presence of GSH. Furthermore, a 4-fold increase of intracellular GSH by the treatment of cells with glutathione isopropyl ester did not diminish the cadmium-induced Hsp70. Gel mobility shift assays of nuclear extracts, from these differently treated cells, with oligonucleotide containing a promoter region of Hsp70 gene revealed that the levels of Hsp70 mRNA observed in the present study corresponded to the changes of transcription. These results imply that the induction of Hsp70 mRNA by cadmium is mediated at least partly via reactive oxygen species and attenuated by cellular GSH and that some part of cadmium-induced Hsp70 can not be eliminated by GSH, suggesting that multiple signals are functioning for this induction.

Base Sequence↗
PubMed1994

Cloning of cDNAs with possible association with senescence and immortalization of human cells.

Normal human diploid fibroblasts (HDF) have a finite life span in vitro and have been used as a model system for the study of in vivo aging. Little is known about how changes in gene expression may affect the immortalization of human fibroblasts. We looked for cDNA clones whose mRNAs were differentially expressed between mortal senescent SV40-transformed human fibroblasts (B-32) and the immortal counterparts (B-32F) derived from B-32 cells. We identified three cDNA isolates by subtractive differential hybridization with 32P-labeled cDNA probes from B-32 cells and B-32F cells. Nucleotide sequence analysis of these cDNA clones revealed that they were homologous to the human vimentin, a human mitochondrial gene and a human gene of unknown nature. Slot blot and Northern blot analyses demonstrated that the former two were preferentially expressed in senescent B-32 cells and the last one was less expressed in B-32F immortal cells.

Brain Chemistry↗
PubMed1994

Structure-activity relationship study of 6-O-methylerythromycin 9-O-substituted oxime derivatives.

In order to develop new-generation macrolide antibiotics active against erythromycin (EM)-resistant strains, a series of 6-O-methyl EM 9-O-substituted oxime derivatives was synthesized and evaluated for antibacterial activity against EM-resistant (S. aureus J-109) and susceptible (S. aureus 209P) strains. To understand how substituents affect the biological activity, the quantitative structure-activity relationships (QSAR) was analyzed using the Hansch-Fujita method. With the EM-resistant strain, the positive coefficient for log P may indicate that higher hydrophobicity of molecules is favorable for antibacterial activity. The negative coefficients of the Sterimol parameters L, B1, and B5 may indicate that long, bulky substituents are unfavorable. With the EM-susceptible strain, the negative coefficient for log P may indicate that hydrophilicity is important for antibacterial activity. A short substituent is also required to improve the activity. Based on the QSAR model, a derivative (87) having an anthracenylmethyl moiety was synthesized to reinforce and confirm the correlation. The activity of 87 against the EM-resistant strain was significant. In QSARs of 6-O-methyl EM-A 9-O-substituted oxime derivatives, the difference of the contribution of log P to the antibacterial activity between EM-resistant and susceptible strains was clearly recognized.

Anti-Bacterial Agents↗
PubMed1994

[Hematologic abnormalities in a patient with chronic myelogenous leukemia with advanced myelofibrosis were improved by G-CSF].

A 56-year-old woman was admitted with pyrexia, cough, and dyspnea on August 21, 1991. Physical examination revealed anemia in the palpebral conjunctivas and moist rales at the right lower lung field. Neither the Liver nor spleen was enlarged. Examination of the peripheral blood showed a hemoglobin level of 8.1 g/dl, a platelet count of 14.8 x 10(4)/microliters, and a white blood cell count of 2,800/microliters, with 7% blasts and 8% megakaryocytes. Tear drop-like erythrocytes, agranular neutrophils, and erythroblasts were also seen in the peripheral blood. Examination of the bone marrow showed 15% peroxidase positive blasts, and many micromegakaryocytes. Cytogenetic studies for bone marrow cells revealed the existence of the Philadelphia (Ph1) chromosome. Bone marrow biopsy showed normal cellularity with increase of megakaryocytes and advanced myelofibrosis. Breakpoint cluster region (bcr) rearrangement analysis using the peripheral blood mononuclear cells revealed M-bcr rearrangement. According to the Hannover classification for myeloproliferative disease, she was diagnosed as having CML with advanced myelofibrosis followed by CML with megakaryocytic increase. Since she had neutrocytopenia and severe infectious disease, she received a subcutaneous injection of 125 micrograms of G-CSF. Not only increase of the white blood cell count, but also disappearance of blasts, improvement of anemia, increase of the platelet count, and improvement of myelofibrosis were observed.

Blood Cell Count↗