Biomedical subjects

K Shimamura

Publications and source records attributed to K Shimamura.

At least 73 records · Page 4Linked to original sources

PubMed1998

[Mutagenicity studies of magnesium sulfate--reverse mutation test with bacteria and chromosomal aberration test with mammalian cells in culture].

The mutagenicity potential of magnesium sulfate was re-assessed using the current procedure of the reverse mutation test with bacteria and chromosomal aberration test with mammalian cells (a Chinese hamster lung fibroblast cell line; CHL/IU) in culture. In the reverse mutation test with bacteria, Salmonella typhimurium TA100, TA98, TA1535 and TA1537 and Escherichia coli WP2 uvrA were use and the maximum dose level was set at 5000 micrograms/plate irrespective of the absence or presence of metabolic activation. Five dose levels (313-5000 micrograms/plate) were selected for all strains except for TA98 without metabolic activation and for TA1537 with metabolic activation, for which 6 dose levels (156-5000 micrograms/plate) were selected. Magnesium sulfate induced no increase in the number of colonies with reverse mutation in any of the strains irrespective of the absence of presence of metabolic activation in the dose-range-finding study or in the main study. In the chromosomal aberration test with mammalian cells, a Chinese hamster lung fibroblast cell line (CHL/IU) in culture was used and the maximum dose level was set at 5.0 mg/mL both in the direct and metabolic activation methods. Three dose levels (1.25-5.0 mg/mL) were selected. Magnesium sulfate induced no increase in the incidence of cells with chromosomal aberration or those with genome mutation (polyploidy) in any of the strains irrespective of the absence of presence of metabolic activation. Thus, it is concluded that magnesium sulfate does not have mutagenic potential under the presence experimental conditions.

Animals↗

PubMed1998

[Environmental factors possibly associated with onset of senile dementia].

Factors associated with senile dementia have not been clarified, and factors, especially those in the living environment which seem to have a close link to the dementia need to be analysed. We conducted a case-control study targeting patients within the jurisdiction of Nagahama Public Health Center in Shiga and Hikone city, who are diagnosed to have senile dementia of the Vascular type, senile dementia of the Alzheimer type, and senile dementia of the Mixed type, and compared them to age matched controls. The outcome of the study by Matched pair analysis (McNemar's test) before the onset of the senile dementia were as follows. 1 The factors related to senile dementia of the vascular type were: Previous histories (Matched Odds Ratio (MOR): 8.0 p < 0.05), disturbance of the lower limbs (MOR = 8.0 p < 0.05). Environmental factors were: strong preference for sweets (MOR = 8.0 p < 0.05 female), smoking (MOR = 3.7 p < 0.10), lower utilization of health care (MOR = 3.3 p < 0.10), such as periodic medical check (MOR = 0/6 p < 0.10), sleep (MOR = 0/5 p < 0.10), less commitment to hobbies (MOR = 2.6 p < 0.10), such as handicrafts (MOR = 0/5 p < 0.10) etc, less intercourse with relatives (MOR = 0/9 p < 0.01), not living together with children's family (MOR = 0.20 p < 0.05 female), and death (MOR = 8/0 p < 0.05) or hospitalization (MOR = 9.0 p < 0.05) of a family member. 2 The factors related to senile dementia of the Alzheimer type and the Mixed type were: some previous histories (MOR = 8.0 p < 0.05), less disturbance of gait (MOR = 0/5 p < 0.10). Environmental factors were: lower utilization of health care, such as periodic medical check (MOR = 0.18 p < 0.05), and lower participation in exercise (MOR = 0/5 p < 0.10) etc, less association with neighbors (MOR = 0.11 p < 0.05), less participation in community activities (MOR = 0.11 p < 0.05), not living together with children's family (MOR = 0/8 p < 0.05), relocation (MOR = 5/0 p < 0.10) and retirement (MOR = 5/0 p < 0.10).

Aged↗

PubMed1997

A Humanized Anti-c-erbB-2 Monoclonal Antibody for the Treatment of Breast Cancer.

The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers that overxpress the c-erbB-2 gene. Its overexpression is also speculated to be correlated with chemoresistance to doxorubicin. The in vitro and in vivo anti-tumor effects of a humanized antibody directed against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 had direct antiproliferative activity against the SK-BR-3 cell line which overexpresses c-erbB-2. The in vivo treatment, using rhu4D5, of SCID mice carrying xenografts of 4-1ST human gastric carcinoma, which overexpresses c-erbB-2, revealed that the recombinant protein had potent anti-tumor activity. Furthermore, the cytotoxic action of human peripheral blood mononuclear cells against the SK-BR-3 cell line was significantly augmented with the administration of rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might be a more efficacious treatment than previously predicted by preclinical studies.

Journal Article↗

PubMed1997

Nitric oxide is a sensory nerve neurotransmitter in the mesenteric artery of guinea pig.

Previous studies have shown that the guinea pig inferior mesenteric artery receives spinal sensory vasodilatory innervation, which can be activated by colon distention and electrical nerve stimulation. In the present study, we investigated the hypotheses that nitric oxide synthase (NOS) is present in guinea pig primary sensory neurons in the dorsal root ganglion (DRG) and in nerve fibers surrounding the mesenteric arteries, and that nitric oxide (NO) is a sensory neurotransmitter in the inferior mesenteric artery in vitro. Double-labeling immunohistochemistry showed that neuronal NOS-IR was found in 12% of cells of guinea pig thoracic and lumbar DRGs; in 95.1% of these cells it was colocalized with substance P (SP), and SP immunoreactivity (SP-IR) was present in 23% of cells of the same DRGs. Neuronal NOS-like immunoreactivity was localized in nerve fibers surrounding guinea pig mesenteric artery and 25% of them were double stained with SP-IR. Endothelium-denuded inferior mesenteric artery preparations in vitro were incubated with guanethidine (30 microns, 30 min) and pre-contracted with methoxamine (30 microns). The NO donors, sodium nitroprusside (1 micron) and L-nitrosocysteine (300 microns), produced 91.0 +/- 5.5 and 90.4 +/- 9.6% vasodilatation of total vasodilatation in the vessel segments, respectively, which was capsaicin- or tetrodotoxin-insensitive. Repetitive electrical field stimulation of the preparations produced a frequency-dependent vasodilatation which was reduced by pretreatment with capsaicin or by tetrodotoxin (10 microns). The NOS inhibitor N omega-nitro-L-arginine (L-NNA) (100 microns, 30 min) diminished the nerve-evoked vasodilatation from 41.8 +/- 8.4 to 21.4 +/- 9.7% at 2 Hz and from 50.8 +/- 5.6 to 19.0 +/- 7.3% at 15 Hz (P < 0.05), whereas NG-nitro-L-arginine methyl ester (L-NAME, 100 microns-1 mM) did not significantly inhibit the relaxation. The stereo isomer nitro-D-arginine (D-NNA, 100 microns, 30 min) was ineffective. These findings suggest that NO is a neurotransmitter released from primary sensory nerves which mediates vasodilation in vitro.

Animals↗

PubMed1997

Effects of amiloride on the neurally mediated contraction of rat mesenteric artery.

The effects of amiloride on contraction evoked by perivascular nerve stimulation were studied in a ring preparation of rat mesenteric artery. The contraction evoked by nerve stimulation was abolished by tetrodotoxin or prazosin. Amiloride depressed the nerve-induced contraction concentration dependently. Noradrenaline induced a tonic contraction in the artery. Amiloride inhibited the noradrenaline-induced contraction concentration dependently. The excitatory junctional potential (e.j.p.) recorded intracellularly was abolished by tetrodotoxin. The amplitude of the e.j.p. was not altered by prazosin or amiloride. These results indicate that amiloride inhibits the perivascular nerve-mediated contraction of mesenteric artery mainly through postsynaptic adrenoceptor inhibition and not through mechanisms related to e.j.p.

Adrenergic Fibers↗

PubMed1997

Granulocyte colony stimulating factor-producing tongue carcinoma.

BACKGROUND: Leukocytosis without infection in patients with malignancies is known as the leukemoid reaction. The mechanisms involved in this phenomenon remain uncertain. METHODS: We describe the clinical, biochemical and immunohistochemical findings in a patient with recurrent tongue carcinoma accompanied by marked leukocytosis as high as 96200/ mm3. RESULTS: The serum granulocyte colony stimulating factor (G-CSF) concentration was increased to 204 (normal: < 30) pg/ml, which paralleled to the elevation of white blood cell (WBC) count and the tumor growth. The G-CSF content of the tumor tissue was also elevated (131 pg/mg protein) compared to that in control patients (6.63 +/- 2.63 pg/mg protein). Production of G-CSF from the tumor was evidenced by immunohistochemical staining with monoclonal antibody against human recombinant G-CSF. CONCLUSIONS: We suggest that the G-CSF production of the tumor participates in the mechanisms of the leukemoid reaction.

Aged↗

PubMed1997

Basaloid squamous carcinoma of the larynx: report of a case.

Basaloid squamous carcinoma (BSC) is a rare neoplasm. We present a case of basaloid squamous carcinoma of the larynx in a 57-year-old male patient. The diagnosis before treatment was supraglottic carcinoma (T3N1MO) and biopsy of the larynx revealed a poorly differentiated squamous cell carcinoma. Total laryngectomy and right radical neck dissection were performed, and pathological studies of a specimen removed from the larynx revealed BSC of the larynx. The patient's postoperative progress was uneventful, however, 12 months later he developed lung metastasis of the left side. The patient underwent partial resection of the lung. He developed recurrence of lung metastasis 6 months later. Chemotherapy with cisplatin (CDDP) and vindesine sulfate (VSD) was administered in two courses, but the efficacy was evaluated as no change (NC). At present, 26 months after the first visit, he has been asymptomatic with lung metastasis, and there was no evidence of recurrence in the neck.

Carcinoma, Basosquamous↗

PubMed1997

Fatal interstitial pulmonary disease in a patient with dyskeratosis congenita after allogeneic bone marrow transplantation.

Chronic restrictive lung disease in a 9-year-old boy with dyskeratosis congenita (DC) 7 years after allogeneic bone marrow transplantation (BMT) is described. When he was 1 year and 10 months old, severe aplastic anemia developed. He received a marrow transplant from his HLA serologically identical, but HLA-DP mismatched brother. He developed grade II acute graft-versus-host disease (GVHD) and thereafter chronic GVHD of progressive type, and was treated with both prednisolone and azathioprine resulting in clinical improvement. Thereafter he complained of dyspnea, and bilateral noncircumscribed interstitial shadows on chest CT scan were present. His pulmonary function showed restrictive changes. Prednisolone was not effective and he died of respiratory failure. Post-mortem examination confirmed interstitial fibrosis, lymphocytic infiltration of the bronchioles and alveoli with luminal fibrosis. There was no evidence of chronic GVHD in the skin and the liver. These findings raise the possibility that this pulmonary complication was associated with DC itself.

Anemia, Aplastic↗

PubMed1997

A ciliated cyst as a component of pleomorphic adenoma of the parotid gland.

A large cyst, lined with ciliated cells (ciliated cyst), was found as a component of a pleomorphic adenoma of the left parotid gland in a 34-year-old Japanese man. The dimensions of the tumor were 25 x 33 mm and it consisted of a solid mass with a centrally located cyst 20 x 23 mm, which contained yellowish-brown material of muddy consistency. The tumor was encapsulated and the solid mass had features typical of a pleomorphic adenoma. The inner surface of the cyst was lined with ciliated cells and scattered mucus-secreting cells in addition to cuboidal-to-flattened cells. In some regions, the neoplastic cells of the pleomorphic adenoma were exposed to the cavity of the cyst. A histological transformation from ciliated cells to pleomorphic adenomatous cells was also observed. These findings indicated that the ciliated epithelium was an element of the tumor. This is the first report, to our knowledge, of a ciliated cyst derived from some elements of a pleomorphic adenoma of the salivary gland.

Adenoma, Pleomorphic↗

PubMed1997

Patterns of gene expression in the neural plate and neural tube subdivide the embryonic forebrain into transverse and longitudinal domains.

The analysis of gene expression patterns in the neural plate and neural tube of the embryonic mouse forebrain shows that, at its earliest stages, the neuroepithelium is subdivided into molecularly distinct domains. Here, and in previous publications, we provide evidence that the patterns of gene expression can be related to primary morphogenetic processes that organize the histological primordia of the embryonic central nervous system into longitudinal and transverse domains. Longitudinal domains are generated by dorsoventral patterning signals produced by the axial mesendoderm and nonneural ectoderm. Transverse domains (proneuromeres and neuromeres) expressing distinct combinations of genes are present in the neural plate and neural tube.

Animals↗

PubMed1997

Inductive interactions direct early regionalization of the mouse forebrain.

The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic neural plate. Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization.

Animals↗

PubMed1997

Effects of chronic treatment with carvedilol on smooth muscle tone and endothelium-dependent relaxation of aorta in stroke-prone spontaneously hypertensive rats.

Effects of chronic treatment of stroke-prone spontaneously hypertensive rats (SHRSP) with carvedilol, an agent which has both alpha and beta-adrenoceptor blocking actions, on spontaneous muscle tone and on structural and functional abnormalities of endothelium were studied. The treatment of SHRSP with the drug of the dose of 30 to 200 mg/kg/day lowered the blood pressure significantly. Spontaneous muscle tone in endothelium-removed preparation disappeared by the treatment. Noradrenaline-induced contraction was depressed by the treatment in endothelium intact preparation but not in endothelium removed preparation. The treatment prevented the structural and functional abnormalities of endothelium. Similar results were obtained by the treatment with propranolol. These results indicate that carvedilol prevented abnormal contraction of SHRSP aorta through protective effects on smooth muscle and endothelium. These effects may play roles in blood pressure lowering effect of carvedilol.

Adrenergic alpha-Antagonists↗

PubMed1997

[Proctocolectomy with ileal W pouch anal anastomosis for ulcerative colitis].

Restorative proctocolectomy with ileal pouch anal anastomosis, which is a relatively new procedure, has become a standard procedure for ulcerative colitis (UC) requiring surgical management. The main impact of this procedure is to cure patients of disease and to avoid permanent ileostomy, preserving better defecatory function and acceptable QOL. Some key aspects of our surgical procedure are as follows: 1) two or three separate staged operation, 2) W-shaped reservoir, 3) distal rectal mucosectomy and handsewn ileo-anal anastomosis, 4) short muscular cuff, and 5) temporary diverting ileostomy. Staged operation and diverting ileostomy are helpful to decrease risk of pelvic infection. Total removal of the rectal mucosa is necessary to cure the disease, and shorter muscular cuff decreases operating time and bleeding and thus the risk of pelvic sepsis. The W-shaped reservoir described by Nicholls brings both spontaneous defecation and improved function. We have adopted ileal W-pouch among several types of reservoir to 58 patients with UC since 1984, and found that a large and wide reservoir might allow better defecatory function. There were no cases of serious complications and no needs to remove the reservoir. Mean daily stool frequency was gradually decreased with time, and 4.9 stools per 24 hours at present day, and clinical score of neorectal function also gradually improved according to reduction of stool frequency. Seventy three percent of patients felt their defecatory function satisfactory and 89% of the patients recovered acceptable QOL no less than that obtained during the medically treated period.

Adolescent↗

PubMed1996

Binding specificity of Lactobacillus to glycolipids.

Lactobacillus, a representative useful bacterium, in the intestinal tract was found to bind to some specific glycosphingolipids, like the pathogenic intestinal bacteria. Thin layer chromatography overlay assays using rabbit antiserum against Lactobacillus casei revealed that the bacteria bound to GA1 and trihexosylceramide strongly, but not to any gangliosides. The bacteria generally bound to glycosphingolipids having short sugar chains and galactosyl moiety in the non-reducing terminal. L.casei did not bind to GM1, but bound to the product after sialidase treatment, GA1. This indicated that sialic acid inhibited the adhesion of L.casei to tissues. L.casei actually bound nonacid glycosphingolipids but not acid glycosphingolipids extracted from the small intestinal mucosa of rats.

Animals↗

PubMed1996

In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product.

The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo anti-tumour effects of a humanised antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its murine counterpart, mu4D5, for the direct antiproliferative activity against the c-erbB-2-overexpressing SK-BR-3 cell line. In vivo treatment of severe combined immunodeficient (SCID) mice carrying the c-erbB-2-overexpressing 4-1ST human gastric carcinoma xenograft with 4hu4D5 revealed that the recombinant protein had potent anti-tumour activity. Furthermore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was significantly augmented with rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might perform better in patients than predicted from preclinical studies.

Animals↗

PubMed1996

Establishment of human granulocyte-macrophage colony stimulating factor producing transgenic SCID mice.

Previous work has shown the usefulness of severe combined immunodeficient (SCID) mice as in vivo models for the growth of normal human haemopoietic cells and leukaemic cells. Many approaches have been made to improve the engraftment of human haemopoietic cells in SCID mice. We established transgenic mice producing human granulocyte-macrophage colony stimulating factor (hGM-CSF) with the homozygote of the scid gene. Endogenous serum hGM-CSF levels were detected by ELISA [mean 9585 pg/ml (line A, n = 4); mean 1610 pg/ml (line B, n = 4)]. Expression of hGM-CSF was observed in all organs tested including the heart, lung, liver, kidney, spleen, thymus, bone marrow and brain of hGM-CSF transgenic (hGMTg) mice. Morphological analysis of organs and peripheral blood cell counts showed no differences between hGMTg mice and their littermates. Murine Ba/F3 cells expressing functional hGM-CSF alpha beta receptor (BAF/alpha beta cells) could be successfully engrafted in hGMTg SCID mice. The cells invaded multiple organs and caused death within a few weeks of transplantation, although they infiltrated only the spleen of their littermates. These results showed that these hGM-CSF-producing SCID mice are useful as an in vivo assay system for investigating leukaemogenesis.

Animals↗

PubMed1996

Nitric oxide concentrations in the follicular fluid and apoptosis of granulosa cells in human follicles.

To study the relationship between follicular atresia, apoptosis, and nitric oxide (NO) generation in follicular development, steroidogenesis, NO levels in follicular fluid and apoptosis were analysed in the various sized follicles of women receiving ovarian stimulation with human menopausal gonadotrophin (HMG)-human chorionic gonadotrophin (HCG) treatments for in-vitro fertilization (IVF)-embryo transfer. The follicles were divided into three groups by diameter: large follicle, > or = 18 mm; medium follicle, > or = 12 and < or = 15 mm; small follicle, < or = 10 mm. Follicular fluid was obtained from 20 women 34 h after HCG administration, and the concentrations of oestradiol, progesterone and testosterone, and nitrite, nitrate, arginine and citrulline were measured. Granulosa cells obtained from each group of follicular fluid were stained with Hoechst dye, and nuclear morphology was examined by a fluorescence microscopy. Oestradiol and progesterone concentrations in large follicles were significantly (P < 0.01) higher than those in medium or small follicles, and testosterone concentrations in small follicles were significantly (P < 0.01) higher than those in large follicles. There were no significant differences in the concentrations of nitrite, nitrate, arginine and citrulline among three groups. The percentage of apoptotic cells with nuclear fragmentation was significantly (P < 0.01) higher in small follicles than in large follicles. The present results suggested that small follicles with poor response to HMG may undergo atresia through apoptosis. No significant difference in the follicular NO level between large and small follicles led us to speculate on a different responsiveness to NO in these two types of follicles.

Adult↗

PubMed1996

Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy.

To investigate the possible role of the superoxide radical and its scavenging system in the human endometrium, the immunohistochemical distribution of superoxide dismutase (SOD), activities of SOD and lipid peroxide concentrations were studied in the human endometrium throughout the menstrual cycle and in early pregnancy. The endometrial epithelium showed a positive immunostaining for Cu, Zn-SOD and Mn-SOD throughout the entire menstrual cycle and in early pregnancy. In the stroma, weak immunostaining for Cu,Zn-SOD and moderate immunostaining for Mn-SOD were observed in the predecidual cells in the late secretory phase. Decidual cells in early pregnancy showed strong immunostaining for Cu,Zn-SOD and Mn-SOD. Total SOD activity in the endometrium increased from early proliferative phase to mid-late proliferative phase and further increased in the mid-secretory phase, and decreased in the late secretory phase. The total SOD activity in the endometrium of of early pregnancy was the same level as that in the mid-secretory phase. Cu,Zn-SOD and Mn-SOD activities changed in a similar manner to total SOD activity throughout the menstrual cycle and in early pregnancy. Lipid peroxide concentration in the endometrium increased from early proliferative phase to mid-late proliferative phase and further increased in the late secretory phase. However, lipid peroxide concentration in the endometrium of early pregnancy was the same as that in the mid-secretory phase. These results suggested that the superoxide radical and its scavenging system may play an important role in the regulation of human endometrial function.

Adult↗