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Biomedical subjects

M Sekimoto

Publications and source records attributed to M Sekimoto.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Laparoscopic splenectomy for a massive splenomegaly using a transcatheter technique].

Laparoscopic splenectomy can be performed more safely today, and therefore it is becoming the first-choice technique for splenectomy when the spleen is of normal size. However, for massive splenomegaly there have been few reports of the use of this technique and its safety has not been confirmed. We performed laparoscopic splenectomy for massive splenomegaly with transarterial embolization of the splenic artery before surgery. A 37-year-old man underwent splenectomy due to the lack of effect of an approximately 4-month course of chemotherapy for chronic myeloid leukemia whose spleen was over 20 cm in length. Before surgery, splenic artery embolization was performed to prevent intraoperative bleeding and to debulk the spleen. Under general anesthesia the patient was positioned in the lateral decubitus position lying on the right side. There was no bleeding from the capsule of the spleen throughout the procedure and no intraoperative complications occurred. Blood loss was 100 ml, and the weight of the resected spleen was 1,100 g. The postoperative course was uneventful. We conclude that laparoscopic splenectomy is safe and feasible in cases of splenomegaly, when combined with preoperative embolization of the splenic artery.

Adult↗
PubMed1997

Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain.

Exposure to stressful events and elevated level of stress hormones are associated with impaired spatial memory and neuronal damage in the hippocampus. These neurons are considered to be maintained by neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) and trk family of neurotrophin receptors. Male Wistar rats (6 weeks old) were exposed to immobilization stress for 8 h and their brains were processed for in situ hybridization histochemistry. Exposure to long-lasting immobilization stress reduced mRNA levels for neurotrophins and their high affinity receptors in the brain, especially in the hippocampus. Our results provide, some new information that may be relevant to the pathogenesis of stress-induced disturbances of memory and learning.

Animals↗
PubMed1997

Plasma volume estimation using indocyanine green with biexponential regression analysis of the decay curves.

We studied seven analytical methods of estimating the plasma volume from the decay curves of indocyanine green. Fifteen volunteers received 1.0 mg.kg-1 of the dye by intravenous injection and the plasma concentration was measured continuously using spectrophotometry. Plasma volumes were calculated using three single-regression methods (1-a, 1-b, 1-c) and four biexponential regression methods (2-a, 2-b, 2-c, 2-d). The means (SD) of 1-a, 1-b and 1-c were 39 (5.0), 44 (5.7) and 54 (11.5) ml.kg-1, respectively, and these were significantly different from each other (p < 0.05). The values for methods 2-b, 2-c and 2-d were similar to each other: 39 (4.6), 40 (4.1) and 40 (4.0) ml.kg-1, respectively. These required more than 3 min circulation or mixing time. When the time allowed for mixing was less than 3 min (method 2-a) the plasma volume was underestimated. We conclude that plasma volume estimation using indocyanine green and spectrophotometry is most accurate when the mixing time is adequate (3-5 min) and the decay curves are analysed using biexponential regression.

Adult↗
PubMed1997

[Molecular-pathological problems of genetic diagnosis for colorectal cancer].

Recent advances in molecular biology have revealed that the alteration of multiple genes, eg., APC, K-ras, p53, DCC, are involved in multistep colorectal carcinogenesis. Some of these alterations can be used as molecular markers in genetic diagnosis. Genetic diagnoses for colorectal cancer are classified into three categories, eg., 1. identification of the career in the family of patient with hereditary disease such as FPC (Familial Polyposis Coli) or HNPCC (Hereditary Non-Polyposis Colorectal Cancer), 2. early diagnosis of colorectal cancer by identifying gene mutations in the stool, 3. assist for histopathological diagnosis, or risk assessment of the metastasis, recurrence or secondary cancer by molecular means. However, there are several problems in these genetic diagnoses. These consist of two categories, eg., 1. problems in the method of gene analyses or assay system and 2. problems in performing genetic diagnoses itself. The former includes the problem of contamination of different tissue, false positive or negative result in PCR-based analyses, heterogeneity of gene mutation in tumor tissue, and the latter includes the social, ethical or economical problems mainly related to the genetic diagnosis for hereditary colorectal cancers. In this paper, we describe the possibility of genetic diagnosis for colorectal cancers and the current problems, especially from the molecular pathological aspect, in genetic diagnosis.

Colorectal Neoplasms↗
PubMed1997

[A case of local recurrence of rectal cancer that achieved a complete response with high-dose interstitial brachytherapy].

We report a case of local recurrence of rectal cancer that achieved complete response with high-dose interstitial brachytherapy. The patient was a forty-nine-year-old woman. In September 1995, she underwent abdominoperineal resection of rectum for rectal cancer (T4 N2 M0, moderately differentiated adenocarcinoma). In February 1996, she complained of genital bleeding. MRI examination revealed a mass of 70 x 22 x 20 mm in the pelvis, which was diagnosed to be recurrent rectal cancer with needle biopsy. Interstitial brachytherapy (60 Gy/twelve fractions/six days) was performed, and a complete response was achieved. One year after the treatment, no tumor was detected in the pelvis. No skin erosion, skin ulcer, urinary cystitis, nor ileitis occurred. High-dose interstitial brachytherapy delivers high-dose irradiation to a tumor while keeping the dose to the surrounding normal organs at a low level. This procedure may be an effective modality for local recurrence of rectal cancer.

Adenocarcinoma↗
PubMed1996

Mutation of the trkB gene encoding the high-affinity receptor for brain-derived neurotrophic factor in stroke-prone spontaneously hypertensive rats.

Brain-derived neurotrophic factor and its receptor, trkB, are thought to play a crucial role for protection against neuronal death induced by brain ischemia, such as in stroke. In the present study we found a missense mutation in the trkB gene from all of the five substrains of stroke-prone spontaneously hypertensive rats (SHRSP) that were examined. This mutation was not found in six out of seven hypertensive but stroke-resistant ancestral strains (SHR) of SHRSP, nor in any of seven strains of normotensive, non-stroke-prone strains. Hippocampal neurons, which are particularly vulnerable to damage in stroke, were shown to be more susceptible to ischemic damage in SHRSP than in either SHR or normotensive, stroke-resistant controls. The association of a mutated trkB gene with the stroke-prone genotype found in this study suggests that the trkB gene merits further study as a promising candidate gene for stroke.

Animals↗
PubMed1996

Mutations of the transforming growth factor beta type II receptor gene and microsatellite instability in gastric cancer.

Forty-three sporadic gastric cancers were analyzed with regard to whether mutations of simple repeated sequences in the transforming growth factor beta type II receptor (TbetaR-II) gene are associated with microsatellite instability (MSI) and gastric carcinogenesis. In 12 of the 43 cancers (28%), MSI was observed at least at 1 of the 2 microsatellite loci. Frameshift mutations of the TbetaR-II gene, all of which were 1 base deletion of 10 adenine repeats, were detected in 3 of 6 cancers, with MSI at 2 loci. However, mutations were not detected in 6 cancers, with MSI only at 1 locus and 31 cancers without MSI. Moreover, microanalysis in these cases revealed that the mutant-type alleles of TbetaR-II were invariably common in different areas within the tumor, in contrast to the markedly variable alleles of microsatellite loci. Our results suggest that frameshift mutation of the TbetaR-II gene may be a critical event associated with MSI and may contribute to carcinogenesis of the stomach. One of the possible mechanisms of escape from growth control by TGFbeta during gastric carcinogenesis could involve frameshift mutations of the TbetaR-II gene caused by DNA replication errors.

Adenine↗
PubMed1996

Mutation of low affinity nerve growth factor receptor gene is associated with the hypertensive phenotype in spontaneously hypertensive inbred rat strains.

We previously reported a missense mutation in the low affinity nerve growth factor receptor (LNGFR) gene of spontaneously hypertensive rats (SHR), proposing this gene as a promising candidate in genetic hypertension. In this study we provide further support for implicating this gene in genetic hypertension using two new inbred strains, WKHT and WKHA rats. These strains originated from crossbreeding SHR rats with normotensive Wistar-Kyoto rats (WKY): WKHT rats are hypertensive but not hyperactive, and WKHA rats are hyperactive but not hypertensive. Nucleotide sequence analysis of the LNGFR gene revealed that WKHT has the same mutation as SHR, whereas WKHA has the normal sequence, as seen in WKY. These results support our original hypothesis that the mutated LNGFR gene is linked to hypertension, since the mutation had co-segregated with the hypertensive trait, and not hyperactivity trait of SHR.

Amino Acid Sequence↗
PubMed1996

Analysis of cytotoxic activity of the CD4+ T lymphocytes generated by local immunotherapy.

We previously reported that the anti-tumour effect of OK-432 is considerably enhanced by its intratumoral injection together with fibrinogen. In the present study, we generated killer T cells by culturing tumour-infiltrating lymphocytes from thyroid cancer patients who had received this local immunotherapy. Phenotypic analysis revealed that the T cells were positive for CD3+, CD4+, Leu8-, CD45RO+ and T-cell receptor (TCR)alpha beta+, as well as showing strong surface expression of HLA-DR, CD25, LFA-1 and ICAM-1. The generated CD4+ T cells secreted interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, TNF-beta, and interleukin (IL)-6 (but not IL-4), and exhibited a high level of cytolytic activity against several tumour cell lines. The cytolytic activity of these T cells for Daudi cells was inhibited by preincubation with an anti-intercellular adhesion molecule (ICAM)-1 antibody, but not by preincubation with anti-TCR alpha beta, anti-CD2, or anti-LFA-1 antibodies. Pretreatment with anti-ICAM-1 antibody inhibited T-cell cytolytic activity, but not conjugation with target cells. In addition, incubation with immobilised anti-ICAM-1 enhanced the secretion of IFN-gamma by T cells. We conclude that ICAM-1 expressed on the effector cytotoxic CD4+ T lymphocytes delivers regulatory signals that enhance IFN-gamma secretion.

Adjuvants, Immunologic↗
PubMed1996

[A patient with unresectable cancer of pancreas head, effectively treated by a local injection of the mixture of OK-432, fibrinogen and thrombin].

The effective treatment of unresectable pancreatic cancer remains to be elucidated. We report herein a patient who underwent a local injection of a mixture of OK-432, fibrinogen and thrombin. Tumor size and tumor markers significantly decreased following this procedure. Local injection therapy with OK-432, fibrinogen and thrombin may be a promising treatment for unresectable pancreatic cancer.

Adenocarcinoma↗
PubMed1996

[RB gene expression in gastrointestinal tract].

pRB, the retinoblastoma tumor suppressor gene product, regulates the cell cycle at G1/S transition negatively. Many cell cycle regulators modulate pRB function through its phosphorylation status. G1 cyclins (cyclin D, E)/cyclin-dependent kinases (cdk2, 4) inactivates pRB through its phosphorylation, while p21 (WAF1) and p16 inhibit cdks. In several kinds of cancer, Rb gene alteration or functional inactivation of pRB has been reported. In esophageal cancer, loss of heterozygosity of Rb gene and cyclin D gene amplification were frequently detected. But in gastric and colorectal cancer, Rb gene loss or deletion has been shown to be rare. In this study we investigated the expression of pRB, G1 cyclins, cdks and cdk-inhibitors in adenoma-carcinoma sequence of colorectum. And we compared the phosphorylation status of pRB in colorectal normal mucosa and cancer tissue. In adenoma only cyclin D and E were overexpressed but not cdks. In cancer in adenoma pRB and cdk2 were overexpressed with high frequency, and cdk4 overexpression was detected in advanced cancer. p16 overexpression was detected in almost all cancers, but in contrast p21 overexpression was rare event. Comparative study showed that pRB-positive cancer cells also expressed both cdc2/cdk2 and cyclin E. Densitometric analysis revealed that in advanced cancer pRB was hyperphosphorylated compared with normal mucosa. These results indicate that overexpression of cyclin D/cdk4 and cyclin E/cdk2 would phosphorylate pRB, and insufficient expression of p21 may accelerate pRB inactivation.

Cell Cycle↗
PubMed1996

[Cyclin D, CDK4 and p16 expression in colorectal cancer].

G1/S transition of cell cycle is regulated by G1 cyclins/cyclin-dependent kinases (CDKs) and their inhibitors. Cyclin D/CDK4 complex phosphorylates retinoblastoma gene product and p16 inhibits CDK4 in competition with cyclin D. Aberrant expression of these proteins may deregulate cell proliferation and moreover may lead to tumor formation and progression. In this study we examined the expression of cyclin D, CDK4 and p16 in adenoma-carcinoma sequence of colorectum. Immunohistochemical staining revealed that cyclin D was overexpressed in 55 of 66 (83%) adenomas, 8 of 8 (100%) carcinomas in adenoma (CIAs), 26 of 45 (58%) advanced carcinomas and even in hyperplastic mucosa. CDK4 was overexpressed in 0 of 52 (0%) adenomas, 0 of 14 (0%) CIAs and 39 of 45 (87%) advanced carcinomas, but not in hyperplastic mucosa. p16 was overexpressed in only 5 of 52 (10%) adenomas, 10 of 14 (71%) CIA and 59 of 60 (98%) advanced carcinomas, but not in hyperplastic mucosa. And comparative study of CDK4 and p16 showed that CDK4-positive cancer cells also expressed p16. Western blot analysis also revealed that primary regions of advanced colorectal cancer tissues showed 4.61, 3.30, 1.65 and 8.03-fold overexpression on the average in cyclin D1, cyclin D2, CDK4 and p16 respectively. These results indicate that both cyclin D and CDK4 may contribute to phosphorylation of pRB. p16 overexpression would be induced as a brake at G1/S transition through pRB phosphorylation by CDK4 overexpression in advanced colorectal carcinomas.

Adenoma↗
PubMed1995

A quantitative sleep-EEG study on the effects of benzodiazepine and zopiclone in schizophrenic patients.

Polysomnographic examinations (PSG) were performed on 6 male schizophrenic outpatients who were being treated with benzodiazepine (BZD) hypnotics in combination with neuroleptics and 6 healthy male volunteers. In schizophrenic subjects, zopiclone (ZPC), 15 mg/day, was substituted for the BZD hypnotics, and PSGs were recorded again during ZPC therapy. All-night sleep stage scoring was carried out by visual analysis, and computerized period-amplitude analysis of sleep EEG was also performed. The schizophrenics showed marked reduction in the amount of slow-wave sleep (SWS) and in the number of delta half-waves during all-night sleep, especially those with higher amplitude, as compared to the normals. The number of delta half-waves in the patients was markedly reduced during the first sleep cycle. The average amplitude of delta half-waves during all-night sleep in the schizophrenics was significantly lower than that in the normals. The half-wave count of total delta waves in the schizophrenics was higher during treatment with ZPC than with BZDs, although no significant differences were observed in the amount of SWS between the two treatments. Soundness of sleep in the subjective sleep assessment was better evaluated during treatment with ZPC than BZDs. These results suggest that reduction of SWS in schizophrenia may be attributable mainly to the decrease in the number of delta waves with higher amplitude and that ZPC may induce deeper sleep in schizophrenics than BZDs.

Adult↗
PubMed1995

[A comparison of intra-arterial chemoembolization and infusion chemotherapy for liver metastases of breast cancer].

Seventeen patients with liver metastases of breast cancer were treated with a combination of intra-arterial chemotherapy and endocrine therapy at our hospital from 1986 to 1994. Of 17 patients, 9 were treated with transarterial chemoembolization through hepatic artery using 40-50 mg/body of 4'epi-adriamycin (epi-ADM) and lipiodol, and the other 8 were treated with hepatic infusion chemotherapy using 20-30 mg/body of epi-ADM every 2 weeks. All patients were followed by endocrine therapy with oral administration of 800-1,200 mg/day of medroxyprogesterone acetate (MPA). The results were as follows: 1) The comparison of response rate between the two groups was not substantially changed (44.4% x 4/9 in TAE group and 50.0% x 4/8 in Reservoir group). 2) Duration of response was 4-45 months (mean 25 months) in TAE group and 3-15+ alpha months (mean 8.7 months) in Reservoir group. But in the latter group, 3 patients are now under treatment. 3) At one year, the survival rates were 44.4 percent in TAE group and 50.0 percent in Reservoir group. We conclude that combination of intra-arterial chemotherapy and endocrine therapy is a useful treatment modality for controlling liver metastases of breast cancer.

Adult↗