Biomedical subjects

M Sekimoto

Publications and source records attributed to M Sekimoto.

At least 91 records · Page 5Linked to original sources

PubMed1999

Laterality of delta waves during all-night sleep.

In order to clarify the functional asymmetry of the brain function during sleep, period-amplitude analysis of delta electroencephalogram activity was performed on polysomnograms in 12 right-handed healthy males. Electroencephalograms were recorded from disc electrodes placed at C3, C4, O1 and O2 (10-20 electrode system), using A1 +A2 for reference. Although there were no significant differences in delta counts between O1 and O2, delta counts of C3 were significantly larger than those of C4. These results suggest that there exists distinct laterality in the number of delta waves in the central region, reflecting the functional asymmetry of the brain during sleep.

Adult↗

PubMed1999

Enhancement of the anti-tumor effect of 5'-deoxy-5-fluorouridine by transfection of thymidine phosphorylase gene into human colon cancer cells.

Thymidine phosphorylase (dThdPase) is an enzyme that converts 5'-deoxy-5-fluorouridine (5'DFUR) to the toxic substance 5-fluorouracil (5-FU); it is also known to be a platelet-derived endothelial cell growth factor. In order to investigate the feasibility of suicide gene therapy against colorectal cancer by means of the combination of 5'DFUR and the converting enzyme dThdPase, we transfected the dThdPase gene into the human colon cancer cell line SW480 and analyzed the growth pattern as well as the sensitivity to 5-FU or 5'DFUR of the dThdPase-transfected cells. The 50% inhibition (IC50) values of 5-FU against the SW480 parental cells, control vector-transfected cells SW480/V1, and dThdPase-transfected cells SW480/dThdPase were approximately 4.9, 6.3, and 2.9 microM, respectively. The IC50 of SW480/dThdPase was lower than that of SW480 or SW480/V1, although the differences were not statistically significant. The IC50 values of 5'DFUR for SW480, SW480/V1, and SW480/dThdPase were approximately 300, 330, and 3.2 microM, respectively. The sensitivity to 5'DFUR of SW480/dThdPase was increased by about 100-fold compared with that of SW480 or SW480/V1. With only 10% transfection efficacy, a high enough sensitivity to 5'DFUR was obtained to suppress the cell growth, indicating that a strong bystander effect was induced by this system. The in vivo growth of the s.c. transplanted SW480/dThdPase tumor in nude mice was significantly suppressed by i.p. injection of 5'DFUR compared with that in control mice that received phosphate-buffered saline (PBS) treatment. These results suggest that gene therapy using the combination of 5'DFUR and the dThdPase gene may be a useful approach for treatment of colon cancer.

Animals↗

PubMed1999

Natural killer T cell ligand alpha-galactosylceramide inhibited lymph node metastasis of highly metastatic melanoma cells.

The role of natural killer T (NKT) cells in the prevention of multiple tumor metastasis was examined. The i.v. inoculation of a highly metastatic subline of B16-BL6 (B16-BL6-HM) melanoma cells resulted in the formation of metastatic nodules in lymph nodes in addition to lung, intrapleural cavity, and ovary. However, treatment of the mice with the NKT cell ligand alpha-galactosylceramide (alpha-GalCer) three times from 1 day after B16-BL6-HM melanoma inoculation caused a significant inhibition of multiple metastasis. Lymph node metastasis of B16-BL6-HM was almost completely blocked by alpha-GalCer treatment. This antimetastatic effect of alpha-GalCer was abolished in NKT cell-deficient mice. These results suggest that alpha-GalCer-activated NKT cells played a critical role in the prevention of lymph node metastasis of melanoma cells.

Adjuvants, Immunologic↗

PubMed1999

Association between delta waves during sleep and negative symptoms in schizophrenia. Pharmaco-eeg studies by using structurally different hypnotics.

We examined the effects of benzodiazepine (BZD) hypnotics and zopiclone (ZPC), a nonbenzodiazepine hypnotic, on sleep and psychiatric symptoms in schizophrenia, as well as the clinical correlates of these variables. Seven male schizophrenic patients chronically taking neuroleptics together with BZD were studied. We replaced BZD with ZPC and performed polysomnography (PSG) and Brief Psychiatric Rating Scale (BRPS) scoring before and after an 8-week ZPC treatment. The replacement of BZD with ZPC increased the mean amplitude of high-amplitude low-frequency delta waves on the frontal derivation recognized by period-amplitude analysis, and it decreased the BPRS negative-symptom score. Under the BZD treatment, the negative-symptom score correlated inversely with the mean amplitude of high-amplitude low-frequency delta waves. This correlation was weak and not significant under the ZPC treatment. Therefore, delta waves during sleep have a close correlation to negative symptoms in schizophrenia, and such a correlation could be influenced by hypnotics. Although these are preliminary findings, it was suggested that, compared with BZD, ZPC might be a beneficial hypnotic in regard to both sleep and negative symptoms of chronic schizophrenic patients.

Adult↗

PubMed1999

Comparative genomic hybridization defines frequent loss on 16p in human anaplastic thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is one of the malignant tumors with the poor prognosis that is thought to arise from well-differentiated thyroid cancer (DTC). To investigate the molecular mechanism of ATC, we studied genomic alterations of eight ATC cell lines and three DTC cell lines by means of the comparative genomic hybridization (CGH) method. Loss of 16p was observed in five of eight ATC cell lines (62. 5%), but none of the three DTC cell lines showed loss of this chromosome arm. It is notable that loss of 18q [7/8 of ATC (87.5%), 2/3 of DTC (67%)] and gain of 20q [5/8 of ATC (62.5%), 3/3 of DTC (100%)] were frequently seen in both histologic types. Our results suggest that there is a gene in 16p that is closely associated with transformation from well-differentiated thyroid cancer to anaplastic cancer.

Carcinoma↗

PubMed1999

[Assessment of oxygen transport in individual splanchnic organs using critical oxygen extraction].

Vulnerability in individual organs under ischemic stress can be assessed by critical oxygen extraction (critical O2ER). We measured critical O2ER in the whole-body, total splanchnic organs, liver and gut using a biphasic regression model of the oxygen delivery-consumption relationship in 7 dogs subjected to hemorrhagic stress under 1% isoflurane anesthesia. The difference in critical O2ER between the whole-body and total splanchnic organs was not significant, while hepatic critical O2ER was significantly larger than that of the gut (P < 0.05), 89.7 +/- 2.4% (mean +/- SD) and 66.1 +/- 5.1%, respectively. This finding indicated that the liver functions well under ischemic conditions due to its excellent ability to extract oxygen. The anatomical character of the sinusoid and the microcirculatory improving effect of isoflurane may affect the ability of oxygen extraction of the liver. The critical threshold of hepatic venous oxygen saturation as a marker of hepatic oxygen imbalance was considered to be below 10%.

Anesthesia, Inhalation↗

PubMed1999

[A case report: effective trans-arterial neoadjuvant chemotherapy with docetaxel for a local advanced breast cancer patient].

Recently, there have been some reports about the effectiveness of docetaxel for breast cancer patients who had polychemotherapy previously in vein. We report here a case of a 47-year-old woman, who had been diagnosed as local advanced breast cancer. She was given trans-arterial chemotherapy with docetaxel after four series of CEF (cyclophosphamide, epirubicin, fluorouracil) therapy resulted in PD (progressive disease). Local disease was successfully controlled, and she could undergo standard radical mastectomy.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Novel alternative splicing in the 5' exon of the neurotrophin-3 gene.

The neurotrophin-3 (NT-3) gene has previously been reported to consist of three exons including two 5' short untranslated exons and a 3' long exon encoding the entire protein, and to give rise to two classes of transcripts by alternative splicing of the 5' exons to the 3' coding exon. In the present study, we demonstrated the presence of at least four new classes of transcripts of the NT-3 gene, in addition to the two known transcripts. The present finding proposes the further complexity of the regulational mechanism for NT-3 expression.

Alternative Splicing↗

PubMed1998

Identification of a novel gene marker specific for epithelial cells by utilizing a 3'-directed cDNA library.

To achieve reliability of molecular diagnosis using reverse transcription-PCR (RT-PCR), we established a unique method to search for a novel gene marker specific for colonic epithelial cells. Of eight candidate genes selected from a 3'-directed cDNA library in colonic mucosa, two genes were expressed in normal mucosa and cancer of the colon but not in either normal lymph node or normal liver tissue. Known sequences of these genes were reported to be located in the 3' noncoding region, and an additional sequence just upstream to gs04094 (one of the candidate genes) was determined. According to the newly identified sequence, we designed a new set of primers so that we could distinguish the DNA fragment amplified in RT-PCR from that in genomic PCR. RT-PCR using these primers demonstrated that gs04094 was expressed in all of 10 primary colon cancers and 4 liver metastases from colon cancer but in none of 5 normal lymph nodes, 10 peripheral blood samples, and 2 normal liver tissues. Sensitivity of this method was so high as to detect gs04094 mRNA in 10(-6) microg of colon cancer RNA per 1 microg of normal lymph node RNA. Thus, our strategy to search for a novel gene marker using 3'-directed cDNA library proved to be highly efficient.

Animals↗

PubMed1998

PyNPase expression in human colon cancer.

Although colorectal cancer tissue is rich in pyrimidine nucleoside phosphorylase (PyNPase), there is no consensus as to whether cancer cells or stromal cells predominately express PyNPase. We micro-dissected OCT compound embedded frozen tissue sections into epithelial and stromal components and then analyzed the extracted samples separately. The PyNPase expression level was higher in stromal cells than in cancer cells and the difference increased with inflammation induced by the immunostimulator OK432. These results suggest that stromal cells are the major PyNPase source in colorectal cancer.

Adult↗

PubMed1998

New retraction technique to allow better visualization of Calot's triangle during laparoscopic cholecystectomy.

BACKGROUND: Bile duct injuries during laparoscopic cholecystectomy (LC) are thought to occur because surgeons tend to confuse the common bile duct (CBD) with the cystic duct. Among reasons for this misidentification, the difference in the way the operating field is exposed in LC compared to open cholecystectomy should be noticed. Using Dr. Reddick's technique, which is commonly practiced, the upward and the lateral traction of the gallbladder results in a narrower Calot's triangle and angulation of the CBD. These anatomical distortions are thought to contribute to ductal injuries during LC. METHODS: We propose a new method to expose Calot's triangle during LC. The principle of this technique is to expose the hepatic hilus by retracting the caudal surfaces of the quadrate and lateral lobes of the liver using an atraumatic curved instrument. RESULTS: The advantages of this technique are that one gains wide exposure of the hepatic hilus, leaves Calot's triangle undistorted, and avoids tenting the CBD. CONCLUSIONS: This new technique may make LC safer and decrease the number of bile duct injuries associated with the misidentification of the anatomy.

Cholecystectomy, Laparoscopic↗

PubMed1998

A polysomnographic study of sleep patterns in normal humans with low- or high-anxiety personality traits.

To clarify the effects of anxiety-related personality traits on sleep patterns, polysomnographic examinations (PSG) were performed over 4 consecutive nights on normal humans who tested within the low- or high-anxiety ranges. The subjects consisted of two groups of six male university students who scored either less than 45 points (low-anxiety group) or more than 55 points (high-anxiety group) on the Spielberger's State Trait Anxiety Inventory. Compared to the levels of sleep change in the high-anxiety group, the low-anxiety group exhibited a greater change in REM sleep and stage 2 sleep. The REM sleep in the low-anxiety group was shorter on the first and second nights compared to the third and fourth nights, and the stage 2 sleep was longer on the first night than on the remaining three nights. Thus, the low-anxiety group showed a first-night effect followed by partial recovery on the second night, while the high-anxiety group exhibited no obvious first-night effect. These results suggest that there is a difference in sleep patterns, assessed by consecutive PSG, between those with low- and high-anxiety traits, and that anxiety-related personality traits attenuate the occurrence of the first-night effect, reflecting a lower adaptability to a novel environment.

Adult↗

PubMed1998

Polysomnography and body temperature changes by phototherapy in a delayed sleep phase syndrome case.

We examined polysomnography (PSG) and body temperature in a patient with delayed sleep phase syndrome who responded to phototherapy. The patient was a 31-year-old woman whose condition had slightly improved by a vitamin B12 administration. Phototherapy was administered to her in combination with the vitamin B12 medication, and this combined treatment successfully advanced her delayed sleep phase. On PSG, the regimen showed shortened sleep latency, decreased total sleep time and stages 1 and 2 sleep, and increased slow wave sleep. Phototherapy also improved temporal distribution of delta half-waves (0.5-2.0 Hz, > or = 31 microV) as well as phase relationship between sleep and body temperature.

Adult↗

PubMed1998

Melatonin treatment for rhythm disorder.

We tried melatonin treatment in two patients with non-24 h sleep-wake syndrome, who did not respond to treatments by vitamin B12, bright light therapy, or hypnotics. In one patient, melatonin 5-10 mg improved difficulty in falling asleep and in waking, although it failed to improve the sleep-wake rhythm. In another patient, melatonin 3 mg successfully changed the sleep-wake rhythm from free-running pattern to delayed sleep phase pattern. However, melatonin re-administration after a 4-month drug-free interval failed to improve his free-running sleep-wake rhythm. These results suggest that melatonin acted as a sleep inducer in one patient and as a phase setter in the other, although the effect on the latter patient was transient.

Adult↗

PubMed1998

Extraction and analysis of diagnostically useful proteins from formalin-fixed, paraffin-embedded tissue sections.

We describe and discuss a method of protein extraction for Western blot analysis from formalin-fixed, paraffin-embedded tissue sections. From 5-mm2 50-micron-thick tissue sections, an abundance of proteins could be extracted by incubating the sections in lysis buffer containing 2% sodium dodecyl sulfate (SDS) at 100C for 20 min followed by incubation at 60C for 2 hr. Extracts yielded discernible protein bands ranging from 10 kD to 120 kD as identified by SDS-polyacrylamide gel electrophoresis (PAGE). Western blot analysis successfully detected membrane-bound protein such as E-cadherin, cytosolic protein such as beta-catenin, and nuclear proteins including proliferating cell nuclear antigen (PCNA), mutant-type p53, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs). With this technique, we could examine cyclin D1 and CDK2 expression in small adenomas compared with cancer tissues and normal mucosa. The simple method of protein extraction described here should make it possible to use large-scale archives of formalin-fixed, paraffin-embedded samples for Western blot analysis, and its application could lead to detailed analysis of protein expression. This new technique should yield valuable information for molecular biology.

Adenoma↗

PubMed1998

Cdk2/cdc2 expression in colon carcinogenesis and effects of cdk2/cdc2 inhibitor in colon cancer cells.

Cyclin dependent kinases propel the cell cycle in collaboration with cyclins. We have examined the expression of cdk2/cdc2 in adenoma and focal carcinoma in adenomatous tissue to explore their role in tumorigenesis of colorectum. Immunohistochemical study revealed that cdk2/cdc2 was overexpressed in a subsets of adenoma (14/50; 28.0%) but this overexpression was much more obvious in focal carcinoma (13/15; 86.7%). These results suggest that cdk2/cdc2 is remarkably upregulated together with a malignant change. In an effort to demonstrate a significant role for cdk2/cdc2 in colon cancer, we investigated growth and apoptosis with butyrolactone I, a specific inhibitor for cdk2/cdc2, using 4 colon carcinoma cell lines (HCT116, LoVo, HT29, Colo 320DM). Butyrolactone I inhibited proliferation of all colon carcinoma cell lines at 100 microM and it induced apoptosis in LoVo cell line with induction of p53. Our findings suggest that inhibition of cdk2/cdc2 may be a useful strategy against colon cancer.

4-Butyrolactone↗

PubMed1998

[Molecular biological assessment of susceptibility to colorectal cancer].

There are two entities in the predisposition for colorectal cancer. One is the hereditary colorectal cancers which include familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), and others. In the case of these hereditary diseases, genetic testing to detect germline mutation in the causative gene in family members is useful for identifying possible gene carriers. For the diagnosis of HNPCC, the present clinical criteria are not sufficient and analysis of DNA replication error (RER) could be useful. Another entity is genetic sensitivity to environmental carcinogens. In particular, the polymorphism of the genes encoding drug-metabolizing enzymes has been shown to be important in recent years. The fast acetylator genotype of N-acetyltransferase (NAT) genes and the null genotype of the glutathione S-transferase M1 gene have been reported to be associated with increased risk of colon cancer. In the strategy against colon cancer, it is extremely important to identify high-risk individuals so that we can prevent cancers or detect them in earlier stages.

Adenomatous Polyposis Coli↗

PubMed1998

Transaxillary endoscopic partial mastectomy for comparatively early-stage breast cancer. An early experience.

For optimal cosmetic results in breast cancer surgery, we developed an alternative operation using endoscopy to remove tumors through a small single incision remote from the breast itself. The tumor is endoscopically resected with electrocautery and low constant suction through a short incision in the axilla, 5 cm long, after which axillary dissection is performed through the same wound in the usual manner, under visualization by the naked eye. Primary reconstruction of the breast is performed with the remaining mammary gland and a subcutaneous fat flap on the serratus muscle. Seven patients underwent this surgery. The postoperative shape of the breasts was judged to be cosmetically satisfactory, and the surgical wounds were not visible from the front in all cases. This operation has the same therapeutic oncological effect as a standard lumpectomy and, in addition, offers a greater cosmetic advantage in cases of early breast cancer.

Adult↗