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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 307 records · Page 17Linked to original sources

Enhancement of 5-fluorouracil cytotoxicity on human colon cancer cells by retrovirus-mediated interferon-alpha gene transfer.

Gene therapy has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells. Several reports documented the clinical effects of interferon-alpha (IFN-alpha) in management of patients with advanced colorectal carcinoma. We report for the first time, the successful transduction of human IFN-alpha gene into colon cancer cells, COLO 201 using a replication-defective retroviral vector. Retrovirus-containing supernatant from PA 317 packaging cells was used to infect colon cancer cells, COLO 201 and NIH 3T3 cells. Transient infection showed that cell proliferation and cell viability were significantly suppressed in colon cancer cells transduced with IFN-alpha gene. Moreover, IFN-alpha-transduced cells acquired less resistance to 5-FU induced apoptosis. These data demonstrate that IFN-alpha gene transfer may have a clinical application and can be combined with chemotherapy for treatment of advanced colorectal cancer.

3T3 Cells↗

Apoptosis of colorectal adenocarcinoma induced by 5-FU and/or IFN-gamma through caspase 3 and caspase 8.

The cytotoxic effect of 5-FU has been shown by the induction of apoptosis in cancer cells, and reported to be enhanced by IFN-gamma. We examined the role of caspases on the apoptosis induction of 5-FU and IFN-gamma using a colorectal adenocarcinoma cell line. The activities of caspase 3 and caspase 8 increased when apoptosis was induced by 5-FU and/or IFN-gamma. Moreover, all apoptotic cells showed high caspase 3 activity in these conditions. Although the inhibitors of caspase 3 and caspase 8 inhibit apoptosis, anti-Fas ligand antibody does not affect the apoptosis induced by 5-FU. Thus, caspase 3 and caspase 8 play crucial roles in apoptosis induced by 5-FU and/or IFN-gamma, regardless of the Fas-Fas ligand system.

Adenocarcinoma↗

The zymogen prothrombin stimulates cell locomotion and calcium influx in murine osteosarcoma cells by different mechanism from thrombin.

The coagulation system plays a role in tumor invasion and metastasis. Prothrombin was previously found to stimulate the motility of melanoma cells. We compared the effect of prothrombin and thrombin on cell motility, calcium influx and actin stress filament contraction in highly metastatic osteosarcoma LM8 cells. Prothrombin and thrombin stimulated chemotaxis and chemokinesis of LM8 cells in a dose-dependent manner. Calcium influx was significantly increased after stimulation with thrombin and prothrombin. Thrombin and prothrombin markedly stimulated actin contraction in LM8 cells. Hirudin inhibited the effects of thrombin but not those of prothrombin. Prothrombin appears to stimulate cell locomotion, actin contraction, calcium influx in LM8 cells by different mechanism from thrombin.

Actins↗

Evaluating response to nutritional therapy using the branched-chain amino acid/tyrosine ratio in patients with chronic liver disease.

The branched-chain amino acid (BCAA)/tyrosine (Tyr) ratio (BTR) recently has been reported to be a good indicator of the severity of hepatic parenchymal injury in patients with chronic liver disease. In the present study, sequential changes of BTR after BCAA administration were determined in patients with chronic liver disease to evaluate the value of BTR as a marker of the clinical response to nutritional therapy in these patients. This study comprised 75 patients with chronic hepatitis and 96 with liver cirrhosis. BTR was significantly decreased in patients with cirrhosis and hepatitis compared with healthy subjects. BTR was significantly correlated with the Child-Pugh score and with other liver function tests. BCAA increased significantly 2 hr after BCAA administration and decreased gradually thereafter. Tyr significantly decreased 4 hr after BCAA administration. BTR significantly increased 2 and 4 hr after BCAA therapy. The increase in BTR 3 hr after BCAA administration was low in patients with decreased basal BTR. The results of this study showed that BTR is a good index of the hepatic parenchymal damage and that it may be a useful marker for monitoring response to nutritional therapy in patients with chronic liver disease.

Amino Acids, Branched-Chain↗

[Clinical results of supratentorial astrocytoma grade II].

At present, there is no consensus concerning the treatment of low-grade gliomas. The authors conducted a retrospective review of surgically treated, histologically verified cases of supratentorial astrocytomas of grade II to evaluate the results of current treatment methods. Thirty-seven patients, 23 males and 14 females, treated from April, 1977 through March, 1997 were analyzed. Median patient age was 36 years (range 2-69 years). All patients were diagnosed by surgical specimens. Thirty were fibrillary, and three were gemistocytic astrocytomas. There were 13 total resections, 7 subtotal resections, 10 partial resections. Of the remaining 7, diagnosis was obtained by stereotactic biopsy. Twenty patients were irradiated and two received chemotherapy. Follow-up information was obtained for 33 patients. The follow-up time ranged from 4 months to 246 months (mean, 9 years). Overall survival rates at 5 and 10 years for the entire treated group were 71% and 57% respectively. Total and subtotal resections were significantly associated with longer survival time, the 5- and 10-year survival rates were 93% and 67%, respectively. They were 40% and 40% in patients with partial resection or needle biopsy. Patients with gemistocytic astrocytoma had a poor prognosis with a median survival of 44.5 months. The influence of radiotherapy was not obvious: 92 and 69% of patients were alive at 5 and 10 years respectively without radiotherapy. The extent of surgery and histological type were by far the most important factors in predicting length of survival. The importance of an accurate histologic diagnosis and a gross total resection is emphasized.

Adolescent↗

[Population genetic study of Huntington's disease--prevalence and founder's effect in the San-in area, western Japan].

In order to confirm the prevalence rate of Huntington's disease (HD) in San-in area, the epidemiological study was performed in 1997. Ten patients were found, so that the prevalence rate of HD was 0.72 per 100,000 population. D4S136 and CCG polymorphism were investigated in HD patients in western Japan, Chugoku Districts, including the San-in area. The frequency of D4S136A3(242bp) type was higher in HD group of San-in area than Chugoku District (each 38.5% and 9.1%). Twelve of 13 HD chromosomes in the San-in area had the (CCG)7 polymorphism, while only 36.4% of HD chromosomes of Chugoku District had the (CCG)7 polymorphism. Although the HD patients in the San-in area may have a common ancestor except for only one patient, the HD patients in other areas of Japan may have the different HD ancestor from the San-in area.

Founder Effect↗

Magnetization transfer contrast of various regions of the brain in liver cirrhosis.

BACKGROUND AND PURPOSE: T1-weighted MR images show high signal intensity in the pallidum of many patients with liver cirrhosis. The purpose of this study was to evaluate quantitative changes in MR signals in patients with liver cirrhosis by using the magnetization transfer technique. METHODS: Magnetization transfer ratios were measured in seven different regions of the brain in 37 patients with liver cirrhosis and in 37 healthy volunteers. RESULTS: The magnetization transfer ratios in patients with liver cirrhosis were significantly lower than those in control subjects in the globus pallidus, putamen, thalamus, corona radiata, and subcortical white matter. CONCLUSION: Abnormal magnetization transfer ratios may be found in otherwise normal-appearing cerebral regions.

Brain↗

Frequent Bax frameshift mutations in gastric cancer with high but not low microsatellite instability.

Widespread microsatellite instability (MSI) due to the defective DNA mismatch repair underlies the pathogenesis of the majority of hereditary non-polyposis colorectal cancer and a subset of various sporadic malignant tumors. Using 5 microsatellite markers and the criteria of MSI proposed by the National Cancer Institute (NCI) workshop, we analyzed 205 gastric adenocarcinomas for MSI. Based on the number of markers showing instability per tumor, the tumors were divided into three groups; those with two or more of the five markers displaying instability (high MSI, MSI-H), those with one of five markers displaying instability (low MSI, MSI-L), and those with no instability (microsatellite stable, MSS). Among 205 tumors, 30 (15%) were MSI-H, 15 (7%) were MSI-L, and 160 (78%) were MSS. All of the 30 MSI-H tumors demonstrated instability at BAT26, a sensitive marker for the widespread MSI, while none of the 15 MSI-L tumors did. MSI-H tumors were significantly associated with distal location and well or moderate differentiation, but MSI-L tumors were indistinguishable from MSS tumors. Bax frameshift mutations were detected in 60% of the 30 MSI-H tumors, while not in any of the 15 MSI-L tumors. These results suggest that microsatellite analysis using the criteria proposed by the NCI workshop may be appropriate for gastric cancers because it unveils real differences in genotype and phenotype.

Adenocarcinoma↗

[A study on the efficacy of combination chemoendocrine therapy consisting of cyclophosphamide, adriamycin, UFT, and tamoxifen for advanced or recurrent breast cancer].

The efficacy of the combination chemoendocrine therapy CAUT against advanced and recurrent breast cancer was examined. One course of this therapy lasted 3 weeks and consisted of adriamycin (i.v.) at 30 mg/m2 on day 1, cyclophosphamide (p.o.) at 65 mg/m2 and UFT (p.o.) at 300 mg/m2 on days 1-14, and tamoxifen (p.o.) at 20 mg/body on days 1-21. Twenty patients were enrolled, of whom 19 were eligible including seven with advanced cancer and 12 with recurrent cancer. One patient achieved CR, ten PR, three NC, and five PD, for a response rate of 58% (95% CI: 29-87%). The response rates according to type of lesion were 73% (8/11) for the soft tissue, 38% (3/8) for the bone, 20% (1/5) for the lungs and pleura, and 50% (2/4) for the liver. Adverse events with a severity of grade 3 or more included a reduction in WBC in six patients (31.6%), a reduction in RBC in one (5.3%), alopecia in four (21.1%), and severe general fatigue in one (5.3%). One patient experiencing a grade 4 reduction in WBC, and one of five patients experiencing a grade 3 reduction with a fever, recovered after treatment with G-CSF. The other four patients recovered following suspension of administration. This therapy is considered useful, exhibiting a high response rate and relatively slight adverse effects.

Adult↗

Combination therapy for advanced breast cancer: cyclophosphamide, doxorubicin, UFT, and tamoxifen.

We evaluated combination therapy for advanced and recurrent breast cancer with cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), UFT (uracil and tegafur), and tamoxifen (Nolvadex) (CAUT), designed as chemoendocrine therapy with a high antitumor effect and less severe adverse reactions. In this therapy, one 3-week cycle consisted of doxorubicin 30 mg/m2 intravenously on day 1, cyclophosphamide 65 mg/m2 orally (po) and UFT 300 mg/m2 po on days 1 to 14, and tamoxifen at 20 mg/day po on days 1 to 21. Twenty patients were registered and 19 were eligible, including seven with advanced breast cancer and 12 with recurrent disease. Six patients had received previous treatment. The comprehensive evaluation for objective response revealed one patient with a complete response and 10 patients with partial responses, producing an overall response rate of 58% (95% confidence interval, 29% to 87%). Three patients experienced no change, and five patients had progressive disease. Adverse events > or = grade 3 were leukopenia in six patients, erythropenia in one patient, alopecia in four, and severe generalized malaise in one. One patient who developed grade 4 leukopenia and one of five patients who developed grade 3 leukopenia recovered after receiving granulocyte colony-stimulating factor. CAUT therapy produced high response rates and relatively mild adverse reactions and is considered useful for the treatment of advanced and recurrent breast cancer.

Adult↗

Serum carnitine concentrations in patients with idiopathic hypertrophic cardiomyopathy: relationship with impaired myocardial fatty acid metabolism.

We evaluated the clinical significance of serum carnitine concentrations in determining the severity of impaired myocardial fatty acid metabolism in idiopathic hypertrophic cardiomyopathy (HCM). We studied 56 asymptomatic or mildly symptomatic patients with HCM. Serum levels of free carnitine and acylcarnitine were measured by the enzymic cycling method. Myocardial scintigraphy with (123)I-labelled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) was performed, and the images were analysed quantitatively and semi-quantitatively. Serum free carnitine levels were significantly higher in HCM patients than in normal subjects (52. 5+/-9.5 and 42.3+/-5.5 nmol/ml respectively; P<0.0001). On the other hand, serum acylcarnitine levels and acyl/free carnitine ratios were lower in HCM patients than in normal subjects (10.2+/-4.0 nmol/ml and 0.19+/-0.08, compared with 13.2+/-3.9 nmol/ml and 0.32+/-0.11 respectively; P<0.0001). Clinical characteristics were not significantly different between the patients showing high and normal free carnitine levels, although female patients with high free carnitine levels were few (P=0.02). Both quantitative and semi-quantitative analyses revealed that the severity of decreased myocardial BMIPP uptake was significantly correlated with serum free carnitine levels (quantitative analysis: r=-0.422, P<0.0012; semi-quantitative analysis: r=0.633, P<0.0001). In the presence of reduced carnitine uptake into the myocardium in HCM, there may also be reduced transport of acylcarnitines out of the myocardium into the plasma. Although inborn errors of fatty acid metabolism and carnitine deficiencies are reported to provoke secondary HCM and are associated with low serum carnitine concentrations, this study has revealed that the levels of carnitine are, in contrast, increased in idiopathic HCM. Moreover, serum carnitine concentrations are a sensitive indicator of the severity of impaired myocardial fatty acid metabolism even in asymptomatic patients with HCM.

Adolescent↗

[The effect of sevoflurane and isoflurane on striatal dopamine of awake freely moving rats observed in an in vivo microdialysis study].

We investigated the effect of sevoflurane and isoflurane on the level of interstitial dopamine of in vivo awake, free moving rats brain striatum using microdialysis techniques. Rats were implanted with a microdialysis probe to the right striatum of the brain and administered with 1.2 MAC of each volatile anesthetics for 1 hour, and dialysates from the probe were determined every 20 minutes. Both anesthetics reduced the amount of dopamine derived from dialysate, and increased the efflux of dopamine with pretreatment of nomifensine 10mg. kg-1 i.p. The change of metabolites of dopamine during anesthesia was increased. No significant difference was found between sevoflurane and isoflurane. We hypothesized that these anesthetics might have special actions on interactions between metabolism and re-uptake of dopamine in rats striatum during anesthesia.

Anesthetics, Inhalation↗

[Urinary retention as a transient neurologic symptom after accidental total spinal anesthesia with mepivacaine hydrochloride].

We report a patient in whom urinary retention as a transient neurologic symptoms (TNS) developed after accidental total spinal anesthesia with mepivacaine hydrochloride. Mepivacaine, an amide local anesthetic, has been used for spinal anesthesia and considered one of the best for spinal anesthesia for its low incidence of TNS. However, we suggest that TNS associated with mepivacaine might not be a rare complication in spinal anesthesia.

Adult↗

[The evaluation of preoperative anesthetic visit in our hospital].

The preoperative visit by an anesthetist has been thought to be important for the assessment of patient and to communicate with them. However, there are few reports on the visit in Japan until now. The effect of preoperative anesthetic visit in our hospital was estimated by interviewing patients just before surgery who had received a visit by their anesthetist. The answers from sequential 346 scheduled surgical patients for 8 weeks were obtained. Only 72 patients were able to recall the name of their anesthetists. About half of patients believed that anesthetist just had put the patient to sleep and relieved them from pain. We measured the number of treatments each patient could remember that had been explained by the anesthetist on the visit, and found it was unexpectedly small at the interview. These data suggest that our preoperative visit may not be satisfying in view of making good relationship between patients and anesthetists, and educating patients for recent anesthesia. We should make an effort to educate the patients about up-to-date and reasonable anesthesia.

Adolescent↗