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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 361 records · Page 20Linked to original sources

Multiple tumors and a novel E2F-4 mutation. A case report.

Defects in the DNA mismatch-repair are known to cause microsatellite instability (MSI) in hereditary nonpolyposis colorectal cancer (HNPCC) as well as sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at the trinucleotide coding region microsatellite (CAG)n in a subset of human sporadic CRC with MSI. We report a 65-year-old man with triple tumors in the abdomen, including colon cancer, stomach cancer, and lipoma of the retroperitoneum, with the analysis of E2F-4 mutation. We report the first case of colon cancer with a homozygous E2F-4 mutation along with a detailed analysis of other cancer related genes as well as a prognosis.

Adult↗

Phase II study of irinotecan and cisplatin as first-line chemotherapy in advanced or recurrent cervical cancer.

Irinotecan (CPT-11) and cisplatin are singly active against cervical cancer. We evaluated the efficacy and toxicity of CPT-11 plus cisplatin as first-line chemotherapy in patients with advanced or recurrent cervical cancer. Twenty-nine chemotherapy-naive patients with advanced or recurrent cervical cancer were treated with CPT-11 (60 mg/m(2)) on days 1, 8, and 15 by intravenous infusion over 90 min, followed by cisplatin (60 mg/m(2) i.v.) on day 1 over 90 min. The patients' median age was 57 years (range 35-75). Nineteen patients (66%) had advanced primary disease. Six patients with recurrent disease (21%) had been treated with prior radiotherapy. The remaining 4 patients (14%) had residual or recurrent disease after radical surgery. The histologic diagnoses were squamous cell carcinoma in 25 patients (87%), adenocarcinoma in 3, and adenosquamous cell carcinoma in 1. All eligible patients were included in the toxicity and response analysis based on the intent to treat. Two patients (7%) achieved a complete response and 15 (52%) a partial response (overall response rate: 59%, 95% confidence interval; 41-74%). Stable disease was recorded in 6 patients (21%) and progressive disease in 3 patients (10%). In 3 patients, image-guided evaluation of response was judged to be unfeasible at the time of independent extramural review (10%). The median time to response was 32 days (range 16-62 days). The median survival was 27. 7+ months (range, 6.4-52.8+ months). Two dose-limiting side effects were observed: grade 3 (28%) or 4 (45%) neutropenia and grade 3 (7%) or 4 (7%) diarrhea. Other severe toxicities included anemia (45%), thrombocytopenia (3%), nausea/vomiting (31%), and alopecia (7%). The combination of CPT-11 with cisplatin is an active regimen for treatment of advanced or recurrent cervical cancer albeit with a significant degree of myelosuppression.

Adult↗

Evaluation of the therapeutic effect of transcatheter arterial embolization for hepatocellular carcinoma.

Transcatheter arterial embolization (TAE) has been widely performed for patients with hepatocellular carcinoma (HCC). However, the method of evaluating the therapeutic effect of TAE has not been established. We examined the rate of necrotic area to whole tumor (TN) by CT, the tumor regression rate (TR) and the reduction rate in serum alpha-fetoprotein (AFP) levels in patients with HCC who received hepatic resection within 3 months after TAE. In the evaluation of TN, the lipiodol accumulation in tumor was regarded as being necrotic. Rates of necrotic area, which were also examined pathologically (PN) in resected tumors, were compared with TN, TR and AFP reduction rates, respectively. Eighty-eight patients were enrolled in this study, and there was a significant positive correlation between TN and PN (r = 0.80, p < 0.001). Although TR significantly correlated to PN (p = 0.001), the correlation coefficient between them was low (r = 0.34). The correlation coefficients between AFP reduction rate and PN was 0.76 (p < 0.001) in 26 patients (30%) with an AFP level >/=200 ng/ml before TAE. The evaluation method using lipiodol accumulation in CT is the most useful for assessing the therapeutic effect of TAE, particularly when a sufficiently long interval exists between TAE and the evaluation, because of the highest correlation coefficient between TN and PN, and the availability of TN for all patients. The reduction rate in serum AFP levels was also useful in patients with AFP levels >200 ng/ml before treatment.

Adult↗

Prognostic factors in patients with metastatic pancreatic adenocarcinoma receiving systemic chemotherapy.

The aim of the present study was to determine prognostic factors in patients with metastatic pancreatic adenocarcinoma (PC) receiving systemic chemotherapy. The relationship between patient characteristics and prognosis was examined in 103 consecutive patients with metastatic PC. The overall median survival time and 1-year survival rate were 3.2 months and 5.6%, respectively. Among the 20 potential prognostic variables investigated, only three variables, a serum C-reactive protein (CRP) level of > or =5 mg/dl, the performance status of 2-3 and a serum carbohydrate antigen 19-9 (CA 19-9) level of > or =10,000 U/ml were identified as the factors independently associated with a shorter survival. A prognostic index based on the regression coefficients of these three factors was proposed to classify the patients into three groups, with good, intermediate and poor prognosis. The median survival time for these three groups was 5.2, 2.6 and 1.4 months, respectively. The findings of this study may be useful in determining treatment strategies and in designing future clinical trials of systemic chemotherapy for metastatic PC.

Adenocarcinoma↗

Scleroderma associated with anemia and thrombocytopenia that responded well to cyclosporin.

A 55-year-old woman came to our hospital because of cutaneous sclerosis of the limbs in September 1996, and was diagnosed with scleroderma based on a skin biopsy. In August 1997, the cutaneous sclerosis became progressive (hemoglobin level, 4.3 g/dl; platelet count, 7 x 10(9)/l). The laboratory results were positive for the direct Coombs test, bone marrow aspiration showed a dry tap, and the bone marrow biopsy showed marked fatty marrow. Indium-111 bone marrow scintigraphy showed a markedly decreasing uptake. These findings indicated bone marrow hypoplasia associated with hemolytic anemia. After prednisolone therapy (60 mg) was initiated, the direct Coombs test became negative but the blood cell count did not increase. Then, 300 mg of cyclosporin was initiated and anemia and thrombocytopenia improved. The cyclosporin dosage was gradually decreased and the patient's hematological condition was good, although the cutaneous sclerosis changed only a little. This is a rare and interesting case of a patient with scleroderma associated with bone marrow insufficiency and hemolysis who responded well to cyclosporin.

Anemia, Hemolytic↗

Cellular activities of 20K- and 22K-hGH do not necessarily correlate with their binding affinities for rat GH receptor.

Even though 20K human growth hormone (20K-hGH) has 3-10% binding affinity for the rat liver and adipose tissue microsomes as compared to 22K-hGH, it was also reported that 20K-hGH has the same potency as 22K-hGH in the hypophysectomized rat weight gain assay. In order to investigate the reason why such controversial data exist, we have studied 20K- and 22K-hGH using the rat GH receptor extracellular domain (rGHR-ECD) and full-length rGHR. When we examined the complex formation of rGHR-ECD with 20K- and 22K-hGH in gel filtration assay, 20K-hGH formed no complex while 22K-hGH formed a 1:1 complex. Next, rGHR cDNA was introduced into Ba/F3 cells and CHO-K1 cells, and stable transfectants (Ba/F3-rGHR and CHO-rGHR) were established. In the proliferation of Ba/F3-rGHR cells, 20K-hGH had 10-fold lower activity than 22K-hGH, which is consistent with their affinities for rGHR. But surprisingly, in the Spi2.1 gene promoter activation in CHO-rGHR cells, 20K- and 22K-hGH had the same activity, which was found not only in stable CHO-rGHR clones but also in CHO-K1 cells transiently expressing rGHR. In conclusion, these results indicate that cellular activities of 20K- and 22K-hGH do not necessarily correlate with their binding affinities for rGHR.

Adipose Tissue↗

Fluvastatin upregulates inducible nitric oxide synthase expression in cytokine-stimulated vascular smooth muscle cells.

Nitric oxide (NO) production by inducible NO synthase (iNOS) may play an important role in the pathogenesis of atherosclerosis. Although fluvastatin has been shown to reduce progression of atherosclerosis, it is not known whether it regulates iNOS expression. We investigated the effects of fluvastatin on iNOS expression and subsequent NO synthesis in vascular smooth muscle cells (VSMCs) and the mechanism by which fluvastatin exerts its effects. Fluvastatin significantly increased interleukin-1ss (IL-1ss)-induced nitrite production by VSMCs in a time-dependent (0 to 24 hours) and dose-dependent (10(-)(8) to 10(-)(5) mol/L) manner. Increased nitrite production by fluvastatin was accompanied by increased iNOS mRNA and protein accumulation. IL-1ss induced nuclear factor-kappaB activation in VSMCs, which was not affected by fluvastatin. Exogenous mevalonate significantly prevented the stimulatory effect of fluvastatin on nitrite production. Cotreatment with geranylgeranyl-pyrophosphate also reversed the effect of fluvastatin. Furthermore, both Rho inhibitor C3 exoenzyme and Rho kinase inhibitor Y-27632 significantly increased IL-1ss-induced nitrite accumulation in VSMCs. These results demonstrated that fluvastatin upregulates iNOS expression and subsequent NO formation in rat VSMCs through inhibition of Rho.

Animals↗

Primary malignant lymphoma of the central nervous system presenting with ascites and pleural effusion.

A 70-year-old woman was admitted to our hospital owing to ascites and pleural effusion. Though malignant cells (B-cell type lymphoma) were detected in both the ascites and pleural effusion, neither lymph node swelling nor a tumor was detected upon chest, abdominal and pelvic computed tomography (CT). After weekly THP-COP therapy for 8 weeks, the ascites and pleural effusion completely disappeared. Two years after the first admission, she was re-admitted because of a disturbance of consciousness, and a brain tumor was detected on CT scan. The immunohistological and genetic data for the brain tumor were identical to those of the malignant cells in the pleural effusion and ascites detected 2 years previously. Whereas the symptoms at onset of a primary lymphoma of the central nervous system (CNS) are usually neurological ones, in this rare case of primary CNS lymphoma, the symptoms at onset were the ascites and pleural effusion without neurological symptoms.

Aged↗

Acute inferior myocardial infarction and coronary spasm in a patient with an anomalous origin of the right coronary artery from the left sinus of valsalva.

A 56-year-old Japanese woman with an acute inferior myocardial infarction was admitted to hospital. Emergency coronary angiography revealed an anomalous origin of the right coronary artery from the left sinus of Valsalva, but there was no stenosis or thrombus in either the right or left coronary artery. Coronary spasm was provoked at the site of the proximal portion of the anomalous coronary artery, which was located between the aorta and pulmonary trunk. This was thought to be the cause of the myocardial infarction.

Acetylcholine↗

Investigation into the 5-hydroxytryptophan-evoked luminal 5-hydroxytryptamine release from the guinea pig colon.

The effect of an endogenous 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan (5-HTP), on the luminal outflow of 5-HT was examined using the luminally perfused isolated colon of the guinea pig, a model that would facilitate the pharmacological analysis of luminal 5-HT release from enterochromaffin cells (EC cells). 5-HTP (1-10 microM) concentration-dependently caused an increase of the luminal outflow of 5-HT. Either tetrodotoxin (0.3 microM) or atropine (0.2 microM) did not affect the 5-HTP-evoked increase in luminal 5-HT outflow, while the L-type calcium channel blocker, nicardipine (1 microM) or diltiazem (1 microM) reduced the 5-HTP-evoked 5-HT outflow by 47% and 61%, respectively. SB203186 (1 microM), a 5-HT4-receptor antagonist, enhanced the 5-HTP-evoked 5-HT outflow, while ramosetron (1 microM), a 5-HT3-receptor antagonist reduced the stimulating effect of 5-HTP by 66%. Ketanserin (0.1 microM), a 5-HT2A-receptor antagonist did not modify the stimulatory effect of 5-HTP. It is concluded that in the guinea pig colon, 5-HTP facilitates the luminal 5-HT release from EC cells, with no involvement of neuronal mechanisms and a non-neuronal cholinergic system. Furthermore, non-neuronal 5-HT3 and 5-HT4 receptors appear to contribute to the regulation of the luminal 5-HT release evoked by 5-HTP. This new bioassay of the guinea pig colon allows the pharmacological characterization of uncomplicated luminal 5-HT release from EC cells.

5-Hydroxytryptophan↗

An experimental teleradiology transmission system using a high-speed ATM backbone network.

We evaluated the performance of an experimental teleradiology system based on a high-speed ATM backbone network. Image acquisition, transmission and the disk-to-display processing times were measured. Computerized tomography (CT) scans printed on 14 inch x 17 inch (36 cm x 43 cm) films were digitized and transferred over the network. The average time for the entire process was 1 min 30 s. Three radiologists interpreted 20 cases. For CT image interpretation, the reading time for one case ranged from 2 to 12 min (mean 6 min 46 s) on a monitor, and from 1 to 3 min (mean 1 min 31 s) with the original film. The ATM backbone network operating at 156 Mbit/s provided sufficient speed for remote consultation. However, further improvements in the operability of the system, especially the image viewing station, are necessary before it will be satisfactory for clinical use.

Computer Systems↗

Polypropylene mesh substitute for the fascial defect after using for the dural repair--technical note.

Use of the anterior sheath of the rectus abdominis muscle (anterior sheath) as a dural substitute and patching of the large defect of the anterior sheath with polypropylene mesh are described. Five patients were treated using the anterior sheath and the mesh. No postoperative complications such as cerebrospinal fluid leakage, infection, or abdominal wall hernia occurred. The mesh is useful as a patch for the sheath defect.

Abdominal Muscles↗

Blood lead level to induce significant increase in urinary delta-aminolevulinic acid level among lead-exposed workers: a statistical approach.

The present study was initiated to examine the quantitative relationship between blood lead (Pb-B) and urinary delta-aminolevulinic acid (ALA-U) among Pb-exposed workers, and to find a threshold Pb-B level to induce an increase in ALA-U. For this purpose, pairs of venous blood and spot urine samples were collected from 8,274 men and 5,856 women (14,130 workers in total) who were occupationally exposed to inorganic lead. The blood and urine samples were analyzed for Pb-B and ALA-U by atomic absorption spectrometry and colorimetry, respectively, and the correlation between pairs of measures were subjected to statistical analysis. The assumption of the 3rd degree regression for correlation gave a substantially greater correlation coefficient (0.645 for men and 0.619 for women) than 1st or 2nd degree regression, whereas only very small improvement in the coefficient was achieved with 4th to 6th degree ones. Logarithmic conversion of the parameters was not effective in improving the correlation. The assumption of the 3rd degree regression followed by calculation of the local minimum gave 22, 29 and 23 micrograms/100 ml Pb-B for men, women, and men + women, respectively, as the threshold Pb-B to induce ALA-U increase. Pb-B to elevate ALA-U to the 95% upper normal limit (8 mg/l, common to men and women) was 62, 50 and 58 micrograms/100 ml for men, women and men + women, respectively. The validity of the 3rd degree regression assumption as a tool to calculate a threshold from experimental or epidemiological data is discussed.

Adult↗

Urinary phenylmercapturic acid as a marker of occupational exposure to benzene.

A hand-saving HPLC method to measure urinary phenylmercapturic acid (PMA) was developed which allows about 35 PMA determinations per day. The method involves conversion of pre-PMA to PMA by the addition of sulfuric acid to a urine sample, extraction into an ether-methanol mixture followed by condensation under a nitrogen stream. The condensate was introduced to a ODS-3 column in a HPLC system, and PMA in the column was eluted into a mobile phase of acetonitrile: methanol: perchloric acid: water. The elution of PMA was monitored at 205 nm. One determination will be completed in 40 min. The method was applied to analysis of end-of-shift urine samples from 152 workers exposed up to 210 ppm benzene, 66 workers exposed to a mixture of benzene (up to 116 ppm) and toluene + xylenes (up to 118 ppm), and 131 non-exposed controls of both sexes. A linear regression was established between time-weighted average intensity of exposure to benzene and urinary PMA. From the regression, it was calculated that urinary PMA level will be about 6.4 mg/l after 8-hour exposure to benzene at 100 ppm, and that PMA in urine accounted for about 0.1% of benzene absorbed. No effects of sex, age, and smoking habit of individuals were detected, and the effect of co-exposure to toluene + xylenes at the levels comparable to that of benzene was essentially nil, which indicates an advantage of PMA as a benzene exposure marker over monoto tri-phenolic metabolites or t,t-muconic acid.

Acetylcysteine↗

Nuclear accumulation of p53 protein and apoptosis induced by various anticancer agents, u.v.-irradiation and heat shock in primary normal human skin fibroblasts.

Relationship between nuclear accumulation of p53 protein and apoptosis induced by both DNA damaging agents (ultraviolet-irradiation and anticancer agents) and heat shock in normal human skin fibroblasts was investigated. Nuclear accumulation of p53 protein and apoptosis were induced dose-dependently by u.v. -irradiation and anticancer agents. Regarding heat shock treatment, intensive nuclear accumulation of p53 protein was induced by treatment at 43 degrees C for 45 min, but, apoptotic cells were never detected. These results indicated that accumulation of p53 protein and apoptosis induced by DNA damaging agents were considered to have a close relationship and the functions of induced p53 protein are different depending on the stimulating factor.

Antineoplastic Agents↗

[Assessment of the psychological stress experienced before and after the use of a hearing aid in elderly patients].

Hearing aids are useful instruments for elderly patients with impaired hearing. However, the psychological effects of wearing a hearing aid have remained unclear until recently. A study was therefore performed at the Tokyo Metropolitan Geriatric Hospital to determine such effects. Eighteen out of 50 questions included in the "Psychological Stress Response Scale (PSRS)" were selected and used to produce a questionnaire. The questionnaire was then given to and completed by 31 elderly patients who received and willingly used hearing aids. Of these patients, 20 were female and 11 were male. Their average age was 80.4 years (+/- 5.3 years ranging from 66-89 years). The questionnaire was completed by each patient on two separate occasions: before the hearing aids were fitted and after. In addition to the PSRS questionnaires, a second "hearing satisfaction" questionnaire was also completed, both before and after the hearing aids were fitted. The scores for depression, anxiety and anger were significantly lower after the hearing aid had been fitted. The score for depression showed a particularly distinctive decrease. The statistics also showed that the use of a hearing aid produced a significant improvement in the level of satisfaction patient's felt regarding their hearing. We conclude that the use of hearing aids by elderly patients not only alleviates their dissatisfaction with being unable to hear, but has additional psychological advantages. These results suggest that the use of a hearing aid not only improves hearing but may also delay or offset the development of dementia. Accordingly, suitable hearing aids should be provided to elderly patients so that they may recover their hearing and benefit from the associated psychological advantages.

Aged↗

[Detection of varicella-zoster virus DNA in tear fluid and saliva of patients with Ramsay Hunt syndrome].

Ramsay Hunt syndrome develops when the varicella-zoster virus (VZV) is reactivated. In the present study, we examined the secretion kinetics of VZV DNA in the tear fluid, submandibular gland saliva and parotid gland saliva of 15 patients with Ramsay Hunt syndrome. The presence of VZV DNA was detected using PCR and a microplate hybridization method. Hybridization signals were measured using the fluorescence density of an enzymatic reaction product using fluoroscan and a system involving streptavidin-conjugated beta-galactosidase. The results were converted into numerical values and used to estimate the number of virus DNA copies. VZV DNA was detected in the tear fluid, submandibular gland saliva and parotid gland saliva of the Ramsay Hunt syndrome patients. The rate of VZV DNA detection in the submandibular gland saliva was 72%, and the detection rate in the parotid gland saliva was 57%. The detection rate in the tear fluid was 27%, which is significantly lower than other two detection rates. Regarding the submandibular gland saliva and the parotid gland saliva, the VZV DNA was detected in samples collected at a comparatively early stage of onset. In the tear fluid, the detection rate increased significantly in samples collected 2 weeks after onset or later. Thus, differences in the detection rate were observed depending on the type of secretory gland and the timing of the sample collection. The VZV DNA in the tear fluid is thought to derive from the ganglion trigeminale. The increase and decrease in the number of VZV DNA copies detected in samples collected at different times is considered to substantiate VZV reactivation in Ramsay Hunt syndrome.

Adult↗

[Statistical efficiency of the object recognition with wire-frame stimuli].

To investigate whether internal object representations in the brain are 2D or 3D, we measured discrimination thresholds and calculated statistical efficiencies in the object recognition task based on the ideal observer analysis. Stimulus images were created by orthographic projection of 3D wire-frame objects on a fronto-parallel plane. The discrimination task with the wire-frame stimuli was performed in the monocular (Experiment 1) and the binocular (Experiment 2) conditions. The results indicate that the subjects' statistical efficiencies relative to the 2D ideal observer exceeded 100%, suggesting that the internal object representations should be 3D. In addition, the results revealed that the object type with high-level symmetry led to better discrimination in both experiments. Furthermore, the interaction between 3D cue values and the object regularity was suggested to cause the viewpoint dependency.

Adult↗