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Biomedical subjects

I Fujimoto

Publications and source records attributed to I Fujimoto.

At least 37 records · Page 2Linked to original sources

Measurement of hemodynamics of auditory cortex using magnetoencephalography and near infrared spectroscopy.

Near infrared (NIR) spectroscopy, a non-invasive optical method for monitoring hemodynamics, was applied to record evoked auditory response of the human brain. Our newly developed system detected the amount of oxygenated and deoxygenated hemoglobin in the area of the local brain located beneath the probes. In the study, we used magnetoencephalography (MEG) and NIR spectroscopy to observe the blood component change near the auditory cortex. The sound stimulus of 1 kHz sine wave at 70 dB SPL was used to elicit evoked responses in both experiments. The active region of the auditory cortex was determined by MEG, and the same area was examined by the NIR system. The results from the NIR experiments showed significant increases of total hemoglobin and deoxygenated hemoglobin, indicating that both blood flow and oxygen consumption at the cortical area increased in response to the sound stimuli. The NIR recordings at the two different depths revealed that the increases of local blood flow and oxygen consumption were observed at depths ranging between 20 and 30 mm from the scalp.

Adult↗

Tissue extract from dopamine-depleted striatum enhances differentiation of cultured striatal type-1 astrocytes.

The effects of tissue extract from dopamine (DA)-depleted striatum (lesion extract, L-ext) on morphological and electrophysiological natures of cultured striatal astrocytes were investigated. L-ext treatment suppressed the proliferation of type-1 astrocytes. They became fibrous in a concentration-dependent manner. These changes were not observed in type-2 astrocytes. By whole cell patch-clamp recording, two kinetically and pharmacologically distinct voltage-activated potassium currents, A current and delayed rectifier, were identified. L-ext treatment enhanced both currents in type-1 astrocytes, but only A current in type-2. Data suggest that in tissue extract from DA-depleted striatum, there are increased trophic activities that promote the differentiation of type-1 astrocytes.

Animals↗

Labeling and identification of living donor cells in brain slices of recipient hemiparkinsonian model rats for physiological recordings: methods for physiological assessments of neural transplantation.

Physiological properties of grafted neurons, such as membrane and intr acellular properties, have not been reported. To fill this lack in knowledge, physiological recordings from the identified grafted cells are required. Fluorescent latex microspheres (FLM) are non-toxic and stable, and thus seem suitable for long-term labeling of donor cells. Therefore, we tested the feasibility of labeling with FLM to identify living donor cells in the recipients' brain slices. We also tested if physiological recordings from the identified cells are possible or not. Cell suspensions were prepared from the substantia nigra (SN) of Embryonic Days 15 or 16 rats with enzymatic and mechanical trituration. Cell suspensions were then incubated with 0.5% FLM for 30 min to 2 h. The longer cells were incubated, the more FLM were taken up. The FLM-labeled SN cell suspensions were injected in the striatum of the hemiparkinsonian model rats. Eight to 13 weeks later, 150-mu m thick coronal brain slices including the graft track were prepared from the recipients. Slices were kept in vitro for several hours. Grafted cells could be clearly identified in the slice preparations by the uptake of FLM under a fluorescence microscope. Voltage-dependent currents and intracellular Ca2+ transcients were successfully recorded from the identified grafted neurons. It is suggested that labeling and identification of living donor cells with FLM is feasible and thus can provide a powerful tool to study the mechanisms underlying graft-induced amelioration of neurological deficits in parkinsonism by enabling physiological assessments of grafted cells.

Animals↗

Microtubule-associated protein 2 expressing COS7 cells are resistant to argyrophilia under oxygen- and glucose-free condition.

Argyrophil III silver impregnation is a very sensitive method to detec t the early damage to neurons following brain ischemia. The argyrophil III staining and microtubule-associated protein 2 (MAP2) immunocytochemistry were performed on PC12D cells and MAP2C cDNA-transfected COS7 cells to detect the changes cytoskeletal proteins (microtubules/MAP2). After exposing these cells to simulated ischemic condition (oxygen and/or glucose free), the correlation between the appearance of the argyrophilia and the disappearance of MAP2 was investigated. The PC12D cells expressed very low MAP2 and became argyrophilic very easily depending on the degree of the ischmeia-like insult, whereas MAP2C cDNA-transfected COS7 cells expressed a higher level of MAP2C and were resistant to argyrophilia, although the diameter of their immunoreactive processes became thinner. Thus, when MAP2C is expressed at a higher level, cells became resistant to argyrophilia, suggesting a correlation between the argyrophilia and the damage on microtubules and MAPs.

Animals↗

GTP-binding protein activation underlies LTP induction by mast cell degranulating peptide.

Mast cell degranulating peptide (MCD) induces long-term potentiation (LTP) in the CA1 region of the hippocampus. MCD has been shown to bind to a voltage-dependent A-type potassium channel with high-affinity (less than 1 nM). However, the concentration necessary to induce LTP is more than 500 nM, suggesting that some other functions of MCD are also fundamental to LTP induction. The concentration of MCD required for LTP induction was greatly reduced by preactivating G proteins. This fact suggests that G protein activation by MCD also plays an important role in LTP induction. MCD-binding proteins were purified from rat brain. G proteins were found to exist in a non-denatured state in this affinity-purified fraction. When reconstituted into a planar lipid bilayer membrane, a potassium-selective and voltage-dependent current could be observed. This channel was blocked by MCD at a high concentration equal to the effective concentration for G protein activation. Addition of GTP-gamma-S significantly blocked the reconstituted current. Thus, we identified a pathway for LTP induction by MCD in which high concentrations of MCD activate G protein which in turns leads to blocking of a potassium channel.

Adenosine Diphosphate Ribose↗

3-Nitropropionic acid produces striatum selective lesions accompanied by iNOS expression.

Systemically administered 3-nitropropionic acid (3-NPA) that inhibits the mitochondrial oxidative phosphorylation induces selective lesions in the striatum. To investigate the nature of these selective lesions, we administered 3-NPA (20 mg/kg, s.c. daily for 2 or 3 days) to Wistar rats and investigated the behavioral disturbance, striatal lesions and their variations after modulating the activity of nitric oxide synthase (NOS). On the second or third day of 3-NPA administration, half the animals manifested behavioral disturbances (paddling, rolling, tremor, abnormal gait, and recumbence). A strong extravasation of immunoglobulin G (IgG) and a decrease in immunoreaction for glial fibrillary acidic protein (GFAP) were detected, and iNOS-like (iNOS-L) immunoreactive small cells appeared in the lateral and central striatum especially around the vessels. A week later, lesions lacking GFAP-immunoreaction were detected in the striatum in survived animals. Pretreatment with N-nitro-L-arginine methyl ester (L-NAME) along with each injection of 3-NPA did not improve the behavioral disturbances nor the survival rate, but attenuated the extravasation of IgG and iNOS-L immunoreaction. Pretreatment with aminoguanidine or FK506 improved the behavioral symptoms and survival rate. Extravasation of IgG and expression of iNOS-L immunoreactivity were attenuated, and the striatal lesion was reduced. Data indicate the involvement of NO in the high vulnerability of the striatum, and that iNOS, one of inflammatory markers, is induced following exposure to 3-NPA.

Animals↗

A case of ureteral reflux identified by ultrasound.

Reflux nephropathy is known to be a major cause of renal failure in children. Vesico-ureteral reflux is usually diagnosed by voiding cysto-urethrography (VCG). However, it has been observed that conventional VCG is not always reliable for the diagnosis of ureteral reflux. In the case of a 5 year old girl with recurrent febrile urinary tract infection, VCG showed no ureteral reflux. Urodynamic study revealed a large bladder capacity and significant residual urine. Renal scintigram delineated a right renal scar. Simple ultrasound examination with videotape recording during voiding definitely demonstrated the presence of significant ureteral reflux when she voided, that is, there was marked dilatation of the right distal ureter and ballooning of the right renal pelvis on voiding, and quick refilling of the bladder concomitantly with the disappearance of the pelvic ballooning. Therefore, an ultrasound during voiding may be useful for diagnosing ureteral reflux in patients where a VCG does not reveal reflux.

Child, Preschool↗

Present status and research activities of cancer registries in Japan.

Population-based cancer registries in Japan were first established in the cities of Hiroshima and Nagasaki in 1957-1958 for assessing radiation effects and in Miyagi in 1959 for promoting epidemiological researches, while most other prefectures in Japan set up cancer registries as a part of their own cancer programs. This resulted in the broader use of registry data in Japan. In 1975, the Research Group for Population-based Cancer Registration in Japan was first organized with a research grant under the National Cancer Research Promotion Program. Since then, continuous efforts have been made by the Group to improve the quantity and quality of registry data and to develop methodologies to utilize it. Studies being conducted using registry data cover (1) descriptive epidemiology, (2) analytical epidemiology, (3) evaluation of screening programs, and (4) evaluation of regional cancer medical care. In 1992, 32 regional cancer registries which were operating in Japan set up the Japanese Association of Cancer Registries. However, there are still many difficulties to overcome in order to achieve completeness of reporting in registries. Further improvement of reporting rate, together with standardization of registry data are left for future efforts.

Epidemiology↗

Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

Animals↗

Survival rates of childhood cancer patients in Osaka, Japan, 1975-1984.

Survival rates for childhood cancers were analyzed with a total of 2,209 cases who were registered in a population-based cancer registry in Osaka, Japan in 1975-1984. These cases were reclassified according to Birch's classification and the survival rate of each diagnostic group was calculated by Kaplan-Meier methods. Death certificate-only cases, which amounted to 3.9% of all incidence, were excluded from the calculation. The five-year cumulative survival rate for both sexes was 46% for all cancer children. Among 12 major diagnostic groups, the most favorable survival was seen in retinoblastoma (87.5%), followed by renal tumors, epithelial neoplasms, and gonadal and germ-cell tumors. The outcome was unfavorable in leukemias, sympathetic nervous system tumors, hepatic tumors and malignant bone tumors. Comparing the survival in 1975-1979 with that in 1980-1984, the rate for all childhood cancer rose from 41% to 51%. Improvement in survival was also observed in 4 groups; acute lymphocytic leukemia, acute non-lymphocytic leukemia, non-Hodgkin's lymphoma and osteosarcoma. One attributable factor for the rise of survival was proved to be improvement of medical treatment by Cox's hazard model analysis. Comparison of survival rates in Osaka with those in England and the U.S. revealed that the prognosis for acute lymphocytic leukemia and acute non-lymphocytic leukemia was less favorable in Osaka than in England and the U.S.

Adolescent↗

[Effects of long-term administration of tamoxifen on vaginal epithelium and complications of endometrial lesions in breast cancer patients].

The effects of tamoxifen (TAM) on 56 postoperative breast cancer patients who were orally administered TAM and followed up at Cancer Institute Hospital from 1989 to 1992 were studied retrospectively. The maturation index (MI) and karyopyknotic index (KPI) were employed to investigate the effects of TAM on vaginal epithelial cells cytologically, and the patients were also monitored for complications. The results were as follows. (1) The relationship between the duration of TAM therapy and the changes in MI and KPI were analyzed. It was found that, for the MI, intermediate cells (IMT) increased and superficial cells (ST) decreased during TAM administration for up to 4 years, but when the TAM therapy was continued for longer than 4 years, IMT showed a gradual decrease and ST increased gradually. The KPI values showed similar changes. (2) Studies of the endometrium (26 cases) revealed a tendency for few of the long-term administration cases to show a picture of atrophy. Of the total of 56 patients, endometrial lesions were observed in five cases (8.9%), consisting of endometrial cancer in three and cystic glandular hyperplasia in two. The mean duration of TAM administration to these five patients was 54 (+/- S.D.26.8) months. These data indicate that long-term oral administration of TAM involves the possibility of having an estrogenic effect on the vaginal epithelium and the uterine endometrium.

Administration, Oral↗

[Clinical and pathological study of 24 patients with fallopian tube malignancy].

Clinical and pathological analyses were carried out in 24 patients with fallopian tube malignancy. The results are as follows: 1. Twenty-three patients had adenocarcinoma (well differentiated 11, moderately 6, poorly 6) and one patient had MMT (Müllerian mixed tumors). 2. There were 11 cases in stage I, 4 in stage II, 8 in stage III and 1 in stage IV according to Dodson's classification. 3. Atypical genital bleeding was the most common symptom, whereas 12.5% of patients had no symptoms. 4. Positive rates in cytology were 25.0% in cervico-vaginal smear and 55.0% in endometrial aspiration cytology. 5. The overall 5-year survival rate is 60.0%. The 5-year survival rates for stage I/II and stage III/IV were 88.9% and 16.7%, respectively. 6. The relapse rate of 16 patients treated with complete surgery was 25.0% (well differentiated 11.1%, moderately 0%, poorly 75.0%). Based on these observation, it is likely that patients with stage I/II have a good prognosis, however, patients with poorly differentiated adenocarcinoma have a high relapse rate, indicating that intensive adjuvant chemotherapy would be necessary in these cases. Cytologic examination, particularly endometrial aspiration cytology, is an effective method to use in detecting cases with fallopian tube malignancy early.

Adenocarcinoma↗

Hypothalamic neurons are resistant to the intoxication with 3-nitropropionic acid that induces lesions in the striatum and hippocampus via the damage in the blood-brain barrier.

Modulation of the function of the blood-brain barrier (BBB) in the hypothalamus was investigated after the intoxication with 3-nitropropionic acid (3-NPA) that inhibits the succinate dehydrogenase. 3-NPA was administered to rats for three days. Following transcardial perfusion, brain sections were studied by immunohistochemistry. On the 2nd or 3rd day after 3-NPA, strong immunoreactions for blood-borne macromolecules, IgG, appeared in the striatum and hippocampus. Glial fibrillary acidic protein (GFAP) positive astroglias distributed heterogeneously, and induced nitric oxide synthase (iNOS) positive cells appeared around the vessels. A week later, bilateral lesions were detected in these areas. In the hypothalamus, there appeared a moderate immunoreaction for IgG, but no expression of iNOS. GFAP positive astroglias were rich especially around the vessels, and no loss in microtubule-associated protein 2 (MAP2) immunoreaction was detected, suggesting an intact BBB structure and no neuronal loss following 3-NPA intoxication. Data indicate that hypothalamic neurons are resistant to 3-NPA that induces specific lesions in the striatum and hippocampus via the damage in the BBB.

Animals↗

Allelotype of uterine cancer by analysis of RFLP and microsatellite polymorphisms: frequent loss of heterozygosity on chromosome arms 3p, 9q, 10q, and 17p.

Cancers in which mutations have been identified in putative tumor suppressor genes, such as the TP53 gene, the retinoblastoma (RBI) gene, the adenomatous polyposis coli (APC) gene, and the Wilms tumor (WTI) gene, frequently show loss of the corresponding allele on the homologous chromosome. To identify locations of tumor suppressor genes involved in uterine cancer, we examined loss of heterozygosity (LOH) by using genomic probes detecting RFLPs in 35 uterine cancers at 29 loci throughout the genome, and with highly informative microsatellite markers in 21 uterine cancers at nine putative or known tumor suppressor gene loci. High frequencies of allelic loss found at loci on 3p (71%), 9q (38%), 10q (35%), and 17p (35%) suggest that tumor suppressor genes involved in uterine carcinogenesis exist in these regions. There were no significant differences in frequencies of LOH between cancers of the uterine cervix and cancers of the uterine endometrium at any of the loci tested.

Adenocarcinoma↗

Combined assay of serum levels of CA125 and CA19-9 in endometrial carcinoma.

Serum levels of CA125 and CA19-9 were examined in 225 cases with endometrial carcinoma before treatment and 32 cases with recurrent endometrial carcinoma. The positive rates in the 225 cases were 27.1% for CA125, 24.0% for CA19-9, and 38.7% for the combined assay. The serum levels of both CA125 and CA19-9 significantly increased with surgical staging. The presence of lymph node metastasis and extrauterine spread exhibited a marked influence on the serum levels of both CA125 and CA19-9. Myometrial invasion and vessel permeation also increased serum levels of CA125, whereas peritoneal cytology and adnexal metastasis exhibited no influence on CA125 levels or CA19-9 levels. Twenty-five of 33 cases who showed either more than 100 U/ml of CA125 level or more than 100 U/ml of CA19-9 level were classified as surgical stage III or IV. The combined assay demonstrated a 71.9% positive rate at the time of detection of the recurrence (65.6% for CA125, 43.7% for CA19-9). In 34.4% of the 32 recurrent cases, elevated levels of the tumor markers were the first sign of recurrence. These data indicate that the use of CA19-9 in combination with CA125 is noteworthy in the management of patients with endometrial carcinoma.

Adult↗

Prevalence of second generation antibody to hepatitis C virus among voluntary blood donors in Osaka, Japan.

To clarify the demographic characteristics of the prevalence of hepatitis C virus (HCV) infection in Osaka, Japan, where hepatocellular carcinoma is common, we investigated the screening data of antibody to HCV (anti-HCV, DAINABOTHCVPHA, second generation assay) in 197,600 voluntary blood donors residing in Osaka. The study found that age-standardized prevalence of anti-HCV was significantly higher than that of HBsAg (2.25 cf 0.86 percent among males, P < 0.001; 2.17 cf 0.55 percent among females, P < 0.001. It was much higher in the blood donors aged 55-64 years than in those aged 16-54 years (8.49 cf 1.32 percent among males, P < 10(-5); 7.26 cf 1.42 percent among females, P < 10(-5)). The prevalence of anti-HCV among males was significantly higher than that of females in the younger (25-34 years) generations (1.02 to 1.49 percent cf 0.71 to 1.13 percent, P < 0.05). A similar tendency was observed in the prevalence of high-titer (> or = 2(12)) anti-HCV. The number of coinfection (both HBsAg and anti-HCV seropositive) was very small, and it was not statistically different from the expected number.

Adolescent↗

Primary liver cancer incidence-rates related to hepatitis-C virus infection: a correlational study in Osaka, Japan.

Osaka, Japan, has one of the highest, primary liver cancer (PLC) incidence-rates in the world, although hepatitis-B virus (HBV) is not endemic. This paper addresses the question of whether the PLC-incidence variation within Osaka Prefecture is due to differences in the prevalence of hepatitis-C virus (HCV) infection. The screening data of antibody to HCV (anti-HCV) and of hepatitis-B virus antigen (HBsAg) in 111,069 male blood-donors, and the incidence data of male PLC obtained from the Osaka Cancer Registry were examined. In a multiple-weighted regression analysis, the age-standardized incidence rate of PLC in the 61 counties within Osaka was correlated significantly with the age-standardized prevalence of anti-HCV with adjustment for that of HBsAg (regression coefficient [RC] = 7.26, P < 0.0001). This finding was consistent with the relationship between the PLC incidence rate and the prevalence of high-titer (> or = 2(12)) anti-HCV (RC = 11.18, P < 0.0001). There was significant association between the prevalence of HBsAg and the PLC incidence rate with adjustment for that of anti-HCV (RC = 7.08, P = 0.018). These findings suggest that the PLC-incidence variation within Osaka is correlated with the geographic pattern of HCV infection as well as that of HBV infection among the residents.

Adolescent↗

Incidence of childhood cancer in Osaka, Japan, 1971-1988: reclassification of registered cases by Birch's scheme using information on clinical diagnosis, histology and primary site.

In 1971-1988, 4,021 malignant tumors occurring among children under 15 years of age were registered in the Osaka Cancer Registry, a population-based registry which covers Osaka Prefecture, Japan. These patients were reclassified into 12 diagnostic groups by Birch's scheme using information on clinical diagnosis, histology and primary site. The annual age-standardized incidence rate for childhood cancer per million children was 130.3 for males and 104.9 for females in 1971-88. Comparing the incidence rates for both sexes in 1981-88 with those in 1971-80 in Osaka, we observed a significant decrease of acute non-lymphocytic leukemia (ANLL) and a significant increase of all cancers, acute lymphocytic leukemia, non-Hodgkin lymphoma, sympathetic nervous system tumors, soft-tissue sarcomas, and gonadal and germ-cell tumors. Age-standardized incidence rates in around 1971-80 of the above-mentioned diagnostic groups were compared among 4 population-based registries; Osaka, Miyagi (Japan), SEER (U.S.), and the National Registry of Childhood Tumors (England and Wales). Rates for ANLL and gonadal and germ-cell tumors were higher and those for other diagnostic groups were lower in Osaka, especially for Hodgkin's disease. Thus, in 1980-88 in Osaka, rates for Hodgkin's disease remained low and rates for gonadal and germ-cell tumors increased, though rates for other cancers appeared to resemble the levels in caucasian populations. The incidence of childhood cancer in Japan was estimated according to the diagnostic groups in Birch's scheme.

Adolescent↗