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Biomedical subjects

R Nishimura

Publications and source records attributed to R Nishimura.

At least 109 records · Page 6Linked to original sources

Establishment and characterization of two cell lines derived from canine spontaneous osteosarcoma.

Two new canine osteosarcoma cell lines were established. One (OOS) was established from a 10-year-old female maltese dog with mandibular osteosarcoma and the other (HOS) from a 7-year-old male mongrel dog with scapular osteosarcoma. Histopathological types of OOS and HOS were mixed and fibroblastic cell type, respectively. Transmission electron microscopic features of HOS revealed prominent rough endoplasmic reticulum, suggesting higher malignancy comparing to OOS. Doubling time of OOS and HOS were 45.0 +/- 0.5 hr and 42.0 +/- 0.1 hr, respectively. Alkaline phosphatase activities of OOS and HOS were quite low. Histological features of tumor tissues produced by transplantation of these cells into nude mice were identical to those of original osteosarcomas.

Alkaline Phosphatase↗

Combination of interleukin-6 and soluble interleukin-6 receptors induces differentiation and activation of JAK-STAT and MAP kinase pathways in MG-63 human osteoblastic cells.

Studies on the role of interleukin-6 (IL-6) in bone metabolism have been accumulating. However, its effects on osteoblasts are still unclear because the results are conflicting depending on the study models employed. We reasoned that these conflicting data are due to variable expression levels of membrane-bound IL-6 receptors (IL-6Rs). In the present study, we found that IL-6 in combination with soluble IL-6R (sIL-6R) consistently caused a marked elevation of alkaline phosphatase and a decrease in proliferation in the human osteoblastic cell line MG-63, which expressed no detectable membrane-bound IL-6R and failed to respond to IL-6. These effects of IL-6/sIL-6R were blocked by neutralizing antibodies to the IL-6 signal transducer gp130, suggesting an involvement of IL-6 signaling in the elicitation of the effects of IL-6/sIL-6R. Upon stimulation with IL-6/sIL-6R, the gp130, cytoplasmic Janus kinases JAK1 and JAK2 were tyrosine phosphorylated. Moreover, signal transducers and activators of transcription STAT1 and STAT3 were also tyrosine phosphorylated, translocated to the nucleus, and bound to the putative STAT-binding DNA elements. In addition, mitogen-activated protein (MAP) kinase was also activated in response to IL-6/sIL-6R These data demonstrate that sIL-6R may enhance the responsiveness of MG-63 cells to IL-6. Thus, IL-6 in collaboration with sIL-6R may modulate differentiation and proliferation of osteoblastic cells, presumably by activating two distinct signaling pathways of JAK-STAT and MAP kinase.

Alkaline Phosphatase↗

Puberty, IDDM, and death in Japan. Diabetes Epidemiology Research International Study Group.

OBJECTIVE: To investigate the impact of age at onset on the prognosis of childhood IDDM in Japan. RESEARCH DESIGN AND METHODS: The study population consisted of 987 prepubertal-onset and 345 pubertal-onset IDDM cases who were registered by two nationwide surveys and who were diagnosed between 1965 and 1979. The living status was identified as of 1 January 1990 with the ascertainment rate of 96.5%. Prognosis was evaluated by cause- and age-specific mortality rates and life-table analyses; in addition, an attained-age-matched case-control study was analyzed by conditional logistic regression. RESULTS: The adjusted mortality rates per 100,000 person-years for the pubertal-onset cases were significantly higher than those of the prepubertal-onset cases (835 [95% CI 573-1,168] vs. 391 [283-526]). Life-table analyses revealed that the survival rate of the pubertal-onset cases was lower than that of the prepubertal-onset cases for each observation period. Life-table analyses after the age of 15 years indicated that the prognosis of pubertal cases was almost the same as that of the prepubertal cases despite having a shorter duration of diabetes. The attained-age-matched case-control study indicated that the pubertal onset was a potent determinant of death. CONCLUSIONS: The prognosis of pubertal-onset IDDM was considerably poorer than that of prepubertal-onset IDDM.

Accidents↗

[Prognostic effect of PyNPase (pyrimidine nucleoside phosphorylase) activity in breast cancer].

To clarify the clinical significance of PyNPase (Pyrimidine Nucleoside Phosphorylase)/ PD-ECGF activity in breast cancer, we examined the possible correlation of PyNPase activity to clinicopathological features and prognosis in 195 patients with primary breast cancer between January 1992 through December 1993. The mean PyNPase activity of primary breast cancer, assayed by ELISA method, was 140.6 U/ml, which was between that of benign breast disease (18.2) and recurrent tumors (270.9). In histological type of breast cancer, tumors with solid-tubular carcinoma had significantly higher levels of PyNPase activity. The activity of ER negative or aneuploid tumors was higher than that of ER positive or diploid tumors, respectively. And there was a significant relationship between PyNPase activity and proliferative activity determined by S-phase fraction (SPF) or DNA polymerase alpha. These findings suggested that PyNPase activity was associated with the degree of malignancy. As regards prognosis, in lower SPF (< 16%) group, patients with higher PyNPase activity had significantly lower disease--free survival rates, whereas those with higher activity had a favorable prognosis in the higher SPF (> or = 16%) group. The contradiction might be explained by the possibility that 5-FU derivatives were effective only in patients with high SPF and PyNPase activity, as all patients were treated by a regimen containing 5-FU derivatives. We suggest that PyNPase activity is associated with progression and proliferation of breast cancer, and that it may be useful for prediction of prognosis and therapeutic efficacy of 5-FU derivatives.

Adult↗

MR of denervated tongue: temporal changes after radical neck dissection.

PURPOSE: The purpose of this study was to evaluate the temporal changes of MR imaging in the denervated tongue after a radical neck dissection. METHODS: One hundred seventy-four consecutive MR studies in 116 patients with radical neck dissections for malignant tumors of the head and neck were evaluated retrospectively. Patients with tumors involving the tongue or hypoglossal nerve were not included in this study. RESULTS: Abnormal signal intensity and/or hemiatrophy on the side of the tongue operated on was seen in 22 patients who had hypoglossal paralysis after radical neck dissection. The denervated side of the tongue appeared hypointense to hyperintense relative to the normal side on T1-weighted images and hyperintense on T2-weighted images. Signal intensity ratios of the abnormal to normal muscles were 0.9-1.6 on T1-weighted images and 1.3-2.8 on T2-weighted images. High signal intensity on T1-weighted images appeared 5 months or more after the dissection, whereas on T2-weighted images, the most prominent increases in signal intensity appeared in the first several months after denervation. Hemiatrophy of the tongue was observed on MR images obtained more than 6 months after surgery. CONCLUSION: MR findings in the denervated tongue are compatible with histologic changes and are characterized by an enlarged extracellular fluid space or fatty infiltration. The pattern of signal intensity and the degree of hemiatrophy suggest the duration of denervation.

Adult↗

[Effect of 5'-DFUR used concurrently in radiotherapy and immunotherapy uterine cervical cancer--pilot study. Study of 5'-DFUR for Uterine Cervical Cancer].

We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR and SPG for patients with uterine cervical cancer, which was regarded as suitable for cases of radiotherapy. The patients were randomly allocated into group A (5'-DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or IV a with histologically diagnosed primary squamous cell carcinoma of uterine cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy-evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%-97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety-evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No significant difference in efficacy and safety was observed between the two treatment groups. These results suggested that the combination therapy of radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness must be confirmed for advanced squamous cell carcinoma of uterine cervix. To confirm dose dependency of 5'-DFUR, it seems further consideration with more patients is needed.

Adjuvants, Immunologic↗

[A case of advanced hepatocellular carcinoma responding to suppository of Tegafur].

We report a case of advanced hepatocellular carcinoma (HCC) successfully controlled by the suppository administration of Tegafur alone. Five months after initiation of the drug, excellent reduction of tumors and decrease of serum alpha-feto-protein (AFP) level were seen without any side effects. Also, twenty-four months after of the treatment, no regrowth of tumors or increase in the serum AFP level was seen. Because Tegafur is a time-dependent agent, advanced HCC may be controlled by continuous administration for a long period.

Antimetabolites, Antineoplastic↗

[A case of neuroblastoma with abnormal LD isoenzyme].

We encountered a patient with neuroblastoma showing remarkably high total LD activity (12,585 IU/l). His liver and heart function was normal. In the serum LD isoenzyme pattern, LD1 was increased, and LD2 extra band (LD2 ex) was observed on the negative pole side of LD2. However, LD2 ex was absent in erythrocytes of the patient, which demonstrates the exclusion of genetic factors. Neither the enzyme counter current method or immunofixation showed immune complexes, excluding anomalies. The LD isoenzyme in a metastatic lymphnode lesion before treatment showed increased LD1. The LD isoenzymes in the tissue, removed after 5 courses of chemotherapy, showed predominance of LD3 and absence of LD2 ex. Rapid decreases in the serum total LD activity and LD1 fraction and the disappearance of LD2 ex after chemotherapy suggest that these changes in the two LD fractions are associated with production of abnormal LD (LD2 ex) by the tumor.

Adrenal Gland Neoplasms↗

MR sialography using half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences.

We describe our preliminary experience with the half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences for MR imaging of the salivary gland ducts. In the majority of patients, the main parotid and/or submandibular gland ducts and large branches within the glands were detectable on MR images obtained in 2 seconds per section and within 3 minutes for the entire examination. MR sialography using HASTE sequences can be combined with conventional MR studies for the salivary glands.

Adult↗

[Two cases of spontaneous hemopeumothorax].

We experienced two cases of spontaneous hemopeumothorax. One case was a 17-year-old male with a complaint of back pain. A chest tube for rapid pleural evacuation disclosed hemorrhage as much as 3,000 ml, with drainage volume being gradually decreased. He needed about two month's admission because of complication of pyothorax. The other case was a 46-year-old male with a complaint of chest pain. Chest X-P gave the diagnosis of right hemopeumothorax. Thirty minutes later, he became shock, and five hours later, we performed an emergency intervention of video-assisted thoracoscopic surgery (VATS). Bleeding site of a funicular structure from the parietal pleura was stopped by clipping, with excellent postoperative results. Spontaneous hemopeumothorax is often indicated for early surgical intervention because of association with a high risk of hemorrhagic shock. In such a case, VATS is very helpful.

Adolescent↗

Extracellular calcium-sensing receptor in rat oligodendrocytes: expression and potential role in regulation of cellular proliferation and an outward K+ channel.

A G protein-coupled, extracellular calcium (Ca(0)2+)-sensing receptor (CaR) cloned from parathyroid, kidney, and brain plays crucial roles in systemic calcium metabolism. In brain, the CaR is located in nerve terminals as well as in fiber tracts, where it may be expressed in glia. Moreover, there is Ca2+- and K+-dependent communication between axons and oligodendroglia. To investigate further the potential role of the CaR in oligodendroglia, we studied expression of CaR mRNA and protein as well as the effects of CaR agonists on cellular proliferation and Ca2+-activated K+ channel activity in immature rat oligodendrocytes in primary culture. Reverse transcriptase polymerase chain reaction and sequencing of CaR transcripts from oligodendrocytes revealed >99% sequence identity with the rat kidney CaR. Northern analysis demonstrated 7.5 and 4.1 kb transcripts in oligodendrocytes, similar to those in rat parathyroid and kidney, while Western analysis and immunocytochemistry with CaR-specific antisera showed the presence of CaR protein. Immunocytochemically, the CaR was colocalized with galactocerebroside in the cultured oligodendrocytes. Raising Ca(0)2+ from 1.8 to 4.8 mM or addition of the polycationic CaR agonist neomycin (300 microM) modestly but significantly increased [3H]-thymidine incorporation into oligodendrocytes. Elevating Ca(0)2+ from 0.75 to 3.0 mM or addition of 100 microM neomycin also produced 2-2.5-fold increases in the open state probability (Po) of an outward K+ channel with a unitary conductance of 88+/-5 pS. Taken together, our data show that the CaR is expressed in immature oligodendrocytes and may be functionally linked to cellular proliferation and an outward K+ channel potentially contributing to local ionic homeostasis in the vicinity of oligodendroglia.

Animals↗

Molecular heterogeneity of hCGbeta--related glycoproteins and the clinical relevance in trophoblastic and non-trophoblastic tumors.

We analyzed immunoreactive hCG/hCGbeta (IR-beta) in the sera and urine of patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme immunoassays (EIAs) specific for intact hCG, free hCG beta, and beta-core fragment of hCG (beta-CF). In trophoblastic diseases, while intact hCG and free hCGbeta were contained in both serum and urine, the beta-CF could be detected only in the urine of the patients. The relative contribution of the beta-CF to the total urinary IR-beta accounted for about 30-50% in normal early pregnancy and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that intact hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic diseases, and suggested that the ratios of intact hCG, free hCGbeta, and beta-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-beta was also investigated in the sera and urine of the patients with cervical, endometrial, ovarian, lung, and bladder carcinomas. We found that even when IR-beta could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-beta. The chromatographic study indicated that these urinary IR-beta were essentially attributed to beta-CF, leading to the evaluation of urinary beta-CF as a tumor marker. The positive rated of urinary beta-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG beta by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when beta -CF is measured in urine of the patients.

Antibodies, Monoclonal↗

MR evaluation of radiation otomastoiditis.

PURPOSE: The purpose of this study was to evaluate the incidence of radiation otomastoiditis, on using T2-weighted magnetic resonance (MR) imaging, in relation to radiation fields, doses, intervals, and clinical symptoms after radiotherapy that included the temporal bone in the fields. METHODS AND MATERIALS: We performed follow-up MR examinations at various intervals after radiotherapy including the temporal bones for 270 ears of 114 patients with various diseases of the head and neck and intracranial regions. The middle ear and mastoid air cells on T2-weighted images were scored as follows; showing no high signal intensity, a local high signal intensity area, or a high signal intensity area occupying the entire middle ear and all mastoid air cells. The radiation fields as depicted on the lateral simulator films classed as anterior to the clival line, posterior to the clival line, or both. RESULTS: The incidence of radiation otomastoiditis depicted on T2-weighted MR images increased in the patients who had received irradiation doses of 50 Gy or more. In the patients with doses of less than 50 Gy, the incidence was 18% within 6 months following radiotherapy, 13% at between 6 and 12 months, and 8% after 12 months, whereas it was more than 50% at any period after radiotherapy in the patients with 50 Gy or more. The incidence of radiation otomastoiditis was quite high in the patients whose radiation fields included region both anterior and posterior to the clival line. CONCLUSION: The incidence of radiation otomastoiditis as demonstrated on T2-weighted MR images is increased at irradiation doses of 50 Gy or more. To reduce the incidence of severe radiation otomastoiditis, the irradiation fields of the temporal bone when the dose is 50 Gy or more should be limited to as small as possible. The clival line is considered to be a good landmark in reducing the irradiation field when doses of 60-70 Gy are delivered in curative radiotherapy.

Adolescent↗

Expression of alpha and beta genes of human chorionic gonadotropin in lung cancer.

To confirm the ectopic production of human chorionic gonadotropin (hCG) in lung cancer, we attempted to detect the presence of mRNA transcripts of the alpha and beta genes for hCG in lung cancer tissues obtained from surgical operations. Although we were able to show the presence of hCG beta mRNA transcripts in lung cancer tissue by Northern blot, the sensitivity of the assay was too low for a precise analysis of hCG beta mRNA transcripts in most lung cancers. Using reverse transcription PCR (RT-PCR) and Southern blot analysis, however, various amounts of mRNA transcripts of hCG beta genes 3, 5, 7 and 8 were demonstrated in 9 of the 14 lung cancer tissues examined, while no mRNA transcripts were detectable in 12 normal lung tissues from the same patients. Our results are consistent with a clear difference in serum and urinary hCG beta levels observed between normal subjects and lung cancer patients. The expression of the hCG alpha gene, however, was detected in normal lung tissues more frequently than in lung cancer tissues using RT-PCR Southern blot. Our results strongly suggest the production of hCG beta as being part of the phenotype of malignantly transformed lung cells and further strengthen its superior specificity over intact hCG or hCG alpha as a tumor marker for lung cancers.

Aged↗

Role of dynamic MRI in the evaluation of head and neck cancers treated with radiation therapy.

PURPOSE: To study the usefulness of dynamic magnetic resonance imaging in the evaluation of head and neck cancers treated with radiation therapy. METHODS AND MATERIALS: Seventy-six patients (58 males and 18 females; ages 20-82) with head and neck cancers (10 nasopharyngeal carcinomas, 22 mesopharyngeal carcinomas, 10 hypopharyngeal carcinomas, 16 oral cavity carcinomas, 11 lingual carcinomas, and 7 laryngeal carcinomas) were treated by radiation therapy combined with concomitant low-dose cisplatinum. Magnetic resonance imaging (MRI) was performed before and 2 weeks after the irradiation in all cases. After bolus administration of gadopentetate dimeglumine (Gd-DTPA) (0.1 mmol kg), images were obtained every 30 s (repetition time 200 ms, echo time 16 ms) using a 1.5 or 0.5-T superconductive unit. Biopsy or surgery was performed after radiation therapy and the histologic findings were correlated with the MRI findings (T1, T2, dynamic, and enhanced T1). RESULTS: Complete remission, partial response, and no response were obtained in 18, 36, and 7 cases, respectively. Dynamic MRI correctly diagnosed 17 of the 18 complete remission cases, 33 of the 36 partial response cases, and all of the 7 no-response cases. The accuracy of dynamic MRI, T1-weighted image, T2-weighted image, and Gd-enhanced T1-weighted image was 94.4%, 68%, 82%, and 86%, respectively. CONCLUSION: Dynamic MRI proved to be useful in the evaluation of the radiation therapy of head and neck cancers.

Adult↗

The effect of azelastine on acute radiation dermatitis in mice models.

PURPOSE: In our previous report we described the clinical value of azelastine, an oral antiallergic agent, as an inhibitor of radiation dermatitis. Here we studied the effect of azelastine on normal skin and tumor size after irradiation in a mouse model. METHODS AND MATERIALS: The modifying effects of azelastine on both the degree of radiation dermatitis and antitumoral effect of radiation therapy were investigated in the normal skin as well as in SCC VII tumors of C3H/He mice. The right hind legs, with or without tumors, were irradiated with 20-60 Gy at 0.62 Gy/min. Azelastine was administered via the mouse chow, and acute skin reactions and tumor growth curves were compared between the azelastine and control groups. RESULTS: The acute skin reactions of the azelastine group were significantly less prominent than those of the control group (p < 0.01). At a dose of 40 Gy the dose modification factors were 1.19-1.25. The tumor growth curves of the azelastine and control groups were almost identical, indicating that the treatment response of irradiation was not affected by administration of azelastine. CONCLUSIONS: Application of azelastine reduces the degree of acute radiation dermatitis without affecting the antitumoral effect of radiation therapy.

Animals↗

Geographic variation in mortality among individuals with youth-onset diabetes mellitus across the world. DERI Mortality Study Group. Diabetes Epidemiology Research International.

The aim of this study was to evaluate the geographic variation in mortality among individuals with youth-onset insulin-dependent diabetes mellitus (IDDM) across the world. The study was based on the currently available IDDM incidence and mortality data. Mortality data for diabetes in the 0-24 year age group were obtained from the World Health Organization (WHO) statistics. The mortality rates were adjusted for the frequency of occurrence of IDDM and dividing the mortality rates by the IDDM incidence rates which were obtained from the WHO DiaMond project. There was a more than 10-fold geographic variation in mortality between the developed countries and Eastern European populations. The areas with the highest mortality rates were located in Japan, Eastern Europe and Russia. The areas having the best outcome associated with IDDM were Northern Europe, Central Europe, and Canada. An ecological study demonstrated a relationship between the incidence-adjusted mortality (estimated case-fatality) with IDDM incidence itself (Spearman's correlation coefficient = 0.45) as well as infant mortality and life expectancy at birth. These data demonstrated the possibility of an enormous geographic variation in mortality of youth-onset diabetic patients even in developed countries. It is important to note that these excess deaths are potentially preventable. The ecological study also suggested that the mortality differences may be in part related to overall and diabetes related care.

Adolescent↗