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Biomedical subjects

R Nishimura

Publications and source records attributed to R Nishimura.

At least 127 records · Page 7Linked to original sources

A major improvement in the prognosis of individuals with IDDM in the past 30 years in Japan. The Diabetes Epidemiology Research International Study Group.

OBJECTIVE: To evaluate the time trends of mortality among individuals with IDDM in Japan. RESEARCH DESIGN AND METHODS: A historical prospective study of two independent population-based cohorts composed of individuals who were diagnosed between 1965 and 1969 (1960s cohort) and between 1975 and 1979 (1970s cohort), which included 286 IDDM patients (onset age < 18 years) for the 1960s cohort and 779 patients for the 1970s cohort, was performed. After 10 years of observation, mortality status and causes of deaths between the two cohorts were compared. RESULTS: The age-adjusted mortality rate per 100,000 person-years of the 1960s cohort was 754 (95% CI, 471-1,141); in contrast, that of the 1970s cohort was only 196 (95% CI, 107-329) (P < 0.001). The standardized mortality ratio of the 1960s cohort was 1,432 (95% CI, 898-2,161), and that of the 1970s cohort was 489 (95% CI, 267-821). Analyses of the causes of deaths revealed a marked decline in recent years in the number of deaths by acute complications and renal disease. CONCLUSIONS: A major decline in the mortality of diabetic children in Japan may be attributed to the dramatic changes in the quality of care and medical infrastructure that occurred after the mid-1970s.

Adolescent↗

[Ectopic production of HCG beta by bladder carcinoma in vitro and in vivo].

BACKGROUND: Ectopic production of immunoreactive hCG/hCG beta (IR-hCG beta) by bladder tansitional cell carcinoma cell lines was investigated in vitro and in vivo. METHODS: As an in vitro study, IR-hCG beta in culture media from 2 bladder transitional cell carcinoma cell lines (KoTCC-1 and HT-1197) was analyzed by three kinds of enzyme immunoassays (EIA) which were specific for intact hCG, free hCG beta and beta-core fragment (beta-CF). As an in vivo study, distribution of IR-hCG beta was analyzed in tumor tissues, sera, and urine of the nude mice and the nude rat transplanted with KoTCC-1 cell line. RESULTS: Both of the cell lines were determined to secrete IR-hCG beta into the media, which consisted principally of free hCG beta. Intact hCG and beta-CF were scarecely detected in the media. Immunohistochemical study revealed the localization of IR-hCG beta in transitional cell carcinoma cells of the transplanted tumor. Although a large amount of IR-hCG beta could be detected in both of the serum and urine from the animals, there were quantitative and qualitative differences between serum and urinary IR-hCG beta. Quantitatively, the concentrations of IR-hCG beta in the urine were consistently much higher than those in the serum. Qualitatively, free hCG beta was exclusively detected in the serum whereas a large amount of beta-CF, in addition to free hCG beta, were found in the urine. Intact hCG could not be detected in both serum and urine. These distributions of IR-hCG beta in the animals bearing tumors were completely analogous to those in patients with bladder carcinoma. CONCLUSION: The present results suggested that ectopic production of IR-hCG beta by bladder carcinoma is not rare phenomenon and it is clinically useful as a tumor marker when beta-CF is measured in the urine.

Animals↗

Anesthesia induced in pigs by use of a combination of medetomidine, butorphanol, and ketamine and its reversal by administration of atipamezole.

OBJECTIVE: To develop an IM administrable anesthetic combination for pigs. DESIGN: Use of a combination of atropine, medetomidine, butorphanol, and ketamine (MB-K) was evaluated as an anesthetic regimen and compared with that of a combination of atropine, xylazine, butorphanol, and ketamine (XB-K). Cardiorespiratory effects of MB-K combination and use of atipamezole as a means of reversing anesthesia induced by MB-K were examined. ANIMALS: 18 castrated, mixed-breed, specific-pathogenfree pigs, aged 8 to 15 (mean, 12.1) weeks and weighing 14.5 to 26.0 (mean, 19.6) kg. were studied. PROCEDURE: Dosages of drugs used in this study were atropine, 25 micrograms/kg of body weight; medetomidine, 80 micrograms/kg; xylazine, 2 mg/kg; butorphanol, 200 micrograms/kg; ketamine, 10 mg/kg; and atipamezole, 240 micrograms/kg. RESULTS: MB-K combination proved to be more effective than XB-K combination as an anesthetic combination. After quick and smooth induction by IM administration, MB-K-induced anesthesia was sustained for 98.8 +/- 22.5 minutes (mean +/- SD, 47.4 +/- 16.5 minutes by XB-K) with accompanying muscular relaxation (91 +/- 18 minutes) and loss of pedal (82 +/- 24 minutes) and laryngeal (75 +/- 19 minutes) reflexes. Loss of these reflexes was of significantly longer duration than the loss induced by XB-K, enabled tracheal intubation, and, thus, supported major surgery for at least 30 minutes after induction. Recovery from MB-K-induced anesthesia was smooth. MB-K combination had a slight stimulative effect on cardiovascular status, and a significant depressant effect on blood gas and acid-base status, but these effects were within biologically acceptable limits. Oxygen consumption of pigs under MB-K-induced anesthesia decreased significantly. MB-K-induced anesthesia could be effectively and quickly reversed by IM or IV administration of atipamezole. CONCLUSIONS: The combination of medetomidine, butorphanol, and ketamine induces excellent surgical anesthesia in pigs, and results in moderate cardiorespiratory effects. A great advantage of the anesthetic regimen is that it can be effectively and quickly reversed by atipamezole. CLINICAL RELEVANCE: Medetomidine, butorphanol, and ketamine-induced anesthesia is available for short-term major surgery in pigs.

Adrenergic alpha-Antagonists↗

[An operative case of suture-granuloma which resulted from an intra-pulmonary treatment 10 years ago and manifested hemoptysis].

We experienced a 27-year-old male patient with recurrent hemoptysis manifested by granuloma which resulted from surgical repair that was performed for right pneumothorax using unabsorbable sutures (braided silk) before 10 years. The patient had been suffering from fever and cough for three months before hemoptysis. Chest X-ray and CT scan films showed a mass shadow in the lateral side of the right lung field. Furthermore, bronchoscopy revealed bleeding in B3 of the right lung. The patient underwent right upper lobectomy, which disclosed that hemoptysis was due to a granuloma (2.3 x 3.2 cm in size) formed around sutures. The granuloma was caused not only by foreign body reaction but also by transbronchial infection.

Adult↗

Benefits of Medroxyprogesterone Acetate (MPA) in Advanced or Recurrent Breast Cancer with Higher Serum Concertration.

The efficacy of medroxyprogesterone acetate (MPA) therapy in controlling progressive measurable metastatic breast cancer was assessed in 61 patients. In addition serum MPA concentrations were measured by high performance liquid chromatography (HPLC) and subjective effects of treatment were monitored. Overall 24 patients (39.3%) achieved an objective response(2 complete responses [ CR ] and 22 partial responses [ PR ]). There was no significant relationships between response to therapy and menopausal status, metastatic sites, previous therapy, histological type, or disease-free interval. Patients with estrogen (ER) and progesterone (PgR) receptor-positive tumors responded more frequently. Significant differences in serum MPA concentrations were seen between responders and non-responders, objective tumor shrinkage being seen in patients with serum levels in excess of 55 ng/ml. There were few cases responding to the therapy with serum MPA concentrations lower than 25 ng/ml. The serum MPA levels significantly correlated with an improvement in the performance status and survival. Patients with serum MPA concentrations lower than 25 ng/ml had significantly poorer survival. There was a significant relationship between MPA level and dose per area of boby surface (mg/ m(2)) in cases with CR or PR or no change (NC). However, the serum levels of patients with progressive disease despite therapy were lower than the expected levels based on the body surface area. This study demonstrated that serum MPA concentration is a determining factor for therapeutic benefit in advanced or recurrent breast cancer.

Journal Article↗

An Evaluation of DNA Polymerase alpha as a Prognostic Predictor in Early Breast Cancers Smaller than 2 cm.

We examined the relationship between proliferative activity determined by DNA polymerase alpha and clinicopathologic variables in breast cancer patients, and evaluated the usefulness of DNA polymerase alpha as a prognostic predictor in 337 early breast cancers with tumors smaller than 2 cm, which had favorable outcomes. About 60% of tumors had lower proliferative activity. A significant correlationwas found between DNA polymerase alpha and ER, PgR, histological type, or the degree of infiltration into lymphatic vessels which reflect the prognosis. Cancers with higher DNA polymerase alpha activity were associated with shorter disease-free and overall survival times. In a multivariate analysis the DNA polymerase alpha was found to be an independent and significant factor in early breast cancer.

Journal Article↗

Expression and secretion of the beta subunit of human chorionic gonadotropin by bladder carcinoma in vivo and in vitro.

Expression and secretion of the beta subunit of human chorionic gonadotropin (hCG) by bladder carcinoma cell lines were investigated in vitro and in vivo. As an in vitro study, immunoreactive hCG beta (IR-hCG beta) secreted into the culture media of two bladder transitional cell lines (KoTCC-1 and HT-1197) was analyzed using three kinds of enzyme immunoassays which were specific for intact hCG, free hCG beta, and beta core fragment (beta-CF). Both of the cell lines were determined to secrete IR-hCG beta into the media, which consisted principally of free hCG beta, but detectable levels of intact hCG and beta-CF were not present in the media. Northern blot analysis revealed that the hCG beta gene was expressed in both KoTCC-1 and HT-1197 cells where the sizes of mRNA from these cells were smaller than those from placental and NJG choriocarcinoma cells. As an in vivo study, distribution of IR-hCG beta was analyzed in the tumor tissues, sera, and urine of the mice and the rats transplanted with KoTCC-1 cells. By the immunohistochemical study, the IR-hCG beta was clearly observed in transitional cell carcinoma cells of the transplanted tumor. High levels of IR-hCG beta were detected in both the serum and urine from the animals, but there were quantitative and qualitative differences between serum and urinary IR-hCG beta. Quantitatively, the concentrations of IR-hCG beta in the urine were consistently much higher than those in the serum. Qualitatively, free hCG beta was exclusively detected in the serum whereas high levels of beta-CF in addition to free hCG beta were found in the urine. Intact hCG could not be detected in the serum and urine. These distributions of IR-hCG beta in the animals transplanted with KoTCC-1 cells were completely analogous to those in a patient with hCG beta-producing bladder carcinoma. The present study shows that the same metabolic pathway of IR-hCG beta is operating in mice and rats as in humans, indicating that IR-hCG beta found in patients with bladder carcinoma originates from the tumor and it may be recognized as a tumor marker when beta-CF is measured in the patient's urine.

Animals↗

Ovarian strumal carcinoid with markedly high serum levels of tumor markers.

We report a 54-year-old woman with ovarian strumal carcinoid in association with dermoid cyst and mucinous cystadenoma in the same ovary and who had markedly high serum levels of CEA (202 ng/ml), CA125 (710 U/ml), and CA19-9 (11,500 U/ml). These tumor markers were not found in the thyroid tissue or carcinoid by immunohistochemical methods, but their serum levels decreased to below the cutoff levels after surgery. In our case, the change of serum levels of these tumor markers may be useful for the follow-up after surgery.

Biomarkers, Tumor↗

Combination assay of urinary beta-core fragment of human chorionic gonadotropin with serum tumor markers in gynecologic cancers.

Ectopic production of the immunoreactive beta-subunit of human chorionic gonadotropin (IR-hCG beta) by gynecologic malignancies has been well recognized, but IR-hCG beta has not yet been established as a clinically useful tumor marker, except for germ cell tumors. We measured the concentrations of IR-hCG beta-related molecules, intact hCG, free hCG beta, and beta-CF, in the sera and urine of patients with various gynecologic cancers (cervical, endometrial, and ovarian cancers) to assess their clinical usefulness as a tumor marker in comparison with serum tumor markers such as CEA, SCC, CA125, and CA19-9. The highest incidence of IR-hCG beta was obtained in the assay for beta-CF in the urine, with positive rates of 47.7% (94 of 197) for cervical, 37.8% (14 of 37) for endometrial, and 84.4% (38 of 45) for ovarian cancers with a cut-off value of 0.2 ng/mg of creatinine. In cervical cancer, there was no significant correlation between the concentrations of urinary beta-CF and serum SCC, and 57.9% (114 of 197) of the patients were detected by the combination assay of these tumor markers. Serial determination in 22 cervical cancer patients with elevated urinary beta-CF level prior to therapy showed that its level decreased after successful treatment, but 4 of 5 patients with persistent or recurrent disease had elevated levels of urinary beta-CF. All of the ovarian cancer patients examined were detected by the combination assay of urinary beta-CF and serum CA125. The levels of urinary beta-CF showed little correlation with those of the serum tumor markers, indicating the usefulness of the combination assay of urinary beta-CF with serum tumor markers for detecting cervical and ovarian cancers.

Biomarkers, Tumor↗

Establishment of a myeloid leukaemic cell line (SKNO-1) from a patient with t(8;21) who acquired monosomy 17 during disease progression.

A novel cell line SKNO-1 was established from the bone marrow cells of a 22-year-old male suffering from acute myeloblastic leukaemia (AML) M2 with t(8;21) whose disease became resistant to chemotherapy after acquisition of 17 monosomy. SKNO-1 has been maintained for more than 36 months as a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent line. Morphologically, SKNO-1 cells were myeloblasts somewhat matured. The cells grow in suspension with a doubling time of 48-72 h. The survival and growth of SKNO-1 cells was absolutely dependent on granulocyte-macrophage colony stimulating factor (GM-CSF). SKNO-1 cells possessed t(8;21) and monosomy 17 which were observed in original leukaemic cells. We confirmed that the AML1 gene, located on chromosome 21, was rearranged and the AML1-MTG8 fusion transcript was expressed in SKNO-1 cells. Over-expression and mutation of the p53 gene were also detected in SKNO-1. It is likely that alterations of AML1 or MTG8 gene and p53 gene contribute to a disease progression in this case. Since t(8;21) translocation is a common chromosome abnormality in AML, and inactivation of the p53 gene may play a crucial role in disease progression in AML, SKNO-1 would be a useful tool for analysing the molecular mechanisms in myeloid leukaemogenesis.

Adult↗

Chemical restraint by medetomidine-ketamine and its cardiopulmonary effects in pigs.

Chemical restraint induced by medetomidine-ketamine (M-K) combination was evaluated compared with that by xylazine-ketamine (X-K) in pigs. The duration of restraint by M-K was 49.4 +/- 13.5 min (mean +/- SD) and longer than that by X-K (34.6 +/- 17.2 min), but the difference was not significant. The effect of X-K was not stable, since one of five pigs was restrained only for 6 min. Both combinations produced muscle relaxation. The duration of muscle relaxation in M-K was 43.6 +/- 12.7 min and was significantly longer than that in X-K (21.0 +/- 14.0 min). M-K combination had a slightly stimulative effect on the cardiovascular system, but scarcely changed the respiratory parameters. This limited effect on cardiopulmonary system was an advantage of M-K combination for chemical restraint in pigs. These results indicated that M-K combination is suitable for chemical restraint with prolonged muscle relaxation and has limited cardiopulmonary effects in pigs.

Anesthetics↗

Potent thyrotropic activity of human chorionic gonadotropin variants in terms of 125I incorporation and de novo synthesized thyroid hormone release in human thyroid follicles.

Using a highly sensitive bioassay for TSH, in which human thyroid follicles incorporate 125I and release de novo synthesized thyroid hormone into the culture medium, the thyrotropic activities of various hCG preparations were studied. Under the culture conditions employed, bovine TSH (bTSH) was approximately 6- to 9-fold more active than human TSH (hTSH). Highly purified hCG prepared from urine of normal pregnant women (CR 127) had only a trivial thyrotropic activity equipotent to 0.00022 microU bTSH/U hCG or 0.0013 microU hTSH/U hCG (19.7 microU hTSH/mg hCG). Hybrid hCG (AB1ER) also elicited low thyrotropic activity (14.0 microU hTSH/mg), whereas crude hCG had moderate thyrotropic activity (0.041 hTSH microU/U hCG or 127 microU/mg protein). Deglycosylated hCG, a very weak LH/hCG receptor agonist, was the most potent agonist in thyroid follicles (588 microU hTSH/mg protein). hCGs purified from urine of patients with trophoblastic tumors had greater TSH-like activity (37-84 microU hTSH/mg protein) than purified hCG. Asialo-hCG purified from a patient with choriocarcinoma had very potent TSH-like activity (468 microU hTSH/mg). Submaximal doses of bTSH and hCG variants produced additive stimulation of thyroid function. Furthermore, the thyrotropic effect of hCG was inhibited by anti-TSH receptor antibody obtained from patients with myxedema. These in vitro findings suggest that although hCG is reported to exert potent cAMP-stimulating activity on rat thyroid-like cells (FRTL-5) and Chinese hamster ovary cells transfected with hTSH receptor complementary DNA (0.092-0.72 microU hTSH/U hCG), the thyrotropic activity induced by authentic hCG in human thyroid follicles is too weak to cause hyperthyroidism in normal pregnancy. However, hCG produced by some trophoblastic tumors, particularly asialo-hCG, has potent thyrotropic activity sufficient to cause clinically overt hyperthyroidism when produced excessively.

Animals↗

Rapid inhalation induction of anesthesia by halothane, enflurane, isoflurane and sevoflurane and their cardiopulmonary effects in dogs.

The rapid inhalation induction of anesthesia (RII) by mask inhalation of halothane, enflurane, isoflurane and sevoflurane at an equianesthetic concentration (2.5 MAC) was evaluated in 24 beagle dogs. The differences in movements, induction and intubation time between anesthetics were mainly associated with the differences in each blood/gas solubility. The most rapid and smoothest induction was observed by sevoflurane inhalation (209.0 +/- 44.2 sec), followed by isoflurane inhalation (285.8 +/- 34.1 sec). Halothane inhalation took the longest induction time (790.3 +/- 75.7 sec). Movements during RII were minimal in sevoflurane group comparing to the other groups. Heart rate, cardiac output and rate pressure product significantly increased after the beginning of inhalation in all the dogs except for those of halothane group. These changes exceeded the physiological level just after the beginning of inhalation, however, rapidly reversed to the maintenance level (1.5 MAC) approximately 10 min after intubation. Consequently, sevoflurane seemed to be the best inhalational anesthetic for RII in dogs without significant problems in respiratory and/or cardiac functions. Isoflurane also induced rapid induction with some degree of the movements.

Analysis of Variance↗

Clinical application of rapid inhalation induction of anesthesia using isoflurane and sevoflurane with nitrous oxide in dogs.

Clinical usefulness of rapid inhalation induction of anesthesia (RII) using 5.0 vol.% isoflurane (GOI) and sevoflurane (GOS) with N2O was evaluated in 124 canine patients. Induction times, loss of various reflexes and movement times were significantly faster in GOI group than in GOS group. Scores for the easiness of intubation and the degree of movements were also significantly less in GOI group than in GOS group. Positive correlation between body weight and degree of movements was observed in both induction groups. Thus, RII using GOI is a practically useful and safe induction modality in small- to medium-sized dogs.

Age Factors↗

Cardiopulmonary effects of medetomidine, medetomidine-midazolam and medetomidine-midazolam-atipamezole in dogs.

Cardiopulmonary effects of medetomidine (20 micrograms/kg)-midazolam (0.3 mg) (Me-Mi) were compared with those of medetomidine alone (80 micrograms/kg) (Me80) in dogs. The intramuscular administration of this combination caused bradycardia and transient mild pressor response. Heart rate decreased soon after the administration and remained significantly below the baseline value with average values of 50-70 beats/min. Blood pressure increased to its maximum within 5 to 10 min then decreased gradually. Cardiac index decreased corresponding the decrease in heart rate. However these changes were less profound than those of Me80 indicating significantly higher values in cardiac index and lower values in systemic vascular resistance. Effects on the respiratory function were slight. The reduction of the dose of medetomidine to one-fourth in Me-Mi was effective to reduce the adverse effect of medetomidine, especially in peripheral vasoconstriction. Atipamezole effectively reversed cardiopulmonary effects induced by medetomidine-midazolam. Heart rate and cardiac index increased and systemic vascular resistance decreased significantly after administration of atipamezole. The possible use of an antagonist as a reversal agent might enhance the value and availability of medtomidine-midazolam as a chemical restraint agent in dogs.

Adrenergic alpha-Antagonists↗

Superselective intraarterial infusion of cisplatin for squamous cell carcinoma of the mouth: preliminary clinical experience.

OBJECTIVE: The purpose of this study was to assess the initial clinical response to superselective intraarterial infusion of cisplatin for treating stage III and stage IV squamous cell carcinoma of the mouth. SUBJECTS AND METHODS: Thirteen patients received intraarterial cisplatin therapy. The tumors were located in the tongue (n = 7), gingiva (n = 3), buccal mucosa (n = 1), hard palate (n = 1), and floor of the mouth (n = 1). A coaxial technique was used to place microcatheters in the lingual, facial, inferior alveolar, buccinator, and distal internal maxillary arteries, depending on tumor location. The feeding vessels were identified by staining the tumor with infusion of indigocarmine dye in the selected vessel. Relatively low-dose cisplatin (30-40 mg/m2) was injected at the rate of 50 mg/hr. Two or three injections were performed, with a 1-week interval between injections. After chemotherapy, eight patients underwent surgery, four had radiation therapy, and one had both. RESULTS: Thirty-four intraarterial infusions were done successfully without any complications. Arterial infusion of indigocarmine dye was useful for exact identification of feeding vessels, especially when the tumor was extensive, at the margin of the arterial supply, or near the midline. The overall response rate was 92% (complete response [tumor completely resolved], 38%; partial response [tumor reduction > or = 50%], 54%). Ten of 13 patients had no recurrence from 4 to 19 months (mean, 10 months) after treatment. Two patients died of metastatic diseases 6 months after surgery or radiation therapy. One patient had local recurrence 8 months after surgery and postoperative irradiation. No systemic toxicity such as renal failure, liver dysfunction, or bone marrow suppression was observed. Mild and transient local toxicity such as edema or mucositis of the infused area was relatively common. Trigeminal neuralgialike symptoms and reduced mouth opening occurred in two cases and one case, respectively, probably due to direct toxicity to the peripheral trigeminal nerve and masticatory muscles, respectively. CONCLUSION: Superselective intraarterial infusion of low-dose cisplatin is feasible and safe and may have important applications in treating advanced carcinoma of the mouth.

Aged↗

Improved lipid visualization with a modified osmium tetroxide method using ultrasonic treatment and intensification with imidazole or triazole.

Formalin fixed autopsy tissue containing lipids were cut into 1-5 mm thick blocks, washed well, then postfixed in 2% OsO4 in 0.03 M veronal acetate buffer for 30, 60, 90, 120, or 180 min with or without ultrasonic treatment. Tissues exposed to ultrasound for 90 min showed superior penetration of OsO4 and well preserved histological architecture. Tissues also were immersed for 1 hr in veronal acetate buffer (pH 7.4) containing 0.5% imidazole or triazole and compared with untreated controls. Paraffin sections, 4 microns thick, were examined under a light microscope with an image analyzer. Both intensity and percentage area of osmium blackening were significantly higher in samples immersed in imidazole or triazole than in untreated controls. No difference was observed between imidazole- and triazole-immersed samples. The OsO4 method, modified by ultrasound treatment and imidazole- or triazole-immersion, can be applied to routine formalin fixed autopsy materials for improved lipid visualization.

Fatty Liver↗