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Biomedical subjects

J Ochi

Publications and source records attributed to J Ochi.

At least 19 recordsLinked to original sources

Low-dose ACTH therapy for West syndrome: initial effects and long-term outcome.

BACKGROUND: Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan. METHODS: The medical records of 138 patients with WS, who were treated with low-dose synthetic ACTH therapy for the first time at the authors' institutions between 1989 and 1998, were analyzed. RESULTS: At the end of ACTH therapy, excellent effect on seizures was noted in 106 of 138 (76%) patients, good effect in 23 (17%), and poor effect in 9 (7%). Initial effects on EEG were excellent in 53 of 138 (38%) patients, good in 76 (55%), and poor in 9 (7%). As for seizure prognosis at the time of follow-up, 51 of 99 (52%) patients were seizure-free, whereas 48 (48%) patients had seizures. Mental outcome was normal in 6 of 98 (6%) patients, mild mental retardation in 16 (16%), moderate mental retardation in 26 (27%), and severe mental retardation in 50 (51%). The initial effects of ACTH on seizures and long-term outcome were not dose dependent (daily dosage 0.005 to 0.032 mg/kg, 0.2 to 1.28 IU/kg; total dosage 0.1 to 0.87 mg/kg, 4 to 34.8 IU/kg). The severity of adverse effects correlated with total dosage of ACTH, and the severity of brain volume loss due to ACTH correlated well with the daily dosage and total dosage of ACTH. CONCLUSION: Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects.

Brain↗

Human monoclonal antibodies isolated from spontaneous Epstein-Barr virus-transformed tumors of Hu-SPL-SCID mice and specific for fusion protein display broad neutralizing activity toward respiratory syncytial virus.

Two human monoclonal antibodies, RF-1 and RF-2, specifically recognize the fusion protein of the human respiratory syncytial virus (RSV). These were isolated from spontaneous tumors in SCID mice reconstituted with human splenocytes and boosted with fusion protein. The tumors consisted of Epstein-Barr virus-transformed human B cells in animals with antigen-specific antibody titers>105. The binding affinity of RF-1 and RF-2 to the fusion protein is 1010 and 109 M-1, respectively. The antibodies bind specifically to a conformational epitope of the fusion protein on RSV-infected HEp-2 cells. Both antibodies display virus-neutralizing properties in vitro at concentrations varying between 8 and 1000 ng/mL. Virus neutralization applies to a broad variety of wild and laboratory-adapted virus strains belonging to both virus types A and B. These antibodies are potential candidates for passive immunotherapy of severe RSV infections.

Animals↗

Immunocytochemical studies on endothelin in mast cells and macrophages in the rat gastrointestinal tract.

To reveal the distribution of endothelin (ET)-containing stromal cells (mast cells and macrophages), we investigated the rat gastrointestinal tract immunohistochemically using antibodies to Big ET-1, Big ET-2, Big ET-3, and mature ETs. In all the regions of the gastrointestinal tract, immunoreactivity for all the antibodies used was found in stromal cells that were located mainly in the lamina propria (not in the submucosa). The number of these cells was largest in the small intestine and smallest in the colon. Moreover, Big ET-2, which was originally identified in the gastrointestinal tract, was also found in many stromal cells, but Big ET-3-containing cells, unexpectedly, were found in almost the same number as Big ET-2-containing cells, while Big ET-1-containing cells were few. These immunopositive stromal cells seemed to be mast cells and macrophages from their histological features. Double-immunohistochemical staining revealed that 92% of the mature ETs-positive cells were mast cells; the rest were macrophages. Furthermore, we confirmed that mature ETs coexisted with ET-A or ET-B receptors in identical cells. Hence, we presume that ETs are synthesized in and secreted from stromal cells in the rat gastrointestinal tract, that their main isotypes are not only ET-2 but also ET-3, and that ETs may act in an autocrine/paracrine fashion.

Animals↗

Gastrinoma with multiple liver metastases: effectiveness of dacarbazine (DTIC) therapy.

Gastrinoma when associated with liver metastasis results in markedly reduced survival. However, a standard chemotherapeutic protocol for patients with unresectable tumors has not been established. We treated two patients with gastrinoma with multiple liver metastases with intravenous administration of 5-dimethyltriazenoimidazole-4-carboxamide (DTIC; dacarbazine) at a dose of 200 mg/body for 5 consecutive days. The first patient showed a marked decrease in serum gastrin levels, from 338 000 pg/ml to 22 900 pg/ml (normal range, >220pg/ml), as well as a decrease in the size and number of peripancreatic and liver tumors, after four courses of DTIC. An additional nine courses of the treatment were given, and the peripancreatic tumor was resected. The patient has been in good overall condition for more than 3(1/2) years. The second patient was treated with a total of ten courses of DTIC. Serum gastrin levels did not increase and the hepatic tumor did not change in size for more than 4 years. DTIC was effective in controlling the clinical and biochemical manifestations of gastrinoma associated with liver metastasis without serious side effects. As the toxity of DTIC is minimal, (e.g., nausea and vomiting) DTIC therapy should be considered useful for islet cell carcinomas with multiple metastases.

Aged↗

Nephrogenic diabetes insipidus and tethered cord syndrome with a lipoma of the cauda equina.

The tethered cord syndrome is characterized by sensory and motor disturbances of the lower extremities and incontinence. We report a 12-year-old girl with a cauda equina lipoma and a tethered spinal cord, whose chief complaints were polyuria and polydipsia. She was diagnosed as having nephrogenic diabetes insipidus. This unusual complication of the tethered cord syndrome was most likely due to a hydronephrosis secondary to a neurogenic bladder. Thus, spinal lesions have to be considered in patients with polyuria and polydipsia.

Cauda Equina↗

[Combination chemotherapy with cis-platinum and ifosfamide for hormone unresponsive prostate cancer].

PURPOSE: There is no effective therapy against hormone refractory prostate cancer. This led us to evaluate the effectiveness and toxicity of cis-platinum (CDDP) and ifosfamide (IFM) combination chemotherapy in the patients with hormone-unresponsive carcinoma of the prostate. METHODS: Patients with hormone-unresponsive prostate cancer were scheduled to receive CDDP 70 mg/m2 intravenously on day 1 and IFM 1.2 g/m2/day intravenously on day 1 through day 5 of 28-day cycle. RESULTS: Twenty seven patients with hormone unresponsive prostate cancer were enrolled onto this trial. Of these patients, seven (26%) demonstrated a partial objective response (PR), and ten (37%) a stable disease (ST). The response duration of PR cases lasted from 6 to 49 months with a median of 16 months and the response duration of PR + ST cases lasted from 3 to 36 months with a median of 10 months. Subjective improvement was obtained in 11 patients (41%). Survival duration of all cases were 4 to 89 months with a median of 23 months and probabilities of survival at 3 years and 5 years were 36% and 24%, respectively. The toxicity of this treatment was mostly mild to moderate, anemia (96%), leukocytopenia (89%), anorexia (81%), alopecia (67%), thrombocytopenia (44%), hematuria (38%), renal dysfunction (19%) and liver dysfunction (7%) were noticed. Severe toxicity was observed in two cases, one acute renal failure and one endotoxin shock. CONCLUSION: We conclude that CDDP and IFM combination chemotherapy was active regimen for hormone unresponsive prostate cancer.

Aged↗

[Comparison of therapeutic effects of SMANCS (+TAE) and Non-SMANCS/LpTAE].

Therapeutic effects of SMANCS and LpTAE were evaluated for hepatocellular carcinoma (HCC). Since June 1995, SMANCS has been used in 59 patients for their first treatment. LpTAE had been performed for HCC before introduction of SMANCS in our hospital, and 71 patients treated after 1992 were chosen for comparison with the therapeutic effect of SMANCS. Among the patients treated with SMANCS, complete and partial responses (CR and PR) were obtained in 24 cases (41%) and 17 cases (33%), respectively. SMANCS accompanied by TAE was more effective than SMANCS alone. The effects did not depend on the level of the hepatic arterial branch at which SMANCS was administered. In patients treated with LpTAE, CR and PR were obtained in 12 cases (17%) and 18 cases (25%), respectively. SMANCS was significantly more effective than LpTAE. Because of our short experience with SMANCS, we could only show a two year survival rate. The one- and two-year survival rates for SMANCS were 71% and 57%, respectively. They were not significantly different from those for LpTAE, at 80% and 60%. Despite good results of treatment for HCC, a better prognosis could not be expected by SMANCS in this study. These results may be explained as follows. The evaluating the cause of death within two years after first treatment, hepatic failure was more common in patients treated with SMANCS. After treatment by SMANCS, 11 patients (55%) died from hepatic failure. On the other hand, 4 patients (15%) died from hepatic failure after LpTAE. Although there is no significant difference of Child Pugh score, this may indicate that SMANCS has been used for patients with lesser hepatic reserve and this leads to early deaths in patients treated with SMANCS. However, because of the short experience in this study, further observation is necessary for precise evaluation of clinical efficacy of SMANCS.

Antineoplastic Agents↗

Topographical distribution of neurons containing endothelin type A receptor in the rat brain.

Endothelin (ET) was originally identified as a vasoactive peptide biosynthesized in vascular endothelial cells. Because ET has also been found in the brain as a neuropeptide, it has been thought to belong to the group of brain-vascular peptide hormones. To date, type A and type B receptors for ET have been found. To elucidate the topographic distribution of type A receptor (ET-AR) in the brain, we raised a specific antibody to the C-terminal (64 amino acids) peptide of rat ET-AR and immunostained rat brain sections with this antibody. Immunoreactivity for ET-AR was detected in neuronal cell bodies and also in the many proximal and some distal parts of their fibers. Nerve cell bodies containing strong ET-AR-immunoreactivity were distributed in the lateral part of the reticular formation, the nucleus of the solitary tract and its surrounding area, the dorsal midline area and medial longitudinal fasciculus, the subependymal layer of the fourth ventricular roof, the caudolateral area of the pontine tegmentum, the locus coeruleus, the rostral pontine area of the lateral reticular formation, the retrorubral area, the substantia nigra, the ventral tegmental area, the periventricular region lateral to the rostral mesencephalic aqueduct and caudal third ventricle, the arcuate hypothalamic nucleus, the caudomedial area of the zona incerta, the periventricular hypothalamic nucleus, the parvocellular portion of the paraventricular hypothalamic nucleus, and the periglomerular region of the olfactory bulb. In addition, the Purkinje cells of the cerebellar cortex, the nerve cells in the mesencephalic trigeminal nucleus, and the magnocellular neurons of the supraoptic and paraventricular hypothalamic nuclei showed weak immunoreactivity. The distribution of highly ET-AR-immunoreactive neurons is quite similar to that ofcatecholamine neurons.

Animals↗

Somatic cell mutation frequency at the HPRT, T-cell antigen receptor and glycophorin A loci in Cockayne syndrome.

Skin fibroblasts of patients with Cockayne syndrome (CS) are hypersensitive to the lethal or mutagenic effect of ultraviolet light, which may cause genetic instability. Up to now, however, no systematic study of in vivo somatic cell mutation in CS cells has been reported. This article describes our investigation of the mutation frequencies (Mfs) at three different loci, i.e. hypoxanthine-guanine phosphoribosyl transferase (HPRT), T-cell antigen receptor (TCR) and glycophorin A (GPA), in six patients with CS. Mfs at the HPRT and TCR loci were found to be within the normal range as determined in age-matched controls. In the GPA locus of two patients, there was a slight increase, but it was much smaller than that reported in other DNA repair deficient syndromes. The frequency of spontaneous HPRT mutation in Epstein-Barr virus transformed B-lymphoblastoid cells derived from CS patients was similar to that in cells from normal children. The molecular characterization of the representative HPRT mutant T cell clones from CS patients did not show any structural alterations. These results may explain, at least in part, why CS is not associated with predisposition to cancer.

Adolescent↗

[Histocytochemical and functional aspects on the "brain-vascular peptides"].

The vasoactive peptides, endothelins (ET-1, ET-2 and ET-3: ETs), natriuretic peptide family (ANP, BNP and CNP:NPs) and angiotensins (I, II, III and IV), exist in not only cardiovascular organs but also in the central nervous system. In the central nervous system, these peptides play important roles to maintain the water balance, electrolyte metabolism and blood pressure control as neural messengers. For this reason, we proposed that these peptides are "brain-vascular peptides" after the model of the "brain-gut peptides." Recent reports showed that these peptides also have the other common character to play significant roles for cell differentiation and/or proliferation or morphogenesis in various peripheral organs as cytokine/growth factors. We have consecutively studied the endogenous digitalis-like substance (sodium transport inhibitor), NPs and ETs by histocytochemical analysis. This article reviews (1) newly developed histological procedure for analyzing the biochemical and functional basis of brain-vascular peptides, e.g., a new technique for raising polyclonal antibody to distinguish their molecular form; c-fos expression analysis; TUNEL staining; culture-in-oculo-chamber; and preparation of transgenic mice; (2) the synthesis and secretion of endothelins, their distributions, target sites, signal transduction and physiological actions; (3) histocytochemical studies on ETs, NPs and angiotensins in the central nervous system as the neural messengers; (4) histocytochemical and pharmacophysiological studies on ETs, NPs and angiotensins as the cytokine/growth factors.

Angiotensins↗

Over-expression of metallothionein and drug-resistance in bladder cancer.

Metallothionein (MT) in tumor cells has been implicated as one of the factors involved in mechanisms of resistance to anti-cancer drugs, including cis-diaminedichroloplatinum (CDDP) and adriamycin (ADM). The relationship between the expression of MT and chemotherapy with anti-cancer drugs was studied in CDDP- and ADM-resistant human bladder cancer cell lines and tissue samples from clinical cases. In drug-resistant cell lines (T-24/ADM, CI-7/CDDP) established in our laboratory, MT expression was studied by immunohistochemistry using the avidin-biotin peroxidase complex (ABC) method and radioimmunoassay (RIA), using anti-MT antibody. In addition, other potential mechanisms of drug resistance, such as P-glycoprotein expression were examined and the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione-S-transferase (GST) determined in these cell lines. The results of these investigations demonstrate that the expression of MT in resistant cell lines increased 2.1- and 2.5-fold when compared with parent cell lines (CI-7, T-24). GSH, GSSG and GST levels were unchanged and P-glycoprotein was not over-expressed. A total of 120 tissue samples from 35 clinical cases of bladder cancer, before and after chemotherapy, were stained for MT which was detected in 10 of the 35 cases before chemotherapy. The incidence of MT expression was significantly higher (p < 0.05) in cases with lower pathological tumor grades.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Atrial natriuretic polypeptide (ANP)-immunoreactivity and specific atrial granules in cardiac myocytes of stroke-prone spontaneously hypertensive rat (SHRSP).

The distribution of atrial natriuretic polypeptide (ANP) and atrial specific granules in the myocytes of the atria and ventricles of an experimental animal model, stroke-prone spontaneously hypertensive rats (SHRSP) and a control, Wistar Kyoto rats (WKY), was examined using immunocytochemical and electron microscopic techniques. In the atria of both SHRSP and WKY, ANP-immunoreactivity was recognized in the perinuclear regions of essentially all cardiac myocytes. In the ventricles of WKY, ANP-immunoreactivity was hardly seen except for the impulse-conducting system. However, in the ventricles of SHRSP, almost all cardiac myocytes possessed immunoreaction products which were scattered evenly throughout the cytoplasm; this distribution pattern differed from that of the atrial wall of this strain.

Animals↗

Distribution of taurine-like immunoreactivity in the mouse liver during ontogeny and after carbon tetrachloride or phenobarbital intoxication.

The ontogenic pattern of development of taurine-like immunoreactivity (TLI) was studied in the mouse liver. The effect on adult mice of carbon tetrachloride or phenobarbital treatment was also examined. Light-microscopically, granules of TLI were first found in the liver from 17-day-old embryos, diffusely distributed throughout the lobules. These positive granules increased with age, were most numerous in the two-week-old mouse, and were notably decreased in the central region of some lobules in the three-week-old mouse. In mature mice, hepatocytes containing TLI-positive granules were distributed unevenly in each liver lobule, and were located predominantly in the peripheral region. Electron-microscopically, TLI was observed in small vesicles in the cytoplasm of hepatocytes and was found mainly in the cisternal lumen of smooth-surfaced endoplasmic reticulum. Some taurine-positive vesicles surrounding the reticulum seemed to associate with the protoplasm. Similar positive vesicles were often located near the bile canaliculi. In carbon tetrachloride-intoxicated mature mice, TLI was no longer limited to the peripheral region of lobules; hepatocytes situated in the central region of lobules also contained intense TLI. In mice injected with a small and repeated dose of phenobarbital, the distribution pattern of TLI was similar to that in the untreated group. However, in mice injected with a large dose of phenobarbital, TLI was markedly increased, especially in the central region of lobules. The results demonstrate that the distribution pattern of TLI in mouse liver changes during development, and that the pattern in mature mice is affected by intoxication with carbon tetrachloride or a toxic dose of phenobarbital.

Animals↗

Histological study on ouabain immunoreactivities in the mammalian hypothalamus.

The endogenous digitalis-like factor (EDLF) which has recently been purified from human plasma and identified as 'ouabain', a cis-trans-cis steroid of plant origin, is thought to be similar to the hypothetical humoral factor, 'endogenous digitalis-like substance (EDLS)'. In order to examine the hypothesis that EDLS is produced in the hypothalamus, we prepared an ouabain-specific antibody, and applied it to rat and macaque brains. Ouabain immunoreactivities were observed in the hypothalamus of both species. The immunopositive neurons were distributed in paraventricular and supraoptic nuclei, and some other hypothalamic regions. Their nerve fibers were seen abundantly in the hypothalamo-neurohypophysial regions. These results strongly support the possibility of existence of cis-trans-cis steroid including EDLF in mammalian brain.

Animals↗

[Establishment and characterization of a cis-diamminedichloro platinum-resistant human bladder cancer cell line].

A cis-diamminedichloroplatinum (CDDP)-resistant cell line, CL-7/CDDP, has been established by chronic exposure of a parent human bladder cancer cell line, T24 (CL-7), to CDDP at progressively increased concentrations for 20 months. CL-7/CDDP was 2.7-fold more resistant to CDDP than CL-7 as determined by colony formation assay. Biological and biochemical characteristics were examined in CL-7/CDDP to compare with CL-7. There were no differences in doubling time and plating efficiency between the two cell lines, but a small one in the mode of chromosome numbers. Intra-cellular CDDP amounts after CDDP exposure showed no difference between the two cell lines, but CL-7/CDDP showed a higher glutathione (GSH) and metallothionein (MT) level. It is suggested that the mechanism of acquired resistance to CDDP is attributed to intra-cellular detoxication, but not to the efflux. CL-7/CDDP may be useful for elucidation of the mechanism of CDDP resistance in human bladder cancer.

Cell Cycle↗

[Phase II study of 5'-DFUR treatment of the bladder and prostatic cancer].

Phase 2 study of 5'-DFUR in bladder and prostatic cancer was conducted at 15 collaborative institutions including Okayama University. 5'-DFUR was orally administered to patients at a daily dose of 800-1200 mg for more than 4 weeks. Forty-one patients with bladder cancer and 12 patients with prostatic cancer were evaluated. The response rate for bladder cancer was 31.7% (CR, 1 case: PR, 12 cases), against no response with prostatic cancer. Moreover, the concentration of 5-FU in bladder tumors was confirmed to be high. Adverse reactions such as diarrhea, anorexia, and nausea were observed. Thus, 5'-DFUR seems to be useful for the treatment of bladder cancer.

Administration, Oral↗