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Biomedical subjects

A Shinoda

Publications and source records attributed to A Shinoda.

At least 19 recordsLinked to original sources

Enhanced therapeutic efficacy of G207 for the treatment of glioma through Musashi1 promoter retargeting of gamma34.5-mediated virulence.

G207 is a conditionally replicating derivative of herpes simplex virus type1 (HSV-1) engineered with deletions of both ICP34.5 loci and a lacZ insertion disabling the ICP6 gene. G207 exhibits an efficient oncolytic activity in vitro and in vivo, yet minimal toxicity in normal tissue, and is now in clinical trial for malignant glioma. According to the results of clinical trials, however, although G207 was proved to be safe, the efficacy was not so impressive. Deletion of the ICP34.5 gene coding for virulence made G207 extremely safe, but it markedly reduced the cytotoxicity mediated by HSV-1. To enhance the therapeutic efficacy of G207 without diminishing its safety, we used a defective vector containing Musashi1 promoter/ICP34.5, with G207 as helper virus. P/musashi1 was functional selectively in human glioma cell lines (U87MG, U251, T98G) in this study and dvM345 showed a much higher therapeutic efficacy both in culture and in the in vivo glioma model, than G207 alone, without diminishing its favorable toxicity profile. These results suggest that transcriptional regulation of ICP34.5 by P/musashi1 can be used to target HSV-1 virulence toward gliomas while maintaining the desirable neuroattenuated phenotype.

Animals↗

Gas chromatographic-mass spectrometric determination of hydrophilic compounds in environmental water by solid-phase extraction with activated carbon fiber felt.

Simple gas chromatographic-mass spectrometric determination of hydrophilic organic compounds in environmental water was developed. A cartridge containing activated carbon fiber felt was made by way of trial and was evaluated for solid-phase extraction of the compounds in water. The hydrophilic compounds investigated were acrylamide, N,N-dimethylacetamide, N,N-dimethylformamide, 1,4-dioxane, furfural, furfuryl alcohol, N-nitrosodiethylamine and N-nitrosodimethylamine. Overall recoveries were good (80-100%) from groundwater and river water. The relative standard deviations ranged from 4.5 to 16% for the target compounds. The minimum detectable concentrations were 0.02 to 0.03 microg/l. This method was successfully applied to several river water samples.

Carbon↗

[Reproductive and developmental toxicity study of S-1090, cefmatilen hydrochloride hydrate (3)--A study on oral administration during the period of organogenesis in rabbits].

Cefmatilen hydrochloride hydrate (S-1090) at dosage levels of 6.25, 12.5 and 25 mg potency/kg/day was administered orally by gavage to groups of 13-16 pregnant rabbits daily during the period of organogenesis, and the effects of S-1090 on dams and fetuses were examined. Control animals were treated with a 0.5 w/v% aqueous solution of methylcellulose. Abortion was noted in 1 of the 16 females of the 12.5 mg potency/kg group and in 1 of the 14 females of the 25 mg potency/kg group, and death was noted in 1 of the 14 females of the 25 mg potency/kg group. Regarding the dams, decreased food consumption was noted in the 12.5 mg potency/kg group in the beginning of the dosing period. Suppressed body weight gain and decreased food consumption were noted in the 25 mg potency/kg group during the pregnancy period. At necropsy, thickening of the gastric mucosa, hemorrhage in the cecum, and higher values of cecum weight were also noted in this group. On the other hand, no effects of S-1090 were noted in general signs, body weight changes, food consumption, necropsy findings, or organ weights in the 6.25 mg potency/kg group. No effects of S-1090 were noted in the number of corpora lutea, number of implantations, implantation rate, death or resorption rate, number of live fetuses, sex ratio of live fetuses, fetal body weight of either sex, incidence of external anomalies, incidence of skeletal anomalies or variations, degree of ossification, or incidence of visceral anomalies. On the basis of the above results, the no observed adverse effect levels of S-1090 are estimated at 6.25 mg potency/kg/day for general toxicity and reproductive functions in dams, and at 25 mg potency/kg/day for development in fetuses under the conditions of the present study.

Administration, Oral↗

Evaluation of central nervous system involvement in nasal lymphomas.

OBJECTIVES: To clarify the usefulness of evaluating central nervous system (CNS) involvement in patients with nasal lymphomas at the initial staging procedure, and of CNS prophylaxis for patients with clinical stage I/II. PATIENTS AND METHODS: We retrospectively reviewed 43 patients with nasal lymphomas who had been treated from 1973 through 1999. The staging procedure included mainly computed tomography (CT), ultrasonography, gallium scintigraphy, upper gastrointestinal study, magnetic resonance (MR) imaging, and bone marrow biopsy. Forty-two patients received radiotherapy, and 25 patients received chemotherapy. All 38 patients with stage I/II were not subjected to CNS prophylaxis. RESULTS: Four patients demonstrated CNS involvement at the staging procedure. MR imaging demonstrated the tumor had directly infiltrated the skull base in 3 patients, but CT demonstrated CNS infiltration in only one patient. In another patient, cerebrospinal fluid (CSF) cytologic analyses demonstrated CNS involvement, but MR imaging and CT did not. These 4 patients complained of frontonasal pain and/or cerebral nerve dysfunction. No patient with stage I/II developed CNS relapse. CONCLUSIONS: MR imaging and CSF cytologic analyses should be performed at the initial staging of nasal lymphomas, especially in patients with frontonasal pain and/or cerebral nerve dysfunction. Patients with stage I/II might not need CNS prophylaxis.

Adult↗

[The stenoses at the terminal portion of the internal carotid artery improved after initiation of antithyroid therapy: a case report].

We reported the case of a 19-year-old female complicated with Basedow disease. She was admitted, complaining of headache and endocrine function tests showed hyperthyroidism. CT scan revealed left intraventricle hemorrhage and angiography revealed the stenoses at the terminal portion of the bilateral internal carotid arteries (ICA) without basal moyamoya vessels. During the angiography, a thyroid crisis occurred and we initiated the antithyroid therapy. Bilateral CAG a month after the onset revealed that the stenoses had improved partially and the stenosis was thought to be vasospasm caused by the intraventricle hemorrhage. But as the collateral circulation had already been established soon after the hemorrhage, we suspected that the stenoses at the terminal portion of the ICA had existed before the intraventricle hemorrhage. Angiography was performed one year after the onset and bilateral CAG revealed that the stenoses at the terminal portion of the ICA had also improved. As some investigators have mentioned that Basedow disease might be associated with the causal genesis of Moyamoya disease, we suspected that Basedow disease might have played an important role in vasospasm after hemorrhage and that the stenoses at the terminal portion of the ICA might have existed before the hemorrhage took place.

Adult↗

[The natural history of a dural arteriovenous fistula associated with sinus thrombosis: a case report].

The patient, a 52-year-old man, complained of vertigo. CT scan revealed right cerebellar infarction and he was admitted to our hospital. MRI revealed a fresh thrombus in the right transverse sinus and angiography revealed the occlusion of the right transverse-sigmoid sinus. He complained of vertigo again and he was re-admitted to our hospital 4 months after the first admission. Angiography revealed a dural arteriovenous fistula (DAVF) of the right transverse-sigmoid sinus fed by the right occipital artery and the right transverse-sigmoid sinus was found to be recanalized. The angiography which was carried out one year after the second admission, revealed also an enlarged DAVF fed by the left occipital artery and the right transverse sinus was occluded again. There are two theories about the pathogenesis of DAVF. One is that it is congenital and the other that it is acquired, but it is still controversial. Our case suggested that sinus thrombosis induced DAVF initially and the DAVF induced sinus thrombosis secondarily. The causal relations between DAVF and sinus thrombosis probably changed inversely over a long term and, when we discuss the pathogenesis of DAVF, we must understand the natural history of DAVF starting from the occurrence of sinus thrombosis.

Arteriovenous Fistula↗

Simultaneous determination of uric acid and creatinine in biological fluids by column-switching liquid chromatography with ultraviolet detection.

A column-switching liquid chromatographic method for the simultaneous determination of uric acid and creatinine in human serum and urine was developed. Creatinine and uric acid were separated by size-exclusion chromatography on a hydrophilic gel column (C1) and creatinine eluted from C1 was separated from proteins by filtration through a longer hydrophilic gel column (C2). The creatinine fraction eluted from C2 was transferred to a weakly acidic cation-exchange column (C3) and then to a strongly acidic cation-exchange column (C4). Uric acid eluted from C1 after creatinine was transferred to an anion-exchange column (C5) and then to a hydrophilic gel column (C6). The mobile phase was a mixed buffer of pH 5.1 (propionic acid-succinic acid-NaOH, 60:15:60 mmol/l in water). Diluted serum and urine could be injected onto C1, and C1 was backflushed after the transfer of uric acid from C1 to C5. Creatinine and uric acid in the eluate were determined by measuring their ultraviolet absorption at 234 and 290 nm, respectively. The recovery of uric acid and creatinine added to diluted serum (20-fold dilution, concentration 20 and 5 mumol/l, respectively) was 98.9 +/- 0.56% and 100.9 +/- 1.29%, respectively. The recovery of uric acid and creatinine added to diluted urine (100-fold dilution, concentration 50 and 100 mumol/l, respectively) was 99.4 +/- 0.72% and 98.7 +/- 1.45%, respectively (mean +/- R.S.D., n = 6).

Chromatography, Gel↗

Inhibition of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline-mediated DNA-adduct formation by chlorophyllin in Drosophila.

The effect of chlorophyllin on 2-amino-3,8-dimethyimidazo[4,5-f]quinoxaline (MeIQx)-mediated DNA-adduct formation in Drosophila was studied. Third-instar larvae of Drosophila were fed MeIQx at 1 mg/6.5 g-feed/bottle, with or without chlorophyllin (100-300 mg). After a 6 h feeding exposure to MeIQx, the larvae were divided into 2 groups. The first group was examined for covalent DNA adducts by 32P-postlabeling assay. The second group was assayed for DNA damage by allowing the larvae to develop to adults and measuring the male/female ratio (males, DNA repair-deficient; females, DNA repair-proficient). The 32 P-postlabeling results indicated a significant decrease in DNA adduct levels in larvae treated with MeIQx and 300 mg chlorophyllin (1.7 +/- 0.7 adducts/10(7) nucleotides) as compared with MeIQx-treated larvae 6.5 +/- 2.1 adducts/10(7) nucleotides). The results on male/female sex ratios also indicated a chlorophyllin-induced decrease in DNA damage by exposure to MeIQx. The suppressive effect of chlorophyllin on the genotoxic actions of a polycyclic mutagen, MeIQx, may be a result of complex formation between chlorophyllin and the mutagen.

Animals↗

2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain.

The effects of anadamide, 2-arachidonoylglycerol and related compounds on the specific binding of a radiolabeled cannabinoid receptor ligand,[3H]CP55940, to synaptosomal membranes were examined. Anandamide, an endogenous cannabinoid receptor ligand, reduced the specific binding of [3H]CP55940 to synaptosomal membranes in a dose-dependent manner: the Ki value was 89 nM. 2-Arachidonoylglycerol was also shown to bind appreciably to the cannabinoid receptor in competitive inhibition experiments. The apparent binding affinity was markedly increased when the binding assay was carried out in the presence of the esterase inhibitor DFP or at 0 degrees C. Free arachidonic acid and N-palmitoylethanolamine were almost inactive in terms of binding to the cannabinoid receptor in synaptosomal membranes. 2-Arachidonoylglycerol may be an endogenous cannabinoid receptor ligand in the brain.

Animals↗

Current status of renal replacement therapy in Japan.

The study of the current status of renal replacement therapy in Japan is based on the analysis of data from the registry reports for regular dialysis therapy and kidney transplantation. The total number of patients receiving regular dialysis therapy was 123,926 at the end of 1992: 117,809 (95.1%) on hemodialysis and 6,117 (4.9%) on peritoneal dialysis. The primary diseases of newly accepted patients were chronic glomerulonephritis (42.2%), diabetic nephropathy (28.4%), nephrosclerosis (5.9%), polycystic kidney disease (2.7%), chronic pyelonephritis (1.6%), and others. The number of kidney transplant patients in Japan was 8,384 at the end of 1991: 6,154 (73.4%) received a living donor transplantation and 2,230 (26.9%) received a cadaver donor transplantation. Overall 5-year survival rates of dialysis patients were 60.4%: 69.7% for chronic glomerulonephritis, 41.7% for diabetic nephropathy, 39.6% for nephrosclerosis, 73.6% for diffuse polycystic kidney disease, and 66.6% for chronic pyelonephritis. The causes of death of dialysis patients were heart failure (31.1%), cerebrovascular accident (13.6%), infectious diseases (11.3%), malignancies (7.1%), cachexia/uremia (6.7%), myocardial infarction (5.8%), and others. The gross mortality rate of dialysis patients was increased in cases of less than 4 hours of the average length of each dialysis session, less than 4% and more than 9% of the average weight loss during each dialysis session, less than 1.0 of Kt/V, and less than 0.9 and more than 1.7 g/kg/d of protein catabolic rate. Overall 5-year patient and graft survival rates of kidney transplant patients since 1964 were 82.7% and 60.3%: 84.4% and 65.0% in living donor cases, and 77.4% and 46.2% in cadaver donor case, respectively. Those since 1983 were 90.1% and 68.2%: 91.3% and 72.6% in living donor cases, and 87.8% and 59.3%, respectively. Graft survival rates were superior in cases treated with combined steroid, cyclosporine and azathioprine or mizoribine, to those treated with other immuno-suppressive regimens, and they decreased as the number of HLA-A, -B and -DR increased.

Actuarial Analysis↗

[A case of pulmonary tuberculoma with pneumoconiosis (graphite lung) that appeared to be lung cancer].

We report a rare case of tuberculoma with pneumoconiosis (Graphite lung). A 62-year-old man was admitted to our hospital for diagnosis of a rapidly growing coin lesion in the right lung (S8). He had worked for 42 years in a foundry and given a diagnosis of pneumoconiosis (Graphite lung). Because transbronchial lung biopsy and percutaneous needle aspiration biopsy were not diagnostic, the right lower lobe was partially resected. Histological examination revealed the presence of caseous necrosis in a solitary mass. Therefore, it is important to consider tuberculoma in the differential diagnosis of a coin lesion in patients with pneumoconiosis.

Diagnosis, Differential↗

Facilitation of copulatory behavior by pCPA treatments following stria terminalis transection but not medial amygdala lesion in the male rat.

In this study, we examined the effect of p-chlorophenylalanine (pCPA), a serotonin synthesis inhibitor, on masculine sexual behavior in male rats following bilateral medial amygdala lesions (MAL) or bilateral stria terminals cuts (STC). Males with MAL and STC both showed a suppression of sexual behavior, compared to that of sham-operated males, when injected with saline. On the other hand, intraperitoneal injections of pCPA increased mount and intromission frequencies in males with STC. Although pCPA injections also slightly increased mount frequency in males with MAL, the injections failed to affect intromission behavior in MAL males. These suggest that the stria terminalis is insufficient as pathway of a whole output of the medial amygdala in regulating copulatory behavior. The medial amygdala may be involved in some other function, such as erection, than that of the stria terminalis.

Amygdala↗

Nasal reconstruction using free temporoparietal fascial flap transfer (Upton's method).

Reconstructive surgery for severe nasal deformity after radical operation of the maxillary antrum was performed by free temporoparietal fascia transfer to the nasal membrane, followed by secondary-rib cartilage grafting. Correction of nasal deformity caused by severe scar contracture and tissue defect in the nasal cavity has been considered difficult. However, skin grafting with temporoparietal fascia transfer to the nasal membrane can make it possible to perform cartilage grafting without exposure. This method should be nominated as a useful procedure for correction of severe nasal deformity caused by nasal membranous scar contracture.

Female↗

[A clinical study on fluconazole against pulmonary mycosis associated with respiratory diseases].

In 34 hospitals in Kyushu area, the clinical effects and safety of fluconazole (FLCZ) against pulmonary mycosis were studied. To a total of 108 patients with respiratory diseases was FLCZ administered. The results were as follows. 1. Sixty-six cases were evaluable for the clinical efficacy of FLCZ. In 8 cases of pulmonary cryptococcosis, the clinical efficacy rate was 100% (8/8). In 58 cases of pulmonary aspergillosis, it was 43.1% (25/38). Overall, the clinical efficacy rate was 50% (33/66). 2. Fungi were eliminated in 3 of 6 cases in which Cryptococcus was detected, and were eliminated in 8 and reduced in 4 of 30 cases in which Aspergillus spp. including A. fumigatus were detected. 3. Side effects were observed in 5 of 87 cases (5.7%), none of them was serious, however. Abnormal results of laboratory tests that might be related to the FLCZ administration were observed in 5 cases (5.7%). 4. From these results, fluconazole appears to be a potent antifungal agent for treatment of pulmonary mycosis.

Adult↗

Cataract in renal transplantation recipients with combination ciclosporin treatment.

Post surgical cataracts induced by corticosteroids as immunosuppressive agents were investigated in recipients undergoing triple therapy with ciclosporin and the results were compared with those who had therapy without ciclosporin administration. The subjects of the triple therapy group were 54 cases with a mean age of 31.7 years. The mean observation period was 25 months. The incidence of posterior subcapsular cataract was 77.8%. 7.9% of them developed progressed cataract. Early cataractous changes were noticed within one post-operative year in half of the cases. 3 out of 22 cases that were followed up over three years showed progressed cataractous changes. The total doses of methylprednisolone during the period of the first post-transplant year in recipients with Grades I or II and over Grade III were 7.7 +/- 1.9g and 9.8 +/- 3.6g, respectively. They were significantly higher than those in the conventional therapy group. However, a 2 to 3 g reduction in the total dose of steroids during the first year had no influence on cataract occurrence.

Adolescent↗