Search PubMed⌕ Search

Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 253 records · Page 14Linked to original sources

1-(2-Tetrahydrofuryl)-5-fluorouracil in combination with uracil suppresses mammary carcinogenesis and growth of tumors induced with 7,12-dimethylbenz[a]anthracene in rats.

The effects of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) on mammary carcinogenesis and growth of tumors induced with 7,12-dimethylbenz[a]anthracene (DMBA) were investigated in rats. Daily oral administration of UFT reduced the incidence and number of mammary tumors compared with those of the DMBA control group, resulting in lower activities in DNA synthesizing enzymes, thymidylate synthetase and thymidine kinase, and a reduction of bromodeoxyuridine-immunoreactive (S-phase) cells in mammary tumors of UFT-treated rats.

9,10-Dimethyl-1,2-benzanthracene↗

The clinical utility of visual evaluation of scintigraphic perfusion patterns for Alzheimer's disease using I-123 IMP SPECT.

The authors examined the role of SPECT perfusion pattern in the diagnosis of Alzheimer's disease (AD) using I-123 IMP. They studied 93 patients who had memory and cognitive disorders, including 42 patients with a diagnosis of probable AD, classifying SPECT images into determined perfusion patterns. The probability of AD was 54% with bilateral temporal and/or parietal defects, 69% with bilateral temporoparietal defects with additional defects, 17% with no defects, and 11% with frontal defects only. The sensitivity of bilateral temporoparietal perfusion defects for AD was 95.2%, whereas the specificity was 56.9%. In the absence of bilateral temporal and/or parietal defects on visual evaluation of SPECT, the diagnosis of AD was unlikely, although it is not pathognomonic for AD, because this sign would be seen in various neuropsychiatric diseases causing memory and cognitive impairments. Visual evaluation of SPECT is of value in the diagnosis of AD among patients with dementia.

Aged↗

Neuroprotective effect of YM90K, a novel AMPA/kainate receptor antagonist, in focal cerebral ischemia in cats.

We studied the effect of a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2, 3(1H, 4H)-quinoxalinedione monohydrochloride], in a focal cerebral ischemia model using anesthetized cats. Cats were subjected to permanent occlusion of the middle cerebral artery (MCA) for 6 h, then killed and examined histologically. The amount of ischemic damage was assessed in 12 stereotaxic coronal sections. Treatment with YM90K (i.v. infusion of 0.5 mg/5 ml/kg/h) starting 10 min after MCA occlusion markedly reduced the volume of ischemic damage (from 2823 +/- 164 mm3 of the cerebral hemisphere in saline-treated cats to 1737 +/- 305 mm3 in YM90K-treated cats). No essential differences were observed between YM90K-and saline-treated cats concerning physiological variables or brain temperature. These results further support the notion that the AMPA/kainate receptor plays an important role in the pathogenesis of focal cerebral ischemia. This evidence for the neuroprotective efficacy of YM90K in a gyrencephalic species suggests its therapeutic potential in the treatment of human stroke.

Animals↗

Acute pancreatitis induced by hypercalcaemia associated with adult T-cell leukaemia: a case report.

A 44 year old Japanese woman with adult T-cell leukaemia (ATL) was admitted to Kyushu University hospital to receive a course of alpha-interferon treatment. She experienced a sudden onset of hypercalcaemia and epigastric pain associated with an increase in the level of pancreatic enzymes. Her serum parathyroid hormone related protein level was above normal although her high sensitive PTH level was within the normal range. Ultrasonography and computed tomography (CT) of the abdomen showed enlargement of the pancreas with indistinct margins and massive accumulation of extrapancreatic fluid. Cullen's sign was observed. A few days after the onset of acute pancreatitis, the serum amylase level increased to 3400 IU/L, and the serum calcium level fell to 4.2 mg/dL from 13.3 mg/dl. Her fasting blood glucose level increased to 242 mg/dL. Although the first episode of pancreatitis appeared to respond to treatment, she experienced a second episode of pancreatitis accompanied by an elevation of the serum calcium level. These findings suggest that acute pancreatitis was caused by hypercalcaemia associated with ATL.

Acute Disease↗

Improvement of peripheral blood lymphocyte subsets in primary biliary cirrhosis after ursodeoxycholic acid therapy.

Immunological abnormalities frequently observed in patients with primary biliary cirrhosis are considered to be related to the pathogenesis of this disease. We performed a prospective trial to evaluate whether immune mechanisms play a role in the effectiveness of ursodeoxycholic acid (UDCA) therapy. Fifteen female patients with primary biliary cirrhosis were followed for 1 year and were then treated with UDCA (600 mg/day) for another year. Laboratory tests, including peripheral blood lymphocyte subsets assessed by dual colour fluorescence analysis using monoclonal antibodies against respective T cell markers, were evaluated at the beginning of the study, at the start of therapy and at the end of therapy. In primary biliary cirrhosis, the proportion of cytotoxic T cells, suppressor inducer T cells and alpha beta-receptor bearing T cells were significantly lower than in healthy controls. No significant changes were observed in the proportions during the year before the therapy. These reductions, however, recovered to normal ranges after 1 year of UDCA therapy. These changes were associated with an improvement in the serum levels of aspartate aminotransferase, alkaline phosphatase, gamma-globulin and IgM. The close correlation between the improvement in the imbalance of lymphocyte subsets after the therapy and the clinical status suggests that an immunological process may play a role in the effectiveness of therapy in primary biliary cirrhosis.

Aged↗

Circulating HCV-RNA, HCV genotype, and liver histology in asymptomatic individuals reactive for anti-HCV antibody and their follow-up study.

The present study was aimed to clarify the virologic status, liver histologies, and the results of follow-up liver tests in symptom-free individuals with anti-HCV antibodies and normal liver tests. Forty-nine individuals with normal liver tests and positive second generation anti-HCV antibody assay were entered into this study. Cases with hepatitis C viremia were evaluated for HCV genotype, amount of circulating HCV-RNA, and liver histology and were followed-up for more than one year. Of the forty-nine individuals, 36 had hepatitis C viremia, indicated by polymerase chain reaction (PCR) assay. Liver histology was as follows: 3 had non-specific changes, 25 had chronic persistent hepatitis (CPH), and 8 had chronic active hepatitis (CAH). Twenty-four cases with CPH and CAH developed an elevated AST and/or ALT concentration (> 30 IU/l) between 12 and 32 months of follow-up. The amount of circulating HCV-RNA ranged from 10(2) to 10(7) copies/50 microliters serum. The distribution of HCV genotypes was nearly the same as that for symptomatic CAH. These data suggest that the histological examination and follow-up examination are very important for following symptom-free individuals with hepatitis C viremia because there are some candidates for interferon therapy among them. There are few individuals who will remain healthy among asymptomatic HCV carriers.

Adult↗

Immunohistochemical localization of transforming growth factor beta, basic fibroblast growth factor and heparan sulphate glycosaminoglycan in gingival hyperplasia induced by nifedipine and phenytoin.

Although drug-induced gingival hyperplasia has been extensively studied, the pathogenesis of this disorder has not been clarified to date. Transforming growth factor beta (TGF beta) and basic fibroblast growth factor (bFGF) have been shown to be implicated in diverse fibrotic and hyperplastic diseases. Heparan sulphate proteoglycan (HSPG), which is composed of heparan sulphate glycosaminoglycan (HSGAG), has also been shown to play an important role in the pathogenesis of tissue overgrowth by enhancing the functions of bFGF. However, the possible implication of these growth factors in gingival hyperplasia has not been studied. Immunohistochemical localization of TGF beta, bFGF, their receptors and HSGAG was studied in 4 nifedipine-induced and 5 phenytoin-induced hyperplastic gingival tissues, and 5 non-hyperplastic control gingival tissues to elucidate the pathogenesis of this disease. Significant immunostaining against TGF beta, bFGF, the receptors of these two growth factors and HSGAG was observed in the lamina propria of hyperplastic gingival tissues while less immunostaining was observed in the controls. The mean numbers of immunostained cells against TGF beta, bFGF, their receptors in a square unit (0.1 x 0.1 mm) of the lamina propria, which were counted to 10 units of each hyperplastic gingival tissue, were significantly higher than those of the controls. The results suggest that the increased synthesis of TGF beta, bFGF, their receptors and HSGAG may be related to the pathogenesis of drug-induced gingival hyperplasia.

Adolescent↗

Promotion of colorectal neoplasia in experimental murine ulcerative colitis.

BACKGROUND: The mechanisms underlying the frequent development of colorectal carcinomas in patients with ulcerative colitis are still unknown. AIMS: To evaluate whether mucosal necrosis and regeneration act as enhancing or promoting factors in colorectal tumorigenesis, development of multiple colorectal tumours was studied in a murine model of ulcerative colitis with azoxymethane pretreatment. METHODS: Periods of chronic ulcerative colitis in mice were induced by three repeated administrations of 3% dextran sulphate sodium subsequent to a single azoxymethane pretreatment, to give conditions similar to the clinically observed active and remission phases. RESULTS: In the chronic colitis group with carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the colorectum. This occurred primarily on the left side of the large intestine or transverse colon, the sites of the most severe colitic injury. The observed lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell proliferation was evidenced by high uptake of bromodeoxyuridine, and increased activities of thymidylate synthetase and thymidine kinase. No tumours were induced in the control groups with azoxymethane pretreatment or chronic colitis alone. CONCLUSIONS: Repeated mucosal erosion with necrosis and regeneration is critical for the development of colorectal tumours in this experimental colitis system.

Animals↗

Pharmacotherapeutic effects of toki-shakuyaku-san on leukorrhagia in young women.

Toki-shakuyaku-san is a traditional Chinese herbal prescriptions that is composed of 6 herbal plants, i.e., peony root, atractylodes lancea rhizome, alisma rhizome, hoelen, cnidium rhizome and Japanese angelica root. Administration with Toki-shakuyaku-san normalized irregular menstrual cycle, healed cervical pseudo-erosion and reduced leukorrhagia in young women who had insufficient luteal function.

Adult↗

Comparison of surface antigens on eosinophils from patients with eosinophilia.

Recent studies have suggested that there may be heterogeneity among human eosinophils. To study this further, surface antigens on blood eosinophils from patients with eosinophilia (23 bronchial asthma, 6 eosinophilic pneumonia, 1 Kimura's disease and 1 adult T-cell leukemia) and from 8 control subjects were examined using a new direct method for fluorescence detection of eosinophils. HLA-DR+ and CD4+ eosinophil counts were higher in patients with bronchial asthma and adult T-cell leukemia (ATL) than in patients from other groups and in control subjects. CD11b+ eosinophil counts in Kimura's disease and ATL were smaller than those in the other groups. CD45RO+ eosinophil counts in bronchial asthma and eosinophilic pneumonia were significantly higher (p < 0.05) compared with Kimura's disease, ATL and control subjects. CD44+ eosinophil counts in eosinophilic pneumonia were significantly higher (p < 0.05) compared with the other groups and control subjects. These results suggest the existence of functional heterogeneity in the different eosinophilic diseases, with eosinophils in bronchial asthma and eosinophilic pneumonia being more highly activated in migration, activation and immunoregulation. On the other hand, eosinophils in Kimura's disease and ATL might be functionally down-regulated. This heterogeneity of eosinophils may reflect differences in the pathogenesis of various eosinophilic diseases.

Adolescent↗

Assessment of early radiation effects on the liver. Comparison of SPECT and MR.

PURPOSE: To evaluate the early effects of radiation on the liver using single photon emission CT (SPECT) with 99mTc-phytate combined with a pinhole collimator and MR imaging with superparamagnetic iron oxide (SPIO) and to compare 2 modalities regarding the assessment of the reticuloendothelial cell function. MATERIAL AND METHODS: The right sides of the livers of 12 anesthetized rats were irradiated with X-rays (4000 cGy). On the 3rd and 4th days postirradiation, SPECT and MR imaging pre- and postcontrast were performed. RESULTS: On SPECT, the irradiated areas appeared as areas with reduced 99mTc-phytate uptake in 9 rats. In the remaining 3 rats, irradiated lesions were not evident on SPECT. On the early postcontrast MR images, differential negative enhancement of the irradiated and nonirradiated areas in the same 9 rats as on SPECT was apparent. However, on the later postcontrast images of 3 of these rats, the irradiated areas, which were brighter than the nonirradiated areas, were visually less clear than those on the earlier postcontrast images. In the remaining 3 rats, no radiation damage was evident on MR images. CONCLUSION: SPECT with 99mTc-phytate and early postcontrast MR imaging with SPIO can show early radiation damage of the liver. The serial assessment of the postcontrast MR images provides functional information on the Kupffer cells.

Animals↗

Recombinant tissue plasminogen activator prevents intimal hyperplasia after balloon angioplasty in hypercholesterolemic rabbits.

The purpose of this study was to clarify whether continuous infusion of recombinant tissue plasminogen activator (rtPA) prevents intimal hyperplasia at the site of arterial injury. Forty-three Kurosawa and Kusanagi hypercholesterolemic (KHC) rabbits which underwent balloon angioplasty of the right common iliac artery were randomly divided into 2 groups; rtPA for 7 days (n = 29) and untreated (n = 14). The former group was subdivided into a high-dose group (n = 15) (2 mg/kg per day continuously for 7 days after 3 mg/kg for 4h) and a low-dose group (n = 14) (0.6 mg/kg per day for 7 days after 0.6 mg/kg for 4 h). Balloon angioplasty was performed with a 2.5-mm balloon (3 x 60-sec, 6-atm inflations at 60-sec intervals) 1 h after the initiation of rtPA infusion via an ear vein. The iliac arteries of the rabbits were histologically studied at 28 days. The cross-sectional areas of the intima, media, and adventitia were calculated at the site of intimal hyperplasia. The intimal cross-sectional area was 0.07 +/- 0.11 (mean +/- SD) mm2 for the high-dose rtPA group and 0.11 +/- 0.07 mm2 for the low-dose rtPA group, and both of these values were significantly less than that for the control group (0.57 +/- 0.21 mm2 p < 0.01). The ratio of the intimal to medial cross-sectional area was significantly (p < 0.01) lower for the rtPA groups than for the control group (high-dose rtPA; 0.10 +/- 0.13, low-dose rtPA; 0.21 +/- 0.19, control; 1.25 +/- 0.55). In conclusion, continuous infusion of rtPA for 7 days prevented intimal hyperplasia after balloon injury.

Angioplasty, Balloon↗

A new monitor with a zinc-oxide thin film semiconductor sensor for the measurement of volatile sulfur compounds in mouth air.

Halitosis, defined as unpleasant oral odor, is a concern among the general public. Halitosis is generally diagnosed by organoleptic examination and by gas chromatographic analysis of the main source of halitosis, volatile sulfur compounds, such as hydrogen sulfide, methyl mercaptan, and dimethyl sulfide. Gas chromatography requires a large-scale system and a long running time. We investigated the use of a zinc-oxide thin film semiconductor sensor for measuring trace volatile sulfur compounds in mouth air. Mouth air samples collected in teflon bags from 21 volunteers were analyzed by 3 methods: the monitor analysis, gas chromatography, and organoleptic examination by 3 judges. The readings of the monitor were correlated with the values of the total volatile sulfur compounds measured by gas chromatography (r = 0.75, P < 0.01) and also with the organoleptic scores given by the judges (r = 0.76, P < 0.01). The organoleptic scores were correlated with the gas chromatographic values (r = 0.71, P < 0.01). These results suggest that this new monitor with a zinc-oxide thin film semiconductor sensor may be used for the diagnosis of halitosis. Its small size and simplicity of handling may enable its use for routine chair-side study and field surveys of halitosis.

Breath Tests↗

YM90K: pharmacological characterization as a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonist.

We investigated the pharmacological properties and neuroprotective actions of a novel alpha-amino-3-hydroxy-5-methylisoxazole-y-propionate (AMPA)/kainate receptor antagonist, [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride (YM90K); formerly YM900], in comparison with those of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX). YM90K selectively displaced [3H]-AMPA binding (Ki = 0.084 microM) and was less potent in inhibiting [3H]-kainate (Ki = 2.2 microM), [3H]-L-glutamate (N-methyl-D-aspartate-sensitive site; Ki > 100 microM) and [3H]-glycine (strychnine-insensitive site; Ki = 37 microM) binding to rat brain membranes. YM90K co-injected with AMPA or kainate into the rat striatum protected cholinergic neurons against AMPA- or kainate-induced neurotoxicity. YM90K showed potent suppressive activity against audiogenic seizure in DBA/2 mice; ED50 values of YM90K and NBQX against tonic seizure were 2.54 and 7.17 mg/kg (i.p.), respectively. The duration of the anticonvulsant effects of YM90K and NBQX was 30 min, indicating that both compounds possess short action. In a global ischemia model, YM90K (15 mg/kg i.p. x 3), NBQX (30 mg/kg i.p. x 3) and CNQX (60 mg/kg i.p. x 3) significantly prevented the delayed neuronal death in the hippocampal CA1 region in Mongolian gerbils when administered 1 h after 5-min ischemia. In addition, the therapeutic time window for the neuroprotective effect of YM90K (30 mg/kg i.p. x 3) was 6 h. In a focal ischemia model, YM90K (30 mg/kg i.v. bolus+10 mg/kg/h for 4 h) reduced the volume of ischemic damage in the cerebral cortex in F344 rats. Thus, YM90K was shown to be a potent and selective antagonist for AMPA/kainate receptors in vitro and in vivo. This compound may provide a therapeutic effect in various neurodegenerative disorders such as ischemic stroke in which glutamate neurotoxicity is thought to play a critical role in neuronal damage.

Animals↗

Regional difference in cerebral blood flow and oxidative metabolism in human cortex.

UNLABELLED: We sought to determine if there are regional differences in cerebral blood flow (CBF) and cerebral metabolic ratio for oxygen (CMRO2) in normal subjects during the resting state. METHODS: Regional CBF, CMRO2 and oxygen extraction fraction (OEF) in 15 normal volunteers (mean age 58.8 +/- 8.2 yr) were measured during rest using PET and a 15O-gas steady-state technique. RESULTS: CBF and CMRO2 in the visual cortex were significantly higher than those in other cortices. Additionally, OEF in the sensorimotor cortex was significantly lower than that in other cortical regions. CONCLUSION: CBF and CMRO2 in the visual cortex are always high, and low OEF in the sensorimotor cortex exists even in resting state in normal subjects. We hypothesize that these regional functional differences would result in different resistances to degeneration.

Brain↗

[Growth of squamous cells lung cancer between alveolar basement membrane and alveolar epithelium].

We examined patterns of growth of cancer cells in specimens of alveoli taken from 41 patients with squamous cell carcinoma (36 men and 5 women, mean age 65 years). For comparison, 8 samples from patients with small cell carcinoma (6 men and 2 women, mean age 64) and 71 samples from patients with adenocarcinoma (48 men and 23 women, mean age 62) were also studied. The samples were fixed in formalin, embedded in paraffin, and then subjected to immunostaining. Glandular structures composed of non-atypical cuboidal cells with negative p53 staining and scanty positive PCNA staining were found in 90% of the samples of squamous cell carcinoma. In small cell carcinoma, 25% of the samples had small numbers of no-atypical glandular structures. In adenocarcinoma, no non-atypical glandular structures were seen. Glandular structures were observed in the periphery of the cancerous tissue. Some of these non-atypical cells were attached to the alveolar basement membranes. We conclude that squamous cell carcinoma grows between the basement membrane and the alveolar epithelium, and leaves noncancerous epithelium with glandular structure.

Adenocarcinoma↗

[Analysis of components in natural food additive "grapefruit seed extract" by HPLC and LC/MS].

The components in a commercial natural food additive "Grapefruit seed extract" and the ethanol extract of grapefruit seeds were analyzed by HPLC and LC/MS. The HPLC chromatogram of the commercial grapefruit seed extract was quite different from that of the ethanol extract of grapefruit seeds. Three main peaks were observed in the chromatogram of the commercial grapefruit seed extract. By comparison of the retention times and the absorption spectra with those of authentic samples, two peaks were ascribed to methyl-p-hydroxybenzoate and 2,4,4'-trichloro-2'-hydroxydiphenylether (triclosan). Triclosan was also identified by LC/MS by using the negative electrospray ionization method.

Chromatography, High Pressure Liquid↗