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Biomedical subjects

K Satake

Publications and source records attributed to K Satake.

At least 19 recordsLinked to original sources

Three-dimensional images for surgical plan of giant sacral schwannoma.

OBJECTIVE: Documentation of three-dimensional (3D) images of a giant sacral schwannoma with intrapelvic expansion. SETTING: Nagoya University, Nagoya, Japan. RESULTS: 3D computed tomography (3D CT) showed a destructed bony region clearly. 3D CT angiography clarified the positional relationship between tumor and iliac arteries. Resection procedure was safely completed based on these 3D evaluations. CONCLUSION: 3D images were helpful to make a surgical plan and to complete this complicated resection combined with sacroiliac reconstruction.

Angiography↗

Immunohistochemical detection of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in human chronic cholecystitis.

AIMS: Recent studies suggest that oxidative DNA damage induced during chronic inflammation may play a role in carcinogenesis in some organs. Although gallbladder carcinomas are frequently observed with a background of chronic cholecystitis, little is known about oxidative DNA damage in chronic cholecystitis. The aims of this study were to investigate the expression of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, in normal and chronically inflamed human gallbladder mucosa and compare its expression with clinicopathological findings. METHODS AND RESULTS: 8-OHdG expression was immunohistochemically examined using a monoclonal antibody against 8-OHdG in human gallbladder specimens. In normal gallbladder (n=5), no 8-OHdG expression was observed. In contrast, nuclear expression of 8-OHdG was detected in 28 of 31cases (90.3%) in gallbladder epithelial cells with chronic cholecystitis. The positive cells were predominantly observed in the areas of active inflammation with prominent cell infiltration. Quantitative analysis revealed that the number of 8-OHdG+ cells (labelling index) significantly (rs=0.671, P < 0.05) correlated with the degree of the activity of mucosal inflammation, while gender, age, and the presence of gallstones did not influence the index. CONCLUSIONS: Oxidative DNA damage is common in chronic cholecystitis, suggesting a possible link between chronic inflammation and gallbladder carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

Airborne uranium contamination--as revealed through elemental and isotopic analysis of tree bark.

A new strategy for characterisation of airborne uranium contamination based on ICP mass spectrometric analysis of tree bark is described. The uranium content of tree barks (50 samples) obtained from diverse locations (remote, rural, industrial) varied over almost four orders of magnitude (0.001-8.3 micrograms/g U) with maximum concentrations recorded in the vicinity of a nuclear fuel fabrication plant (0.70-8.3 micrograms/g U). Elevated concentrations were also observed near a coal-fired power station (0.25-0.38 microgram/g U). Isotopic analysis revealed significant deviation from the natural uranium isotope ratio (235U/238U, 0.00725) at four nuclear installations (235U/238U, 0.0055-0.0097). These findings indicate that tree bark serves as an effective biomonitor for uranium and, with isotopic analysis, discrimination between nuclear and non-nuclear emissions is realised.

Air Pollutants, Radioactive↗

The potential of elemental and isotopic analysis of tree bark for discriminating sources of airborne lead contamination in the UK.

Samples of tree bark, which accumulate airborne material, were collected from seven locations in the UK to provide an indication of the magnitude and source of lead pollution. Measurement of the Pb content and 206/207Pb stable isotope ratio by inductively coupled plasma mass spectrometry revealed significant differences between the sites. The concentration of Pb varied over almost four orders of magnitude from 7.2 to 9,600 micrograms g-1, the maximum values being found near a 'secondary' Pb smelter. The 206/207Pb isotope ratios varied from 1.108 +/- 0.002 to 1.169 +/- 0.001. The lowest Pb concentrations and highest isotope ratios were detected in bark samples from the Scilly Isles, reflecting the low-level of industry and road traffic. In contrast, samples obtained from a city centre (Sheffield) and near a motorway (M1) contained 25-46 micrograms g-1 Pb and recorded the lowest 206/207Pb ratios. Higher concentrations in the vicinity of a coal-fired power station recorded a 206/207Pb ratio of 1.14, suggesting a significant contribution from fly-ash. The relative contribution of lead from petrol (206/207Pb = 1.08) and other sources such as coal (206/207Pb = 1.18) were thus estimated using mass balance equations. Tree bark near the lead smelter recorded an intermediate 206/207Pb ratio of 1.13 reflecting the processing of material of mixed origin.

Air Pollutants↗

Mapping airborne lead contamination near a metals smelter in Derbyshire, UK: spatial variation of Pb concentration and 'enrichment factor' for tree bark.

Samples of tree bark, collected over an area of 4 km2 near a small non-ferrous metals smelter in Derbyshire, UK, were analysed for Pb and Al by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Analyte concentrations varied from 100 to over 25,000 mg kg-1 and 5 to 1000 mg kg-1, respectively. While an inverse relationship between the Pb content of bark and distance from the smelter was observed, concentrations fluctuated, indicating a variability in sample collection efficiency and problems in standardization. To overcome these effects, the Pb/Al ratio was calculated and subsequently normalized to the average Pb/Al ratio in continental crust (0.00015). On the assumption that the time-averaged concentration of airborne Al in this area is relatively constant and derived principally from wind-blown soil, the measurement represents an anthropogenic 'enrichment factor' (PbEF). PbEF varied from 10,000 to over 1,000,000, and showed a consistent reduction with distance from the smelter. Isolines of equal PbEF were subsequently defined on a map of the sampled area. Pb contamination was greatest in the vicinity of the smelter, and preferential transport along the NW-SE axis of the valley (in which the smelter is situated) was observed. The use of enrichment factors thus proved valuable in defining the relative level of airborne-derived Pb pollution.

Air Pollutants↗

[A case of breast cancer 5 cm in diameter treated with a breast preserving approach after preoperative intra-arterial chemotherapy].

The patient was a 59-year-old female with a mass in the right breast (area C). At the initial examination, the mass was 5.0 x 4.5 cm on palpation, aspiration cytology was Class V, and a diagnosis of T2aN1aM0, Stage II breast cancer was made. Since the patient strongly desired a breast preserving treatment, a reduction in the size of the mass was attempted by local intra-arterial chemotherapy. Docetaxel (TXT) was administered at 60 mg into the internal thoracic artery and lateral thoracic artery at a rate of once a month for a total of 5 times. After the fifth treatment, the mass was reduced in size to 2.8 x 2.5 cm on palpation, and breast-preserving resection was then carried out. On histopathological examination, cancer was observed in an area of 3.0 x 2.2 cm. Careful follow-up is still needed, but preoperative intra-arterial chemotherapy is considered to be significant as a step before breast preserving surgery for breast cancer with a diameter of 3-5 cm.

Antineoplastic Agents, Phytogenic↗

Reduced expression of p16 and p27 proteins in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high incidence in east Asian countries. Inactivation of cyclin-dependent kinase (CDK) inhibitors (CKIs) and overexpression of G1 cyclin has been thought to be important for tumor development. To determine whether reduction of CKI (p16 and p27) expression was associated with NPC development, we performed immunohistochemical staining of NPC specimens from 20 patients. We found that p16 and p27 proteins were negative in 8 of 20 and 16 of 20 cases, respectively; that either p16 or p27 proteins were negative in 17 of 20; and that both p16 and p27 were negative in 7 of 20. Excepting the cases in which both CKIs were negative, negativity of p27 alone was statistically higher than that of p16 (9/20 versus 1/20, P = .022), suggesting that the reduction of p27 protein is an important event for the multi-step process of NPC development.

Carcinoma, Squamous Cell↗

Nitric oxide via macrophage iNOS induces apoptosis following traumatic spinal cord injury.

To investigate the pathophysiological mechanisms involved in post-traumatic impairment of the spinal cord, we analyzed expression patterns of the inducible nitric oxide synthase (iNOS) gene following acute injury of rat spinal cord using a weight drop technique. PCR analysis revealed that iNOS mRNA appeared at 3-12 h after injury and declined thereafter. Immunohistochemical analysis showed that iNOS-positive cells invaded the lesioned area through the perivascular space at 6 h after injury. The population of these cells peaked at 24 h and then declined to disappear 3 days after injury. The iNOS-positive cells were also stained with ED-2 but not with ED-1 or OX-42, indicating that these cells were macrophages and/or perivascular cells. In parallel with the appearance of iNOS-positive cells, other cells emerged that were positively stained by the terminal deoxynucleotidyl-transferase-mediated dUDP-biotin nick end-labeling (TUNEL) assay. TUNEL-positive cells were scattered in the lesioned area 1 day after injury, but some in the surrounding area close to iNOS-positive cells. Administration of L-Ng-nitro-arginine methylester, a competitive inhibitor of NOS, resulted in a reduction of TUNEL-positive cells in the lesioned area. These results suggest that nitric oxide generated by iNOS of macrophages and/or perivascular cells plays a significant role in eliminating damaged cells from the lesioned area by apoptosis.

Animals↗

Increase in neurotrophin-3 expression followed by Purkinje cell degeneration in the adult rat cerebellum after spinal cord transection.

Changes in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) contents following thoracic spinal cord transection were investigated in the cerebral cortex, hippocampus, and cerebellum of rats. The NT-3 content became significantly elevated at 3 days after transection only in the cerebellum and gradually declined to the control level by 6 days after the injury, remaining unchanged in the cerebral cortex and hippocampus. No significant change in the BDNF content was observed in any of the regions tested. Immunohistochemical analysis showed that the labeling indicating NT-3-like immunoreactivity was intensified in both cerebellar granule and Purkinje cells 3 days after the injury. The number of Purkinje cells with aggregation of chromatin around the nuclear membrane and swelling of the cytoplasm and/or organelles gradually increased with time starting 4 days after the injury, demonstrating morphological changes indicative of necrosis. However, no abnormal morphology was found in cerebellar granule cells at any time examined. We suggest that it is reasonable that increased NT-3 stimulated the death of Purkinje cells, because 1) the degeneration was necrosis, which is known to be accelerated by neurotrophins under certain pathological conditions, and 2) the increase in NT-3 occurred prior to Purkinje cell degeneration. Therefore, our present results may imply that spinal cord injury-induced NT-3 accelerates injury rather than alleviates degeneration of Purkinje cells.

Animals↗

Up-regulation of glial cell line-derived neurotrophic factor (GDNF) following traumatic spinal cord injury.

We investigated the temporal and spatial expression patterns of the GDNF gene after subjecting rats to an acute contusion injury of the spinal cord using the weight drop technique. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that GDNF transcription in the spinal cord began to increase within 30 min after injury and peaked within 3 h. Immunohistochemical analysis showed GDNF immunoreactivity to be present mainly in microglia and macrophages 1 day after injury, but not in neurons or astrocytes. This immediate upregulation of GDNF gene expression may be a component of an inflammatory process and probably exerts a protective effect on neurons following spinal cord injury (SCI).

Animals↗

Therapeutic effect of 1 M tegafur-0.4 M 5-chloro-2, 4-dihydroxypridine-1 M potassium oxonate (S-1) on head and neck squamous carcinoma cells.

1 M Tegafur (FT)-0.4 M 5-chloro-2,4-dihydroxypridine (CHDP)-1 M potassium oxonate (Oxo) (S-1), was developed as a new oral antineoplastic agent based on biochemical modulation of fluorouracil (5-FU) by CHDP and Oxo. The antitumor effect of S-1 on human head and neck squamous carcinoma cells was evaluated in xenografts and a metastasis model, in comparison with combined drug of 1 M FT and 4 M uracil (UFT). Mice treatment with S-1 showed a significant higher concentration of 5-FU in the tumor and the serum than UFT treated mice. S-1 showed higher tumor growth inhibition and metastasis inhibition than UFT. The mice in which metastasis was inhibited lived more than twice as long as the control mice. These results suggest that S-1 will have a higher clinical therapeutic effect against advanced squamous cell carcinoma of the head and neck in humans.

Administration, Oral↗

Selenium dioxide oxidations of dialkyl-3H-azepines: the first synthesis of 2-azatropone from oxidation of 2, 5-Di-tert-butyl-3H-azepine

Oxidation reactions of 2,5- and 3,6-di-tert-butyl-3H-azepines (1 and 2) with selenium dioxide (SeO(2)) were performed. The oxidation of 1 with SeO(2) gave 3-tert-butyl-7,7-dimethyl-4-oxo-octa-2,5-dienal 3 in 36% yield, 4-tert-butyl-5-(3,3-dimethyl-2-oxo-butylidene)-1, 5-dihydro-pyrrol-2-one 4 in 13% yield, 2, 6-di-tert-butyl-2-pyridinecarbaldehyde 5 in 12% yield, and 4, 7-di-tert-butyl-2H-azepin-2-one (2-azatropone) 6 in 6% yield, respectively. Oxidation of 2 with SeO(2) gave 2, 2-dimethyl-1-[2-(5-tert-butyl)-pyridyl]propanol 7 in 55% yield, and 3,6-di-tert-butyl-2H-azepine 8 in 5% yield, respectively. We found that selenium dioxide oxidation of 1 affords 4-oxo-octa-2,5-dienal 3 by a new ring cleavage reaction of 1, and we described the first synthesis of 2-azatropone 6 from this oxidation of 1. In the case of 2, pyridylpropanol 7 was obtained as the major product. We now report in detail result of these oxidation reactions, which have led to the synthesis of a novel azatropone derivative.

Journal Article↗

An experimental model of tumor dormancy therapy for advanced head and neck carcinoma.

An experimental model of tumor dormancy therapy for advanced head and neck carcinoma was developed. After transplantation of KB cells into nude mice, the mice were given tiracoxib, a selective cyclooxygenase (COX)-2 inhibitor, probucol, an antioxidant, and S-1, an oral pro-drug of 5-fluorouracil (5-FU), or combinations of two of them. The combined administration of tiracoxib with probucol significantly inhibited the tumor growth. The angiogenesis in this group was markedly reduced. Tiracoxib and probucol did not affect the intratumoral concentration of 5-FU when coadministered with S-1. The combined use of tiracoxib and probucol is thus a candidate for use in maintenance therapy after the primary therapy for patients with advanced head and neck carcinoma.

Animals↗

Neuroendocrine carcinoma of the sigmoid colon: report of a case.

Neuroendocrine carcinoma of the colon is a rare entity; however, this type of tumor is known for its aggressive progression and poor prognosis. A case of a 56-year-old Japanese male is presented in this report. A huge, child's head-sized tumor was found to have grown extraluminally on the sigmoid colon with multiple liver metastases. The tumor measured 16.5 x 15 x 8.2 cm in size and weighed 1 300 g. The patient died of hepatic failure due to massive liver metastases 6 months after operation. The pathological findings including an electron microscopic analysis were correlated with those of neuroendocrine carcinoma. We reviewed the English literature, and analyzed 94 cases of neuroendocrine carcinoma which had been reported previously. The nomenclature and definition of this disease still remains somewhat unclear, and not a small population of this disease may thus have been misdiagnosed and treated as other less aggressive entities. The necessity to make an accurate differential diagnosis in such cases is thus emphasized.

Carcinoma, Neuroendocrine↗

Therapeutic effects of loxiglumide on experimental acute pancreatitis using various models.

We investigated the therapeutic effects of a cholecystokinin A (CCK-A) receptor antagonist, loxiglumide, on various models of experimental pancreatitis. This study shows that loxiglumide ameliorated caerulein-induced acute pancreatitis in mice as previously reported. The effects of loxiglumide on hemorrhagic and necrotizing acute pancreatitis is controversial. This study, however, shows that loxiglumide improves the survival rates in necrotizing acute pancreatitis induced by intraductal injection of taurocholate, followed by caerulein injection. In addition, the administration of loxiglumide improved both the biochemical and pathological changes of edematous acute pancreatitis induced by a closed duodenal loop in rats. It is concluded that the CCK-A receptor antagonist, loxiglumide, has therapeutic and/or prophylactic effects on acute pancreatitis in various models of experimental acute pancreatitis.

Animals↗

Clinical evaluation of cholecystokinin-A- receptor antagonist (loxiglumide) for the treatment of acute pancreatitis. A preliminary clinical trial. Study Group of Loxiglumide in Japan.

The therapeutic effects of loxiglumide on human acute pancreatitis was investigated in 104 Japanese institutes from October 1992 to March 1994. Acute pancreatitis was diagnosed by the Japanese Criteria of Acute Pancreatitis. Soon after the diagnosis was made, one of three doses of loxiglumide (100, 300 and 500 mg/day) were injected intravenously twice a day for 14 days. The efficacy of the treatment was evaluated by clinical signs, physical signs, and biochemical findings. 189 patients were included in this trial. The clinical signs, such as abdominal pain, disappeared in 20% of the patients on the 1st day after treatment, and the rate of improvements increased thereafter. Physical signs also improved. Serum amylase levels returned to normal within 3 days after treatment, and serum lipase showed almost the same changes as serum amylase levels, but serum lipase levels in the high-dose group (500 mg/day) returned to normal more quickly compared with the other two doses. It is concluded that the cholecystokinin A receptor antagonist, loxiglumide, may become a useful drug in the treatment of acute pancreatitis in man, although more detailed investigations are needed.

Abdominal Pain↗

Insulinoma with hyperproinsulinemia during hypoglycemia and loss of expression of vacuolar-type H(+)-ATPase (V-ATPase) in the tumor tissue.

Hypoglycemia with a low serum immunoreactive insulin (IRI) level and serum immunoreactive C-peptide (IRC) level was found in a 74-yr-old female. Although a fasting test induced hypoglycemia, the responses of IRI and IRC during the fasting test, and the results of a glucose tolerance test, glucagon test, and secretin test did not indicate the presence of an insulinoma. However, the serum proinsulin level before the fasting test was 130.5 pmol/L (N: 3.0-10.0 pmol/L), and this high level was maintained throughout the test. Soon after surgical enucleation of the tumor, the patient's blood glucose levels increased. Postoperatively, the hypoglycemic status resolved, and the serum proinsulin levels returned to normal (2.8 pmol/L). Histopathological studies revealed a typical insulinoma. Immunohistochemical studies by the recently developed method for vacuolar-type H+ (V-ATPase), which is responsible for acidification of the intracellular compartments in eukaryotic cells, showed that normal islets stained positive, but not the tumor. This finding indicates that the insulin-secretory granules in the insulinoma cells existed in a microenvironment in which V-ATPase activity had been lost. This suggests that the reduced activity of V-ATPase on the endomembrane of the insulin-secretory granules in insulinomas may result in loss of the acidic microenvironment and impaired conversion of proinsulin by converting enzymes.

Aged↗