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Biomedical subjects

M Furukawa

Publications and source records attributed to M Furukawa.

At least 37 records · Page 2Linked to original sources

Simultaneous separation of common mono- and divalent cations on a zirconium-modified silica gel column by ion chromatography with non-suppressed conductimetric detection and tartaric acid-15-crown-5 as eluent.

The application of laboratory-made zirconium-modified silica gels (Zr-silicas) as cation-exchange stationary phases to ion chromatography with conductimetric detection (IC-CD) for common mono- and divalent cations (Li+, Na+, NH4+, K+, Mg2+ and Ca2+) was carried out. Zr-silicas were prepared by the reaction of the silanol group on the surface of silica gel with zirconium tetrabutoxide (Zr(OCH2CH2CH2CH3)4) in ethanol. Zr-silica adsorbed on 10 mg zirconium g(-1) silica gel was a suitable cation-exchange stationary phase in IC-CD for the separation of these mono- and divalent cations. Excellent simultaneous separation and highly sensitive detection for these cations were achieved in 10 min by IC-CD using a Zr-silica column (150x4.6 mm I.D.) and 10 mM tartaric acid containing 10 mM 15-crown-5 (1,4,7,10,13-pentaoxacyclopentadecane) as the eluent. The proposed IC-CD method was successfully applied to the determination of major mono- and divalent cations in natural water samples.

Cations, Divalent↗

Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells.

Cyclooxygenase-2 (COX-2) is an inducible form of COX and is overexpressed in diverse tumors, raising the possibility of a role for COX-2 in carcinogenesis. In addition, COX-2 contributes to angiogenesis. The Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), is detected in at least 70% of nasopharyngeal carcinoma (NPC) and all EBV-infected preinvasive nasopharyngeal lesions. We found that in specimens of LMP1-positive NPC, COX-2 is frequently expressed, whereas LMP1-negative NPC rarely express the enzyme. We next found that expression of LMP1 in EBV-negative nasopharyngeal epithelial cells induced COX-2 expression. Coexpression of IkappaBalpha(S32A/S36A), which is not phosphorylated and prevents NF-kappaB activation, with LMP1 showed that NF-kappaB is essential for induction of COX-2 by LMP1. We also demonstrate that NF-kappaB is involved in LMP1-induced cox-2 promoter activity with the use of reporter assays. Two major regions of LMP1, designated CTAR1 and CTAR2, are signal-transducing domains of LMP1. Constructs expressing either CTAR1 or CTAR2 induce COX-2 but to a lesser extent than wild-type LMP1, consistent with the ability of both regions to activate NF-kappaB. Furthermore, we demonstrate that LMP1-induced COX-2 is functional because LMP1 increased production of prostaglandin E(2) in a COX-2-dependent manner. Finally, we demonstrate that LMP1 increased production of vascular endothelial growth factor (VEGF). Treatment of LMP1-expressing cells with the COX-2-specific inhibitor (NS-398) dramatically decreased production of VEGF, suggesting that LMP1-induced VEGF production is mediated, at least in part, by COX-2. These results suggest that COX-2 induction by LMP1 may play a role in angiogenesis in NPC.

Cyclooxygenase 2↗

Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma.

Matrix metalloproteinase 2 (MMP-2) plays a crucial role in invasion and metastasis of malignant tumors. Membrane type 1-MMP (MT1-MMP) was originally identified as an activator of MMP-2. Tissue inhibitor of MMP-2 (TIMP-2) was identified as an inhibitor of MMP-2 and MT1-MMP. However, TIMP-2 was reported to be essential for cell-mediated activation of MMP-2 and thus, the contribution of TIMP-2 to tumor invasion has remained controversial. This study was designed to analyze the role of TIMP-2 for activation of MMP-2 and its prognostic value in tongue squamous cell carcinoma (SCC). Expression of MMP-2, MT1-MMP and TIMP-2 protein was analyzed by immunohistochemistry, and their association with clinical factors was evaluated in 51 patients treated surgically for tongue SCC. Expression of MMP-2, MT1-MMP and TIMP-2 was significantly correlated with local and distant metastatic tumor recurrence and poor prognosis (MMP-2 and MT1-MMP, p < 0.0001; TIMP-2, p = 0.0002). Activation of MMP-2, analyzed by gelatin zymography in 17 fresh specimens, was remarkably associated with expression of MMP-2 (r = 0.779, p < 0.0001), MT1-MMP (r = 0.674, p < 0.0022) and TIMP-2 (r = 0.858, p < 0.0001). Increased expression of TIMP-2, as well as MMP-2 and MT1-MMP, was an important prognostic factor in patients with tongue SCC.

Adult↗

Impact of olfactory impairment on quality of life and disability.

OBJECTIVE: To determine whether olfactory loss affects patients' quality of life or level of disability. DESIGN: Retrospective survey using questionnaire data and clinic database review. SETTING: Two university medical center smell and taste clinics. PATIENTS: A total of 1407 patients were tested for smell and taste disturbances from 1984 through 1998. Surveys were mailed to 1093 patients who had abnormal test scores; 420 (38.4%) returned completed surveys. Patients were grouped by self-rated ability to smell as "impaired" (those reporting persisting deficits) or "improved" (those reporting no smell problem when surveyed). MAIN OUTCOME MEASURES: Response frequencies were compared between the 2 groups for questions regarding ability to perform common activities of daily living and quality-of-life issues. RESULTS: Mean (+/-SD) number of activities of daily living affected by olfactory loss was 4.70 +/- 3.56 for the impaired group and 0.61 +/- 1.58 for the improved group (P < .001). Among specific activities, the most common cited impairments were ability to detect spoiled food (impaired vs improved groups, 75% vs 12%; P < .001), gas leaks (61% vs 8%; P < .001), or smoke (50% vs 1%; P < .001); eating (53% vs 12%; P < .001); and cooking (49% vs 12%; P < .001). Differences in quality-of-life issues were reported primarily in the areas of safety and eating. Overall satisfaction with life was reported by 87% of the improved group but only 50% of the impaired group (P < .001). CONCLUSIONS: Patients reporting persistent olfactory impairment after previously documented olfactory loss indicate a higher level of disability and lower quality of life than those with perceived resolution of olfactory compromise.

Activities of Daily Living↗

MRI in seven cases of tacrolimus (FK-506) encephalopathy: utility of FLAIR and diffusion-weighted imaging.

We assessed the utility of fluid-attenuated inversion-recovery (FLAIR) and diffusion-weighted (DWI) images in investigation of tacrolimus (FK-506) encephalopathy, and to see whether we could predict its cause from clinical and imaging data. In seven patients with presumed FK-506 toxicity the areas involved on MRI were similar to those in cyclosporin A (CsA) toxicity. The abnormal signal was most evident on FLAIR in all cases. In three of four patients who underwent DWI, no diffusion abnormalities were detected; in the remaining patient, increased diffusion was seen in the deep white matter bilaterally on the apparent diffusion coefficient map, consistent with the findings on T2-weighted spin-echo and FLAIR images. Five of the six patients for whom we had clinical data showed sudden changes in electrolyte or fluid equilibrium due to diarrhoea, a polyuria or oliguria one day before or on the day of onset of the central nervous system disturbances. We speculate that FK-506 encephalopathy is triggered by the disturbance of the electrolyte and/or fluid equilibrium, given a certain serum level of FK-506.

Adolescent↗

Induction of c-Met proto-oncogene by Epstein-Barr virus latent membrane protein-1 and the correlation with cervical lymph node metastasis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is distinctive in head and neck carcinomas for its close association with Epstein-Barr virus and its highly metastatic nature. Up-regulation of cell motility is essential for enhancement of metastatic potential. The expression of c-Met proto-oncogene, a high-affinity receptor for hepatocyte growth factor/scatter factor, has been reported to correlate with metastatic ability of the tumor cell. We observed close association of c-Met expression with cervical lymph node metastasis (P = 0.0272) in 39 NPC specimens studied immunohistochemically. Epstein-Barr virus-encoding latent membrane protein-1 (LMP-1) is a primary oncogene and is suggested to enhance the metastatic property of NPC. Previously, we reported that LMP-1 enhanced the motility of Madin-Darby canine kidney (MDCK) epithelial cells that was mediated by activation of Ets-1 transcription factor. Therefore, we examined the interrelationships of LMP-1, Ets-1, and c-Met. In immunohistochemical studies, the expression of LMP-1, Ets-1, and c-Met correlated significantly with each other in NPC (LMP-1 versus Ets-1, P < 0.0001; Ets-1 versus c-Met, P = 0.0012; LMP-1 versus Met, P = 0.0005). Transfection of LMP-1-expressing plasmid in MDCK cells induced c-Met protein expression. The c-Met protein was also induced by Ets-1 expression, and induction of c-Met by LMP-1 was suppressed by introducing a dominant-negative form of Ets-1 in LMP-1-expressing MDCK cells. These results suggest that LMP-1 induces c-Met through the activation of Ets-1, which may contribute in part to the highly metastatic potential of NPC.

Animals↗

Predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: In order to elucidate the predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma (ICC), we evaluated 7 patients who survived for more than 5 years (5-year survivors). METHODS: We examined the clinicopathologic and biologic factors of the 5-year survivors, and these findings were then compared with those in 20 patients who died within 5 years after surgery (control group). RESULTS: In the 5-year survivors, the gross appearance of the tumors included a mass-forming (MF) type in 5 cases, an intraductal growth (IG) type in 1, and another type (microcarcinoma with hepatolithiasis) in 1. No case demonstrated a periductal infiltrating (PI) type. Except for 1 case with an IG type tumor, no lymph node metastasis was seen in any patients. All of the 5-year survivors were classified from stage I to III, and all also underwent a curative resection. The clinicopathologic factors demonstrating significant differences between the 5-year survivors and the control group included the gross type of the tumor, lymph node involvement, the surgical margin, curability, and pTNM stage. CONCLUSION: The predictive factors for long-term survival in patients with ICC are thus suggested to include not only tumor staging and curability, but also lymph node metastasis and the gross type of the tumors.

Actuarial Analysis↗

Barotraumatic blowout fracture of the orbit.

We report a rare case of a barotraumatic blowout fracture of the orbit. A 32-year-old woman presented with sudden swelling of the right orbital region after vigorous nose blowing. Computed tomography scan revealed a blowout fracture of the medial wall of the right orbit with orbital emphysema and herniation of the orbital soft tissue. She was treated with prednisolone and an antibiotic, and did not show diplopia or visual disturbance. Three different theories have so far been proposed to explain the mechanism of blowout fractures, globe-to-wall contact theory, hydraulic theory, and bone conduction theory. The present case indicates that blowout fractures of the orbit can be induced solely by a sudden change of pressure, thereby suggesting the validity of the hydraulic theory.

Adult↗

Homogeneous liquid-liquid extraction method for the selective spectrofluorimetric determination of trace amounts of tryptophan.

Twenty-one amino acids were derivatized with fluorescamine (FLA) under basic conditions (pH 9) and the extraction of the amino acid-FLA derivatives was investigated using a homogeneous liquid-liquid extraction with perfluorooctanoic acid (HPFOA) based on phase separation under strongly acidic conditions. Under the optimum concentration conditions for the reagents ([PFOA]T = 3 x 10(-3) mol dm-3, [acetone]T = 3 vol.%, [HCl]T = 1.8 mol dm-3), the concentration factor was approximately 1000-fold (i.e., 30 microliters of the sedimented liquid phase was produced from 33 ml of the homogeneous aqueous solution). The percentage extraction (E) was determined for the 21 amino acid-FLA derivatives; the value for the tryptophan (Trp)-FLA derivative was 80.9%, whereas the other derivatives were not almost extracted (E < 0.4%). The Trp-FLA derivative was selective for the extraction using the homogeneous liquid-liquid extraction method with HPFOA. After the sedimented liquid phase containing Trp-FLA has been placed on a polytetrafluoroethylene filter-paper, the fluorescence intensity was determined using a spectrofluorimeter with filter-paper as the solid-sample holder. The calibration graph of Trp was linear over the range 1.0 x 10(-8)-1.5 x 10(-6) mol dm-3. The relative standard deviation for the central value of the calibration graph was 4.5% (five determinations) and the detection limit (S/N = 3) was 8.9 x 10(-9) mol dm-3. When the proposed method was applied to the highly sensitive spectrofluorimetric determination of Trp in animalin-L syrup, the results were satisfactory.

Spectrometry, Fluorescence↗

Further observation of content uniformity of d-alpha-tocopheryl acetate as an oily drug in granules obtained by wet granulation with a high-shear mixer.

Using d-alpha-tocopheryl acetate (VE) as a model drug, we investigated the effects of the amount of binder solution on content uniformity of oily drugs in granules obtained by, wet granulation with a high-shear mixer. When the amount of binder solution was below the water volume for the plastic limit, the content of VE was less than 50% in the fractionated fine granules, but was more than 200% in the fractionated large granules. Large variations were seen in the contents of VE even if the granulation time was extended up to 30 min. This large variation was not decreased by the milling process. On the other hand, when the amount of binder solution was at or above the water volume for the plastic limit, less variation was observed in the content of VE throughout the granules, and the content of VE was fairly uniform. Nuclei rich in VE were formed when VE was adsorbed with the powder before granulation. When the amount of binder solution was below the water volume for the plastic limit, the shearing force of mixer blades to the granules was low, so that the nuclei rich in VE were not fragmented. This led to the nonuniformity of VE content throughout the granules. On the other hand, when amount of binder solution was at or above the water volume for the plastic limit, the shearing force of mixer blades against the granules increased and became sufficient to fragment the nuclei. This led to the uniformity of VE content throughout the granules. This study showed that content uniformity of VE in the granules can be achieved by controlling the physical shearing force of mixer blades by regulating the amount of binder solution.

Antioxidants↗

Clinical bitterness masking test for phantogeusia.

It is difficult to determine the reason why a patient complains of a bitter taste when their mouth is empty. We examined a new diagnostic test using a bitterness masking substance. The bitterness masking substance, 'Benecoat BMI-60' (hereafter BMI-60), is a masking substance specific to the taste cells' bitterness receptors. After patients gargled with BMI-60 solutions, the phantom sensation of bitterness was masked in some patients, but was not masked in others. Bitter substances in saliva seemed to be masked by BMI-60, but bitterness did not seem to be masked when the locus of the phantom sensation was within the peripheral nerve and/or the brain. The bitterness masking test is useful for diagnosis of the phantom sensation of bitter taste.

Aged↗

Natural progression of untreated hepatolithiasis that shows no clinical signs at its initial presentation.

GOALS: To elucidate the natural progression of hepatolithiasis that showed no signs at the time of initial presentation. STUDY: Over a 17-year period, we observed 122 of 311 patients with hepatolithiasis who reported no symptoms and, thus, who received no treatment at initial presentation. The follow-up period was for up to 15 years (mean, 10.08 years). RESULTS: Fourteen of 112 patients (11.5%) developed some symptoms attributed to hepatolithiasis. The interval until the onset of symptoms ranged from 9 months to 7.33 years (mean, 3.42 years ). The developing symptoms included abdominal pain, hepatic abscess, cholangitis, and cholangiocarcinoma. Nine of the 14 patients (64.3%) developed stone migration to the extrahepatic bile duct at the onset of clinical symptoms. The incidence of lobar liver atrophy on computed tomography in the patients with symptomatic hepatolithiasis (13 of 14 patients; 92.9%) was significantly higher than that in the patients with asymptomatic hepatolithiasis (14 of 108 patients; 13.0%). The prognosis of the patients with symptomatic hepatolithiasis were as follows: 2 died of cholangiocarcinoma, 1 died of hepatic failure, and 11 survived. Fifteen of asymptomatic patients died, but none of these deaths were attributed to hepatolithiasis. CONCLUSIONS: Close observation is an alternative management at initial presentation for patients with asymptomatic hepatolithiasis without extrahepatic stones or lobar liver atrophy.

Adolescent↗

Proliferation and functional changes of pancreatic gastrin cells in neonatal rat.

INTRODUCTION: Although gastrin cells are not found in the adult pancreas, they are found transiently in the neonatal pancreas. It has been suggested that gastrin may play a role in pancreatic development. However, cell kinetics as well as the fate and the role of gastrin cells are not clear. METHODOLOGY: Proliferation and functional changes of pancreatic gastrin cells in neonatal Wister rats were studied by immunohistochemistry and [(3)H]thymidine autoradiography. RESULTS: Numbers of pancreatic gastrin cells in neonatal rats showed a peak immediately after birth and then decreased rapidly. Gastrin cells were observed within approximately 2 weeks after birth in islets and within approximately 4 weeks after birth among exocrine cells. In contrast with the decrease of gastrin cell numbers, numbers of duodenal cholecystokinin cells increased remarkably after 7 days of age. Proliferative activity of acinar cells showed two peaks at age 2 days and 9 days. Despite a decrease in gastrin cell numbers, gastrin cells maintained a certain degree of proliferative activity. The "re-staining method" for gastrin and insulin revealed that immunoreactive cells for both gastrin and insulin were rarely found a few days after birth. CONCLUSION: These results suggest that pancreatic gastrin cells do not die off or change to another type of endocrine cell and that some gastrin cells change to insulin cells.

Aging↗

Antitumor beta glucan from the cultured fruit body of Agaricus blazei.

Agaricus blazei is a medically important mushroom widely eaten and prescribed in Japan. Polysaccharide fractions were prepared from cultured A. blazei by repeated extraction with hot water (AgHWE), cold NaOH (AgCA), and then hot NaOH (AgHA). By chemical, enzymic, and NMR analyses, the primary structures of AgHWE, AgCA, and AgHA were mainly composed of 1,6-beta-glucan. Among these fractions, the NaOH extracts showed antitumor activity against the solid form of Sarcoma 180 in ICR mice. To demonstrate the active component in these fractions, several chemical and enzymic treatments were applied. These fractions were found to be i) neutral beta-glucan passing DEAE-Sephadex A-25, ii) resistant to periodate oxidation (I/B) and subsequent partial acid hydrolysis (I/B/H), iii) resistant to a 1,3-beta-glucanase, zymolyase, before I/B, but sensitive after I/B/H. In addition, after I/B/H treatment of the neutral fraction of AgCAE, a signal around 86 ppm attributable to 1,3-beta glucosidic linkage was detectable in the 13C-NMR spectrum. These facts strongly suggest that a highly branched 1,3-beta-glucan segment forms the active center of the antitumor activity.

Agaricus↗