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Biomedical subjects

Y Tsukamoto

Publications and source records attributed to Y Tsukamoto.

At least 19 recordsLinked to original sources

Enzymatic sialylation of N-linked oligosaccharides using an alpha-(2,3)-specific trans-sialidase from Trypanosoma cruzi: structural identification using a three-dimensional elution mapping technique.

alpha-(2,3)-Sialylated biantennary and triantennary oligosaccharides were enzymatically prepared from pyridyl-2-amino-oligosaccharides with terminal Gal residues, using an alpha-(2,3)-specific trans-sialidase from Trypanosoma cruzi (Lee, K. B., and Lee, Y. C. (1994) Anal. Biochem. 216, 358-364). From the pyridyl-2-amino-derivatives of neutral and alpha-(2,6)-monosialylated biantennary oligosaccharides from human fibrinogen, 5 different sialyl biantennary oligosaccharides were obtained. From two different asialo-triantennary oligosaccharides from fetuin, 35 sialyl oligosaccharides were obtained. The trans-sialidase transferred sialic acids effectively and indiscriminately to different galactosyl residues in the different positions on the substrates. Since the starting materials are neutral oligosaccharide of established structure, and the only alpha-(2,3)-sialyl residues are added to the nonreducing Gal terminal residues, the structures of these oligosaccharides could be identified unambiguously by using the three-dimensional mapping technique (Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y., and Tomiya, N. (1995) Anal. Biochem. 226, 139-146.) in combinations with strategic digestion with beta-galactosidase, beta-N-hexosaminidase, and sialidase L.

Animals

Effects of the catechol-O-methyltransferase inhibitor tolcapone in Parkinson's disease: correlations between concentrations of dopaminergic substances in the plasma and cerebrospinal fluid and clinical improvement.

We compared the concentrations of dopaminergic substances in the plasma and cerebrospinal fluid (CSF) with clinical severity in patients with Parkinson's disease (PD) under L-dopa/carbidopa treatment and under L-dopa/carbidopa+tolcapone treatment. Compared with treatment with L-dopa/carbidopa alone, the co-administration of tolcapone produced a significant decrease in clinical severity; a remarkable reduction in the 3-O-methyldopa (3-OMD) concentration and significant increase in the L-dopa concentration both in the plasma and CSF; and a significant increase in the dopamine concentration in the CSF. The clinical effects of tolcapone were closely correlated with the reduction in the 3-OMD concentration, but not with the increase in the dopamine and L-dopa concentrations in the CSF.

3,4-Dihydroxyphenylacetic Acid

Effect of administering calcium carbonate to treat secondary hyperparathyroidism in nondialyzed patients with chronic renal failure.

We administered calcium carbonate orally to determine its safety and efficacy in treating nondialyzed patients with mild to moderate renal failure and secondary hyperparathyroidism. Twenty patients with chronic renal failure (creatinine clearance levels ranging from 7.9 to 42.7 mL/min) participated in this study. After a 6-month control period, 3 g calcium carbonate was administered daily for 6 months. We studied the effect for another 6 months after discontinuation of the regimen. We found that serum-intact parathyroid hormone was suppressed from 183 +/- 149 pg/mL to 85 +/- 61 pg/mL (P < 0.05) by treatment. This suppression was achieved with no increase in serum concentrations of 1,25(OH)2D3. Serum phosphorus levels decreased from 3.4 +/- 0.7 to 3.0 +/- 0.7 mg/dL (P < 0.01) and Ca2+ concentration increased significantly from 2.40 +/- 0.12 mEq/L to 2.57 +/- 0.08 mEq/L (P < 0.001) at 6 months. These changes were reversed after the 6-month period of withdrawal from calcium carbonate. Deterioration of renal function was not exacerbated by the therapy. Calcium carbonate administration also suppressed the serum concentrations of alkaline phosphatase and osteocalcin, indicating that improvement of hyperparathyroid bone disease is possible without a vitamin D3 supplement at an earlier stage of renal failure. Thus, administration of 3 g oral calcium carbonate daily was highly effective in treating secondary hyperparathyroidism in patients with mild to moderate renal failure.

Administration, Oral

Endoscopic assessment of invasion of colorectal tumors with a new high-frequency ultrasound probe.

The present study was carried out to clarify the usefulness of and problems associated with a new ultrasound probe in the assessment of invasion of colorectal tumors. Normal colorectal wall of 23 resected specimens from colorectal cancer cases was examined in vitro with the probe. Fifty-one patients with colorectal carcinoma and 16 patients with rectal carcinoid tumor were presurgically examined using the probe via the biopsy channel of a conventional colonoscope. After endoscopic and ultrasonographic examination, 27 patients underwent endoscopic resection and 40 underwent surgical resection. The ultrasonographic findings were compared with histologic findings in all cases. Carcinomas and carcinoid tumors were visualized as an echo-poor region with the probe. The overall accuracy rate for depth of invasion was 76% (39/51) for colorectal cancer. The accuracy rates for tumors limited to the mucosa and tumors invading the submucosa were 83% and 90%, respectively; these rates were higher than those for tumors invading the muscularis propria (50%) and beyond the muscularis propria (73%). In all 16 cases of carcinoid tumor, the depth of invasion was accurately shown to be limited to the submucosa. This probe is useful to assess invasion of colorectal tumors, especially small and flat lesions limited to the mucosa or submucosa.

Adult

Expression of gicerin in development, oncogenesis and regeneration of the chick kidney.

Neurite outgrowth factor, which promotes neurite extension from neuronal cells, is an extracellular matrix glycoprotein belonging to the laminin family. Gicerin is a protein that binds neurite outgrowth factor. Its cDNA cloning has revealed that it is a novel cell adhesion molecule belonging to the immunoglobulin super-family. Functional analysis demonstrates that gicerin possesses homophilic binding activity as well as heterophilic binding activity with neurite outgrowth factor. We examined the role and expression of neurite outgrowth factor and gicerin in chick kidney during development. In the embryonic kidney, gicerin was found to be highly expressed both on ureteric bud cells and metanephrogenic mesenchymal cells, when the mesenchymal cells become condensed to be converted into polarized epithelial cells. In the adult kidney, the expression of gicerin was decreased and restricted to the glomerulus, proximal tubule and medullary loop. On the other hand, neurite outgrowth factor was constitutively expressed in the basement membranes of tubules and the matrices of glomeruli during development. As some molecules which are expressed during embryogenesis and suppressed after maturation are re-expressed in tumor cells or tissues during regeneration, we also examined the expression of gicerin in chicken Wilms' tumor and regenerating kidney in interstitial nephritis. Gicerin was remarkably upregulated in Wilms' tumor and re-expressed in collecting ducts recovering from interstitial nephritis. These findings suggest that gicerin could play a role not only in normal renal development but also in oncogenesis and regeneration.

Animals

The coexistence of esophageal submucosal tumor and carcinoma.

The coexistence of esophageal submucosal tumor and carcinoma has been reported only in very few cases up to now, and the relationship between them is unclear. To elucidate the incidence and the pathogenesis of their coexistence, endoscopy and endoscopic ultrasonography (EUS) were sequentially performed in 95 patients who were suspected of having a submucosal tumor of the esophagus. EUS revealed 83 submucosal tumors and 12 cases of extraluminal compression. Two cases of esophageal carcinoma were observed in the series. In one patient, intraepithelial carcinoma was present on a leiomyoma originating in the muscularis mucosae, and in the other patient, multiple superficial carcinomas were presented.

Aged

Pathophysiology and treatment of secondary hyperparathyroidism in patients with chronic renal failure.

Following four etiologies are considered as the possible reason for secondary hyperparathyroidism in the previous reports. First, a decreased serum concentration of 1,25(OH)2D3 directly stimulates PTH secretion. Second, hypocalcemia directly stimulates PTH secretion which is independent of 1,25(OH)2D3 action. Third, the presence of decreased calcemic response to PTH. Fourth, there is a strong possibility that hyperphosphatemia indirectly and/or directly may stimulate PTH secretion. The treatment of secondary hyperparathyroidism should be modified according to the stage of uremia. Excess suppression of PTH secretion could cause an adynamic bone disease. Early start of the treatment would be beneficial to prevent the bone from the development of PTH resistance.

Administration, Oral

Endosonographic evaluation of the quality of ulcer healing induced by proton pump inhibitors.

We studied 26 gastric ulcer patients who were treated with a proton pump inhibitor to evaluate the quality of ulcer healing using endoscopic ultrasonography (EUS), and we examined the relationship between ulcer recurrence and contraction demonstrated on ulcer echoes (study I). The effect of lansoprazole versus an H2-receptor antagonist on the contraction of ulcer echoes (study II) was also investigated. In study I, gastric ulcer patients who demonstrated early healing by endoscopy often had shallow Ul-II or Ul-III ulcers and small cross-sectional areas on ulcer echoes. The early contraction on ulcer echo was associated with lower rates of ulcer relapse, and might therefore be indicative of a good quality of healing. In study II, the ulcer contraction rate after 8 weeks of treatment with lansoprazole was 71.8%, significantly higher than that achieved with H2-receptor antagonists. However, the mean cross-sectional area of gastric ulcer after 8 weeks of treatment with lansoprazole was 113.9 mm2. In conclusion, although lansoprazole was suitable for initial therapy in peptic ulcer patients, the quality of ulcer healing based on EUS findings did not appear to be adequate in patients treated for the short periods of time in this study.

2-Pyridinylmethylsulfinylbenzimidazoles

Possible role of osteopontin in deposition of calcium phosphate in human pilomatricomas.

Human pilomatricomas are benign epidermal appendage tumors composed of hair matrix-like basaloid cells and keratinized remnant cells referred to as shadow cells. Deposition of calcium phosphate usually occurs in the shadow cell nests. Because osteopontin is believed to be involved in the deposition of calcium phosphate in bones, we asked whether osteopontin messenger RNA also is expressed in pilomatricomas. Using Northern blotting and in situ hybridization we detected osteopontin messenger RNA in pilomatricoma tissues but not in normal skin tissue. By the combination of in situ hybridization and immunohistochemistry, osteopontin messenger RNA-expressing cells were identified as CD68-positive macrophages surrounding the shadow cell nests. Immunohistochemistry of anti-human osteopontin antibodies revealed that the localization of osteopontin protein was consistent with that of calcium phosphate. The present results suggest that osteopontin produced by macrophages may play a significant role in the deposition of calcium phosphate in the shadow cell nests of pilomatricomas.

Amino Acid Sequence

Two phenotypically distinct B lymphocytes (IgMhighIgDlow and IgMlowIgDhigh) in chronic gastric ulcer in the rat.

We determined the kinetics and phenotypes of infiltrating B cells in gastric ulcer in the rat induced by gastric injection of acetic acid (day 0). Few B cells were found in the lesion in the early stages of ulceration. On day 40, two kinds of B cells with phenotypes of IgMhighIgDlowOX33 (CD45)+OX19 (CD5)- and IgMlowIgDhighOX33 (CD45)+OX19 (CD5)- were scattered in the granulation tissue of open ulcers, but not in the healed scar tissue. On day 180, those two kinds of B cells formed primary follicles in the granulation tissue of open ulcers, but were absent from the healed scar tissue. The IgMhighIgDlowOX33 (CD45)+OX19 (CD5)- B cell was considered to be identical to the marginal zone B cell of rat spleen. This phenotype of B cell might be associated with inflammatory process in chronic gastric ulcer.

Acetates

Lack of an effect of Madopar on the disposition of tolcapone and its 3-O-methylated metabolite in rats.

The effect of Madopar (benserazide and L-dopa, 1:4) on the disposition of the new selective inhibitor of catechol-O-methyltransferase, tolcapone, in rats was investigated. There was no statistically significant difference in the pharmacokinetic parameters of tolcapone in the presence or absence of Madopar except for a change in the mean residence time after oral administration. Thus, we rejected the hypothesis that the consumption of S-adenyl-L-methionine by Madopar would change the disposition of tolcapone. There were no statistically significant differences in the cumulative amount absorbed of drug and the absorption rate in the presence or absence of Madopar. We concluded that there was no interaction between tolcapone and Madopar.

Animals

Alterations of bone matrix protein mRNA expression in rat aorta in vitro.

We examined the expression of matrix Gla protein (MGP), osteopontin (OPN), and osteonectin (ON) mRNAs in aortic rings excised from 3-month-, 10-month-, and 2-week-old rats during 72-hour incubations in serum-free media. In the aortic rings from 3-month-old rats, the expression of MGP mRNA was strong before incubation and increased during the 72-hour incubation. The expression of OPN mRNA was first detected after a 5-hour incubation and increased thereafter, and that of ON mRNA was strong before the incubation and decreased during the incubation. The expression of MGP and OPN mRNAs in 10-month- and 2-week-old rats was similar to that in 3-month-old rats. In contrast, expression of ON mRNA in 10-month-old rats and the expression of ON mRNA in 2-week-old rats was stronger than that in 3-month-old rats at every incubation period. In situ hybridization and immunohistochemistry identified the MGP, OPN, and ON mRNA-expressing cells as vascular smooth muscle cells. These results suggest that the expression of these mRNAs was regulated in incubation time-dependent and age-specific ways. We believe that this organ culture model is useful for further studies of the function of these bone matrix proteins and regulation of their expression in the vessel wall.

Animals

Perfusion imaging of the brain by B-mode ultrasonography. An experimental study in rabbits.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the ultrasonic imaging of normal rabbit brain by using echocontrast enhancer to identify the brain tissue perfusion. METHODS: A solution of SH/TA-508 (containing microbubbles of mean size 2 to 4 microns; n = 4) was used for contrast enhancement of rabbit brain tissue and was administered through the left internal carotid artery. Contrast enhancement in the ipsilateral parietal area was examined by placing a 7.5-MHz transducer on the dura after a craniectomy. Throughout the experiment, we measured parameters including arterial blood pressure, arterial blood gases, and serum glucose and hematocrit levels. We investigated whether the administration of an echocontrast enhancer would be safe for the brain tissue (n = 4). RESULTS: After injection of 100 mg/mL SH/TA-508, contrast enhancement was clearly observed within approximately 1 second in the left hemisphere (especially in the left cerebral cortex) in all animals and disappeared within 3 seconds after the end of injection. All physiological parameters remained within the normal range throughout the experiment. No focal abnormalities were observed on hematoxylin-eosin staining of the brain tissue. CONCLUSIONS: Contrast enhancement was observed in the ipsilateral hemisphere with the administration of SH/TA-508. Contrast enhancement on B-mode brain imaging would be useful for real-time identification of brain tissue perfusion and should become a promising method for bedside clinical assessment of brain tissue perfusion.

Animals

T-614, a novel antirheumatic drug, inhibits both the activity and induction of cyclooxygenase-2 (COX-2) in cultured fibroblasts.

To elucidate the mechanism for the selective inhibition of prostaglandin E2 (PGE2) production in inflammatory tissue by T-614 (3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne), its effects on both the activity and the induction of cyclooxygenase (COX)-2 were investigated in vitro. T-614 inhibited the activity of purified COX-2 enzyme (IC50: 7.7 micrograms/ml), but was inactive against both COX-1 activities of microsomal and purified enzymes (IC50: > 300 micrograms/ml). On the other hand, when the inhibition of PGE2 production by T-614 was examined in the cultured fibroblasts stimulated with bradykinin, T-614 at 1 microgram/ml or less inhibited PGE2 release more effectively than that in the above cell-free system. Therefore, we examined which of the COX enzymes was expressed in bradykinin-stimulated fibroblasts by using both the reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analyses. As a result, COX-1 mRNA was constitutively expressed in the cells, whereas COX-2 mRNA was not detected without stimulation with bradykinin, but was expressed within 30 min when stimulated. Furthermore, it was found that the addition of T-614 reduced the COX-2 mRNA levels in 30 min after stimulation. These studies suggest that at least some of inhibitory effects of T-614 on prostanoids production are mediated by the synergy of the inhibition of COX-2 activity and the inhibition of induction, and such an action of T-614 may explain the pharmacological properties of this drug.

3T3 Cells

Lungworm, Filaroides osleri, infection in a dog in Japan.

A 7-month-old male Pomeranian had severe dyspnea for 2 weeks. The lateral bronchogram showed a stenosis of the trachea. Inspite of supportive therapy including supplemental oxygen, the dog died 5 days later. Six pedunculated nodules were recognized in the mucosal surface of the trachea at necropsy. The tracheal nodules were histopathologically granuloma characterized by many coiled parasites containing a little collagen fibers, lymphocytes, plasma cells and macrophages. Female parasites had a lot of embryonated eggs in the uterus. Immature worms were observed in the dilated lymph vessels of bronchial and bronchiolar wall in the lungs. The worms were identified as Filaroides osleri based on the parasitological examinations.

Animals

Microbial conversion of milbemycins: oxidation of milbemycin A4 and related compounds at the C-25 ethyl group by Circinella umbellata and Absidia cylindrospora.

Microbial oxidation of milbemycin A4 at the C-25 ethyl group was performed. Milbemycin A4 was converted to 31- and 32-hydroxy derivatives by Circinella umbellata SANK 44272 along with 24- and 30-hydroxy derivatives. Related compounds, 5-ketomilbemycin A4 5-oxime and 13 beta-fluoromilbemycin A4 were similarly converted to the hydroxylated compounds by this microorganism. Absidia cylindrospora SANK 31472 converted milbemycin A4 to the corresponding 32-oic acid, 24-hydroxy derivative and a few oxygenated compounds including at the C-25 ethyl group.

Anthelmintics

Ultrasonographic and endoscopic ultrasonographic angiography in pancreatic mass lesions.

Extracorporeal ultrasonographic (US) angiography and endoscopic ultrasonographic (EUS) angiography were performed in 40 lesions on 39 patients with various pancreatic diseases to evaluate characteristic findings. Pancreatic cancer (duct cell carcinoma) showed negative or slight enhancement. Islet cell tumor, serous cystadenoma composed of microcysts, and intraductal papillary adenoma showed strong enhancement. Solid and papillary tumor showed enhancement in the central lesion. Four of 6 cases with pseudotumorous pancreatitis had iso-enhancement which disappeared earlier than that in the pancreatic parenchyma. However, 2 cases showed slight or negative enhancement similar to pancreatic duct cell carcinoma. US angiography is useful in evaluating the vascularity of various pancreatic lesions, especially small lesions, in dynamic real-time images. EUS angiography is also useful in evaluating the vascularity in lesions that cannot be detected by US.

Carbon Dioxide

Effects of FK506, an immunosuppressive agent, on genesis of water-immersion stress-induced gastric lesions in rats.

We examined the effects of FK506, an immunosuppressive agent, on the genesis of water immersion stress-induced gastric lesions in rats. Using high-performance liquid chromatography, four kinds of prostaglandins, ie, 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, and prostaglandin D2, were detected, and no leukotrienes were detected in gastric mucosa in rats without stress. After 6 hr of stress, gastric lesions developed with decreases in all prostaglandin contents, and the emergence of peptide leukotrienes was observed. Intramuscular administration of FK506 (0.1, 0.25, 0.5, 1.0, and 2.0 mg/kg) reduced lesion index dose-dependently. Administration of FK506 at doses over 0.25 mg/kg decreased all prostaglandin contents, but did not affect the increase in leukotriene contents. Pretreatment with famotidine or omeprazole reduced lesion index, and the protective effects were equivalent to those of 1.0 mg/kg of FK506, although FK506 did not affect gastric secretion during water-immersion stress. Water-immersion stress did not change the activities of xanthine oxidase in either stomach or serum. Polyoxyethylene-modified superoxide dismutase did not prevent gastric lesions. Water-immersion stress significantly increased myeloperoxidase activity in gastric mucosa, and FK506 reduced the increase in myeloperoxidase activity induced by stress. From our results, other factors besides gastric acid secretion and tissue eicosanoid contents, such as chemoattractant factor, might also be involved in the genesis of water-immersion stress-induced gastric lesions in rats.

Animals