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Biomedical subjects

Tomohiro Tanaka

Publications and source records attributed to Tomohiro Tanaka.

29 records · Page 2Linked to original sources

Objective and rapid assessment of pancreas graft viability using 31P-nuclear magnetic resonance spectroscopy combined with two- layer cold storage method.

BACKGROUND: With the current shortage of donors, there is a critical need to optimally use "less-than-ideal" donors for pancreas transplantation. Objective and rapid means for assessing graft viability and suitability for transplantation are mandatory. This study examined the possibility of graft viability assessment and posttransplant outcome prediction using (31)P-nuclear magnetic resonance (NMR) spectroscopy combined with the two-layer cold-storage method (TLM). METHODS: Canine pancreas grafts were preserved with TLM for 24 hours after 0, 60, or 120 minutes of warm ischemia (groups 1, 2, or 3, respectively). After preservation, we determined intragraft phosphate metabolites noninvasively using (31)P-NMR spectroscopy. Time required for this assessment was 5 minutes. Because our previous studies demonstrated that all grafts in groups 1 and 2 were successfully transplanted (the viable group), whereas all in group 3 failed to survive (the nonviable group), the possibility of posttransplant outcome prediction was examined on the basis of the comparison between these two groups. RESULTS: The ratios of inorganic phosphate/gamma-adenosine triphosphate (Pi/gamma-ATP) and Pi/beta-ATP reflected the extent of graft damage, and the differences were statistically significant among groups 1, 2, and 3. On the basis of analyses of receiver operator characteristic curves, the optimum cutoff levels between the viable and nonviable groups were 1.6 and 2.2 for Pi/gammaATP and Pi/betaATP, respectively. The accuracy rates of these ratios were both 83%. CONCLUSION: (31)P-NMR spectroscopy combined with TLM preservation could provide an objective, rapid, and possibly noninvasive means to assess pancreas graft viability and to determine suitability of damaged pancreata for organ transplantation.

Animals↗

Periaxin mutation causes early-onset but slow-progressive Charcot-Marie-Tooth disease.

Periaxin (PRX) plays a significant role in the myelination of the peripheral nerve. To date, seven non-sense or frameshift PRX mutations have been reported in six pedigrees with Dejerine-Sottas neuropathy or severe Charcot-Marie-Tooth neuropathy (CMT). We detected a PRX mutation in three patients in the screening of 66 Japanese demyelinating CMT patients who were negative for the gene mutation causing dominant or X-linked demyelinating CMT. Three unrelated patients were homozygous for a novel R1070X mutation and presented early-onset but slowly progressive distal motor and sensory neuropathies. Mutations lacking the carboxyl-terminal acidic domain may show loss-of-function effects and cause severe demyelinating CMT.

Adult↗

Reverse hydroxamate-based selective TACE inhibitors.

Reverse hydroxamate-based selective TACE inhibitors are described. They have potent TACE inhibitory activities and excellent selectivities against MMP-1, 2, 3, 8, 9, 13, 14, and 17. One representative compound, 18 has demonstrated an excellent oral inhibitory activity of the lipopolysaccharide (LPS)-stimulated TNF-alpha production in rats.

ADAM Proteins↗

Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition.

(-)-Quinine-catalyzed intramolecular oxo-Michael addition (IMA) of 7-hydroxy-5-methoxy-8-tigloylcoumarins was developed for the enantioselective construction of 2,3-dimethyl-4-chromanone systems in the context of the asymmetric synthesis of anti-HIV-1 active Calophyllum coumarins. Combination of the IMA and MgI(2)-assisted demethylation of the 5-methoxy group along with isomerization of the formed chromanone systems as key steps successfully led to the concise synthesis of (+)-inophyllum B and (+)-calanolide A, possible candidates for AIDS drugs. Further examination of the asymmetric IMA with cinchona alkaloids lacking a methoxy group on the quinoline skeleton suggested the influence of the methoxy substituent on stereoselectivity at the stereogenic centers of the chromanone systems.

Anti-HIV Agents↗

Gene and phenotype analysis of congenital generalized lipodystrophy in Japanese: a novel homozygous nonsense mutation in seipin gene.

Congenital generalized lipodystrophy (CGL), Berardinelli-Seip syndrome, is a rare metabolic disorder characterized by a near total lack of adipose tissue from birth or early infancy. Recently, seipin, encoding a 398-amino acid protein of unknown function, and AGPAT2, encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase 2, were identified as causative genes for CGL. Seipin mutations were found in patients from families originating from Europe and the Middle East. AGPAT2 mutations were found predominantly in African ancestry. However, no information is available on these genes in the pathogenesis of CGL in Asian ancestry. We examined the sequences of the entire coding region of seipin and AGPAT2 in four Japanese CGL patients from independent families. Their average body fat content was 4.7 +/- 0.5%, and the plasma leptin level was 1.15 +/- 0.14 ng/ml. We identified a novel nonsense mutation of seipin at codon 275 (R275X). Of four CGL patients, three were homozygous for R275X. No seipin mutation was found in any exon in one patient. We did not find any AGPAT2 mutations in our Japanese patients, suggesting that AGPAT2 is a minor causative gene, if any, for CGL in Japanese. This is the first report on gene and phenotype analysis of CGL in Japanese.

Adolescent↗

[A case of advanced gastric cancer with simultaneous multiple bone metastases and double occurrence of disseminated intravascular coagulation successfully controlled with combined chemotherapy].

A 41-year-old man was found to have advanced gastric cancer with simultaneous multiple bone metastases when pyloric stenosis was being diagnosed in our hospital. We performed gastrojejunostomy from the lower third of the stomach to the upper third of the duodenum to relieve the obstruction. However, at 8 days after surgery, disseminated intra-vascular coagulation (DIC) occurred. Therefore, the patient was administered combined chemotherapy with TS-1 plus low-dose cisplatin in addition to anti-DIC therapy. TS-1 (150 mg/day) and cisplatin (10 mg/body intravenously over the course of 30 minutes) were administered on days 1 to 5, 8 to 12, and 15 to 19 (weekday-on/weekend-off schedule). There was remarkable response to this chemotherapy, and the patient was shifted from inpatient to outpatient treatment. The treatment course was repeated for 4 cycles until remission was observed. Because of hematologic relapse due to DIC at 6 months after the first treatment, he was readmitted for administration of combined chemotherapy. Fortunately, DIC once again responded to the same chemotherapy regimen. In this pathologic condition, combined chemotherapy is unavoidable when DIC occurs with cancer. Accordingly, it is necessary that an effective combined chemotherapy with mild bone marrow suppression be chosen. A companion drug should be chosen in consideration of delayed homo-toxicity and of the possibility of relapse into DIC in the drug withdrawal period. In addition, it is indispensable that careful consideration be given to the most favorable dose and regimen.

Adenocarcinoma↗

[Novel transgenic mouse model of the metabolic syndrome].

Locally-enhanced glucocorticoid action within cells has been implicated in the pathophysiology of the metabolic syndrome, which is characterized by a cluster of visceral fat obesity, insulin resistance, dyslipidemia, hypertension and liver steatosis. Evidence has accumulated that enzyme activity of intracellular glucocorticoid reactivating enzyme, 11 beta-hydroxysteroid dehydrogenase type 1(11 beta-HSD1) is commonly elevated in fat depots in patients with the metabolic syndrome. Fat-specific 11 beta-HSD1 transgenic mice, those have increased enzyme activity to a similar extent seen in obese humans, develop visceral fat obesity with major components of the metabolic syndrome. In adipocytes, antidiabetic PPAR gamma agonists substantially reduce 11 beta-HSD1 mRNA and enzyme activity, suggesting that suppression of 11 beta-HSD1 in fat cells may be one of the pivotal mechanisms whereby these class of drugs exert beneficial metabolic outcome. Taken together, recent data highlight the importance of adiposteroid in the pathophysiology of the metabolic syndrome.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

Successful 24-hour preservation of ischemically damaged canine small intestine by the cavitary two-layer method.

BACKGROUND: The purpose of this study is to examine the possibility of a long-term preservation of the ischemically damaged intestine by the cavitary two-layer method (TLM) in canine small intestinal transplantation. METHODS: The grafts were allotransplanted without preservation immediately (group 1) or after 30 minutes of warm ischemia (group 2). The ischemically damaged grafts were also allotransplanted after cold preservation for 24 hours in University of Wisconsin (UW) solution (group 3) or the cavitary TLM (group 4). Seven-day survivals, tissue adenosine triphosphate (ATP) concentrations, absorption tests, and histopathology were examined. RESULTS: seven-day survivals in groups 1, 2, 3, and 4 were 8 of 8, 6 of 8, 0 of 8, and 6 of 8, respectively. In group 4, significant recovery of ATP tissue level was seen after preservation compared with group 3, and absorption function and regeneration of the graft mucosa recovered at day 14. CONCLUSIONS: Ischemically damaged canine small intestine could be preserved for 24 hours by the cavitary TLM.

Adenosine↗

Metabolic effects of D-psicose in rats: studies on faecal and urinary excretion and caecal fermentation.

D-psicose (D -ribo-2-hexulose), a C-3 epimer of D-fructose, is one of the "rare sugars" present in small quantities in commercial carbohydrate complex or agricultural products. We investigated the absorption and excretion of D-psicose when orally administrated (5g/kg body weight) to Wistar rats, and the fermentation of D-psicose was measured as caecal short-chain fatty acids (SCFAs) when fed to rats in controlled diets (0, 10, 20 and 30%). Urinary and faecal excretions of D-psicose over the 24 h, following a single oral administration, were 11-15% of dosage for the former and 8-13% of dosage for the latter. Serum D-psicose concentration and D-psicose in the contents of stomach and small intestines decreased progressively after administration. D-psicose in caecum contents was detected after 3h and 7h administration, but not after 1h. Rats fed on D-psicose diets showed short-chain fatty acid production with caecal hypertrophy. These results suggest that D-psicose is partly absorbable in the digestive tract and is excreted into urine and faeces. As with other poorly absorbed dietary carbohydrates, D-psicose is fermented in the caecum by intestinal microflora.

Administration, Oral↗

Thermodynamic quantities of surface formation of aqueous electrolyte solutions. V. Aqueous solutions of aliphatic amino acids.

The surface tension of aqueous solutions of glycine, L-alanine, L-valine, and L-leucine has been observed using the drop volume method as a function of temperature and concentration. The L-leucine molecules form an adsorbed film, while glycine affects the water surface in accordance with simple salts which dissociate into cations and anions completely. The surface tension data have been analyzed in view of K. Motomura's thermodynamic treatment (J. Colloid Interface Sci.64, 348 (1978)), and the thermodynamic quantities relevant to the surface have been shown systematically.

Adsorption↗

Effects of oral acute administration and subchronic feeding of several levels of D-psicose in rats.

The effects of oral acute administration and subchronic (34 d) feeding of several levels of D-psicose, a C3-epimer of D-fructose, were studied in rats. In the acute administration test, five groups of eight male Wistar rats (3 wk old) were orally given D-psicose in doses of 8, 11, 14, 17, and 20 g/kg. Three rats receiving 14 g/kg, three rats receiving 17 g/kg and eight rats receiving 20 g/kg of D-psicose died within 2 d after administration. The calculated LD50 values were 16.3 g/kg by the Behrens-Karber method and 15.8 g/kg by the Litchfield-Wilcoxon method. In the subcronic feeding test, eight groups of seven male Wistar rats (3 wk old) were fed diets containing 0 (control), 10, 20, 30, and 40% for 34 d. One rat fed 30% D-psicose diet and five rats fed 40% D-psicose diet died during the experimental period. Body weight gain, food intake and food efficiency were more extensively suppressed by the higher D-psicose diets. The weights of heart, spleen and abdominal adipose tissue were smaller in the order of dietary D-psicose concentration. Cecal weight increased with increasing D-psicose concentration in the diets. Cecal hypertrophy was observed in rats fed 10-40% D-psicose diets. These results suggest that D-psicose differs in nutritional characteristics from D-glucose or D-fructose. The feeding of diets extremely high in D-psicose seems to be harmful to the intestinal tract.

Administration, Oral↗