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Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 253 records · Page 14Linked to original sources

A facile synthesis of 4'-thio-arabinonucleosides as potential antiviral agents from D-glucose.

As potential antiviral agents, 4'-thio-arabinonucleosides were synthesized. Methyl 3-O-benzyl-xylo-furanoside, readily obtained from D-glucose, was converted to 1,4-anhydro-4-deoxy-4-thio-arabinitol. The protection of hydroxyl groups and the Pummerer rearrangement, followed by Lewis acid induced glycosylation afforded 4'-thio-arabinonucleosides. The compounds showed anti HSV-1 activity.

Antiviral Agents↗

A novel synthesis of antineoplastic 4'-thionucleosides using D-glucose as a chiral synthon.

We have synthesized 2'-deoxy-2'-methylene-4'-thiocytidine as a potential antineoplastic agent. Isopropylidene-3-O-benzylxylose, readily obtained from D-glucose in 5 steps, was converted to 1,4-anhydro-4-deoxy-4-thio-arabinitol. After manipulation at 2-position, unique Pummerer type glycosylation at the alpha-position of sulfoxides gave the target compound. Antineoplastic effect of this compound is also reported.

Antineoplastic Agents↗

Synthetic study on carbocyclic analogues of cyclic ADP-ribose.

Cyclic ADP-ribose (cADPR, 1) is a newly discovered general mediator involved in Ca2+ signaling. Carbocyclic analogues of 1, namely, 2 and 3, were designed as a stable isosteres of 1, and their synthesis was studied. The reaction of a triflate 9 which was derived from known diol 4, and inosine derivative 10 gave desired N1-alkyl derivative 11 in 38% yield, and then it was converted to diphosphate derivative 12.

Adenosine Diphosphate Ribose↗

Thyrsiferyl 23-acetate is a novel specific inhibitor of protein phosphatase PP2A.

Thyrsiferyl 23-acetate (TF23A), a cytotoxic compound from marine red alga, has been shown to potently and specifically inhibit serine/threonine protein phosphatase 2A (PP2A) with IC50 values of 4-16 microM, depending on the enzyme concentration. TF23A did not affect activity of protein phosphatase 1 (PP1), 2B (PP2B), 2C (PP2C), or protein tyrosine phosphatases (PTP) up to 1 mM. It inhibited PP2A activity in a crude extract of a human T cell line, Jurkat cell, as well as the purified catalytic subunit. Thus, TF23A proved to be a novel useful probe for clearly distinguishing the activity of PP2A from those of the other protein phosphatases in crude cell extracts and identification of cellular processes that are regulated by PP2A.

Cell Line↗

Relationship between obesity and concordance rate for type 2 (non-insulin-dependent) diabetes mellitus among twins.

In order to analyse the relationship of genetic factors and the role of obesity in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus, we compared body mass index (BMI) and other parameters in 71 monozygotic and 17 dizygotic twins (MZT and DZT) with Type 2 diabetes, and analysed the relationship of maximal BMI in the past (max BMI) with the concordance and discordance for diabetes. Data were collected by mail from the members of the Japan Diabetes Society. Concordance rate for diabetes was higher in MZT than in DZT (72% vs. 41%, P = 0.017). Concordance rate in MZT varied in relation to the max BMI of the index twins who developed diabetes earlier. It was higher in non-obese and slightly obese groups (82% and 80% for those with max BMI < 24 and 24-27.9, respectively) than in obese group (36%, max BMI > or = 28) (P = 0.003). In MZT, diabetic twins of discordant pairs were significantly more obese at the survey and in the past than index twins of concordant pairs (mean BMI: 23.9 vs. 21.7, P = 0.007; mean max BMI, 27.7 vs. 24.3, P = 0.001). A similar tendency of differences in BMI was also observed in DZT. Intrapair comparison in discordant MZT and DZT pairs showed that diabetic twins were more obese than non-diabetic cotwins (mean max BMI, 27.7 vs. 24.7, P = 0.004 for MZT; and 27.3 vs. 23.9, P = 0.002 for DZT). In concordant DZT pairs, index twins with earlier onset of diabetes had been less obese than cotwins (mean max BMI, 23.6 vs. 26.0, P = 0.004). In conclusion, the comparison of the max BMI in twins suggests that the degree of diabetogenic role of obesity varies in heterogeneous genetic background. The index twins of discordant pairs had been more obese than those of concordant pairs, suggesting that obesity plays a more important role in those with weaker genetic susceptibility for diabetes.

Adult↗

B cell Ag receptor mediates different types of signals in the protein kinase activity between immature B cell and mature B cell.

Ig receptor (IgR) on the surface of B cells mediates the Ag-specific stimulatory signal for B cell proliferation and differentiation. In immature B cells, the stimulatory signal causes an inhibitory effect which is believed to be a key phenomenon in B cell tolerance or B cell anergy. Here, we studied the molecular mechanism of the inhibitory response of the IgR-mediated signal transduction that results in the programmed cell death of immature B cells. To analyze the downstream molecules of the IgR-mediated signal transduction, we prepared a mAb against a 160-kDa membrane protein (p160) that can coprecipitate the kinase molecule(s) acting on serine, threonine, and tyrosine residues. Anti-IgR stimulation induces the increase of the kinase activity coprecipitated with the p160 protein in mature B cell BAL17 and normal adult spleen B cells. This result suggest that the p160-associated kinase activity is one of the downstream events of the IgR-mediated signal transduction cascade. Interestingly, immature B cell lymphoma WEHI-231 and the neonatal spleen B cells showed the adverse reaction of the p160-associated kinase which results in the transient loss of the kinase activity. Moreover, the transient decrease of the p160-associated kinase was caused by the tyrosine phosphatase activity induced by the stimulation of IgR in WEHI-231. The results suggest that this molecular difference in the downstream events of the IgR-mediated signal transduction between immature B cells and mature B cells already begins at the transmembrane level in the IgR-mediated signal transduction pathway.

Animals↗

Mutagenicity of 5-bromouracil and N6-hydroxyadenine studied by yeast oligonucleotide transformation assay.

The mutagenicity of 5-bromouracil (BrU) and N6-hydroxyadenine (HA) was tested by means of the yeast oligonucleotide transformation procedure. BrU-containing oligonucleotide was not mutagenic; although two mutants (per 200 micrograms oligonucleotide) were obtained, they were attributed to base insertion or base substitution at positions different from BrU. This result supports the view that BrU mutagenesis is dependent on intracellular nucleotide pool imbalance. In contrast, HA-containing oligonucleotide was highly mutagenic; 56 mutants (per 140 micrograms oligonucleotide) were obtained. Of 21 induced mutants examined, 20 had G and one had C at the HA position, a result indicating that HA-->G changes took place. To provide back-up evidence, we carried out a general reversion assay for base HA using a set of yeast tester strains, and the results showed that HA induces exclusively AT-to-GC and GC-to-AT transitions. We conclude that in S. cerevisiae HA is a classic base analog mutagen, causing AT-to-GC and GC-to-AT transitions by ambiguous base pairing. The present work has clearly demonstrated the usefulness of the oligonucleotide transformation procedure for elucidating mutagenicity of modified bases.

Adenine↗

Purification and properties of Saccharomyces cerevisiae cystathionine beta-synthase.

Cystathionine beta-synthase (beta-CTSase), which catalyses cystathionine synthesis from serine and homocysteine, was purified to homogeneity from Saccharomyces cerevisiae. The molecular mass of the enzyme was estimated to be 235 kDa by gel filtration and 55 kDa by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, indicating that it is a homotetramer. The N-terminal amino acid sequence of the enzyme perfectly coincided with that deduced from the nucleotide sequence of CYS4, except for the absence of initiation The purified beta-CTSase catalysed cysteine synthesis from serine (or O-acetylserine) and H2S. From this finding, we discuss the multifunctional nature and evolutionary divergence of S-metabolizing enzymes.

Amino Acid Sequence↗

Diabetic twins in Japan.

By the cooperation of members of the Japan Diabetes Society, we collected data on 144 twin pairs with diabetes or glucose intolerance. By the diagnosis of reporting physicians, the concordance rate of diabetes in monozygotic twins (MZ) was 47% (9/10) for IDDM and 87% (68/78) for NIDDM. The concordance rate in dizygotic twins (DZ) was 8% (1/13) and 43% (9/21) for IDDM and NIDDM, respectively. The concordance rate was higher in MZ than in DZ and in IDDM than in NIDDM. In MZ, the concordance rate was higher in twin pairs in which probands developed diabetes at an older age. The discordant period for diabetes was not shorter in discordant pairs than in concordant pairs. The period of living together was irrelevant to concordance for diabetes. When co-twins of NIDDM twins were examined by oral glucose tolerance test, 98% of co-twins of MZ and 92% of co-twins of DZ had diabetes or a milder degree of glucose intolerance, while in IDDM pairs 45% of MZ and 50% of DZ co-twins had normal glucose tolerance. The insulinogenic index (the ratio of the increment of insulin to that of blood glucose 30 min after a glucose load) in discordant NIDDM co-twins was similar to subjects with the same degree of glucose intolerance.

Adolescent↗

Family history of diabetic patients in Japan.

The frequency of a positive family history of diabetes in diabetic patients has increased in recent studies. In this study, it was 16-33% for type 1 diabetes and 43-49% for type 2 diabetes. It was significantly higher than in non-diabetic subjects, and in type 2 than in type 1 diabetic patients. The prevalence of diabetes in parents and siblings of type 2 diabetic patients was higher than in those of type 1 patients, and it was particularly high in parents of young onset type 2 patients. Among type 2 diabetic patients, positive family history was somewhat lower in those with marked obesity in the past. Comparison of groups with varying degrees of glucose intolerance revealed that a family history of diabetes increased in parallel with the impairment of glucose tolerance. The results suggest that genetic factors in the pathogenesis of diabetes are more important in type 2 than in type 1 diabetes, and in the younger onset and less obese subjects than in older onset and more obese patients for type 2 diabetes.

Adult↗

Gangrene and ulcer of the lower extremities in diabetic patients.

In diabetic patients in Japan, gangrene, and ulcers of the lower extremities were found in 2% of out-patients and in 4% of hospitalized patients. This prevalence in Japan is much less than in Western countries, as already shown by the Multinational Study on Vascular Diabetic Diseases. The ratio of ulcers due to neuropathy is 3 or 4 times more than that caused by ASO. But recent trends showed a gradual increase in ASO among diabetic patients. According to the API measured by the ultrasonic Doppler method, the prevalence of ASO is estimated as being 10% of diabetic patients, and about one tenth of ASO patients will develop gangrene in future.

Adult↗

Hepatocellular carcinoma: treatment with a combination of transcatheter arterial chemoembolization and transportal ethanol injection.

PURPOSE: To evaluate the efficacy and complications of transportal ethanol injection (TPEI) combined with transcatheter arterial chemoembolization to achieve complete tumor necrosis and prevent intrahepatic metastases in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In 13 patients with HCC, chemoembolization was performed with injection of a mixture of iodized oil and doxorubicin hydrochloride followed by administration of gelatin sponge; 1-4 weeks later, TPEI was performed with percutaneous transhepatic portography. Ethanol (15-65 mL) was injected in the portal veins around the tumor until occlusion. RESULTS: TPEI was successfully performed in all patients. Two patients subsequently underwent surgery; their tumors were resected completely. Two died of hepatic failure. Seven of the nine other patients showed no recurrence or intrahepatic metastasis during follow-up (7-42 months). Histologic examination, performed in nine patients, showed complete necrosis of tumor and scattered or severe necrosis of surrounding tissues. CONCLUSION: This treatment has a strong anticancerous effect and is expected to be used in treatment of properly selected patients with HCC.

Aged↗

A case of neuroretinitis associated with long-standing polyarteritis nodosa.

We reported a 45-year-old man suffering from neuroretinitis with long-standing polyarteritis nodosa and anterior uveitis. Fluorescein angiography, made at the stage when optic disk swelling developed, demonstrated a hypofluorescent area at the temporal part of the optic disc presenting exudates in its prelaminar region. When the swelling of the optic disc had resolved as verified ophthalmoscopically, and the hypofluorescence was angiographically undetectable, a macular star was observed, showing a configuration corresponding to Henle's layer.

Humans↗