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Biomedical subjects

S Sugai

Publications and source records attributed to S Sugai.

At least 19 recordsLinked to original sources

T-Cell type acute lymphoblastic leukemia following cyclosporin A therapy for aplastic anemia.

Cyclosporin A (CsA) is used to prevent rejection in transplantation and to treat autoimmune and hematologic diseases such as aplastic anemia. However, the tumor growth-promoting effect of CsA remains controversial. We report the case of a 24-year-old man who developed acute lymphoblastic leukemia of precursor-T-cell origin after 75 months of treatment with CsA for aplastic anemia. The surface antigen phenotype of his leukemic cells was CD2+, CD3+, CD5+, CD7+, CD4-, CD8-, CD10-, CD20-, CD34-, CD41-, and CD56-. Southern blot analysis revealed a monoclonal rearrangement of T-cell receptor-Jgamma nongermline fragments in HindIII digestion.

Adolescent↗

[A case of Sjögren's syndrome with dermatomyositis who died of rapidly progressive interstitial pneumonia].

We report a case of 55 year-old woman with six year history of Sjögren's syndrome developed fatal rapidly progressive interstitial pneumonia. She had been well until February 1999. She developed swelling and erythematous lesions in the cheek and hands in spring 1999. She was admitted to our hospital for investigations of skin lesions in May 1999. Physical examination on admission revealed small hemorrhagic lesions in the nailfold. Serum CK level was slightly elevated. Electromyogram and MRI suggested mild myositis in the proximal upper extremities. She was suspected to have dermatomyositis along with Sjögren's syndrome. Prednisolone 10 mg/day had been given for her skin problems since March 1999. Suddenly, dyspnea on exertion was appeared on 34th day of admission. Chest X-ray film showed an acute worsening of interstitial pneumonia. Methylprednisolone pulse therapy (1000 mg for 3 days) and cyclophosphamide pulse therapy (500 mg for a day) were started, and she was subsequently treated with 60 mg/day of prednisolone and 250 mg/day of Cyclosporin A. However, interstitial pneumonia did not respond to the treatment, and pneumomediastinum and pneumothorax have developed. She died of respiratory failure on 55th day. We consider that most likely explanation for fatal interstitial pneumonia is concomitantly occurred dermatomyositis.

Cyclophosphamide↗

Anisotropic optical spectra of PrBa2Cu4O8: possible Tomonaga-Luttinger liquid response of the quasi-one-dimensional metallic CuO double chains.

The optical spectra of PrBa2Cu4O8 show large in-plane anisotropy. For the a polarization (E perpendicular chain), the spectrum is characterized by a gap of 1.4 eV, indicating the charge-transfer insulating nature of the CuO2 planes. For the metallic chain direction (E // b), the spectrum deviates from a simple Drude response; reflectivity R(b)(omega) shows a sharp edge at approximately 1 eV but it also shows a dip at approximately 15 meV, which splits the conductivity spectrum into two parts--a zero-energy mode with small weight and a pronounced 40 meV mode. These features are discussed in terms of a Tomonaga-Luttinger liquid in a doped 1D Mott insulator and compared with 1D Bechgaard salts.

Journal Article↗

Relation between the superconducting gap energy and the two-magnon raman peak energy in Bi(2)Sr(2)Ca(1-x)Y(x)Cu(2)O(8+delta)

The relation between the electronic excitation and the magnetic excitation for the superconductivity in Bi(2)Sr(2)Ca(1-x)Y(x)Cu(2)O(8+delta) was investigated by wide-energy Raman spectroscopy. In the underdoping region the B(1g) scattering intensity is depleted below the two-magnon peak energy due to the charge-spin interactions. The depleted region decreases according to the decrease of the two-magnon peak energy, as the carrier concentration increases. This two-magnon peak energy also determines the B(1g) superconducting gap energy as 2Delta approximately alphaPlanck's over 2piomega(two-magnon) approximately J(eff) (alpha = 0.34-0.41) from under to overdoping hole concentration.

Journal Article↗

Molten globule structure of equine beta-lactoglobulin probed by hydrogen exchange.

The molten globule structure of equine beta-lactoglobulin has been inferred from the hydrogen exchange protection of the backbone amide protons. In order to make it possible to measure the hydrogen exchange kinetics of the individual backbone amide protons, the uniformly (15)N-labeled recombinant protein was expressed in Escherichia coli and the NMR peak assignment was obtained for most of the backbone protons. The chemical shift and NOE results obtained under the condition where the protein assumes the native structure are fully consistent with the known secondary structure of bovine beta-lactoglobulin, indicating that the equine protein has a similar native conformation to that of the bovine protein. The hydrogen exchange rate of the individual backbone amide protons was measured under the conditions where the protein assumes the native and molten globule states. In the native state, strong protection was observed for the residues located in the eight (A to H) strands, which form a barrel structure, and residues of a major helix. In the molten globule state at acidic pH conditions, significant protection from the exchange has been observed for residues located in the A, F, G and H strands in the native structure. The pattern of protection is consistent with a native-like beta-sheet formation by these strands. The residues located in a major helix of the native structure are also protected, suggesting that this helix is formed in the molten globule and is packed against the sheet as in the native structure. These results indicate that a native-like subdomain is formed in the molten globule state of equine beta-lactoglobulin.

Amides↗

Increased in situ expression of nitric oxide synthase in human colorectal cancer.

There is growing evidence that nitric oxide (NO) has an important role in tumor growth. However, information on the expression of NO synthase (NOS) in colorectal cancers is scanty. We therefore investigated the distribution and expression of NOS in human colorectal cancers. The expression of three types of NOS, inducible (iNOS), endothelial (eNOS) and neuronal (nNOS), was examined by immunohistochemistry in 25 cases of colorectal cancer. The expression of iNOS was also investigated at the mRNA level using the reverse transcriptase polymerase chain reaction (RT-PCR) in 6 cases. Correlations were made between iNOS expression and the histopathological findings. Immunoreactive iNOS was detected in the tumor cells in 22 cases (88%) with diffuse cytoplasmic reactions. Expression of iNOS-mRNA detected by RT-PCR in three tumor tissues was over five-fold that in normal mucosa. Intensified immunoreactivity of iNOS was associated with vascular invasion. iNOS expression did not correlate with pathological staging, tumor size, lymph node metastasis, p53 expression or tumor vessel density. Immunoreactive eNOS stained more strongly in the endothelial cells of microvessels within and around the tumor than in the areas remote from the tumor. There is enhanced expression of iNOS and eNOS in human colorectal cancers, which may correlate with tumor growth and vascular invasion.

Adult↗

4-Sulfenyl-2-carbamoyl-4-isoxazolin-3-ones: biological isostere to 4-chloro-2-carbamoyl-4-isoxazolin-3-ones.

4-Sulfenyl-2-carbamoyl-4-isoxazolin-3-ones (4) were designed on the basis of biological isosterism and prepared in four steps. Some of these compounds showed sufficient pre-emergent herbicidal activities against various kinds of weeds. Among the synthesized compounds, 2-(N-(4-chlorophenyl)-N-isopropylcarbamoyl)-4-ethylthio-5-methyl-4 -isoxazolin-3-one (4cd) exhibited the most promising activity.

Carbamates↗

[Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) accompanied by hemophagocytosis and salivary gland swelling in a patient with systemic lupus erythematosus].

After 2 years of steroid therapy that had effectively controlled her systemic lupus erythematosus, a 37-year-old woman presented with fever, erythema (face, upper chest), and low CH50. Increased oral steroid (prednisolone from 15 mg to 40 mg) and intravenous methylprednisolone (mPSL) (80 mg for 3 days) alleviated these symptoms except for the fever. Subsequently, the patient's fever worsened and leukocytopenia, abnormal liver function, lymphadenopathy (neck, axilla), and salivary gland swelling developed. Lymph node histology revealed features characteristic of Kikuchi-Fujimoto's disease (KFD). Laboratory examinations showed WBC 600/microliter, Hb 9.5 g/dl, platelets 90,000/microliter, GOT 766 IU/l, GPT 646 IU/l, LDH 4,228 IU/l, TG 1,622 mg/dl, and ferritin 6,330 ng/ml. Serum interferon gamma was also elevated (673 U/ml). Because a bone marrow smear revealed hemophagocytosis, mPSL pulse therapy (1 g for 3 days) was started for treatment of hemophagocytic syndrome. The fever promptly disappeared, and the patient's clinical symptoms resolved within 2 weeks. The abnormal laboratory data related to KFD and hemophagocytosis returned to normal within 4 weeks after the initiation of mPSL pulse therapy. We speculated that the hemophagocytosis and salivary gland involvement in this patient were also symptoms of KFD. This case indicated that corticosteroid pulse therapy is effective for KFD with serious clinical symptoms.

Adult↗

Expression of a dominant negative SHP-2 in transgenic mice induces insulin resistance.

To elucidate the roles of SHP-2, we generated transgenic (Tg) mice expressing a dominant negative mutant lacking protein tyrosine phosphatase domain (DeltaPTP). On examining two lines of Tg mice identified by Southern blot, the transgene product was expressed in skeletal muscle, liver, and adipose tissues, and insulin-induced association of insulin receptor substrate 1 with endogenous SHP-2 was inhibited, confirming that DeltaPTP has a dominant negative property. The intraperitoneal glucose loading test demonstrated an increase in blood glucose levels in Tg mice. Plasma insulin levels in Tg mice after 4 h fasting were 3 times greater with comparable blood glucose levels. To estimate insulin sensitivity by a constant glucose, insulin, and somatostatin infusion, steady state blood glucose levels were higher, suggesting the presence of insulin resistance. Furthermore, we observed the impairment of insulin-stimulated glucose uptake in muscle and adipocytes in the presence of physiological concentrations of insulin. Moreover, tyrosine phosphorylation of insulin receptor substrate-1 and stimulation of phosphatidylinositol 3-kinase and Akt kinase activities by insulin were attenuated in muscle and liver. These results indicate that the inhibition of endogenous SHP-2 function by the overexpression of a dominant negative mutant may lead to impaired insulin sensitivity of glucose metabolism, and thus SHP-2 may function to modulate insulin signaling in target tissues.

Animals↗

Absence of genetic alteration at codon 531 of the human c-src gene in 479 advanced colorectal cancers from Japanese and Caucasian patients.

Activation of c-src, a cellular human gene homologous in sequence to the v-src gene of Rous sarcoma virus, had been thought to play an important role in the progression of several types of human cancers, without having undergone any genetic changes. However, recently truncating mutations at codon 531 of the c-src gene were reported in 12% of the advanced colon cancers, and it was also demonstrated that this change was activating, transforming, tumorigenic, and metastasis promoting. To investigate whether the codon 531-specific mutation could be involved in the carcinogenesis of colorectal cancer in the Japanese and Caucasian populations, we examined a total of 479 advanced colorectal cancers from 421 Japanese patients (46 of them with liver or lung metastases) and from 58 Caucasian patients (11 of them with liver metastases). Using the PCR-RFLP assay and additional single-strand conformation polymorphism analysis, we detected no genetic alteration in any of the advanced colorectal cancers. Our results suggest that the codon 531-specific mutational activation of c-src is unlikely to play a significant role in the malignant progression of colorectal cancers among most Japanese and Caucasian patients.

Asian People↗