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Biomedical subjects

Y Suga

Publications and source records attributed to Y Suga.

At least 55 records · Page 3Linked to original sources
PubMed1998

Novel combretastatin analogues effective against murine solid tumors: design and structure-activity relationships.

A series of combretastatin A-4 (CA-4) analogues were synthesized, and their cytotoxic effects against murine Colon 26 adenocarcinoma and inhibitory activity on tubulin polymerization were evaluated. Since CA-4 has limited aqueous solubility, the target compounds were designed to improve solubility by introduction of a nitrogen-containing group. Among the compounds synthesized, those with an amino moiety in place of the phenolic OH of CA-4 showed potent antitubulin activity and cytotoxicity against murine Colon 26 adenocarcinoma in vitro. Some of the compounds which were potent in vitro were evaluated in the murine tumor model Colon 26 in vivo. Among these, 13bHCl, 21aHCl, and 21bHCl showed significant antitumor activity in the animal model, while CA-4 was ineffective. 13bHCl and 21aHCl were further evaluated in two murine tumor models (Colon 38 and 3LL) and human xenografts HCT-15. These compounds showed potent antitumor activity comparable or superior to that of CDDP. The structure-activity relationships of this series of compounds are also discussed.

Acrylonitrile↗
PubMed1998

A novel helix termination mutation in keratin 10 in annular epidermolytic ichthyosis, a variant of bullous congenital ichthyosiform erythroderma.

Annular epidermolytic ichthyosis is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma that has recently been described in two separate kindreds. Individuals with this variant present with bullous ichthyosis in early childhood and hyperkeratotic lichenified plaques in the flexural areas and extensor surfaces at later ages. Characteristically, they also develop intermittent bouts of annular and polycyclic, erythematous, scaly plaques on the trunk and proximal extremities. We now describe a third kindred with annular epidermolytic ichthyosis. Molecular analysis of this family revealed a novel mutation resulting in an isoleucine to threonine substitution at residue 107 (codon 446) within the highly conserved helix termination motif at the end of the rod domain of keratin 10.

Adult↗
PubMed1997

Thermal conversion from low- to high-activity forms of catalase I from Bacillus stearothermophilus.

Catalase I from Bacillus stearothermophilus has the interesting property of increasing its enzyme activity on heating. It was confirmed that after heating at 70 degrees C for 10 min or 65 degrees C for 20 min, almost all the enzyme molecules were converted irreversibly to the activated form. The increase in kcat from 1400 to 3930 s-1 and the decrease in Km for H2O2 from 4.4 to 2.7 mM by heat activation indicate changes in the kinetic property of the enzyme molecule. Therefore, it follows that catalase I has two active forms, a high-activity form and a low-activity form. The heat activation process followed the first-order kinetics with an activation enthalpy (DeltaH*) of 191 kJ/mol while the heat denaturation process had a DeltaH* of 545 kJ/mol. The CD spectra of the two enzyme forms had small but marked differences. The conversion of the low-activity form to the high-activity form was an endothermic process with a Tm of 56 degrees C, which is much lower than that of the heat denaturation (Tm = 76 degrees C), and the enthalpy change for the transition was only 5% of that for the denaturation. It has to be noted that the high-activity form of the enzyme was converted back to a low-activity form through the process of denaturation, refolding, and reconstitution with heme. In addition, the newly obtained low-activity form was brought to a high-activity form by heating. These results suggest that the native state of catalase I has two active conformations that are roughly the same but not identical and are separated by a high energy barrier.

Calorimetry, Differential Scanning↗
PubMed1997

Cytoplasmic processing of human profilaggrin by active mu-calpain.

The differentiation of keratinocytes involves numerous steps including the formation of the cornified envelope and the aggregation of keratin filaments by filaggrin monomer molecules. In this study, we investigated whether mu-calpain is involved in the processing of profilaggrin to filaggrin monomers by using both an active mu-calpain specific antibody and a 27-mer synthetic calpastatin peptide, a cell-permeable calpain-specific inhibitor. Upon incubation of cultured keratinocytes with Ca2+ for 96 hours, active mu-calpain with a molecular mass of 76 kDa appeared preceded by an increase in mu-calpain mRNA. In synchrony with the appearance of active mu-calpain, the processing of profilaggrin occurred. Furthermore, the Ca2+-induced activation of mu-calpain and the processing of profilaggrin were affected by the addition of the synthetic calpastatin inhibitor. These results indicate that the activation of mu-calpain plays a major role in the profilaggrin processing.

Amino Acid Sequence↗
PubMed1997

Validation of curve-fitting method for blood retention of 99mTc-GSA: comparison with blood sampling method.

We investigated a curve-fitting method for the rate of blood retention of 99mTc-galactosyl serum albumin (GSA) as a substitute for the blood sampling method. Seven healthy volunteers and 27 patients with liver disease underwent 99mTc-GSA scanning. After normalization of the y-intercept as 100 percent, a biexponential regression curve for the precordial time-activity curve provided the percent injected dose (%ID) of 99mTc-GSA in the blood without blood sampling. The discrepancy between %ID obtained by the curve-fitting method and that by the multiple blood samples was minimal in normal volunteers 3.1 +/- 2.1% (mean+/-standard deviation, n = 77 sampling). Slightly greater discrepancy was observed in patients with liver disease (7.5 +/- 6.1%, n = 135 sampling). The %ID at 15 min after injection obtained from the fitted curve was significantly greater in patients with liver cirrhosis than in the controls (53.2 +/- 11.6%, n = 13; vs. 31.9 +/- 2.8%, n = 7, p < 0.0001). There was a highly linear correlation between the %IDs of 99mTc-GSA and the plasma retention rate for indocyanine green (r = -0.869, p < 0.0001, n = 27). These results indicate that the curve-fitting method provides an accurate %ID of 99mTc-GSA and could be a substitute for the blood sampling method.

Adult↗
PubMed1997

Serial assessment of sympathetic reinnervation in a patient with myocardial infarction.

Resting [123I]MIBG and 201TI imaging were performed at 2 wk and 4 and 12 mo after successfully reperfused myocardial infarction. Although [123I]MIBG uptake of the infarcted segments revealed significant improvement in the early image at 4 mo, delayed image displayed decreased [123I]MIBG uptake. However, decreased [123I]MIBG uptake of the delayed image became almost uniform at 12 mo. These observations suggest that reinnervation initially occurs in norepinephrine uptake and then in retention ability. On the other hand, a 201TI defect remained in the infarcted segments at 12 mo. Thus, reinnervation can occur not only in the peri-infarct area but also in the infarcted area.

3-Iodobenzylguanidine↗
PubMed1996

Potentiation of antitumor and antimetastatic activities of adriamycin by a novel N-alkylated dihydropyridine, AC394, and its enantiomers in colon cancer-bearing mice.

PURPOSE: We have previously shown that a series of N-alkylated 1,4-dihydropyridines potentiate the therapeutic efficacy of vincristine in vincristine-resistant P388 leukemia. The purpose of this study was to investigate the ability of one of the compounds, AC394, and its enantiomers to potentiate the antitumor activity of adriamycin against colon cancer cells in vitro and in vivo. METHODS: The effects of AC394 on potentiation of adriamycin cytotoxicity and enhancement of its accumulation were evaluated using colon 26, HCT-15 and MCF-7 cells. Furthermore, the activities of AC394 and its enantiomers were compared. We also studied the combined effects of (+)-AC394 and adriamycin on subcutaneously (s.c.)-implanted and liver metastasis tumor models. RESULTS: AC394 potentiated the cytotoxicity of adriamycin and enhanced its accumulation in colon cancer cells (colon 26 and HCT-15), which are known to express P-GP (P-glycoprotein) intrinsically. Enhancement of adriamycin accumulation by AC394 was found in s.c.-implanted colon 26 cells in vivo. Although both enantiomers of AC394 showed equal activity in vitro, (+)-AC394 was more effective than (-)-AC394 given orally. (-)-AC394 was found to be cleared more rapidly from the plasma than (+)-AC394. Thus, (+)-AC394 was evaluated for further study. Administration of (+)-AC394 significantly potentiated the antitumor activities of adriamycin in human colon cancer HCT-15 cells implanted s.c. Furthermore, in the liver metastasis model using colon 26 cells, a model completely resistant to adriamycin, the combination therapy of adriamycin with (+)-AC394 produced superior antitumor effects over adriamycin alone. CONCLUSIONS: A newly synthesized N-alkylated 1,4-dihydropyridine derivative, (+)-AC394, showed superior effects on the potentiation of adriamycin antitumor and antimetastatic activities in vivo. These results suggest that this combination may have therapeutic efficacy not only against primary colon cancers but also against metastatic liver cancer.

Animals↗
PubMed1996

Successful treatment of vitiligo with PUVA-pigmented autologous epidermal grafting.

BACKGROUND: The methoxypsoralen-ultraviolet A-light (PUVA)-induced pigmented epidermal grafting procedure appears to be a more effective treatment for vitiligo than similar treatments presently available. This finding was based on: 1) a more vigorous and completely homogeneous repigmentation was observed in the vitiliginous area and 2) that the treatment was safe, easy, inexpensive, and not time-consuming (approximately 3-4 hours), thus making it a suitable outpatient clinic treatment procedure for vitiligo patients. PATIENTS AND METHODS: Twenty-eight patients with amelanotic depigmented lesions that had been refractory to conventional therapy were treated using suction blisters from autologous epidermal sheets. These had 8-methoxypsoralen (8-MOP) solution applied and had been exposed to ultraviolet A light (topical PUVA) in order to stimulate melanogenesis. RESULTS: Successful repigmentation was obtained after transplantation in all patients with segmental and localized vitiligo. The most homogeneous repigmentation was obtained within 3 months after grafting. CONCLUSIONS: This novel procedure is an excellent tool by which to treat segmental and localized vitiligo lesions that have failed to respond to other therapies.

Adolescent↗
PubMed1996

[Double-primary cancer of the lung and trachea].

A 70-year-old woman with no history of smoking was admitted to the hospital because of a persistent cough and pneumonia in the right lower lobe. Examination with a fiberoptic bronchoscope revealed an intratracheal polypoid tumor and a polypoid tumor almost completely obstructing the right bronchus B(8). Biopsies were done, and histological diagnosis of both tumors was squamous cell carcinoma. A sleeve resection of the trachea with end-to-end anastomosis and right lower lobectomy were done. Examination of specimens resected from both tumors revealed moderately differentiated squamous cell carcinoma. Synchronous double-primary cancer (both squamous cell carcinoma) of the lung and trachea in a non-smoker is very rare.

Aged↗
PubMed1996

[Visual evaluation of liver function with 99mTc-GSA scintigraphy: interobserver variation and intraobserver variation].

We introduced a new imaging grade to evaluate liver function with 99mTc-GSA and studied its diagnostic value using interobserver variation and intraobserver variation. One hundred four patients with liver disease were injected 185 MBq/3 mg of 99mTc-GSA. Anterior images of cardiac blood-pool and liver at 5 min after injection were divided into four grades on the basis of following four categories. Faint cardiac blood-pool image, without clear demonstration of its peripheral boundary was classed in grade I; weaker cardiac blood-pool than liver was grade II; almost same appearance of blood-pool with liver was grade III and stronger blood-pool than liver was grade IV. Three radiologists reviewed the images independently. They followed the same process three months after initial evaluation. kappa-Test was employed to evaluate the goodness of agreement. Three pairs in the first reading showed excellent interobserver agreement (0.88, mean kappa-value) and another three pairs in the first and second reading also showed excellent intraobserver agreement (0.87, mean kappa-value). Quantitative indices obtained from time-activity curves for blood-pool and liver showed significant differences across four groups. Plasma retention rate of indocyanine green also showed significant difference between grade II and grade III. Imaging grade possesses high intra- and interobserver agreement and provides a good discrimination for liver function.

Adolescent↗
PubMed1995

Efficacy of famotidine in patients with acute gastric mucosal injury after continuous infusion of cisplatin plus vindesine.

The effect of famotidine (H2 blocker) on the gastroduodenal mucosal injury induced by chemotherapy in non-small-cell lung cancer patients was prospectively evaluated from the clinical and endoscopic findings obtained in a randomized double-blind study. The patients, who were administered cisplatin (25 mg/m2/day, continuous infusion, days 1-5) and vindesine (3 mg/m2, bolus, days 1 and 8), were randomized into two groups, those administered famotidine (40 mg/day, oral) and those administered the placebo. The patients were examined by gastroduodenoscopy within 7 days before and after chemotherapy. There were 27 patients in the famotidine group and 28 patients in the placebo group. The gastric mucosal score after chemotherapy was significantly lower in the famotidine group than in the placebo group (P < 0.01), and in the 42 patients without symptoms than in the 13 patients (placebo group: 8, famotidine group: 5) with upper gastrointestinal symptoms (P < 0.01). The pH of the gastric juice after the chemotherapy significantly decreased in the placebo group (P < 0.05), and was significantly lower in the placebo group than in the famotidine group (P = 0.01). The co-administration of famotidine was effective in the prevention and control of chemotherapy-induced gastric mucosal injury.

Adult↗
PubMed1995

Phase II study of infusional cisplatin in combination with etoposide in the treatment of small cell lung cancer.

The efficacy of a 5 day continuous infusion of cisplatin, 25 mg/m2/day, in combination with a bolus infusion of etoposide, 100 mg/m2/day over 2 h for 3 days (PiE therapy), was evaluated in a phase II study of previously untreated patients with small cell lung cancer (SCLC). There were 39 evaluable patients, of whom 17 had limited disease (LD) and 22 extensive disease (ED). The overall response rate was 92% (LD, 100%; ED, 86%). The complete response rate was 21% (LD, 41%; ED, 5%). The median survival time was 45.6 weeks (LD, 123.2 weeks; ED, 28.8 weeks). The major side-effects were grade 3 or 4 leucopenia (55%), neutropenia (88%) and thrombocytopenia (20%). There were no episodes of bleeding, severe infection or treatment-related deaths. PiE therapy was associated with significant myelosuppression, but was effective, with an especially encouraging response rate and survival for LD patients.

Adult↗
PubMed1995

A case of Behçet's disease aggravated by gingival infection with methicillin-resistant Staphylococcus aureus.

We report a case of Behçet's disease aggravated by gingivitis and carious teeth infected with methicillin-resistant Staphylococcus aureus. Recurrent severe ulcers in the mouth, and on the genitalia and legs were closely linked with the infection, and dramatically improved after extraction of the carious teeth and administration of systemic vancomycin hydrochloride.

Anti-Bacterial Agents↗
PubMed1995

Phylogeny of Sym plasmids of rhizobia by PCR-based sequencing of a nodC segment.

To understand the host specificity of rhizobia and the relationship between the evolution of Sym plasmids and that of host plants, we determined partial nodC sequences of 10 representative rhizobium strains and then constructed an evolutionary tree for the deduced amino acid sequences with four published sequences. These coding sequences yield a phylogenetic tree similar to that for leghemoglobin of host plants, suggesting that the evolution of common nodulation genes may be linked to host legume evolution and speciation.

Amino Acid Sequence↗
PubMed1995

Remarkable N2-fixing bacterial diversity detected in rice roots by molecular evolutionary analysis of nifH gene sequences.

To demonstrate the extent of phylogenetic diversity of diazotrophic bacteria associated with rice roots, we characterized phylogenetically 23 nifH gene sequences obtained by PCR amplification of mixed organism DNA extracted directly from rice roots without culturing the organisms. The analyses document the presence of eight novel NifH types, which appear to be a variety of significant components of the diazotrophic community, dominated mainly by proteobacteria.

Amino Acid Sequence↗
PubMed1995

Genetic diversity of N2-fixing bacteria associated with rice roots by molecular evolutionary analysis of a nifD library.

The rhizosphere of wetland rice has significant N2-fixing activity. It has been suggested that N2 fixation in the rice root zone is associated with the activity of various N2-fixing heterotrophic bacteria that inhabit the rice rhizosphere. Because of the generic diversity, many different isolation media and conditions are required to count and isolate these bacteria. In an attempt to overcome any bias from culture-dependent methods we amplified nifD segments from crude rice root DNA by the polymerase chain reaction. The nifD fragments were then cloned into a pT7 Blue T-vector to construct a nifD library. Sixteen cloned nifD genes chosen at random from the library were sequenced. A comparison with published sequences indicated the presence of seven novel groups of NifD proteins, which implies the existence of at least seven components in the diazotrophic community of rice roots, dominated mainly by proteobacteria. We also observed genetic variability within the clusters, which suggests the coexistence of many closely related bacterial lineages. However, we did not find Azospirillum-like nifD clones, although many reports indicated the widespread presence of Azospirillum spp. Therefore, it remains to be clarified whether Azospirillum species are the widespread N2-fixing bacteria in rice roots.

Amino Acid Sequence↗
PubMed1995

Clinical significance of S-T segment elevation in lead aVR in anterior myocardial infarction. Assessment by thallium-201 exercise scintigraphy.

The significance of exercise-induced S-T elevation in aVR was studied in 57 patients with recent anterior infarction and single-vessel disease. S-T elevation in aVR was found at peak exercise in 24 patients. Although the initial defect area was similar in the groups with and without S-T elevation in aVR, the redistribution area was larger in the former group (p < 0.01). When three electrocardiographic criteria were used in the multivariate analysis, S-T elevation in aVR was the significant variable related to redistribution in the anterior wall. Thus, S-T elevation in aVR may indicate ischemia of the anterior wall.

Adult↗