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Biomedical subjects

H Saeki

Publications and source records attributed to H Saeki.

At least 37 records · Page 2Linked to original sources
PubMed2001

ATP-dependent chromatin remodeling facilitates nucleotide excision repair of UV-induced DNA lesions in synthetic dinucleosomes.

To investigate the relationship between chromatin dynamics and nucleotide excision repair (NER), we have examined the effect of chromatin structure on the formation of two major classes of UV-induced DNA lesions in reconstituted dinucleosomes. Furthermore, we have developed a model chromatin-NER system consisting of purified human NER factors and dinucleosome substrates that contain pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) either at the center of the nucleosome or in the linker DNA. We have found that the two classes of UV-induced DNA lesions are formed efficiently at every location on dinucleosomes in a manner similar to that of naked DNA, even in the presence of histone H1. On the other hand, excision of 6-4PPs is strongly inhibited by dinucleosome assembly, even within the linker DNA region. These results provide direct evidence that the human NER machinery requires a space greater than the size of the linker DNA to excise UV lesions efficiently. Interestingly, NER dual incision in dinucleosomes is facilitated by recombinant ACF, an ATP-dependent chromatin remodeling factor. Our results indicate that there is a functional connection between chromatin remodeling and the initiation step of NER.

Adenosine Triphosphatases↗
PubMed2001

Prognostic significance of lymphocyte infiltration following preoperative chemoradiotherapy and hyperthermia for esophageal cancer.

PURPOSE: Lymphocyte infiltration (LI) around cancerous lesions is an important immune response. The purpose of this study is to evaluate the prognostic significance of LI after preoperative treatment for esophageal cancer. METHODS AND MATERIALS: Preoperative chemoradiotherapy (CR therapy), either bleomycin 30 mg or cisplatin 120 mg/m(2) plus radiation 30 Gy, was performed on 51 cases with esophageal cancer, while hyperthermo-chemoradiotherapy (HCR therapy) was also indicated in 71 cases. Using resected specimens, both the histopathologic effectiveness and degree of LI to cancerous lesions were evaluated. RESULTS: The incidences of the cases in which preoperative treatment was effective were 56% and 92.3% in LI (-) and LI (++) group (p < 0.05). The presence of LI resulted in favorable prognosis; the 5-year survival rates of LI (++) and LI (+) patients were 75.5% and 46.1%, both of which were significantly better than LI (-) (27.8%, p < 0.05 and p < 0.01, respectively). Especially among cases whose preoperative treatment was moderately effective, a multivariate analysis revealed LI to be a favorable prognostic factor independent of other clinicopathologic factors (p = 0.0171). Regarding the preoperative treatment, the incidence of LI (++) was higher in the HCR group (16.9%) than in the CR group (2.0%, p < 0.01). CONCLUSIONS: LI appears to be a prognostic predictor after preoperative CR therapy while, in addition, simultaneous hyperthermia may stimulate LI in cases with esophageal cancer.

Analysis of Variance↗
PubMed2001

Nucleotide sequence analysis of a human monoclonal antibody TONO-1 with cytotoxic potential for T-leukemia/lymphoma cells.

A human monoclonal antibody (HuMab) TONO-1 (IgM, lambda) recognizes cell surface antigens associated primarily with human T-leukemia/lymphoma cells. In this study, we investigated the reactivity against T-leukemia/lymphoma cells in detail, cytotoxic potential and primary nucleotide and deduced amino acid sequences of the rearranged heavy and light chains of the HuMab TONO-1. Expression of the molecules (TONO-1 Ags) detected by a HuMab TONO-1 was significantly heterogeneous even in the same T-leukemia/lymphoma cell lines HPB-MLT and MOLT-4F. The flow cytometric curves showed an unusual broad-based spread of fluorescence intensity. HuMab TONO-1 was shown to have the ability to kill the T-leukernia/lymphoma cells efficiently in the presence of rabbit complements. However, HuMab TONO-1 did not demonstrate significant antibody-dependent cellular cytotoxic activity. Furthermore, HuMab TONO-1 heavy and light chain variable regions were cloned, sequenced and analyzed. HuMab TONO-1 uses a V(H) gene member of the V(H)IV gene family V(H)71-4, and is productively rearranged with the germ line D(H) gene D(XP')1, and the germ line J(H)5 gene with multiple somatic mutations. HuMab TONO-1 Vlambda belongs to the lambda light chain variable subgroup I family and is derived from the Vlambdalc germ line gene Humlv1042, and germ line gene Jlambda1 without somatic mutations. The results reveal that the production of HuMab TONO-1, with cytotoxic potential for human T-leukemia/lymphoma cells, is achieved by rearrangement of the V(H)71-4/Humlv1042 germ line variable region gene combination, that is associated with the autoimmune repertoire.

Amino Acid Sequence↗
PubMed2001

Repression of fatty-acyl-CoA oxidase-encoding gene expression is not necessarily a determinant of high-level production of dicarboxylic acids in industrial dicarboxylic-acid-producing Candida tropicalis.

The synthesis of dicarboxylic acids (DCAs) in Candida tropicalis is thought to be induced by a decrease in fatty acyl-CoA-oxidase activity. However, in the present study we demonstrate that repression of the POX4 gene, encoding fatty acyl-CoA oxidase, does not directly lead to high-level production of DCAs. No fatty acyl-CoA-oxidase activity was detected if the POX4 gene of C. tropicalis strain 1098 (wild-type strain) was disrupted. Furthermore, introduction of the POX4 gene from C. tropicalis strain M1210A3, which is a mutant derived from strain 1098 and is used as an industrial DCA-producing strain, still exhibited low-level fatty acyl-CoA-oxidase activity. Nevertheless, production of DCA was not observed in either case. Furthermore, the increase in acyl-CoA-oxidase activity by expression of the POX4 gene in strain M1210A3 did not reduce high-level production of DCA. These results suggest that alterations in acyl-CoA-oxidase activity are not necessarily related to production of DCA in industrial DCA-producing C. tropicalis M1210A3.

Acyl-CoA Oxidase↗
PubMed2001

Mutated SEA-D227A-conjugated antibodies greatly enhance antitumor activity against MUC1-expressing bile duct carcinoma.

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we have directed our attention to superantigens (SAgs), the most potent known activators of T lymphocytes. In our previous study, staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 mAb, which recognizes the MUC1 cancer-associated antigen, and shown to enhance the specific cytotoxic activity of T-LAK cells against MUC1-expressing BDC cells (TFK-1) in vitro and in vivo. However, it is probable that SEA might cause side-effects because of nonspecific binding to class II positive cells. In order to overcome these, we generated mutated SEA (mSEA) by changing Asp at position 227 of native SEA to Ala, which has reduced affinity to MHC class II molecules, but retains the potential for T cell activation. When mSEA-D227A was administered to rabbits to examine effects on blood pressure, 500 times more mSEA-D227A was tolerated than native SEA. This prompted us to construct a mSEA-D227A-conjugated mAb, reactive with MUC1. It augmented the antitumor activity of T-LAK cells significantly, and furthermore, mSEA-D227A could be conjugated to two bispecific antibodies, BsAb (anti-MUC1 x anti-CD3) and BsAb (anti-MUC1 x anti-CD28), which in combination had greater enhancing effects than mSEA-D227A-conjugated anti-MUC1 mAb, and combination of unconjugated BsAbs. These findings indicate a utility of mSEA-D227A-conjugated antibodies for targeted cancer immunotherapy.

Amino Acid Substitution↗
PubMed2001

Significance of preoperative elevation of serum C-reactive protein as an indicator of prognosis in esophageal carcinoma.

BACKGROUND: Preoperative elevation of serum C-reactive protein (CRP) has been reported to be a prognostic indicator in gastric carcinoma and colorectal carcinoma. The aim of this study was to establish the significance of preoperative elevation of serum CRP as an indicator of prognosis in patients with esophageal carcinoma. METHODS: Two hundred sixty-two patients with esophageal carcinoma who had been treated by esophageal resection and reconstruction of digestive tracts were evaluated, excluding patients with neoplasms in other organs. Preoperative serum CRP was measured, and the relation between the elevation of serum CRP and the clinicopathological factors and prognosis of the patients was investigated. RESULTS: The mean size of the tumors and the proportions of lymph node metastasis and lymphatic invasion were significantly larger in patients with preoperative elevation of serum CRP than in patients without preoperative elevation of serum CRP (5.8 +/- 2.5 cm versus 4.8 +/- 2.5 cm, P <0.01, 59.5% versus 35.4%, P <0.001, and 35.7% versus 23.6%, P <0.05, respectively). 1-, 3-, and 5-year survival rates in patients with preoperative elevation of serum CRP (60.6%, 18.4%, and 11.5%, respectively) were significantly lower than those in patients without preoperative elevation of serum CRP (88.7%, 70.9%, and 68.4%, respectively; P <0.0001). Multivariate analysis demonstrated that the preoperative elevation of serum CRP was an independent prognostic factor in esophageal carcinoma (P <0.0001). CONCLUSIONS: The preoperative serum elevation of CRP can be a marker of the malignant potential of the tumor and an independent prognostic indicator in esophageal carcinoma.

Adenocarcinoma↗
PubMed2001

Clinicopathologic characteristics of esophageal squamous cell carcinoma in younger patients.

BACKGROUND: The aim of the current study was to find out the clinicopathologic characteristics of younger patients with squamous cell carcinoma of the esophagus. METHODS: A total of 259 patients with esophageal squamous cell carcinoma who had been treated by esophagectomy and reconstruction within 10 years between January 1990 and December 1999 were studied. Clinicopathologic characteristics were compared between 27 patients younger than 50 years and 232 patients 50 years and older. RESULTS: A significant difference was observed with regard to the size of the tumor (6.3 +/- 3.8 cm in younger patients versus 5.0 +/- 2.4 cm in older patients; p = 0.017). The proportion of patients with TNM stage III or IV in younger patients (59.3%, 16 of 27) was significantly higher than that in older patients (38.3%, 89 of 232; p = 0.020). Nevertheless, no significant difference in the 1-, 3-, and 5-year survival rates was observed between younger patients (77.2%, 54.7%, and 54.7%, respectively) and older patients (81.9%, 54.2%, and 48.8%, respectively). CONCLUSIONS: Although the prognosis of younger patients with esophageal squamous cell carcinoma did not differ from that of older patients, esophageal squamous cell carcinoma in younger patients has more malignant potential and aggressive activity.

Adult↗
PubMed2001

Isolation and characteristics of trypsin inhibitor from the hepatopancreas of a squid (Todarodes pacificus).

Trypsin inhibitor was purified from the hepatopancreas of squid (Todarodes pacificus). The final inhibitor preparation was nearly homogeneous by SDS-PAGE with an estimated molecular weight of approximately 6300. The squid trypsin inhibitor was acid- and heat-stable, and active against trypsins from the pyloric ceca of starfish (Asterias amurensis) and saury (Cololabis saira) and porcine pancreatic trypsin. Amino acid composition of the squid trypsin inhibitor was compared with other invertebrate trypsin inhibitors. The squid trypsin inhibitor inhibited the autolysis of walleye pollock (Theragra chalcogramma) myofibrillar proteins.

Amino Acids↗
PubMed2001

Effect of Maillard reaction with glucose and ribose on solubility at low ionic strength and filament-forming ability of fish myosin.

It was previously reported that water-soluble fish meat can be prepared by the Maillard reaction with reducing monosaccharides. To clarify the molecular mechanism of the solubility improvement caused by the glycosylation, carp myosin and myosin rod region were reacted with glucose and ribose, and their solubilities and filament-forming abilities at low ionic strength were investigated. The solubility of myosin in 0.1 M NaCl increased with the glycosylation and reached the same level as in 0.5 M NaCl. Although the same solubility improvement was observed in glycosylated myosin rod and the alpha-helix content remained unchanged, the filament-forming ability was completely lost by the glycosylation. These results suggest that the solubility improvement of fish meat at low ionic strength is caused by the solubilization of myosin and the dissociation of myosin filaments.

Animals↗
PubMed2001

Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer.

Vascular endothelial growth factor-C (VEGF-C) is a specific ligand which induces lymphangiogenesis. We examined the expression of VEGF-C protein to determine its role in the progression of breast cancer. Immunohistochemical analysis revealed that VEGF-C was overexpressed in 39 of 98 breast cancer specimens (39.8%) but not in adjacent normal mammary glands. The expression of VEGF-C showed a significant correlation with lymphatic vessel invasion (p = 0.0004). It is noteworthy that the 5-year disease free survival rate of the VEGF-C positive group was significantly poorer than that of negative group (p = 0.0356). We suggest that as expression of VEGF-C is not implicated in lymphatic spread, it may prove to be a promising marker to predict the recurrence of breast cancer.

Adult↗
PubMed2001

Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity.

BACKGROUND: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of TH2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) is a chemokine that attracts CC chemokine receptor 4-positive (CCR4+) or CCR8+ cells. OBJECTIVE: The purpose of this study was to investigate the participation of TARC in AD. METHODS: We measured serum TARC levels in 40 patients with AD, 20 healthy control subjects, and 20 patients with psoriasis. We also examined disease activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor, IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as correlations between TARC levels and these factors. The positivity of CCR4 of CD4+CD45RO+ cells in PBMCs was examined by using FACS analysis. Immunohistochemical staining of TARC and GM-CSF was performed in the lesional skin of patients with AD. RESULTS: The serum TARC levels of patients with AD were significantly higher than those of healthy control subjects and patients with psoriasis. The serum TARC levels significantly correlated with eosinophil number (r = 0.61), SCORAD score (r = 0.60), and serum soluble E-selectin levels (r = 0.58) and weakly correlated with serum soluble IL-2 receptor levels (r = 0.34) in patients with AD. The TARC levels of patients with AD decreased after the treatment in accordance with the improvement of clinical symptoms. The CCR4 positivity of CD4+CD45RO+ cells in PBMCs of patients with AD was also higher than that of healthy control subjects. Immunohistochemical staining revealed that TARC was positive in keratinocytes in the epidermis and in vascular endothelial cells, T cells, and dendritic cells in the dermis. CONCLUSION: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD.

Administration, Oral↗
PubMed2001

Genetic alterations in the human Tcf-4 gene in Japanese patients with sporadic gastrointestinal cancers with microsatellite instability.

Disruption of the APC/beta-catenin/Tcf pathway has been proposed as an important step in the development of cancer. The Tcf-4 transcription factor gene was reported to be one of the targets of microsatellite instability (MSI) in colorectal cancers in with MSI. We carried out a sequencing analysis of the Tcf-4 gene in 41 Japanese patients with gastrointestinal tumors with MSI as well as in cancer cell lines. Three of 21 (14.3%) colorectal tumors with MSI contained a mutant Tcf-4 gene encoding 1-bp deletion in an (A)9 repeat, leading to carboxyl terminal truncation of Tcf-4 protein. No Tcf-4 mutations were detected in 20 gastric tumors with MSI, or in gastric cancer cell lines. Additionally, we found a novel transcript of the Tcf-4 gene which contained a segment of 73 bp in front of the (A)9 repeat of the Tcf-4 coding sequence. Sequencing analysis revealed that the inserted fragment was 60% homologous to that of exon IXA of the Tcf-1 gene. It is of interest that this insertion resulted in truncation of Tcf-4, similar to the 1-bp deletion in the (A)9 repeat. Therefore, in part of the Japanese colorectal tumors with MSI, frameshift mutations in Tcf-4 may be of functional significance. Functional alterations in the Tcf-4 signaling network in gastrointestinal tumorigenesis require further investigations.

Adenocarcinoma↗
PubMed2001

Antiarrhythmic drug, cibenzoline, can directly improve the left ventricular diastolic function in patients with hypertrophic cardiomyopathy.

The effect of cibenzoline on left ventricular diastolic function was investigated in patients with hypertrophic cardiomyopathy (HCM). Before and 2 h after an oral administration of 200 mg of cibenzoline, echocardiographic, apexcardiographic and gated radionuclide angiographic studies were performed in 12 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 7 with hypertrophic nonobstructive cardiomyopathy (HNCM). After administration of cibenzoline, the left ventricular pressure gradient decreased from 96+/-33 mmHg to 29+/-22 mmHg (<0.0001). Fractional shortening decreased from 53.3+/-7.5 to 45.4+/-6.2% (p=0.0008) in patients with HOCM and from 49.9+/-8.7 to 40.9+/-7.5% (p=0.0039) in patients with HNCM. On the other hand, E-wave velocity increased and A-wave velocity decreased in both groups. The time between the second heart sound and O point was shortened from 253+/-53 to 176+/-21 ms (p<0.0001) in patients with HOCM and from 245+/-54 to 185+/-44 ms (p=0.0050) in patients with HNCM. The time to peak filling rate was shortened from 248+/-79 to 190+/-40 ms (p=0.0072) in patients with HOCM and from 218+/-33 to 163+/-26 ms (p=0.0052) in patients with HNCM. These results indicate that in patients with HCM, cibenzoline suppresses left ventricular systolic function, but can markedly improve left ventricular diastolic dysfunction through its direct action.

Adult↗
PubMed2001

Magnesium deficiency in patients with recent myocardial infarction and provoked coronary artery spasm.

This study sought to clarify the relationship between magnesium (Mg) deficiency and coronary artery spasm provoked by pharmacologic agents in patients with a recent acute myocardial infarction (AMI). Twenty-three consecutive patients suffering from AMI were investigated with a Mg retention test (Mg: 0.1 mmol/kg for 4 h) in both the acute phase (within I week (3+/-2 days) of onset) and the subacute phase (3-4 weeks (24+/-6 days) of the onset). Early coronary arteriography was performed in all patients. Coronary stenosis in the infarct-related artery was less than 90% in all patients in the subacute phase. The spasm provocation test was performed in the subacute phase and coronary spasm was defined as transient subtotal or total occlusion in association with angina or electrocardiographic ST-segment deviation. Coronary artery spasm was provoked in only 13 of the 23 patients. Compared with the control subjects (12 patients without coronary artery disease or coronary spasm), the 24-h Mg retention was significantly higher in patients with AMI (acute phase: 78+/-27%, subacute phase: 66+/-32%, vs control: 48+/-12%, p<0.05). In the subacute phase, the 24-h Mg retention decreased in patients without coronary spasm (43+/-26%), but a high level of Mg retention was still observed in patients with coronary spasm (84+/-25%). There was no difference in the serum concentrations of Mg, calcium and phosphorus between the 2 groups on both phases. In conclusion, both Mg deficiency and provoked coronary artery spasm were noted in more than half of the Japanese patients with a recent AMI, suggesting a close association between Mg deficiency and AMI.

Aged↗
PubMed2001

Hypoglycemic syncope induced by a combination of cibenzoline and angiotensin converting enzyme inhibitor.

A 65-year-old Japanese woman with dilated cardiomyopathy, hypothyroidism and refractory sustained ventricular tachycardia experienced a near-death hypoglycemic syncope. The attack seemed to be induced by a high level of serum insulin, probably due to cibenzoline and by concomitant use of an angiotensin converting enzyme inhibitor (ACEI). Additionally, decreased food intake because of a severe toothache may have contributed to the deterioration of her condition. This case warns cardiologists that a combined cibenzoline and ACEI therapy can provoke serious adverse effects such as hypoglycemic syncope in the elderly. Therefore, the possibility of a hypoglycemic attack associated with these drugs should be explained to patients who are in poor condition.

Aged↗
PubMed2000

Expression of ets-1 transcription factor is correlated with penetrating tumor progression in patients with squamous cell carcinoma of the esophagus.

BACKGROUND: The Ets-1 transcription factor is proposed to play a role in tumor invasion. To evaluate the biologic significance of Ets-1 in the progression of squamous cell carcinoma of the esophagus, the authors investigated Ets-1 expression in tumors from 90 patients using immunohistochemical procedures. METHODS: The Ets-1 positive ratio (Ets-1 ratio) was determined in the center and deep margin areas of invasive sites and in the center and outer edge areas of intraepithelial spread contiguous with invasive disease. RESULTS: Ets-1 expression was heterogeneous within tumor tissue. The Ets-1 ratio was significantly higher at invasive sites compared with intraepithelial spread sites, and at deep margin areas compared with center areas (P < 0.0001 and P < 0.05, respectively, by two-way analysis of variance). No differences were noted in the Ets-1 ratio at the deep margin areas at each depth of invasion. Investigating the Ets-1 ratio at deep margin areas in each pathologic phenotype, the ratio of the small nest type was found to be higher than that of the large nest type (P < 0.0001). CONCLUSIONS: The authors propose that Ets-1 plays an important role in penetrating tumor progression, even very early in the invasive process (especially in the case of infiltrative invasive type tumors) at the deep margin areas of invasive sites in patients with squamous cell carcinoma of the esophagus.

Aged↗
PubMed2000

CYFRA 21-1 determination in patients with esophageal squamous cell carcinoma: clinical utility for detection of recurrences.

BACKGROUND: While there are reports that CYFRA 21-1 is a useful tumor marker, to our knowledge the clinical utility of this marker to detect recurrences for squamous cell carcinoma of the esophagus has not been addressed. METHODS: By immunoradiometric assay, human serum levels of CYFRA 21-1, SCC antigen and CEA were measured in esophageal squamous cell carcinoma patients prior to their initial treatment. Monthly follow-ups of these tumor markers was done after surgery. RESULTS: The diagnostic sensitivity of CYFRA 21-1 was 43.9% (18 of 41), a value superior to that for SCC antigen (26.8%) and CEA (17.0%) (P < 0.05). The positive rates of CYFRA 21-1 increased with progression of the disease, 22.2% of pTNM Stage 0-IIA and 77.8% of pTNM Stage IIB/III (P = 0.013), whereas SCC antigen and CEA rates were not related to pTNM stage. Among 13 patients with clinical evidence of a recurrence, 76.9% (10 of 13) exhibited an increase in CYFRA 21-1, and this increase was evident before clinical detection of the recurrence in 9 of these 13 patients (69.2%). Consequently, postoperative elevations of serum CYFRA 21-1 levels were indicative of a tumor recurrence 1-13 months before acquisition of clinical and radiological data. CONCLUSIONS: The assay of CYFRA 21-1 is useful not only for diagnosis but also for close monitoring of patients with esophageal squamous cell carcinoma.

Antigens, Neoplasm↗