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Biomedical subjects

S Hayashi

Publications and source records attributed to S Hayashi.

At least 343 records · Page 19Linked to original sources
PubMed1999

Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes.

Genomic instability induces an accumulation of genetic changes and may play a role in the pathogenesis of myelodysplastic syndromes (MDS). To clarify the possible association between genomic instability and clinical outcome in MDS patients, we compared telomere dynamics to the recently established International Prognostic Scoring System (IPSS) risk groups for MDS. We measured the terminal restriction fragments (TRFs) of 93 patients with MDS at the time of diagnosis, and telomerase activity was analyzed in 62 patients with MDS using the PCR-based telomeric repeat amplification protocol (TRAP) assay. A total of 53 of 93 MDS patients had TRFs within the age-matched normal range, and the remaining patients showed shortened TRFs (35 patients) or elongated TRFs (5 patients). MDS patients with shortened TRFs had a significantly low hemoglobin concentration (P = 0.04), a high percentage of marrow blasts (P = 0.02), and a high incidence of cytogenetic abnormalities (P < 0.05). The incidence of leukemic transformation was significantly high in patients with shortened TRF length (P < 0.05). In addition, patients with shortened TRF length were frequently seen in the IPSS high-risk group (P < 0.01). Most of the MDS patients had normal-to-low levels of telomerase activity, suggesting that changes in TRF length rather than telomerase activity may more accurately reflect the pathophysiology of MDS. MDS patients with shortened TRF length had a very poor prognosis (P < 0.01), suggesting that telomere dynamics may be linked to clinical outcome in MDS patients. Thus, an abnormal mechanism of telomere maintenance in subgroups of MDS patients may be an early indication of genomic instability. This study demonstrates that telomere stability is frequently impaired in a high-risk group of MDS patients and suggests that, in combination with the IPSS classification system, measurement of TRFs may be useful in the future to stratify MDS patients according to risk and manage the care of MDS patients.

Acute Disease↗
PubMed1999

[Prognostic factors for oral tongue carcinoma treated with intra-oral cone electron beam irradiation].

Twenty-five patients with squamous cell carcinoma of the oral tongue were treated with intra-oral cone electron beam irradiation (IOC) during the period from 1985 to 1995. We analyzed the prognostic factors for local control and complications. IOC was applied for T1 (16 cases) and T2 (9 cases) tumors. Hypofractionation was used for IOC (20, 10, or 8 Gy/fr, 1f/wk). The total dose delivered ranged from 40 Gy to 78 Gy. Radiation dose homogenization was done through calculation of the normalized total dose (NTD) for alpha/beta = 10 (tumor) and alpha/beta = 3 (late normal tissue). The two-year local control rates for T1 and T2 were 80.4% and 77.8%, respectively. The two-year local control rates for patients whose overall treatment time (OTT) was < or = 28 days (n = 16) was 100% vs. 41.7% for patients whose OTT was > 28 days (n = 9) (p = 0.002). Multivariate analysis was applied to identify possible prognostic factors for local control. OTT (p = 0.02) was the only variable that significantly influenced local control. The incidence of radiation ulcer was 33.3% (7/21). Significant indicators of ulceration were fraction size (>> 10 Gy) and NTD (alpha/beta = 3) (>> 130 Gy) (p < 0.05). These results indicate that prolonged OTT was the major reason for the failure of IOC radiotherapy to control local disease and that the relatively high rate of ulceration was due to large fraction size and high NTD (alpha/beta = 3).

Adult↗
PubMed1999

The utility and limitations of an ultrasonic miniprobe in the staging of gastric cancer.

To determine the utility and limitations of an ultrasonic miniprobe (UMP) in the staging of gastric cancer, we evaluated 46 patients who underwent endoscopic ultrasonography (EUS) using an UMP and who were histologically determined to have gastric cancers. In every case, UMP findings were compared with histopathological findings after treatment. The total accuracy of UMP relative to the depth of tumor invasion was 71.7% (33/46 cases). Accuracy with respect to T1-m tumor diagnosis was 75.7% (22/29 cases), and for T1-sm, 76.9% (10/13 cases), but accuracy for T2 tumor diagnosis was low, due to ultrasound attenuation. When the analysis was carried out based on the size of tumor, the accuracy for UMP was 50.0% (9/18 cases) for all tumors over 20 mm and 85.7% (24/28 cases) for all tumors smaller than 20 mm. We conclude that UMP is suitable for investigation of tumor extension when the lesion is superficial and/or small gastric cancers which do not cause ultrasonic attenuation, but not when the tumor is large or located in certain sites, although conventional EUS is useful in some of these cases.

Aged↗
PubMed1999

Role of dipyridamole myocardial scintigraphy in abdominal aortic aneurysm repair.

BACKGROUND: We evaluated the usefulness of preoperative dipyridamole myocardial scintigraphy (DMS) under low-level exercise in predicting postoperative cardiac problems in patients undergoing elective abdominal aortic aneurysm (AAA) repair. METHODS EXPERIMENTAL DESIGN: retrospective comparison of patients who did and did not undergo the investigation preoperatively. SETTING: at the Keio University Hospital and the Kawasaki City Hospital. PATIENTS: eighty-five patients who had abdominal aortic aneurysm repair consecutively from 1986 to 1990 without undergoing dipyridamole myocardial scintigraphy preoperatively were compared with 118 patients who underwent the repair consecutively from 1991 to 1997 after having had preoperative scintigraphy. MEASUREMENTS: postoperative occurrences of myocardial infarction and angina pectoris in the two groups of patients were compared statistically. RESULTS: In the group not having scintigraphy, cardiac events occurred in 12 patients (14.1%) after repair. Ten patients had a myocardial infarction; six died within 30 days of operation and four died after the 31st postoperative day. The other two patients had angina pectoris; both survived. In the group having scintigraphy, there were no postoperative cardiac events (p<0.001). Seventeen patients had positive results on preoperative scintigraphy. Seven of them had undergone coronary artery bypass grafting and five coronary angioplasty before the repair. In the five other patients, scintigraphy, was found to have yielded false positive results. CONCLUSIONS: Dypiridamole myocardial scintigraphy is an accurate predictor of postoperative myocardial infarction and angina pectoris in patients being evaluated for elective abdominal aortic aneurysm repair and should be used routinely.

Aged↗
PubMed1999

Cochlear implantation for symptomatic hereditary deafness.

Recently, the effectiveness of cochlear implantation for hereditary deafness has been reported. We performed cochlear implantation for two patients with symptomatic hereditary deafness. Deafness in one patient was thought to be a result of albinism-deafness syndrome and in the other patient, a result of chronic progressive external ophthalmoplegia syndrome. Since their speech perception abilities improved dramatically, we believe that cochlear implantation should be actively performed for these two syndromes.

Adult↗
PubMed1999

p38 Mitogen-activated protein kinase regulates IL-8 expression in human pulmonary vascular endothelial cells.

The aim of this study was to examine the role of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-8 expression in tumour necrosis factor (TNF)-alpha- and IL-1alpha-stimulated human pulmonary vascular endothelial cells. To this end, the phosphorylation and activation of p38 MAP kinase and the effect of SB 203580, a specific inhibitor of p38 MAP kinase activity, on p38 MAP kinase activity and IL-8 expression in TNF-alpha- and IL-1alpha-stimulated human pulmonary vascular endothelial cells were examined. TNF-alpha- and IL-1alpha- induced phosphorylation and activation of p38 MAP kinase and IL-8 expression in human pulmonary endothelial cells. Inhibition of TNF-alpha- and IL-1alpha-induced p38 MAP kinase activity by SB 203580 inhibited TNF-alpha- and IL-1alpha-induced IL-8 protein production as well as IL-8 messenger ribonucleic acid (mRNA) expression, indicating that SB 203580 was effective at the transcriptional level. These results indicate that p38 mitogen-activated protein kinase plays an important role in the tumour necrosis factor-alpha- and interleukin-1alpha-activated signalling pathway which regulates interleukin-8 expression in human pulmonary vascular endothelial cells.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Thermosensitivity, incidence of apoptosis and accumulations of hsp72 and p53 proteins of murine L cells in wild type status of p53 gene.

Murine L cells showed markedly high lethal thermosensitivity. Survivals from fractionated heating at 44 degrees C with variety of interval time at 37 degrees C (44 degrees C for 10 min--variety of interval time at 37 degrees C-44 degrees C for 10 min) increased markedly in accordance with elongation of the internal time; i.e. survival fraction of 0.9% from 44 degrees C for 20 min alone without the interval time to those of 25% from the fractionated heating with interval time at 37 degrees C for 3-10 hrs. Incidence of apoptosis of the L cells from heating at 44 degrees C for 6.5 min (LD50) increased from 7% immediately after the heating to 30% 6-12 hrs after the post-incubation time at 37 degrees C. Accumulation of both hsp72 and p53 proteins markedly increased after a heating at 44 degrees C for 10 min alone in accordance with elongation of post-incubation time at 37 degrees C, representing a peak 6 hrs after the post incubation. Status of p53 gene in L cells were determined with Reverse Transcription-Polymerase Chain Reaction-Single Strand Conformational Polymorphism (RT-PCR-SSCP), i.e. wild type.

Animals↗
PubMed1999

[Efficacy and side effect of continuous intra-arterial infusion of high-dose 5-FU for liver metastases of colorectal cancer].

Fifteen patients with liver metastases of colorectal cancer were entered in our study, and 5-FU was given continuously by hepatic intra-arterial route at 1 g/day over 6 days. No leukopenia (< 3,000/mm3), anemia (< 10 g/dl), or thrombocytopenia (< 75,000/mm3) occurred, and no elevation of serum AST (> 150 IU/l) or serum T-Bil (> 2 mg/ml) appeared. One patient (4.2%) had nausea with vomiting 1-5 per day, and another (4.2%) had mucositis requiring treatment. In patients with multiple liver metastases, survival of the continuous infusion group [total dose of 5-FU > or = 12 g] (n = 5) seems to be longer than those of the hepatectomy only group (n = 3) or the control group (n = 7). We suggest that this continuous intra-arterial infusion of high-dose 5-FU is a useful chemotherapy with few side effects or complications.

Adult↗
PubMed1999

[The efficacy and limitation of hepatic arterial infusion chemotherapy for colorectal liver metastases].

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.

Administration, Oral↗
PubMed1999

Cancer mortality of thorotrast patients in Japan: the second series updated 1998.

The 150 male patients exposed to Thorotrast who were confirmed by a 1975-1978 national survey with diagnostic X rays of 50,860 war-wounded soldiers were followed up between 1979 and 1998 (Aichi series or second series). Age-adjusted rate ratios of deaths from all causes were 3.0 times higher in Thorotrast patients compared to controls; this was statistically significant. Rate ratios for liver cancer, liver cirrhosis and leukemia were 35.0, 7.5 and 18.2, respectively.

Adult↗
PubMed1999

Summary of entire Japanese thorotrast follow-up study: updated 1998.

Updated data from two series in a cancer mortality study for a total of 412 Japanese Thorotrast patients were combined. The rate ratio for all deaths of Thorotrast patients, compared to controls, started to increase after a latent period of 20 years after injection of Thorotrast. Rate ratios for liver cancer, liver cirrhosis, leukemia and lung cancer were 35.9, 6.9, 12.5 and 2.0 times higher, respectively, than those for controls.

Adult↗
PubMed1999

[An early phase II study of autologous peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission. Japan Blood Cell Transplantation Study Group].

We performed a multicenter, an early phase II clinical trial to evaluate the feasibility, safety and efficacy of myeloablative therapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of acute myelogenous leukemia (AML) in first remission. A total of 105 patients were enrolled in the study, and 56 patients in first complete remission received auto-PBSCT. The median age was 44 years. Of the 56 patients, 34 (60.7%) had M2 or M3 AML by the French-American-British Classification system. The median concentration of infused CD34+ cells was 2.3 x 10(6)/kg by recipient body weight. Median days to reach an absolute neutrophil count > 500/microliter and a platelet count > 20000/microliter were 14 and 16, respectively. The median disease-free survival rate was estimated to be 62.0% at a median follow-up time of 534 days. Although the study enrolled a small number of patients and the follow-up period was relatively short, the preliminary results were encouraging and indicated that myeloablative chemotherapy with auto-PBSCT is feasible and can be performed safely as a post-remission therapy for AML. A prospective randomized clinical trial of auto-PBSCT versus standard chemotherapy alone will be necessary to assess the efficacy of high-dose therapy facilitated by auto-PBSCT as a post-remission therapy for AML.

Adolescent↗
PubMed1999

[The sensitivity, specificity and predictive value of PAIgG, reticulated platelets, thrombopoietin levels, and platelet size for the differential diagnosis of thrombocytopenia].

We evaluated measurements of PAIgG, reticulated platelets (RP), plasma thrombopoietin (TPO) levels, and platelet size to determine whether these parameters were useful for the differential diagnosis of idiopathic thrombocytopenic purpura (ITP), aplastic anemia (AA), and hypoplastic thrombocytopenia (HypoT). The percentage of RP (%RP) in patients with ITP was significantly higher (25.2 +/- 11.0%, P < 0.001) than in normal subjects (7.9 +/- 2.8), and the sensitivity, specificity, and predictive value of %RP in diagnosing ITP were 82%, 95%, 96%, respectively. On the other hand, TPO levels in patients with AA and HypoT were significantly higher (355.5 +/- 218.7 pg/ml, P < 0.001, and 376.4 +/- 347.2, P < 0.001, respectively) than in normal subjects (36.7 +/- 23.0). The sensitivity, specificity, and predictive value of TPO in diagnosing AA and HypoT were 88%, 89% and 86%, respectively. We also sought to determine whether the simultaneous measurement of %RP and TPO improved their value in the differential diagnosis of ITP, AA, and HypoT. However, simultaneous measurement did not yield significant improvements in sensitivty, specificity, or predictive value. These results indicated that measurements of %RP will suffice for the diagnosis of ITP, and that measurements of TPO are adequate for the diagnosis of AA and HypoT.

Aged↗
PubMed1999

Association of Helicobacter pylori with gastroduodenal diseases.

Helicobacter pylori was first cultured in vitro in 1982. This bacterium is a spiral gram-negative rod which grows under microaerophilic conditions. The ecological niche is the mucosa of the human stomach which had been thought to be aseptic before the discovery of this bacterium. This organism causes a long-lasting infection throughout a person's life if there is no medical intervention. Numerous persons are infected with the organism around the world, and the rate of infection in Japan is nearly 50% of the population. However, the route of infection remains unclear because the organism has not been isolated from any environment other than several animals. H. pylori is now recognized as a causative agent of gastritis and peptic ulcers. Though gastritis, and especially chronic active gastritis, is observed at least histologically in all persons with H. pylori, peptic ulcers develop in only some infected persons. Specific factors in the host and/or the bacteria are needed for the development of peptic ulcer disease. Furthermore, H. pylori is considered to be related to the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, especially those of low grade. Also, H. pylori infection is a major determinant for initiating the sequence of events leading to gastric cancer. In some patients with low-grade gastric MALT lymphoma, the eradication of H. pylori led to a regression of lesion. Gastric cancer has been induced in Mongolian gerbils with long-term H. pylori infection. The combinations of drugs, which consist of an antisecretory agent (acid-suppressing agent) and antimicrobial agents, are used for the eradication of the organism. Eradication therapy is recommended at least for patients with peptic ulcers.

Animals↗
PubMed1999

Vital immunohistochemical staining for a novel method of diagnosing micro-cancer. Examination of immunohistochemical staining of non-fixed fresh tissue.

It becomes possible to establish a novel diagnostic method for micro-cancer by modulating the signals from the lesion, if lesions can be labeled with substances which can be detected by video endoscopy. The authors have already succeeded in synthesizing indocyanine green (ICG) derivatives for a fluorescent labeling substance which emits near-infrared rays. Before the antibodies labeled by these substances can be used, it is necessary to establish a method of vital immunohistochemical staining. So, we investigated the responses of antibodies exposed to non-fixed fresh tissue specimens as a basic study on vital immunohistochemical staining. The responses of fresh esophageal and gastric specimens (biopsied or surgically resected) to immunohistochemical staining with anti-epithelial membrane antigen (EMA) antibodies under various conditions using the ABC method were examined. These tissue specimens were stained immunohistochemically, and incubated with anti-EMA antibodies for 10 and 30 minutes (esophagus), and for 60 and 120 minutes (stomach) at 37 degrees C. These results suggest that vital immunohistochemical staining is possible under optimum conditions. If an infrared fluorescent endoscopy catching this excited fluorescence can be developed, it will be possible to establish a new endoscopic diagnostic method on the basis of vital immunohistochemical staining.

Adult↗
PubMed1999

Effect of adenovirus E1A on ICAM-1 promoter activity in human alveolar and bronchial epithelial cells.

In previous studies we demonstrated that the E1A DNA and proteins of group C adenovirus are present in excess in the lungs of patients with chronic obstructive pulmonary disease (COPD). Because adenovirus EIA gene products are known to regulate the expression of many genes by interacting with cellular transcription factors, we postulated that E1A enhances the production of inflammatory mediators and exacerbates the inflammatory process in smokers' lungs. We reported that LPS-induced ICAM-1 expression in A549 cells is upregulated by E1A. In the current study we investigated whether this regulation is mediated through the ICAM-1 promoter. A549 cells and primary human bronchial epithelial (HBE) cells were transiently cotransfected with a plasmid containing the ICAM-1 enhancer-promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene (pBS-CAT-P) and either a plasmid carrying the adenovirus 5 E1A gene (pE1Aneo) or a control plasmid (pneo). To compare the effect of transient versus stable E1A expression on the activity of this promoter, we also transiently transfected stable E1A-expressing A549 cells with pBS-CAT-P. Transient cotransfection of pE1Aneo and pBS-CAT-P had no effect on basal ICAM-1 promoter activity in A549 or HBE cells. After stimulation of A549 cells with TNF-alpha, IFN-gamma, or LPS, promoter activity was increased by two- to threefold in the presence of adenovirus EIA. In HBE cells, on the other hand, E1A repressed the ICAM-1 promoter after stimulation with IFN-gamma and LPS with little change after TNF-alpha stimulation. In stable E1A transfectants, ICAM-1 promoter activity was 2 to 2.5 times higher than in control transfectants with or without stimulation with TNF-alpha or LPS. These findings suggest that EIA can modulate the activity of the ICAM-1 promoter in lung epithelial cells and this modulation is different in cells of alveolar origin compared to bronchial epithelial cells.

Adenovirus E1A Proteins↗