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Biomedical subjects

T Ishida

Publications and source records attributed to T Ishida.

At least 865 records · Page 48Linked to original sources

Immunohistochemical evidence of autocrine growth factors in adenocarcinoma of the human lung.

We immunohistochemically examined 131 primary human lung adenocarcinomas for the possible presence of autocrine factors. Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) were considered growth factors with epidermal growth factor receptor (EGFR) as the receptor. Of these tumors, 87 (66%) showed a high expression of TGF alpha, 66 (50%) showed a high expression of EGF, and 55 (42%) were positive for EGFR reactivity. In the EGFR-positive cases, the 5-year survival rates of patients with high TGF alpha and low TGF alpha were 36% and 85%, respectively (P less than 0.05). The 5-year survival rates of patients with high EGF and low EGF were 25% and 77%, respectively (P less than 0.05). In contrast, in the EGFR-negative cases, there was no statistical difference between the 5-year survival rates of patients with either high TGF alpha or EGF and low TGF alpha or EGF. Because autocrine growth mechanisms are present in adenocarcinoma of the human lung, these events may contribute to clarification of tumor development, and perhaps even to a better prognosis.

Adenocarcinoma↗

A comparison between the binding modes of a substrate and inhibitor to papain as observed in complex crystal structures.

On the basis of the crystal structures of papain complexed with the substrate analogue benzyloxycarbonyl-L-phenylalanyl-L-alanine chloromethyl-ketone (Drenth, J., Kalk, K.H., and Swen, H.M. (1976) Biochemistry 15, 3731-3738) and with the inhibitor E-64-c, the binding modes were compared at the atomic level to clarify the functional difference between the substrate and inhibitor. Irrespective of the reverse chemical bonding in the peptide bonds, both the molecules are located at the S subsites of papain with similar interactions. However, the inhibitory activity of E-64-c is characterized by the stereochemical function of a carboxyoxirane ring and the tight binding of the isopentylaminoleucyl side chain to the S subsites.

Amino Acid Chloromethyl Ketones↗

[Clinical evaluation of radiotherapy for endocrine ophthalmopathy].

Ten patients with severe endocrine ophthalmopathy were treated by radiotherapy at Hyogo Medical Center for Adults from May 1984 to February 1988. All but one of the patients had poorly responded to previous systemic or topical corticosteroid therapy. The target of the radiotherapy was both retrobulbar tissues. The radiation field used was about 4 x 4 cm, excluding the pituitary gland and the brain, and was angled 5 degrees posteriorly to avoid the contralateral lens. A total of 2000 cGy was given to each patient over a 2 week-period. Eight of the ten patients showed some response, with 5 of them (50%) having a good to excellent response. Treatment was more effective for soft tissue changes, proptosis and keratopathy, while myopathy was less responsive. As for the duration of the eye signs and symptoms, those of a shorter duration (less then 12 months) responded better. It was also noted that the degree of the eye muscle enlargement on the pre-treatment orbital CT scan was directly correlated to the results of the treatment. Although three of the patients experienced transient headache, there were no serious acute reactions or long term complications. In conclusion, retrobulbar radiotherapy is a well-tolerated, safe and effective treatment for severe endocrine ophthalmopathy.

Adult↗

[Clinical evaluation of sodium alginate on oral mucositis associated with radiotherapy].

We evaluated the effect of sodium alginate on 39 patients with oral mucositis associated with radiotherapy. Sodium alginate was administered during radiotherapy to 17 patients with head and neck cancer. Compared with 22 patients without administration, sodium alginate reduced the pain and the erosion of oral mucosa significantly. Consequently the interval of radiotherapy was shortened. It is, therefore, expected that the effect of radiotherapy improves by the administration of sodium alginate.

Adult↗

An attempt to structurally convert mu-selective morphine toward delta-receptor binding: dimerization based on enkephalin conformation.

In order to elucidate the substrate specificities for mu- and delta-opioid receptors, dimerization of the mu-specific morphine molecule was attempted, based on the hypothesis of the possible relationship between the molecular conformation of endogenous enkephalin and its selectivity for each opioid receptor. The NOR2 ([normorphine]N-CH2-CH2-N[normorphine]) thus synthesized exhibited agonist activity showing a preference for binding with the delta-opioid receptor, compared with the parent morphine molecule. Antagonist activity was also observed for NOR3 ([normorphine]N-CH2-CH2-CH2-N[normorphine]).

Animals↗

A clinicopathologic study on multiple gastric cancers with special reference to distal gastrectomy.

Simultaneous multiple gastric cancer was seen in 49 (5.8%) of 852 resected stomachs. Patients with multiple cancers were older than those with single gastric cancers (P less than 0.01) and the incidence of multiple gastric cancer was significantly higher in male patients than in female patients (P less than 0.05). The incidence rates of multiple carcinomas were 9.6% of early gastric carcinomas and 4.0% of advanced gastric carcinomas. With regard to histologic type, the incidence rate of the differentiated type was 71% and the incidence rate of the undifferentiated type was 29%. In 68 serially resected stomachs, 5 (7.4%) new multiple cancers were detected microscopically, whereas 4 (5.9%) had already been diagnosed grossly. The incidence rate of multiple carcinoma increased to 13.2% by this procedure. The cases that were cut serially showed that most of the multiple cancers were located distally from the F-line presenting the line along which intestinal metaplasia appeared. This study suggests that the surgeon is required to resect the area including the F-line at the time of distal gastrectomy so as not to leave another cancer in the gastric remnant.

Adult↗

The importance of Val-157 hydrophobic interaction for papain inhibitory activity of an epoxysuccinyl amino acid derivative. A structure-activity relationship based on the crystal structure of the papain-E-64-c complex.

Based on the crystal structure of the papain-E-64-c complex, 3-dimensional binding modes of a series of epoxysuccinyl amino acid derivatives to the papain active site have been constructed and the structure-inhibitory activity relationship has been analyzed using the accessible surface area and nonbonded energy parameters. The result indicates the importance of the hydrophobic interaction between the amino acid side chain of the inhibitor and the papain Val-157 residue for revealing the potent inhibitory activity.

Amino Acid Sequence↗

[An overview of breast cancer mass screening in Japan].

To establish the effective mass screening projects for the breast cancer, our study group cosponsered by the Welfare Ministry was organized by 11 regional groups. From 1968 to 1986, 643, 513 women at the initial screening and 719, 189 women at the subsequent screening were examined by physical examination. Out of them, abnormalities were present in 24, 864 women (3.9%) and 23,880 (3.3%), respectively. A detection of cancer was made in 833 women (detection rate 1.3%) and 428 women (0.6%), respectively. As the examinees increased from year to year, the subsequent examinees were over the initial ones. It was suggested that most of examinees had been fixed year by year and the detection rate of initial screening had been higher than that of the subsequent one. Then more initial examinees are expected to be increased. Women 30 to 59 years of age were mostly screened, but women aged 60 or more should be increased. Of women with abnormal physical findings, women over 90% took the second examination. But more effective, economical and safer screening instruments are expected to be developed and be used at the first examination.

Adult↗

Orosomucoid typing by isoelectric focusing: genetic variation of orosomucoid in Asian macaques (genus Macaca).

Genetic variation of orosomucoid (ORM) in the genus Macaca was investigated. Plasma samples were subjected to isoelectric focusing in a pH range of 4-6.5, followed by immunoprinting with anti-human ORM antibodies. A total of 25 alleles were identified in 231 Asian macaques belonging to 13 species from 23 populations and 22 members belonging to a family of M. fascicularis. Family data presented evidence for a codominant mode of inheritance with multi-alleles at a single autosomal locus. A population study revealed enormous intra- and interspecies variations. The heterozygosity values varied from 0.855 in M. fascicularis (Malaysia) to 0.000 in M. radiata (India), M. silenus (India) and M. arctoides (Malaysia).

Animals↗

Metabolites of (+)-dehydroabietic acid in rabbits.

The seven metabolites of (+)-dehydroabietic acid (DHA) were newly isolated from rabbit urine by liquid chromatography. On the basis of chemical and spectral data their structures were established to be (15S)-8,11.13-abietatrien-16,18-dioic acid, 2 alpha-hydroxy-8,11,13,15-abietatetraen-18-oic acid, (15R)-15,16-dihydroxy-8,11,13-abietatrien-18-oic acid, 2 beta,15-dihydroxy-8,11,13-abietatrien-18-oic acid, (15S)-2 beta,16-dihydroxy-8,11,13-abietatrien-18-oic acid, 2 alpha,15-dihydroxy-8,11,13-abietatrien-18-oic acid, and (15S)-2 alpha,16-dihydroxy-8,11,13-abietatrien-18-oic acid. The possible hydroxylation routes of DHA in rabbits and the difference between the metabolism of DHA in microorganisms and that in rabbits are discussed.

Abietanes↗

Distribution of fibronectin in adenocarcinoma of the lung: classification and prognostic significance.

Fibronectin (FN) was investigated in 75 stroma from lung adenocarcinoma patients. Distribution of FN was classified into three patterns based on immunohistochemical evidence: dense, moderate, and sparse distribution. The incidence of the sparse pattern in both stage I and stage III disease was significantly greater in the infiltrating than in the noninfiltrating areas. The patients were divided into two groups, long-term survivors and short-term survivors. In the group with stage I disease, the incidence of the sparse pattern was significantly greater in the infiltrating than in the non-infiltrating areas. In both areas, the incidence of sparse pattern was greater in the short-term than in the long-term survivors. These data suggest that the disappearance of FN reflects the aggressiveness of the tumor and presumably plays an important role in the prognosis of adenocarcinoma of the lung.

Adenocarcinoma↗

Surgical treatment of patients with nonsmall-cell lung cancer and mediastinal lymph node involvement.

Between 1974 and 1988, 115 patients admitted to our surgical unit underwent resection of nonsmall-cell lung cancer in the presence of mediastinal lymph node involvement (N2 disease). The overall 5 year survival rate was 18%, and the rates in patients with curative and noncurative operation were 26% and 9%, respectively (P less than 0.05). Based on the morphological evidence of N2 disease, the patients were placed in three groups: those with microscopic metastasis, moderate metastasis, and gross metastasis, the incidences being 29%, 28%, and 43%, respectively. The survival rates were 41%, 6%, and 16%, respectively. The difference among microscopic vs. moderate and microscopic vs. gross metastasis was statistically significant (P less than 0.01). Survival rates in patients with intranodal and extranodal invasion, as seen in the histologic examinations, were 34% and 11%, respectively (P less than 0.01). The incidence of gross metastasis and/or extranodal invasion was higher in those who underwent noncurative operation. Postoperatively adjuvant irradiation was not effective in prolonging the survival in patients with curative operation, but the local residual disease was controlled. Therefore, our working criteria are, if N2 lung cancer is present, a complete resection of the primary tumor and the mediastinal lymph nodes should be done. Patients with microscopic metastasis and intranodal invasion can expect a fairly long survival.

Adult↗

Prognostic significance of laminin in adenocarcinoma of the lung.

The distribution of laminin in tumor-associated basement membrane was immunohistochemically investigated in 115 cases of adenocarcinoma of the lung. The distribution of laminin was classified into continuous and discontinuous staining patterns. The incidence of the discontinuous pattern was less in early-stage disease than that in advanced stages (P less than 0.01). In patients with stage I, the incidence of discontinuous patterns was greater in short-term survivors than in long-term survivors (P less than 0.05). By contrast, in patients with stage III, the discontinuous pattern of laminin was frequently seen in both long-term survivors and short-term survivors, with no difference between the two groups. These data suggest that the discontinuous pattern of laminin in tumor-associated basement membrane reflects the spread and dissemination of tumor, hence a close relationship to the prognosis.

Adenocarcinoma↗

Clinical applications of the pathological properties of small cell carcinoma, large cell carcinoma, and adenoid cystic carcinoma of the lung.

Lung cancer has considerable treatment problems, with a poor 5-yr survival rate after surgery. Application of histopathological and immunohistopathological subtyping have proven to be powerful tools for the assessment of prognosis. Results in 33 patients with small cell carcinoma, 44 with large cell carcinoma, and five with adenoid cystic carcinoma of the lung are discussed. The 5-yr survival rates in patients with small cell carcinoma of the oat cell type and intermediate type were 24 and 44%, respectively. Argyrophilic granules and neuron-specific enolase, neuroendocrine markers, were detected more frequently in the oat cell type rather than in the intermediate type. In contrast, keratin, epithelial membrane antigen, and carcinoembryonic antigen, epithelial origin markers, were present more frequently in the intermediate type than in the oat cell type. The 5-yr survival rates with large cell carcinoma of the compact growth type and the loose structure type were 46 and 28%, respectively, based on evidence of morphologically intercellular cohesion. The epithelial origin markers were detectable and more frequent in the compact growth type than in the loose structure type. The growth patterns of adenoid cystic carcinoma are classified as tubular, cribriform, and solid. The solid pattern was the most aggressive with extensive perineural invasion. We propose that the pathological properties of lung cancer should be examined as a prognostic implication of subtyping.

Adult↗

DNA ploidy level and S-phase fraction as prognostic factors in breast cancer.

Imprint smears from sixty cases of breast cancer made after mastectomy were stained by the Feulgen method and the nuclear DNA content measured by a cytofluorometer equipped with an incident illumination system. After logarithmic transformation of the fluorescence intensity, the ploidy level and S-phase fraction (SPF) were calculated with a microcomputer and the correlation between the ploidy level or SPF and the clinicopathological prognostic factors studied. Patients with tumors of a larger diameter and more extensive lymph node involvement had higher levels of ploidy and SPF and the ploidy level in the metastatic lymph nodes was higher than that in the primary lesion. Moreover, a significant increase in SPF was observed in the metastatic lymph nodes and a high ploidy level found to be associated with tumors having a negative estrogen receptor. When the tumors were divided into a diploid group and an aneuploid group, the diploid group showed a significantly better prognosis than the aneuploid group, in 6-year survival. Similarly, the groups in which SPF was less than 20.0 per cent had significantly better prognoses than the group in which SPF was 20.1 per cent or more. These prognostic factors were evaluated with Cox's proportional hazard model and a significant correlation observed in lymph node status, ER status, ploidy level and S-phase fraction. It was thus concluded that ploidy level and SPF are important and independent prognostic factors for predicting the postoperative course of breast cancer patients.

Breast Neoplasms↗

Strategy for lymphadenectomy in lung cancer three centimeters or less in diameter.

We have surgically treated 221 patients with a primary lung cancer 3.0 cm or less in diameter. There were 8 patients with a tumor 1.0 cm or less in diameter (group A), 84 with a tumor 1.1 to 2.0 cm in diameter (group B), and 129 with a tumor 2.1 to 3.0 cm in diameter (group C). The incidence of N0, N1, and N2 disease was 100%, 0%, and 0%, respectively, for patients in group A; 83%, 5%, and 12% in group B; and 62%, 12%, and 25% in group C (N0 versus N2, p less than 0.01). For the 63 patients with regional lymph node involvement, "skipping" metastasis was present in 28.6%. The 5-year survival rate was 80% for group A, 74% for group B, and 51% for group C (group B versus group C, p less than 0.01). Of the 121 patients who underwent complete resection and were followed up for 5 years, 41% had recurrence, 8% with local recurrence and 33% with distant metastasis. Therefore, it is important to do as complete a resection as possible together with mediastinal lymphadenectomy. Efforts to detect systemic spread should be made at the time of preoperative evaluation, even when the lung tumor is small.

Adult↗

Long-term results of operation for non-small cell lung cancer in the elderly.

We surgically treated 185 patients with non-small cell lung cancer who were 70 years old or older. The operative mortality rate was 3%, and the 5-year survival rate was 48%. The mortality and prognosis were similar to those in younger patients. The number of elderly patients who smoked heavily or who had ventilatory defects was high, but the incidence of pneumonectomy was low. There were no differences based on age in regard to histological type, TNM classification, and curability. Pulmonary complications occurred in 21% of the elderly patients and were correlated with preoperative pulmonary function and smoking habits. When the elderly are to undergo elective pulmonary resection for lung cancer, the preoperative evaluation of pulmonary function should be thorough, and both preoperative and postoperative physical therapy should be given. If postoperative pulmonary function is predicted to be less than 0.8 L/m2 of vital capacity and 0.6 L/m2 of forced expiratory volume in 1 second, a limited resection or nonsurgical therapy should be considered.

Adult↗