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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 559 records · Page 31Linked to original sources

A clinicopathologic study of gastric carcinoma with reference to age of patients.

We carried out a clinicopathologic study on gastric carcinomas excised from 36 young (< 40 years), 34 elderly (61 or 62 years), and 34 aged (> or = 80 years) patients. The young group was characterized by long duration (6.9 months) of epigastric pain (64%), tumor location rarely along the lesser curvature (31%), grossly depressed type in early stage (100%), and histologically undifferentiated type (92%). The aged group was characterized by preexisting disorders (85%), limited lymph node dissection (74%), short operative time (136 min), blood transfusion (74%), tumor location in the lower stomach (59%), and noncurative operation (47%), mainly because of locally advanced disease (59%). The 5-year survival rate in the aged (40%) was much lower than that in the young (72%) and elderly (67%). However, the 5-year survival rate for curatively treated patients did not differ among the young (85%), elderly (81%), and the aged (74%). Thus, gastric carcinomas in the young were mostly of the undifferentiated type resembling peptic ulcers, and resection led to a good prognosis. Aged patients with gastric carcinoma often had preexisting clinical disorders and locally advanced diseases; the limited feasibility of surgical excision sometimes led to a less satisfactory outcome.

Adult↗

The distribution of lymph node metastases in right-sided colon cancer.

We reviewed the surgical results of 57 patients with right-sided colon carcinoma (RCC) with special reference to lymph node metastasis. In 45 cured patients, 25 showed no lymph node metastasis (n0), 19 showed a low or moderate degree of lymph node metastasis (n1, n2), and only one showed a high degree of lymph node metastasis (n3). As for the remaining 12 cases, the reasons that operation did not lead to a cure were liver or lung metastasis (66%), peritoneal spread (17%), or extensive lymph node metastasis (17%). Among these patients, only one may have died from insufficient lymph node dissection (R2 < n3). The presence of lymph node metastasis was predicted by the serum carcinoembryonic antigen level (> 3.0 ng/ml) and histologic type (other than well differentiated). These results indicate that complete removal of the group 1 and 2 nodes (R2 dissection) is a feasible operation for RCC.

Aged↗

Dukes's classification: a valid prognostic indicator for gastric cancer.

Dukes's classification for colorectal cancer is simple, and correlates well with survival. This study assessed whether the principles of Dukes's classification applied to gastric cancer resulted in the separation of prognostically useful groups. The cumulative survival curves determined by Dukes's, Astler-Coller's (another classification for colorectal cancer), and the Japanese classification for gastric cancer were evaluated using 476 curatively treated patients with gastric cancer. Of the three staging systems, both Dukes's and the Japanese classifications showed a step-wise relationship between the stage of the tumour and the survival of patients. The prognostic value of Dukes's classification was reinforced when Dukes's C cases were subdivided according to the number of positive nodes (1-6 v > or = 7) or the level of positive nodes (n1 v n2,n3) but not when the subdivision was made according to the depth of wall invasion. A modified Dukes's classification in which Dukes's cases are subdivided according to the number of metastatic nodes (Dukes's Ca = 1-6 nodes, Dukes's Cb > 6 nodes) could be both simply and accurately applied to gastric cancer.

Evaluation Studies as Topic↗

Bilateral ovarian metastasis from left renal cell carcinoma.

We report a case of left renal cell carcinoma with bilateral ovarian metastasis which was demonstrated 3 years after radical nephrectomy. The patient is alive without any evidence of disease 36 months after bilateral salpingo-oophorectomy.

Carcinoma, Renal Cell↗

Relationship between the tissue distribution and antitumor activity of highly branched (1-->3)-beta-D-glucan, SSG.

Distribution of 3H-labeled (1-->3)-beta-D-glucan([3H]SSG) obtained from the culture filtrate of Sclerotinia sclerotiorum IFO 9395, in various tissues in tumor-bearing mice was examined. [3H]SSG administered intra-peritoneally was mainly detected in liver, spleen, kidney and tumor masses. In contrast to i.p. administration, intra-lesionally administered [3H]SSG was not released from the tumor. Similarly, in a double grafted tumor system, [3H]SSG was located in the administered tumor and not distributed in the distant site tumor, in spite of the fact that significant antitumor effect was shown in both tumor sites in this system. Winn assay confirmed the activation of the systemic antitumor immunity. These results suggested that the distribution of glucans would be one important factor in determining their antitumor effects. However, this would not always be necessary if systemic immunity could be induced.

Animals↗

Preparation and antigen specificity of an anti-(1-->3)-beta-D-glucan antibody.

Antibody for (1-->6)-branched (1-->3)-beta-D-glucan was prepared using rodents. An antitumor (1-->6)-beta-monoglucosyl branched (1-->3)-beta-D-glucan (GRN: grifolan) was conjugated with bovine serum albumin and used as an immunogen. The antibody titer in serum was determined by ELISA using biotin-conjugated GRN. Administration of the antigen raised the antibody titer only in the rabbit, with mouse and rat showing no significant antibody titer for the glucan. The antigen specificity of the anti-GRN antibody was determined by competitive ELISA. The rabbit anti-GRN antibody bound to structurally related antitumor (1-->6)-branched (1-->3)-beta-D-glucans such as lentinan, schizophyllan and SSG, whereas it did not react with linear (1-->3)-beta-D-glucan, curdlan or GRN-derivatives obtained by periodate-oxidation and Smith degradation. These facts strongly suggest that the hapten site of the antibody was the monoglucosyl branched moiety of (1-->3)-beta-D-glucan. These results indicate that this antibody would be a useful probe for the detection of (1-->6)-branched antitumor glucans administered to the host.

Adjuvants, Immunologic↗

Enhancement of cytokine production by macrophages stimulated with (1-->3)-beta-D-glucan, grifolan (GRN), isolated from Grifola frondosa.

The ability of grifolan (GRN), a purified fungal (1-->3)-beta-D-glucan, to induce various cytokines from macrophages was examined in vitro. Interleukin-6 (IL-6) activity in supernatants from the culture of macrophage cell line, RAW264.7 was dependent on increasing doses of GRN. The level of IL-6 induced with 500 micrograms/ml of GRN was comparable to that induced with lipopolysaccharide (LPS) 10 micrograms/ml. Enhancement of the mRNA level of IL-6 by treatment with GRN was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The effect of GRN on production of IL-6 was also observed using peritoneal macrophages from C3H/HeJ mice which did not respond to endotoxins. This data suggested that the ability of GRN to activate IL-6 production of macrophages is not due to contamination of endotoxins in the preparation. Enhanced production of cytokine by GRN was observed not only with IL-6, but also with interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). In the production of TNF alpha, GRN was more effective than LPS used in this study. Other soluble or gel-forming(1-->3)-beta-D-glucans from various sources did not enhance the production of such cytokines although they are structurally similar to GRN. The above results indicate that GRN is a novel macrophage activator which augments cytokine production without dependence on endotoxins.

Adjuvants, Immunologic↗

Monoclonal antibody to proteoglycan derived from Grifola frondosa (Maitake).

A murine monoclonal antibody (MAb) was prepared by immunizing BALB/c mice with a proteoglycan fraction derived from Grifola frondosa (Maitake mushroom), followed by the hybridization of spleen cells with mouse myeloma cells. The MAb (subclass; Ig G2b), designated MPG2, reacted with schizophyllan (SPG), curdlan, scleroglucan, laminarin and lentinan, but not with dextran, pullulan, mannan and xylan. Immunohistochemistry (ABC-GO method) showed that MAb MPG2 reacted with lysosomal proteoglycan and (1-->6)-beta-branched laminaritriose taken up by rabbit peritoneal macrophages. These results suggest that this MAb may recognize mainly (1-->3)-beta-D-glucan, and may be useful for determining the immunological properties of Grifola frondosa-derived proteoglycan.

Animals↗

Analysis of cytokine mRNAs induced by the administration of a highly branched (1-->3)-beta-D-glucan, OL-2.

OL-2, a highly branched (1-->3)-beta-D-glucan, is an antitumor glucan showing strong hematopoietic activity with weaker adjuvant activity than schizophyllan (SPG), another antitumor glucan and one which is used clinically. This paper deals with the gene expression of cytokines in mice by OL-2 and SPG in order to characterize their immunopharmacological activity. Gene expression was examined by a reverse transcriptase-polymerase chain reaction method after intraperitoneal administration of OL-2 or SPG (250 micrograms/mouse). The OL-2 administered mice strongly expressed the interleukin 1 receptor antagonist (IL-1ra) gene but SPG administered mice did not. The difference would be strongly related to the antigen-specific response between OL-2 and SPG. In the genes related to haematopoiesis, OL-2 induced G-CSF and GM-CSF, but SPG induced IL-3. These differences would relate to the pattern of haematopoietic response. Comparing the cytokine gene expression in ICR and AKR mice by OL-2 administration, the changes in cytokine gene expression were less in AKR mice administered OL-2. These findings suggest that the immunopharmacological characteristics of OL-2 are closely related, at least in part, to the activation of the complement system. The data shown in this paper also suggest that cytokine gene expression by beta-glucan would be significantly affected by the structure of these glucans.

Animals↗

Synthesis and structure-activity relationships of new (5R,8R,10R)-ergoline derivatives with antihypertensive or dopaminergic activity.

A series of new (5R,8R,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were tested in conscious spontaneously hypertensive rats and in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra. (5R,8R,10R)-6-Alkyl-8-ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-methylergoline (4s, maleate: BAM-1110) exhibited potent dopaminergic activity, about 18-fold greater than that of bromocriptine mesylate. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-propylergoline (8b, fumarate: BAM-1602) showed extremely potent dopaminergic activity, being about 220 and 1.15 times more active than bromocriptine mesylate and pergolide mesylate, respectively. Several compounds exhibited potent antihypertensive activity. Structure-activity relationships for antihypertensive and dopaminergic activities are discussed.

Animals↗

Synthesis and structure-activity relationships of new (5R,8S,10R)-ergoline derivatives with antihypertensive or dopaminergic activity.

A series of new (5R,8S,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were evaluated in conscious spontaneously hypertensive rats and in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra, respectively. (5R,8S,10R)-6-Methyl-8- ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8S,10R)-8-(1-Imidazolylmethyl)-6-methylergoline (5a, BAM-2101) and (5R,8S,10R)-2-bromo-6-methyl-8-(1,2,4-triazol-1-ylmethyl) ergoline (7c, BAM-2202) exhibited potent antihypertensive activities. The maximum falls of systolic blood pressure after oral administration of 5a and 7c at 3 mg/kg were 95 and 132 mmHg, respectively, while those of cianergoline, bromocriptine mesylate, hydralazine, and nifedipine at the same dose were 40, 37, 47, and 49 mmHg, respectively. The durations of significant antihypertensive effects of these compounds except nifedipine were more than 7 h. None of the ergolines exhibited potent dopaminergic activity. Structure-activity relationships are discussed.

Animals↗

[Changes in the concentrations of chlornitrofen (CNP) and CNP-amino in river and faucet water in Niigata, Japan].

It has been reported that the standardized mortality ratios (SMRs) of biliary tract cancer (BTC) (female gallbladder cancer (GBC) in particular) are high in the Niigata plain and low in other parts of Niigata Prefecture. Based on epidemiological studies, the presence of environmental water pollution by agricultural chemicals is likely to be associated with the occurrence of GBC, and one of the most suspected of these is a diphenylether herbicide, chlornitrofen (CNP). The purpose of the present study was to investigate whether or not there was a difference in concentrations of CNP and its reduction product (CNP-amino) in river and faucet water between Niigata and Joetsu Cities, which are located in the Niigata plain and another part of Niigata, respectively. By employing a new method for CNP and CNP-amino extraction, the detection of CNP and CNP-amino was undertaken by using a gas-chromatograph with an electron-capture detector. The maximum levels of CNP concentrations were 871 and 554 ng/l in river and faucet water, respectively on May 6, 1992 in Niigata City. The concentration of CNP in faucet water was well correlated with that in river water. In Joetsu City, the maximum concentration in river water was 183 ng/l on May 6 and had decreased rapidly towards the background level on July 29, 1992. As to the concentrations of CNP in faucet water in Joetsu City, they fluctuated between the levels of 2 and 9 ng/l. In the case of CNP-amino concentrations in faucet water, a clear-cut difference was evident between the two cities; 384 ng/l in Niigata and under the quantity limit in Joetsu.(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary Tract Neoplasms↗

Efficacy of ivermectin against Setaria microfilariae in calves and cerebrospinal setariosis in sheep and goats.

Ten calves harboring microfilariae (Mf) were injected with ivermectin at a single dose of 200 micrograms/kg body weight. Thereafter, the number of calves harboring Mf was gradually reduced to 7, 2 and 0 by 1, 4 and 12 weeks, respectively and remained negative for microfilariae by 16 weeks after injection. Furthermore, none of 221 goats and sheep injected twice with ivermectin at a dose of 200 micrograms/kg body weight developed setariosis while 17 out of 303 non-injected animals suffered from that disease. Therefore, ivermectin was much effective for the eradication of Mf in calves and the prevention of setariosis in sheep and goats.

Animals↗

Possible role of bovine serum albumin for the prevention of aflatoxin B1-absorption from the intestinal tract in young chicks.

The deleterious effect of aflatoxin B1 (AFB1) on the liver after intragastric inoculation and the protective influence of bovine serum albumin (BSA) from AFB1 damage was biochemically and histologically examined using one-day-old chicks. Three mg/kg weight of AFB1 was inoculated intragastrically into the chicks, the dosage being based on the results of a preliminary toxicity test that indicated it was the minimum dose for lesion production. The resulting histological changes were confined to the liver and were characterized by bile duct proliferation, vacuolation of hepatic cells in the peripherolobular regions, and necrosis of hepatic cells in the centrilobular regions. In a subsequent experiment, 3 groups of one-day-old chicks were each inoculated with AFB1 alone, AFB1 + BSA and dimethyl sulfoxide alone (control), respectively. BSA provided protection from AFB1 as evidenced by the less pronounced changes in the liver of chicks inoculated with AFB1 + BSA and the same quantitative value of plasma isocitrate dehydrogenase released from the liver, maintaining its activity at nearly the same level with the control. Moreover, AFB1 contents in the plasma and liver were significantly lower in the AFB1 + BSA inoculated chicks than those with AFB1 alone. AFB1 in the plasma and liver of both groups receiving AFB1 attained its maximum level 6 hr after inoculation. This was immediately followed by a rapid decline with both parts having similar final levels. These results indicate that BSA may have AFB1-binding ability in the intestinal tract of young chicks and may also be excreted with AFB1.

Aflatoxin B1↗

Extrathymic differentiation of a T cell bearing invariant V alpha 14J alpha 281 TCR.

We found that a homogenous CD4-/CD8- T cell bearing an invariant TCR encoded by V alpha 14J alpha 281 with a one-base N-region is highly dominant in the periphery (2-3% in spleen). Surprisingly, the high expression of this invariant V alpha 14 TCR is a general phenomenon in all laboratory strains irrespective of MHC haplotype and in some wild mouse subspecies. The majority of V alpha 14+ TCR is associated with J alpha other than J alpha 281 during the neonatal stage, after which the frequency of invariant V alpha 14J alpha 281 TCR expression increases with time reaching a maximum at around 5-8 weeks after birth. The dominant expression of V alpha 14J alpha 281 TCR is found in both euthymic and athymic mice. These results indicate that homogenous V alpha 14J alpha 281 T cells are positively selected in the periphery without thymic influence and that their VJ junction is important for positive selection. We also demonstrate that V alpha 14+ TCR gene rearrangements take place at extrathymic sites, such as bone marrow, liver, and intestine, since frequent nonproductive V alpha 14 TCR products and V alpha 14-J alpha 281 gene mediated signal sequences in circular DNA are detected as a result of TCR rearrangements in extrathymic tissues rather than in the thymus. This indicates the extrathymic development of V alpha 14J alpha 281 T cells. Furthermore, the biological roles of homogenous T cells bearing V alpha 14J alpha 281 TCR and the human counterpart of this invariant TCR are also discussed.

Amino Acid Sequence↗

Identification of the thromboxane A2 receptor in hepatic sinusoidal endothelial cells and its role in endotoxin-induced liver injury in rats.

The presence of the thromboxane A2 receptor in sinusoidal endothelial cells was investigated and its pathogenic role in endotoxin-induced liver injury examined. The receptor was measured with a binding assay using a specific thromboxane A2 receptor antagonist, [3H]S-145. Scatchard analysis of the binding indicated the presence of a single class of high-affinity binding sites with a dissociation constant of 5.00 +/- 0.96 nmol/L, a maximal binding of 22.85 +/- 2.71 fmol/10(6) cells and 13.80 +/- 1.60 x 10(3) binding sites per cell. The addition of a cyclooxygenase inhibitor, indomethacin, during the cell preparation increased the maximal binding value and the number of binding sites of 37.34 +/- 3.01 and 22.50 +/- 1.80 x 10(3) sites/cell, respectively. The binding was displaced by various thromboxane A2 analogs such as ONO-3708 and STA2 but was not effectively competed for by other prostaglandins. Endotoxin injection reduced dissociation constant, maximal binding and the number of binding sites in sinusoidal endothelial cells to 3.49 +/- 0.87 nmol/L, 6.03 +/- 0.64 fmol/10(6) cells and 3.65 +/- 0.39 x 10(3) sites/cell, respectively. A cyclooxygenase inhibitor and a Kupffer cell inhibitor added before endotoxin treatment significantly prevented the reduction in the number of thromboxane A2 receptors. It is possible that these effects were due to a reduction in the agonist-induced internalization of the thromboxane A2 receptor brought about by the prevention of thromboxane A2 production. Preadministration of both a cyclooxygenase inhibitor and a thromboxane A2 receptor antagonist attenuated the degree of endotoxin-induced liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗