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Biomedical subjects

J Sakamoto

Publications and source records attributed to J Sakamoto.

At least 163 records · Page 9Linked to original sources
PubMed1988

[The minimization method in a medium size clinical trial. Study of immunochemotherapy with PSK in gastric cancer].

One of the objectives of randomization is to balance the number of patients in each level and combination of levels of prognostic factors. However, as the number of possible prognostic factors increases, some imbalance may occur and make the results of the analysis less interpretable. In order to balance the marginal distribution of each factor and to facilitate more interpretable trial results, the "minimization method" reported by Pocock was applied in our multi-center immunochemotherapy clinical trial. Balancing in every institution was achieved by using Zelen's prespecified value d = 3 for replacing provisional assignment in the individual institution. Nonmetric principal component analysis in S, N factors which were used in minimization process showed good equilibration between groups. Also, in uncontrolled background factors, such as cancer pathology or Borrmann types, acceptable balance was obtained spontaneously at the end of the trial.

Clinical Trials as Topic↗
PubMed1988

[Participation in a simple large-scale randomized trial organized by EORTC through an international computer network].

Case registration and treatment allocation was achieved in a "Simple large-scale trial against colorectal cancer" designed by the European Organization for Research and Treatment of Cancer (EORTC) using an international computer network system VENUS-P. The access to the central computer "EuroCODE" was obtained by simple equipment including ordinary microcomputer, modem and telephone line. Subscription to the KDD data network VENUS-P using a Packet Assembler/Disassembler (PAD) was necessary to connect to the EuroCODE. Intraoperative patient registration and allocation of treatment were possible through this system regardless of the time difference between countries. To organize a large-scale trial as a means to detect moderate but medically worthwhile treatment differences, this method proved to be particularly effective especially for international cooperative studies.

Colonic Neoplasms↗
PubMed1987

Localization of radioiodinated monoclonal antibody in colorectal cancer. Initial dosimetry results.

HT-29-15 is an IgG1 monoclonal antibody reacting with a neuraminidase-sensitive determinant on a cell-surface antigen (molecular weight, 200,000 daltons) present on the colon cancer cell line HT-29. HT-29-15 was selected for a tumor localization study because the antigen was shown to be present, by immunohistochemical staining, in a high percentage of primary and metastatic colorectal cancers. HT-29-15 labeled with iodine 131 was given intravenously over a dose range of 0.2 to 10.0 mg to 23 patients with colorectal cancer. No significant toxicity was seen. Imaging of hepatic metastases was successful from days 5 to 7. Analysis of tissue radioactivity by biopsy showed that the tumor-liver ratio increased from day 1 to day 7, suggesting more rapid clearance of antibody from normal tissue than from tumor. Thus, tissue biopsy specimens and scintigraphy have shown that imaging of metastatic colorectal cancer is possible with monoclonal antibody HT-29-15. Tissue biopsy specimens are essential for demonstrating specificity of localization. Scans alone provide insufficient evidence of specific localization by monoclonal antibodies. Simultaneous infusion of a nonreactive control antibody would be necessary for specific localization to be demonstrated unequivocally.

Animals↗
PubMed1987

A stomach oncofetal antigen recognized by monoclonal antibody GC302.

A monoclonal antibody, GC302, was established by fusing murine myeloma NS/1 cells with the splenocytes of a BALB/c mouse immunized with a human gastric cancer cell line, NU-GC-3. The serological specificity of GC302 was analyzed by an anti-mouse Ig mixed-hemadsorption (MHA) test on a panel of human cell lines, and an immunoperoxidase method using the frozen sections of tumors and normal tissues of adult and fetus. GC302 reacted with cancers of the stomach and colorectum but did not react with hepatocellular carcinomas, melanomas, or astrocytomas in the MHA tests. By the immunoperoxidase method, GC302 was found not to react with normal adult gastric mucosa, but to react with the mucosa in the fetal stomach, intestinal metaplasia, and almost all of the cancer of the stomach. GC302 also reacted with the normal mucosa of the intestine, colon, and rectum as well as with cancers of these origins. In normal liver sections, the antibody reacted with the bile ducts, but not with the hepatic cells. These results indicate that the antigen detected by GC302 is characterized as an oncofetal antigen in the stomach, and also as a differentiation antigen whose localization discriminates between the gastrointestinal tracts of the forgut origin and those of the midgut and hindgut origin. The molecular weight of the GC302 antigen was estimated to be ca. 40,000 by the Western blot analysis. Periodic acid treatment on the antigen suggested that the antigenic determinant is a carbohydrate.

Animals↗
PubMed1987

[A cylindrical thermistor probe for experiments on suppositories in rabbits].

A cylindrical thermistor probe with a rubber disk stopper, which is beneficial for inserting a suppository into the rectum of rabbits without removal of the probe from the rectum, was developed. It is possible to measure body temperature continuously by using this probe in an experiment to assess the effects of a suppository on the body temperature of rabbits. After insertion of a suppository, leakage of the melted suppository from the rectum was not observed. No differences between this thermistor probe and an ordinary thermistor probe in the ability of the probe to detect the febrile response of rabbits injected with a bacterial pyrogen were observed. From these results, it could be concluded that this newly improved cylindrical thermistor probe is suitable for studying the effect of suppositories on the body temperature of rabbits.

Animals↗
PubMed1986

Immunohistologic expression of blood-group antigens in normal human gastrointestinal tract and colonic carcinoma.

A panel of 7 mouse monoclonal antibodies and the lectin from Ulex europeus, detecting blood-group-related antigens of the ABH and Lewis systems, have been used to define the distribution of these antigenic structures within the human gastrointestinal tract, and to characterize their expression and modulation in colorectal carcinomas. The reagents employed detect the following blood-group specificities: A (all variants), B, H (type 2), Lewisa, Lewisb, X (Lewisx), Y (Lewisy) and type 1 precursor chain. Immunohistochemical studies demonstrate that these antigens are differentially expressed in various cell types and developmental stages of the human gastrointestinal tract. ABH expression undergoes developmental modulation in the human colorectal tract from positive to negative during embryogenesis, and is lost in adult cells. Colorectal tumors exhibit neosynthesis of ABH specificities that appear in tumor cells, and accumulation of the precursor antigens. They also show increased expression of Lewis antigens, especially Y determinant, which has a restricted pattern of distribution in normal tissues and is not found in normal colonic mucosa. Enhancement of the Lewis antigens is observed in all colorectal tumors analyzed, regardless of blood-group type and secretory status of the individuals studied. Tumor modulation of these antigens may be related to activation of suppressed genes and enhancement of fucosyltransferases.

ABO Blood-Group System↗
PubMed1986

Reproductive toxicity of acrylamide and related compounds in mice--effects on fertility and sperm morphology.

Acrylamide and its three neurotoxic analogues, which are known to induce testicular damage in animals, were tested for reproductive toxicity in male and female mice and for the effect on germ cells in males, after subchronic treatment. After mating the treated males with untreated females, a decrease in fertility rate for all analogues except for N-hydroxymethylacrylamide, and an increase in the number of resorptions/dam for all test compounds were found. When untreated males were mated with treated females, an increase in the number of resorptions/dam was seen only after acrylamide dosing without any effect on the fertility rate. The reproductive toxicity appeared with only slight or no testicular atrophy, and without any apparent neurotoxicity after treatment with all test compounds. High doses of all test compounds produced both a decreased sperm count and an increase in abnormal sperm morphology.

Acrylamides↗
PubMed1986

The enhancing effects of amastatin, phosphoramidon and captopril on the potency of [Met5]-enkephalin in rat vas deferens.

The enkephalin-inactivating enzymes in rat vas deferens were studied by using the relatively specific inhibitor of each enzyme. The results showed that the rat vas deferens, like the other three preparations, guinea-pig ileum, mouse vas deferens and striatal membranes of guinea-pig brain, which had been investigated previously, contained three distinct enkephalin-hydrolyzing peptidases. Additionally, the enkephalin-hydrolyzing aminopeptidase, endopeptidase-24.11 and peptidyl dipeptidase A in rat vas deferens were found to be inhibited maximally with 1 microM of amastatin, 1 microM of phosphoramidon and 1 microM of captopril, respectively. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase were suggested not to be involved significantly in the inactivation of exogenously given enkephalin in rat vas deferens. The characteristics of the enkephalin-degradative enzymes in rat vas deferens were discussed in terms of their similarities to and differences from those in the other preparations.

Animals↗
PubMed1986

[A randomized controlled trial of surgical adjuvant therapy with mitomycin C, 5-fluorouracil and OK-432 in patients with gastric cancer].

The effect of postoperative immunochemotherapy with mitomycin C (MMC), 5-fluorouracil (5-FU) and OK-432 was evaluated as an adjuvant therapy after curative resection for gastric cancer. Immediately after surgery, patients were randomly allocated to the following three treatments: (A) chemotherapy with MMC and 5-FU (32 cases); (B) chemoimmunotherapy with MMC, 5-FU and OK-432 (33 cases); and (C) surgery alone as control (34 cases). There were no significant differences in the background factors influencing survival time among the groups, and there was no dose-distribution of chemotherapeutic agents between groups A and B. While the differences were not statistically significant, the survival rate and disease-free interval of group B were better than those of groups A or C. Side effects such as gastroenteric disorder, leukopenia (less than 3,000/mm3), thrombocytopenia (less than 7 X 10(4)/mm3) and increase of serum transaminase level (GPT greater than or equal to 100 units) were less frequently observed in group B than in group A. The results of the present study seemed to indicate that chemoimmunotherapy with OK-432 may be effective for surgical adjuvant therapy.

Aged↗
PubMed1986

Expression of Lewisa, Lewisb, X, and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines.

Serological and immunopathological analysis of the expression of Lea, Leb, X, and Y blood group antigens on cell lines and tissues was performed using a panel of mouse monoclonal antibodies. The distribution of the antigens was determined on 155 malignant tumor cell lines of various types and 10 short term cultures of normal fibroblasts and kidney cells. Among colon cancers, all four blood group antigens were expressed on the majority of cell lines. On lung, breast, bladder, and ovarian cancer cell lines, X and Y antigens were the main specificities found, whereas few of the renal and hematopoietic tumor cell lines demonstrated any of the four blood group antigens. No blood group antigens could be detected on astrocytoma or melanoma cell lines. The expression of the antigens was also analyzed on frozen sections of colon carcinoma and adjacent normal colon tissue from 42 patients using the immunoperoxidase method. Lea and X were detected throughout the normal colon and on most colonic tumors. In poorly differentiated colon cancer and in metastatic cancer, decrease of Lea antigen was observed. Leb and Y expression was observed in only 20-45% of normal tissue samples but in almost all colonic carcinoma tissues. A selected number of tumor and normal specimens from patients whose secretor status was known were examined in more detail. Both the staining of the tissues and the reactivity of blood group glycolipids from the same specimens were determined. These studies confirmed the above findings and demonstrated the unexpected ability of tumors of nonsecretors to express Leb and/or Y antigens. In such individuals, in whom the expression of Leb and Y antigens in normal tissues is absent or minimal, these antigens provide possible targets for immunodiagnosis and therapy.

Antibodies, Monoclonal↗
PubMed1985

Analysis of the specificity of five murine anti-blood group A monoclonal antibodies, including one that identifies type 3 and type 4 A determinants.

The specificity of five mouse monoclonal anti-A blood group antibodies (Ab), four of which were produced by immunization with cultured human cancer cells and one with a synthetic antigen, has been determined by examining their reactivity with purified A glycolipids, erythrocyte glycolipids, oligosaccharides, ovarian cyst glycoproteins, and salivary glycoproteins. Two of the antibodies (HT29-36 and CB) reacted with all A variant structures tested and have a broad anti-A reactivity. Ab CLH6 did not agglutinate A erythrocytes and reacted preferentially with the type 1A structure. Ab S12 agglutinated all A1 erythrocytes and reacted best with simple, monofucosyl type 2 A structures, such as Aa-2, Ab-2, and A tetrasaccharide. Ab M2 has a novel, but complex, spectrum of reactivity. It reacts with type 3 and type 4 A chains and not with type 1 and type 2 A chains. It appears to recognize both an external A structure (formula; see text) (I) (found) in type 3 and type 4 chains) and also an internal structure (II) found in type 3 chains. Ab M2 agglutinates all A and AB erythrocytes but does not react with salivary glycoproteins.

ABO Blood-Group System↗
PubMed1985

Effect of acrylamide and related compounds on glycolytic enzymes in mouse brain in vitro.

The effects of acrylamide and eight analogues on mouse brain glycolytic enzymes were studied in vitro. Most of the neurotoxic and non-neurotoxic analogues showed inhibitory effects on enolases. Their inhibitory constants, I50, for both mouse brain total enolases and purified bovine neuron specific enolase were similar for each analogue, being lowest for N,N'-methylene-bis-acrylamide and highest for methacrylamide. A neurotoxic compound, N-isopropylacrylamide, and a non-neurotoxic compound, N,N'-methylene-bis-acrylamide, showed non-competitive inhibition towards mouse brain total enolase. After preincubation of anologues in vitro for 90 min with hepatic S-9 fraction prepared from normal mice, their inhibitory potency towards brain total enolase was also seen. When the S-9 fraction was prepared from mice pretreated with phenobarbital, the inhibitory potency was not different from that of the control. After preincubation with S-9 fraction prepared from either diethyl maleate-, or piperonyl butoxide-pretreated mice the inhibitory potency was significantly greater than with non-pretreated control mice. Many of the test analogues also showed inhibition of glyceraldehyde 3-phosphate dehydrogenase activity, the highest inhibitory potency being seen with acrylamide, but no compounds inhibited phosphofructokinase.

Acrylamides↗
PubMed1985

Effect of acrylamide and related compounds on glycolytic enzymes in rat sciatic nerve in vivo.

The effect of acrylamide and six analogues on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and enolase in sciatic nerve was examined in rats after their prolonged administration in drinking water. After 15 days' treatment with acrylamide and N-isopropylacrylamide, slight signs of peripheral neuropathy were produced with no changes in the activity of either enzyme. N,N-dimethylacrylamide, a non-neurotoxic analogue, produced only body weight loss at this stage. After 30 days' treatment, acrylamide and N-isopropylacrylamide produced moderate signs of neuropathy, but no changes in enzyme activity. N,N-dimethylacrylamide produced a reduction in GAPDH activity as well as body weight loss. After 45 days' treatment, acrylamide, N-isopropylacrylamide, N-hydroxymethylacrylamide and N-methylacrylamide produced severe signs of neuropathy as well as body weight loss. All these analogues also produced a reduction in the two enzyme activities, except for enolase after N-isopropylacrylamide. N,N-dimethylacrylamide produced inhibition of GAPDH as well as body weight loss without neuropathy. N-tert-butylacrylamide and N,N'-methylene-bis-acrylamide induced neither neuropathy nor inhibition of either enzyme.

Acrylamides↗