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Biomedical subjects

A Watanabe

Publications and source records attributed to A Watanabe.

At least 541 records · Page 30Linked to original sources
PubMed1993

Induction of antibodies to a kappa V region by gene immunization.

Direct gene transfer into muscle can lead to sustained gene expression at the injected sites. Here we tested the ability of in vivo gene transfection to immunize mice against an isolated human IgV region. The Humkv325 germline kappa L chain V gene encodes the kappa L chain in V regions of several human IgM autoantibodies and is used frequently in chronic lymphocytic leukemia. This gene was inserted into a mammalian expression vector, pREP7, to produce pREVk3. Mice injected i.m. with pREVk3 produced antibodies against the V region of Glo, a human monoclonal IgM paraprotein whose kappa L chain is encoded by Humkv325. Co-injection of an expression vector encoding IL-2 enhanced anti-Glo antibody production fivefold and induced a localized delayed hypersensitivity reaction. Antibody production also was induced when vectors encoding Humkv325 and IL-2 were injected s.c. These experiments demonstrate that gene immunization vectors can stimulate immune responses to antibody V region determinants.

Animals↗
PubMed1993

Clinical usefulness of computer-assisted diagnosis using combination assay of tumor markers for pancreatic carcinoma.

BACKGROUND: There has been extensive use of serum tumor markers in diagnosing pancreatic adenocarcinoma. There is no tumor marker, however, that alone has sufficient diagnostic accuracy. It is necessary to know which combination of tumor markers should be used to detect pancreatic cancer, with respect to clinical usefulness and cost effectiveness. METHODS: Serum levels of 17 kinds of tumor markers were determined in 145 patients and 40 healthy volunteers. Thirty-five patients with proven pancreatic adenocarcinoma, and 32 with benign pancreatobiliary disease (14 chronic pancreatitis and 18 biliary stones) were selected. For analysis of the usefulness of each tumor marker to differentiate these two groups, scatterplot and relative operating characteristic (ROC) analyses were used. A multivariate discriminant system to differentiate these two groups was developed using stepwise discriminant analysis by backward elimination selection. RESULTS: The significance of each tumor marker varied according to the tumor volume. By ROC analysis, the markers were divided into four subgroups according to their usefulness in discriminating pancreatic adenocarcinoma from benign pancreatobiliary disease. A discriminant system consisting of two different discriminant functions using nine tumor markers (CA 19-9, DUPAN-2, TPA, elastase-1, lipase, amylase, gamma-glutamyl transpeptidase, alkaline phosphatase, and lactate dehydrogenase) was developed and designated CAMPAS-P; it could differentiate between all 35 cases of pancreatic adenocarcinoma and 32 cases of benign pancreatobiliary disease. On the other hand, CAMPAS-P showed a low positive rate in pancreatic tumors of unusual histologic type, and poor organ-specific diagnostic ability in various digestive organ malignancies. CONCLUSIONS: CAMPAS-P may be very useful for differential diagnosis between pancreatic adenocarcinoma and benign pancreatobiliary disease.

Adenocarcinoma↗
PubMed1993

Systemic immunological effects of cytokine genes injected into skeletal muscle.

Somatic gene therapy is an interesting approach for the delivery of cytokines for prolonged periods. The present experiments show that direct injections into mouse skeletal muscle of cDNA expression vectors encoding interleukin 2 (IL-2), IL-4, or type beta 1 transforming growth factor (TGF-beta 1) induce biological effects characteristic of these cytokines in vivo. Mice injected intramuscularly with a vector encoding IL-2 had enhanced humoral and cellular immune responses to an exogenous antigen, transferrin, that was delivered at a separate site. These IL-2 effects were abolished by coadministration of a vector directing synthesis of TGF-beta 1. The TGF-beta 1 vector by itself depressed the anti-transferrin antibody response and caused an 8-fold increase in plasma TGF-beta 1 activity. The TGF-beta 1 plasmid injection did not cause muscle infiltration with monocytes or neutrophils and there was no evidence for fibrotic changes. Muscle injection with a cDNA encoding IL-4 selectively increased IgG1 levels but did not alter the cellular immune response to transferrin. In lupus-prone mice (MRL/lpr/lpr), injection with IL-2 expression vectors increased and TGF-beta 1 vectors decreased auto-antibodies to chromatin. These results demonstrate that intramuscular injection of cytokine genes, in the absence of infectious viral vectors, can regulate humoral and cellular immune responses in vivo.

Animals↗
PubMed1993

Adenoma accompanied by superficial squamous cell carcinoma of the esophagus.

BACKGROUND: Adenoma of the esophagus is a rare type of esophageal submucosal tumor. METHODS: An immunohistochemical and histopathologic study is reported of specimen from a patient with adenoma of the esophagus. RESULTS: The eighth reported case of esophageal submucosal adenoma without Barrett epithelium is described. The patient was a 58-year-old man with an adenoma and carcinoma of the esophagus. The adenoma showed papillotubular structures lined with two layers of cuboidal cells within the submucosa and lamina muscularis mucosae, and the carcinoma was of the superficial squamous cell type confined to the submucosa. CONCLUSIONS: Morphologic findings suggested that this adenoma had originated from the duct of the esophageal gland proper.

Adenoma↗
PubMed1993

Effects of phospholipid adsorption on nonthrombogenicity of polymer with phospholipid polar group.

Polymers with phospholipid polar groups, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers, have excellent nonthrombogenic properties. The effects of adsorption of phospholipids on platelet adhesion and activation on the MPC copolymer with n-butyl methacrylate (BMA) were investigated with particular attention to the structure of the phospholipids adsorbed onto the polymer surface. The electrical nature of the phospholipids adsorbed on the polymer surface affected the thrombogenicity of the polymer. On the MPC polymer surface treated with an aqueous liposomal solution of acidic phospholipids, phosphatidylserine, platelet adhesion and activation occurred to a greater extent when compared to a poly(MPC-co-BMA) surface. However, on the MPC polymer surface treated with electrically neutral phosphatidylcholines, reduced thrombogenicity could be observed. Therefore, the adsorption of the phosphatidylcholines was an important factor in reducing the thrombogenicity on the polymers. Moreover, by comparison of the poly(MPC-co-BMA) to a poly(BMA), platelet adhesion and activation on these polymer surfaces depended on the adsorption state of the phosphatidylcholines. The amount of phosphatidylcholine adsorbed on the poly(MPC-co-BMA) increased with an increase in the MPC mole fraction of the copolymer. This indicates that the MPC moieties have affinity for the phosphatidylcholines. We conclude that the poly(MPC-co-BMA) can adsorb large amounts of phosphatidylcholines and that these phospholipids organize themselves. The organized adsorption layer of the phosphatidylcholines on the surface, which construct biomembrane-like surfaces, can reduce platelet adhesion and activation effectively.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

Production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with diabetic nephropathy.

The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate (PMA), n-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP), aggregated human IgG, or Staphylococcus aureus was determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). H2O2 production by PMN after stimulation was measured using flow cytometry. Thirty-six patients with NIDDM were divided into four stages as follows: 1) stage I: non-microalbuminuric stage; 2) stage II: microalbuminuric stage; 3) stage III: proteinuric stage without impairment of renal function; and 4) stage IV: proteinuric stage with impairment of renal function. H2O2 production after PMA stimulation in all stages of NIDDM patients was higher than that in healthy controls. This increase of H2O2 production by PMN was particularly observed in stage IV of NIDDM patients after stimulation. Furthermore, H2O2 production in patients in stage IV was higher than that in patients with non-diabetic disease with impairment of renal function. It appears that reactive oxygen species produced by PMN after stimulation under some conditions may play an important role in the progression of diabetic nephropathy.

Blood Glucose↗
PubMed1993

Prognostic significance of tumor-host interaction in clinical gastric cancer: relationship between DNA ploidy and dendritic cell infiltration.

DNA ploidy of tumor cells and the degree of infiltration of dendritic cells were determined in 93 gastric cancer tissue specimens, and the mechanisms of tumor-host interaction on the prognosis were investigated. DNA ploidy patterns were grouped into low and high ploidy, and the degree of infiltration of dendritic cells (DC) was graded into marked and slight infiltration. In the low ploidy group, the 5-year survival rates in patients with marked and slight DC infiltration were 80.7% and 61.5%, respectively (P < 0.05). In the high ploidy group, however, there were no significant differences. In cases of low ploidy, the incidence of lymph node metastasis was significantly lower in the marked DC infiltration group compared with findings in the slight DC group. Thus, markedly infiltrating dendritic cells in gastric cancer tissue may lead to prolongation of survival time for patients with a carcinoma of the low ploidy profile, by preventing widespread nodal involvement.

Dendrites↗
PubMed1993

Basic FGF maintains some characteristics of the progress zone of chick limb bud in cell culture.

The apical region of chick limb buds (progress zone, PZ) is known to be essential for limb pattern formation. In the PZ, the cells are in an uncommitted state and change their positional values under the influence of the apical ectodermal ridge (AER). Using a culture system of chick PZ cells, we have examined the factor(s) which helps to maintain some of the characteristics of PZ cells. It was found that basic FGF (bFGF) stimulated the expression of AV-1 and Msx 1 mRNA, which are rich in PZ cells at early stages, in the cultured PZ cells. These two molecules were rapidly lost in the control culture without the bFGF. Further, bFGF promoted growth and inhibited chondrogenesis of the cultured PZ cells. When quail PZ cells were cultured in FGF medium, harvested, and grafted to the apical region of chick limb buds, in about half of the grafts, the cells distributed to form a long band along the proximodistal axis and participated in normal host cartilage pattern formation as did intact PZ tissues. In contrast, those cultured in the medium without bFGF distributed as a cluster and did not participate in host cartilage pattern formation. The culture with conditioned medium of BRL cells increased the percentage of the grafts participating in normal pattern formation. These results indicate that bFGF helps to maintain some of the characteristics of PZ cells in culture and suggest that bFGF may be a PZ maintenance factor from the AER.

Animals↗
PubMed1993

Alpha-fetoprotein-producing esophageal adenocarcinoma: report of a case.

This paper describes a rare case of adenocarcinoma located in the middle portion of the esophagus with liver metastasis. An 80-year-old man was admitted to our hospital with dysphagia and vomiting, following which an upper gastrointestinal series and esophagoscopy located an elevated-type carcinoma in the middle thoracic esophagus. Computed tomography revealed an esophageal tumor invading the left atrium and aorta, and multiple intrathoracic lymph node swellings, and an ultrasonograph of the liver showed multiple liver metastases. The serum carcinoembryonic antigen, carbohydrate antigen 19-9, and squamous cell carcinoma-related antigen levels were normal, but the serum alpha-fetoprotein (AFP) level was 351.5 ng/ml. The patient died 124 days after undergoing an esophageal bypass operation. On post-mortem histological examination, the original esophageal tumor was diagnosed as a poorly differentiated adenocarcinoma without a squamous component and immunohistochemical staining for AFP showed positive granules in the cytoplasm. All the metastatic nodules, including the lymph nodes, liver, spleen, and lungs, showed the same histological type and AFP-staining pattern as the original esophageal tumor. To our knowledge, this is the first case of AFP-producing esophageal carcinoma to be reported in Japan.

Adenocarcinoma↗
PubMed1993

Newly established human pancreatic carcinoma cell lines and their lectin binding properties.

Two human pancreatic carcinoma cell lines, designated HuP-T3 and HuP-T4, were established from the ascites of pancreatic cancer patients with carcinomatous peritonitis. The cell lines were grown in monolayer cultures and had population doubling times of 38.6 and 37.1 h, respectively. HuP-T4 secreted large amounts of CEA and CA19-9 into the medium, and HuP-T3 produced a small amount of CEA, but no CA19-9. Both cell lines showed tumorigenicity in nude mice. Histologically, the HuP-T3-derived tumor was poorly differentiated adenocarcinoma, and the HuP-T4-derived tumor was well differentiated papillotubular adenocarcinoma. In lectin histochemistry at both light and electron microscopic levels, the most striking difference between the lectin binding properties of the two cell lines and those of control normal pancreatic ductal cells was that soybean agglutinin (SBA) bound to both cell lines, but not to controls. These newly established cell lines should be useful models that will contribute to clarifying the biological and biochemical characteristics of pancreatic cancer.

Adenocarcinoma↗
PubMed1993

Left ventricular pseudoaneurysm and intracardiac fistulas after replacement of mitral valve prosthesis.

Operation was performed on a 61-year-old woman with left ventricular pseudoaneurysm, left ventricular-right atrial fistula, and left ventricular-coronary sinus fistula after mitral valve replacement. The diagnostic and therapeutic approaches to these complications are described briefly, and the literature on intracardiac fistula after mitral valve replacement is reviewed.

Cardiomyopathies↗
PubMed1993

Involvement of the fimbria fornix in the initiation but not in the expression of methamphetamine-induced sensitization.

To put forward our previous finding that the lesion of the fimbria fornix, a hippocampo-accumbal pathway, blocked the development of behavioral sensitization induced by repeated methamphetamine (MAP) administrations, we examined the role of the fimbria fornix in the expression of sensitization in this study. After rats had shown locomotor augmentation following repeated drug injections, they received either the fimbria fornix lesion or a sham operation. Both groups of rats still exhibited a similar sensitized locomotor response to MAP as before the surgeries. In addition, we evaluated dopamine metabolism in the nucleus accumbens of these rats following a challenge injection of MAP after the behavioral study. The data obtained correspond to the results of behavioral experiments in that 3-methoxytyramine, one of the dopamine metabolites, increased significantly after MAP challenge only in the groups of sensitized animals. These findings further support the recent concept that there may exist different neural mechanisms in the initiation and expression of sensitization phenomenon.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Effect of TYB-2285 on histamine release from human basophils in the presence/absence of IL-3.

1. The present study was carried out to investigate the effect of TYB-2285 (3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile) on histamine release from human basophils upon stimulation with anti-IgE in the presence/absence of recombinant interleukin 3 (rIL-3). 2. Histamine release was enhanced by the pretreatment of basophils with rIL-3 (0.3-10 U/ml) in 18 out of 22 subjects. 3. Histamine release in the presence of rIL-3 was inhibited by TYB-2285 and disodium cromoglycate (DSCG) in a dose-dependent manner (1-100 microM). 4. Histamine release in the absence of rIL-3 was not inhibited by TYB-2285 or DSCG at concentrations less than 1 mM. 5. From these results, it is suggested that TYB-2285 and DSCG might regulate allergic inflammation by the suppression of mediator release enhanced by IL-3.

Antibodies, Anti-Idiotypic↗
PubMed1993

Effect of TYB-2285 on antigen-induced histamine release from mouse bone marrow-derived persisting cells (P-cells) primed with interleukin-3-containing conditioned medium (IL3-CM).

1. The present study was carried out to investigate the effect of TYB-2285 [3,5-bis(acetoxyacethylamino)-4-chlorobenzonitrile] on histamine release from persisting cells (P-cells) primed with interleukin-3-containing conditioned medium (IL3-CM). 2. IL3-CM enhanced antigen-induced histamine release from P-cells, although IL3-CM did not affect spontaneous histamine release. 3. TYB-2285 inhibited antigen-induced histamine release in the presence of IL3-CM, although it did not inhibit histamine release in the absence of IL3-CM. 4. The enhancement of histamine release by IL3-CM was reproduced by recombinant IL-3 (1-100 U/ml). 5. These results demonstrate that TYB-2285 inhibits the histamine release primed with IL-3 and also suggests that TYB-2285 might regulate allergic inflammation in vivo by the suppression of mediator release primed with IL-3.

Animals↗
PubMed1993

Characterization of two distinct monoclonal antibodies to paired helical filaments: further evidence for fetal-type phosphorylation of the tau in paired helical filaments.

Two monoclonal antibodies C5 and M4 raised against Sarkosyl-insoluble paired helical filaments (PHF) specifically labeled fetal tau, but hardly labeled normal adult tau. C5 immunoreactivity was eliminated by alkaline phosphatase treatment at 37 degrees C, whereas M4 reactivity could be removed only by the treatment at 67 degrees C. Epitope analysis showed that C5 and M4 recognition sites are in residues 386-406 and 198-250, respectively, according to the numbering of the longest human tau isoform. Thus, the phosphorylation sites are located in the amino- and carboxyl-terminal portions of the microtubule-binding region. These two well-characterized monoclonals should be valuable in the identification of a protein kinase(s) that converts normal tau into PHF-tau.

Alzheimer Disease↗