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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 829 records · Page 46Linked to original sources

Diagnostic value of measurement of serum type I procollagen carboxy terminal peptides in patients with scirrhous carcinoma of the stomach.

We have evaluated the radioimmunoassay for type I procollagen carboxy terminal peptide (type I C-peptide), which is liberated from type I procollagen during its conversion to collagen, in the serodiagnosis of scirrhous carcinoma of the stomach. The mean (SD) serum concentration of type I C-peptide in 39 normal subjects was 41.7 (19.7) ng/ml. The mean serum values and the positive ratio of type I C-peptide in 11 patients with stages II and III scirrhous carcinoma of the stomach were 91.2 (41.9) ng/ml and 54.5%, respectively. In 10 patients with other types of gastric carcinoma, the mean type I C-peptide values were not significantly different from the normal value. Serum type I C-peptide values reflected the clinical course of scirrhous gastric carcinoma in five patients who underwent either operation or chemotherapy. The measurement of serum type I C-peptide concentrations could provide a useful way of diagnosing and monitoring scirrhous carcinoma of the stomach.

Adenocarcinoma, Scirrhous↗

Interleukin-4 gene expression and IgE responsiveness.

Interleukin-4 (IL-4) gene expression by stimulation with concanavalin A (Con A) in murine spleen cells was examined. The amount of IL-4 mRNA induced by Con A was greatest in spleen cells obtained from IgE high responder strains of mice. A trace amount of IL-4 mRNA was induced in spleen cells from IgE low responder (SJL) mice. The amount of IL-4 mRNA induced in spleen cells from an IgE intermediate responder (C57BL/6) was smaller than that from high responders, but significantly greater than that from low responders. Spleen cells from IgE nonresponders (SJA/9) developed only a negligible amount of IL-4 mRNA. IL-4 mRNA was detected in human peripheral blood mononuclear cells (PBMC) stimulated with Con A. The IL-4 gene expression seemed to be greater in PBMC obtained from highly atopic patients and was decreased in PBMC from individuals showing hypo-IgE immunoglobulinemia (less than 10 IU/ml). The results obtained in the present study may indicate that high and low IgE responder traits are determined depending on their levels of IL-4 mRNA expression.

Animals↗

Studies on an enzymatically synthesized antitumor polysaccharide SPR-901.

An antitumor polysaccharide SPR-901 was found in a fermented broth of a kind of lactic acid bacteria isolated from rice bran. SPR-901 is a high molecular alpha-glucan and its linkages are almost linear alpha-1,6 glucosidic ones with a small amount (ca. 5%) of branches at C-3 positions. It is a highly purified alpha-glucan and it contains no protein and no inorganic salts. SPR-901 showed significant antitumor activities against murine allogeneic and syngeneic tumors by both intraperitoneal and oral administration, and enhanced carbon clearance ability in mice, while it showed no direct cytotoxicities in vitro. The mechanism of antitumor activities of SPR-901 is supposed to be a host-mediated one, and this substance is classified as one of the biological response modifiers. These properties of SPR-901 were identical to those of RON, which was obtained from rice bran, therefore we concluded that these two polysaccharides were the same substance.

Animals↗

Targeting SOD by gene and protein engineering and inhibition of free radical injury.

Although oxygen toxicity of tissues can be decreased by a variety of antioxidants and some enzymes, such as SOD and catalase, their protective effect on tissue injury in various diseases are fairly small predominantly because of their unfavorable in vivo behavior. To minimize oxidative stress in various diseases, such as ischemic myocardial injury, circulatory disturbance and corneal inflammation, we synthesized three types of SOD derivatives by gene and protein engineering technique. One type of SOD (SM-SOD covalently linked with hydrophobic anions) circulates bound to albumin with a half life of 6 h and accumulates in tissues whose local pH is decreased. The other type of SOD (AC-SOD covalently linked with long chain fatty acids via the epsilon-amino group of lysyl residues) anchors onto membrane/lipid bilayers of various cells. The last type of SOD (HB-SOD synthesized by constructing a fusion gene coding human CuZn-type SOD and a C-terminal heparin-binding domain) binds to heparin-like proteoglycans on vascular endothelial cell surface. Intravenous administration of either SM-SOD or HB-SOD markedly inhibited postischemic reflow arrhythmias in the rat. When the left anterior descending artery was occluded permanently, about 65% of animals died within 30 min predominantly due to irreversible ventricular fibrillation; the motality of animals decreased to 15% by administering SM-SOD either before or after occlusion. Topically administered AC-SOD bound to the corneal epithelial cell surface and polymorphonuclear leukocytes and efficiently dismutated superoxide radicals at their cell surface. Thus, endotoxin-induced keratitis was inhibited markedly by topical instillation of AC-SOD.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Interactions between novel tumor necrosis factor-alpha mutants and receptors on tumor and normal cells.

We prepared several TNF mutants by protein engineering techniques and compared their biological properties with those of the wild-type TNF. The mutant that lacked 7 N-terminal amino acids had higher cytotoxicity and higher binding activity to receptors on tumor cells. In contrast, the mutagenesis of Arg32 or Ala84, in combination with the deletion of 7 N-terminal amino acids, eliminated the cytotoxicity and the receptor binding. These mutants also lacked acute lethal toxicity in normal mice. Therefore, we concluded that the N-terminus, Arg32 and Ala84 of TNF might be concerned with binding to the TNF receptor. It was also suggested that the receptor molecules on tumor cells bound to the same or neighboring sites on TNF molecules as normal cell receptors.

Animals↗

Immunohistochemical localization of physiologic urinary proteins in Wistar rats.

Rat physiologic urinary proteins were immunohistochemically localized. In male Wistar rats, urinary protein antigens were present in both hepatic and epithelial cells of the salivary ducts, the coagulating gland, and the prostate gland. In female rats, urinary protein antigens were present in the same proportion of the salivary glands as in males and in the uterine glands, but to a lesser extent than in salivary glands. The results of this study indicate multiple origins of rat urinary proteins. It remains to be determined if female uterine glands contribute to urinary proteins.

Animals↗

[Nucleolar organizer regions, nuclear DNA content, and proliferative activity in adenocarcinoma of the lung].

The relationship between the quantity of silver-binding nucleolar organizer regions (AgNORs), nuclear DNA content, and proliferative activity was studied in 61 patients with adenocarcinoma of the lung. The proliferative activity of adenocarcinoma was estimated by tumor volume doubling time based on chest X-ray findings. There was a high, inverse correlation between the AgNORs and the tumor doubling time (p less than 0.001, r = -0.815), and the contribution rate was high value (2 = 0.664). However, the AgNORs value was an independent prognostic factor for survival time. A better 5-year survival rate was observed in patients with DNA diploidy than in DNA aneuploidy, but there was no statistical difference between the two groups. There was an inverse correlation between the DNA index and tumor doubling time (p less than 0.05, r = -0.565), but the contribution rate had a low value (r2 = 0.319). These results indicate that the AgNORs value is important in providing an estimate of the proliferative activity of adenocarcinoma.

Adenocarcinoma↗

[Comparison of clinical features of childhood and adult onset Still's disease].

Physical findings, laboratory data, treatments and prognosis were investigated in detail using 26 Japanese childhood Still's disease (CHSD) patients and 19 Japanese adult onset Still's disease (AOSD) patients as the subjects. High spiking fever and arthritis were present in all the patients. Seventy and seven percent of CHSD and 53 percent of AOSD had polyarthritis (the number of joints involved being 5 or more during the first 6 months of the disease). A comparison of the groups showed no significant difference in the initial systemic manifestations except for sore throat (CHSD: AOSD; 19%: 68%). Initial laboratory data were the same for these groups except for serum iron levels (CHSD: AOSD; 20.8 +/- 13.7 micrograms/dl: 83.0 +/- 54.2 micrograms/dl). As to joints and physical prognosis, the results were also the same for CHSD and AOSD under the similar treatment. On the basis of these data, we conclude that CHSD and AOSD are of the same disease entity so far as the present clinical features are concerned.

Adolescent↗

[Evaluation of 201Tl SPECT in patients with glioma: a comparative study with histological diagnosis, clinical feature and proliferative activity].

The purpose of this study is to clarify the usefulness of 201Tl brain SPECT in the prediction of clinical degree of malignancy. Quantitative evaluation of 201Tl uptake in the tumor was expressed as count ratio of tumor site over contralateral normal region (D/C ratio) on 201Tl SPECT image. Fourteen patients with gliomas received an intravenous administration of bromodeoxyuridine (BUdR) at surgery to label tumor cells in the DNA synthesis phase. BUdR-positive cells in excised tumor specimen were stained with anti-BUdR monoclonal antibody by indirect immunoperoxidase staining. Percentage of labeled cells in relation to the total number of tumor cells in microscopic fields was defined as labeling index (BUdR-LI). D/C ratio in patients with grade IV glioma (198.7 +/- 31.7) was higher than that in patients with grade III glioma (138.3 +/- 33.9) or more low-grade gliomas (94.2 +/- 11.9, p less than 0.001). BUdR-LI in patients with high-grade glioma was also higher than that in patients with low-grade glioma. D/C ratio correlated well (r = 0.753) with BUdR-LI, which is considered to represent proliferative activity of the tumor. D/C ratio does not only correlate well with histological grade of glioma, but with clinical course or prognosis of individual patient with glioma. In conclusion, degree of 201Tl uptake in the tumor may provide non-invasive prediction of malignancy grade of gliomas and accurate estimation of efficacy of the therapy and early detection of recurrence or malignant transformation of the tumors, by delineating viable tumor tissue in patients with gliomas.

Adult↗

[Antibody responses in human being to pre-S2 and related hepatitis B virus-envelope antigens in vivo and in vitro].

Although hepatitis B (HB) virus-associated pre-S2 Ag may be important in facilitating the uptake of virions into hepatocytes, it is not clear whether the anti-pre-S2 antibody plays a substantial role in the protection from infection in man. The mechanisms underlying the nonresponsiveness to the HB vaccine are not clear. To evaluate the immunological background in nonresponders to pre-S2 Ag, HLA-DR/DQ antigens and the production of antibodies to pre-S2 Ag and HBs Ag were estimated in vitro on medical healthy personnel. Ninety-one males and 213 females were vaccinated with pre-S2 Ag positive plasma-derived HB vaccine three times. Four months after the third vaccination, blood was withdrawn for pre-S2 antibody test by ELISA. Antibodies to pre-S2 Ag were found in 19.8% of the individuals. Nonresponders were observed at a higher frequency in males than females, and they were seen more frequently in the elderly than young individuals. In aged subjects, aging seemed to be the major factor in their unresponsiveness. A high frequency of HLA-DR4.DRw53.DQw3 haplotype was observed in the subjects with nonresponsiveness against pre-S2 Ag. In order to induce the secretion of anti-HBs antibody, we investigated the effect of simultaneous administration of HBs Ag and immunoglobulin containing anti-HBs antibody on the antibody responses in vitro. In vitro stimulation of mononuclear cells from 10 individuals who failed to respond or responded poorly to HB vaccine induced a significant amount of anti-HBs antibody in 5 cases, whereas stimulation with HBs Ag alone failed to induce the antibody secretion in most cases.

Adult↗

Permeabilized hepatocyte couplets. Adenosine triphosphate-dependent bile canalicular contractions and a circumferential pericanalicular microfilament belt demonstrated.

The motility of bile canaliculi was examined in hepatocyte couplets permeabilized with palmitoyl lysophosphatidyl choline in a dosage regimen that drastically affected secretory function, yet maintained relative integrity of the cellular cytoskeleton. The permeabilized cells showed no exclusion of trypan blue, notable cytoplasmic organelle and membrane damage, and no uptake or secretion of either fluorescein diacetate or sodium fluorescein. However, bile canalicular structure remained relatively intact and actin and myosin were localized immunocytochemically in the pericanalicular region. Coincident with the administration of 1 mM ATP, 2 mM Mg2+, and 1 microM Ca2+, the canaliculi contracted with partial or complete luminal closure. ADP, AMP, or AMP-PCP could not be substituted for ATP. A dose-dependent relationship was shown between ATP concentration and canalicular contraction rate. The permeabilization procedure also provided enhanced visualization of pericanalicular microfilaments, believed to be actin filaments, and their organization into two layers: an inner membrane-associated network, and an outer filament bundle that inserted into belt junctions (zonulae adherentes). The organization of the microfilament belt of contiguous hepatocytes was such that it formed a circumferential band of microfilaments around the canaliculus. It is analogous to contractile filament belts found in the apical terminal web region of other epithelia. It was also observed that with canalicular luminal closure, there was a change in the organization of the pericanalicular microfilaments. It is concluded that in hepatocyte couplets, differential sensitivity of cell components to permeabilization can be achieved with palmitoyl lysophosphatidyl choline. In addition, the results provide evidence that the bile canaliculus has the capacity to be a contractile structure even in the absence of secretion, that canalicular contraction is ATP-dependent, and hence is a dynamic process.

Actin Cytoskeleton↗

[A remarkable effect of K-18 (IgG-melphalan complex) in a case of RAEB with hypoplastic marrow].

A 63-year-old male with refractory anemia with excess of blasts (RAEB) and hypoplastic marrow was treated with K-18 (240 mg/day P.O.). On admission, peripheral blood revealed pancytopenia. Bone marrow specimen revealed severe hypocellularity with 18.9% of the blast cells. Ten months later, the blast cells in the bone marrow decreased to 3.8%, and complete remission (CR) was obtained. CR was eight weeks. Duration of response (CR + PR) continued for about eight months. K-18 is an antitumor agent with minimal side effects, and seems to be effective for RAEB with hypoplastic marrow.

Anemia, Refractory, with Excess of Blasts↗

[Accuracy and clinical problems involved in the measurements of extravascular lung water, using the thermal-sodium double indicator dilution technique].

In this report, we evaluated and discussed the accuracy and the clinical problems involved in measurements of extravascular lung water volume (EVLW), using the thermal-sodium double indicator dilution technique. We measured EVLW in 2 groups, group I (normal cardiac function group) consisting of 20 patients with esophageal cancer, and group II (low cardiac function group) consisting of 27 patients with heart valvular disease. No significant difference was found between the two groups in the reproducibility (SDM/Average X 100) of measurements of Cardiac output (CO), MTT (Mean Transient Time), and EVLW. No correlation was found between circulatory parameters and the reproducibility of measurement of EVLW. So we assumed that cardiac function has no influence on the reproducibility of EVLW measurement. But the CO measured with EVLW catheter was significantly higher than that measured with Swan-Ganz catheter in group II. We thought that EVLW should be calculated using the CO measured with Swan-Ganz catheter in cases of low cardiac function. Infection, thromboembolism and bleeding after the insertion of the catheter, overload of water and sodium due to the injection of the indicator were thought to be complications of measurement of EVLW. But in our clinical cases there was no such complication.

Esophageal Neoplasms↗

Thymectomy in ulcerative colitis: a report of cases over a 13 year period.

Seventy eight patients with ulcerative colitis were treated by thymectomy combined with conventional therapy. An interim analysis was made after a median follow-up of 40 months in the thymectomized group and after 25 months in 173 from a non-thymectomized group. The percentage of remission periods in the thymectomized group was significantly higher than that in the non-thymectomized group as estimated by the "patient-month" method. Histological examination of the excised thymus revealed hyperplasia of the thymic epithelial cells and/or the formation of lymphoid follicles. Anticolon antibody activity of the serum from the thymectomized patients decreased gradually and disappeared in 5 years or more. "Thymectomy via the suprasternal notch with parasternal incision" which was applied in this study, is simple and not invasive. Therefore, it is recommended that thymectomy should be considered as one of the treatment for patients who are resistant to conventional therapy.

Adolescent↗