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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 631 records · Page 35Linked to original sources
PubMed1995

Detection and quantification of soluble asialoglycoprotein receptor in human serum.

We describe the first evidence that soluble asialoglycoprotein receptors (AGPR) are present in human serum and that they are quantifiable by an enzyme-linked immunosorbent assay (ELISA). An affinity chromatography gel immobilized with monoclonal antibodies (McAbs) against human liver AGPR was mixed with normal sera, and the bound fraction was analyzed both by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by Western blot analysis. Immunoreactive bands corresponding to 35 to 40 kd were obtained, which were lower than those of liver AGPR (41 kd and 46 kd). Soluble AGPR in human serum was able to bind to D-galactose-immobilized beads, indicating that the soluble AGPR remained ligand-binding activity. In order to quantify soluble AGPR, we established an ELISA using a monoclonal antibody (30220 McAb)-immobilized microplate and horseradish peroxidase-labeled F(ab')2 of another monoclonal antibody (30201 McAb). Reproducibility of intra- and interassay of the ELISA were 4% to 14% and 7% to 14%, respectively. Analytical recoveries ranged from 93% to 99%. The detection limit was estimated to be 0.1 micrograms/L. By nonparametolic analysis, a median and a 90% tile of serum AGPR level obtained from 283 normal volunteers were 0.4 micrograms/L and 2.4 micrograms/L, respectively.

Antibodies, Monoclonal↗
PubMed1995

[Two cases of adult T-cell leukemia . lymphoma (ATL) with long-term remission by chronic daily administration of low-dose etoposide].

We tried long-term oral administration of low-dose etoposide (LDE) for seven patients with adult T-cell leukemia . lymphoma (ATL) at Asahikawa Red Cross Hospital in 1988. Two long-term survivors are presented. Case 1: A 53-year-old man was diagnosed as acute ATL in 1987. Because VEPA therapy was not effective, LDE (50 mg/day) therapy was started. Five months after entering CR, a lymphoma recurrence in the skin was observed. Retreatment with LDE and radiation therapy was effective, but he died of reprogression of ATL three years and seven months following initial diagnosis. Case 2: A 43-year-old woman was diagnosed as acute ATL in 1989. With LDE (50 mg/day) therapy for 40 days, she entered CR. The lymphoma recurred in the central nervous system (CNS) and skin in 1992. After radiation of CNS and LDE therapy, she showed CR again. She is alive now over five years and eight months after diagnosis.

Administration, Oral↗
PubMed1995

[Assessment of tumor viability by 201Tl SPECT in VX-2 tumor-bearing rabbits after irradiation: comparison with X-ray CT and pathohistologic findings].

In order to evaluate 201Tl SPECT for the assessment of tumor viability after radiation therapy. Twenty rabbits were implanted with VX-2 tumor in the left femoral muscles and were classified into four groups as follows: normal control group (N), 20 Gy irradiated response group (A), 20 Gy irradiated non-response group (B), and 40 Gy irradiated group (C). Eight days after implantation, 201Tl SPECT and CT studies were performed to assess the changes in 201Tl uptake and tumor volume at 0, 1, 2, 3, and 4 weeks after single irradiation. Histologic specimens were also taken. In group N tumors continued to increase in volume, but 201Tl uptake showed a steady decrease after 2 weeks. In group A tumors continued to increase in volume, but 201Tl uptake showed a transient decrease at 2 weeks, then a steady increase. In group B tumors showed a transient increase in volume at 2 weeks, then a continuous decrease, but 201Tl uptake showed a continuous decrease throughout the study. In group C there was a continuous decrease both in volume and 201Tl uptake with the later more prominent. 201Tl uptake was decreased earlier than tumor volume both in group B and C, at one week that was significant (p < 0.01). 201Tl uptake by tumor reflects the burden of viable tumor on histology; therefore 201Tl SPECT is of great use in assessing the therapeutic effects on tumors.

Animals↗
PubMed1995

[Surgical repair of distal aortic arch aneurysm with hypothermic retrograde cerebral perfusion through standard left postero-lateral thoracotomy].

Five patients with aneurysm involving distal aortic arch underwent graft replacement of distal aortic arch and, in two patients, reconstruction of left subclavian artery through standard left postero-lateral thoracotomy with hypothermic retrograde cerebral perfusion. Retrograde cerebral perfusion with oxygen saturated venous blood could be performed by simply elevating central venous pressure to 20-23 mmHg in the Trendelenburg position and under controlling venous drainage from PA during deep hypothermic (19 degrees C) perfusion of the lower half of the body with the descending aorta occluded. Cardioplegia was induced by administration of cold blood cardioplegic solution into coronary circulation through Foley balloon catheter wedged in ascending aorta. Retrograde cerebral perfusion time was 30-77 min (mean 55 +/- 17 min), and pump time was 156-193 min (mean 168 +/- 15 min). There were no complications neurologically. In conclusion, this method rendered surgical repair of distal aortic arch aneurysm through left postero-lateral thoracotomy with both cerebral and cardiac protection able. Since any clamping of aortic arch and its branch was not necessary during above surgical procedure, cerebral emboli due to atheroma or luminal thrombus in aortic arch was prevented.

Aged↗
PubMed1995

Presurgical diagnosis of a primary carcinoid tumor of the thymus with MIBG.

A primary carcinoid tumor of the thymus showing ectopic ACTH syndrome was evaluated scintigraphically with four radiopharmaceuticals and a fluorescence method. Iodine-123-MIBG and 201Tl-Cl scintigraphy clearly demonstrated the tumor. Gallium-67-citrate and 99mTc(V)-DMSA showed no tumor uptake. The fluorescence method confirmed numerous storage granules of norepinephrine. Iodine-123-MIBG scintigraphy could be useful in the presurgical diagnosis of carcinoid tumors of the thymus.

3-Iodobenzylguanidine↗
PubMed1995

A case of autoimmune hemolytic anemia induced by IFN-beta therapy for type-C chronic hepatitis.

A 51-year old woman who had type-C chronic hepatitis developed autoimmune hemolytic anemia after 4 weeks treatment with a total 48 million interferon-beta, 6 million 8 times. Indirect Coomb's test turned from negative to positive through IFN therapy and a complication of asymptomatic primary biliary cirrhosis was confirmed by histologic findings of the biopsied liver which was performed during IFN therapy and a presence of anti-mitochondrial antibody. After stopping IFN therapy and adding prednisolone anemia improved in getting negative indirect Coombs test but remaining positive direct Coombs test.

Anemia, Hemolytic, Autoimmune↗
PubMed1995

Idiopathic thrombocytopenic purpura complicated by intracranial hemorrhage in a 78-year-old male.

A 78-year-old male was admitted to our hospital with cutaneous hemorrhage, aphasia and somnolence. On physical examination, he appeared drowsy and complained of epistaxis and multiple purpura. His platelet count was 8,000/microliters with a high level of PA-IgG, but the coagulation time was normal. A CT scan of the head revealed a left temporal and right frontal hemorrhage. Bone marrow aspiration revealed abundant megakaryocytes. He was diagnosed as having idiopathic thrombocytopenic purpura with intracranial hemorrhage. He was treated with prednisolone and azathioprine in addition to platelet infusions and high doses of gamma-globulin. After two months of treatment, the platelet count had risen to 40,000/microliters and his symptoms had subsided.

Aged↗
PubMed1995

Effects of a combined use of steroidal and nonsteroidal anti-inflammatory drugs on E. coli endotoxin-induced uveitis in pigmented rabbits.

The effects of a combined use of steroidal and nonsteroidal anti-inflammatory topical drugs on uveitis were studied. Uveitis was induced by intravenous injection of E. coli endotoxin (10 micrograms/kg) in pigmented rabbits. A solution of 0.5% indomethacin (IM) and/or 0.1% betamethasone (BM) was instilled 4 times: at 1 hour before and at 0, 2 and 4 hours after the endotoxin injection. The aqueous protein was quantified by laser flare-cell measurements hourly after the injection. The prostaglandin E2 concentration was assayed and venous leukocytes and thrombocytes were counted 5 hours after the endotoxin injection. The aqueous protein reached a peak concentration (27 mg/mL) about 4 hours after the endotoxin injection. IM, BM and a combination of IM and BM (IM + BM) inhibited the aqueous protein rise by 17, 63 and 94%, respectively. IM, BM and IM + BM almost completely inhibited the increase of aqueous prostaglandin E2. IM + BM inhibited both leukocytopenia and thrombocytopenia. IM alone had no effect on these counts, and BM alone inhibited leukocytopenia only. The data suggest that the combined use of topical IM and BM is more useful for the therapy of endotoxin-induced uveitis than each drug alone. The inhibitory effects may be synergistic, probably acting on unknown mediators which may be derived from the systemic circulation.

Administration, Topical↗
PubMed1994

FK506 treatment of noninfectious uveitis.

PURPOSE: We studied the clinical effects of the immunosuppressive agent FK506 in patients with noninfectious uveitis. METHODS: This study was designed as a multicenter open clinical trial in Japan. Sixteen patients with noninfectious uveitis who had visited the Uveitis Survey Clinic of the Yokohama City University Hospital were given FK506. Eight had Behçet's disease; five, Vogt-Koyanagi-Harada syndrome; one, sympathetic ophthalmia; one, retinal vasculitis; and one, sarcoidosis. In patients with Behçet's disease, ocular attack score before and after therapy was compared to judge clinical status. For the other diseases, the ocular inflammatory symptoms were observed after the initiation of FK506 treatment. All patients underwent blood and urine examinations, electrocardiography, and chest x-rays before and after FK506 treatment. RESULTS: Of the patients with Behçet's disease, five improved, one remained unchanged, one deteriorated, and the status of one could not be determined. Of the patients with Vogt-Koyanagi-Harada syndrome, four improved, and one remained unchanged. The patient with sympathetic ophthalmia improved, the patient with retinal vasculitis remained unchanged, and the status of the patient with sarcoidosis could not be determined. Major adverse effects were sensations of warmth, hypomagnesemia, renal dysfunction, glucose intolerance, nausea, vomiting, and disorders of the central nervous system. All adverse effects disappeared or improved when FK506 was stopped or when the dosage was decreased. Renal dysfunction and glucose intolerance appeared when the blood level of FK506 was high. CONCLUSIONS: FK506 was effective in patients with uveitis, but it is important to monitor the occurrence of adverse effects.

Adult↗
PubMed1994

Pharmacokinetics of pretargeted monoclonal antibody 2D12.5 and 88Y-Janus-2-(p-nitrobenzyl)-1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) in BALB/c mice with KHJJ mouse adenocarcinoma: a model for 90Y radioimmunotherapy.

Three-step pretargeting for radioimmunotherapy in BALB/c mice with KHJJ tumors was done with monoclonal antibody (mAb) 2D12.5, which is specific for yttrium-1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) but nonspecific for the tumor. Tumor uptake was by passive diffusion of mAb through leaky neovasculature in the tumor. The three steps were: (a) anti-hapten mAb 2D12.5 (0 h); (b) polyvalent haptenprotein conjugate chase (20 h); and (c) 88Y-labeled monovalent DOTA or bivalent Janus-DOTA haptens (21 h) and organ and tumor bioassay (24 h). Rapid tumor (T) uptake and high tumor:blood ratio (T:BL) was seen 3 h after injection after step c. For monovalent 88Y-DOTA, T = 1.7%/g* and T:BL = 16:1; for bivalent 88Y-Janus-DOTA, T = 4.41%/g* and T:BL = 21:1 at 3 h (*, P < 0.001). Blood and bone plus marrow were << 1%/g, and liver was < 1%/g. The 24-h whole body retention was approximately 5% of injected dose with 1% in tumor (20% of total), 1.8% in other organs, and 2.2% in carcass; the 24-h whole body retention of covalent nonspecific antibody conjugates was > 80% of injected dose. The biological half-life in the tumor of 0.9 microCi 88Y-Janus-DOTA was approximately 24 h, measured daily for 5 days. Activity in microCi/g of tumor and blood for 90Y equimolar to the amount of 88Y injected (0.9 microCi 88Y = 0.744 pmol = 36.47 microCi 90Y) was used for calculating the area under the curve of tumor and blood in microCi-h/g of 90Y. The 90Y radiation absorbed dose (RAD) from multiplying microCi-h/g x the 90Y absorbed dose constant, 1.99 RAD-g/microCi-h, gave T = 89 RAD and BL = 3.7 RAD. The therapeutic ratio from RAD T:RAD BL = 24:1. These results indicate that pretargeting 90Y hapten-specific mAb for radioimmunotherapy has considerable promise.

Acetates↗
PubMed1994

A cholecystokinin receptor antagonist, loxiglumide, stimulates biliary secretion in conscious rats.

The effects of the CCK receptor antagonists loxiglumide [D,L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxy-propylpentylam ino)-5-oxo- pentanoic acid, CR 1505] and MK-329 [3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzo-diazepine-3-y l)-1H - indole-2-carboxamide, L-364,718], on bile flow were investigated in conscious rats. The bile duct of male Wistar rats was cannulated to directly collect pure bile, and the second cannula was inserted into the duodenum for reinfusion of bile. On the 4th through 7th postoperative days loxiglumide (25, 50 or 100 mg/kg body weight), MK-329 (1 mg/kg body weight) or the respective solvent (saline and 80% dimethyl sulfoxide) was injected subcutaneously. Loxiglumide caused dose-dependent increases in bile flow and bile acid output with a slight non-dose-dependent increase in bilirubin output. The integrated increments of bile flow during a 3-h period after saline and 100 mg/kg body weight loxiglumide were -14 +/- 71 and 982 +/- 61 microliters/100 g body weight, respectively, and those of bile acids were 2.5 +/- 1.4 and 23.1 +/- 4.1 mumol/100 g body weight, respectively. In contrast, MK-329 markedly decreased the bile flow (-439 +/- 76 vs. control; -32.8 +/- 76 microliters/100 g body weight/3 h, P < 0.001) and bile acids output (-16.3 +/- 6.8 vs. control; 3.4 +/- 3.8 mumol/100 g body weight/3 h, P < 0.001), while it significantly increased bilirubin output (86.4 +/- 15.6 vs. 43.5 +/- 1.1 mg/100 g body weight/3 h, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Expression and function of multidrug resistance P-glycoprotein in a cultured natural killer cell-rich population revealed by MRK16 monoclonal antibody and AHC-52.

Natural killer (NK) cells have been reported recently to be the highest in expressing multidrug resistance (MDR) P-glycoprotein among normal mature lymphoid cells. Using a cultured NK cell-rich population, we have examined the expression and function of P-glycoprotein, in particular its role in NK cell-mediated cytotoxicity, by employing two MDR-reversing agents (nicardipine and AHC-52, a nicardipine analog almost devoid of calcium channel blocking activity) and monoclonal antibody against P-glycoprotein (MRK-16). The expression of P-glycoprotein was detected by flow cytometry and polymerase chain reaction of reverse transcribed mRNA. P-glycoprotein was functional in terms of rhodamine dye excretion and its susceptibility to the MDR-reversing agents. Since the concentration of nicardipine required for 50% inhibition (IC50) of rhodamine dye excretion (2 microM) was close to that of AHC-52 (5 microM), it was suggested that their inhibitory effects were not due to calcium channel blocking activity, and that ACH-52 is a selective inhibitor for P-glycoprotein. The IC50 of nicardipine for NK cell-mediated cytotoxicity (33 microM) was also close to that of AHC-52 (26 microM), indicating that P-glycoprotein is involved in NK cell-mediated cytotoxicity. In support of this, MRK16 inhibited NK cell-mediated cytotoxicity in a concentration-dependent manner. Both binding of target cells to NK cells and post-binding events were affected by AHC-52, suggesting that P-glycoprotein is involved in several steps in NK cell-mediated cytotoxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Tumor angiogenesis in human lung adenocarcinoma.

BACKGROUND: Hematogenous metastasis requires angiogenesis within the tumor. Previous studies have shown that microvessel counts in histologic sections of the primary tumor, which reflect angiogenesis, are correlated with metastasis in breast, prostate and Stage I nonsmall cell lung carcinoma. In this study, the authors investigated the association between angiogenesis, hematogenous metastasis and lymph node metastasis in all stages of lung adenocarcinoma. METHODS: Microvessels were highlighted by immunostaining endothelial cells for factor VIII. We counted microvessels within the tumors of 42 patients who had surgical resection (25 with relapse and 11 without relapse more than 5 years after surgical resection). Without knowledge of patient outcome, microvessels were counted on a 200x field (0.723 mm2) in the most active areas of neovascularization. RESULTS: The microvessel counts from patients with relapse after surgical resection (mean +/- standard deviation, 75.4 +/- 64.3) were significantly higher than those without relapse more than 5 years after surgical resection (42.6 +/- 26.0) (P = 0.027). Analysis of regional lymph node metastases (factor N) revealed that the microvessel counts were 62.6 +/- 35.1 for N0 (no regional lymph node metastasis), 51.7 +/- 22.2 for N1 (metastasis in ipsilateral, peribronchial and/or ipsilateral hilar lymph nodes, including direct extension), 75.4 +/- 75.3 for N2 (metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes), and 74.0 for N3 (metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node[s]), and these values were not significantly different from each other. CONCLUSIONS: Angiogenesis assessed by microvessel counts, correlated positively with relapse after surgical resection and hematogenous metastasis in all stages of lung adenocarcinoma; there was no correlation with lymph node metastasis in lung adenocarcinoma.

Adenocarcinoma↗
PubMed1994

IL-4 production in mediastinal lymph node cells in mice intratracheally instilled with diesel exhaust particulates and antigen.

To clarify the relationship between air pollutants and IgE antibody production, interleukin 4 (IL-4) production was investigated in BALB/c mice intratracheally injected with diesel exhaust particulates (DEP) mixed with antigen (Ovalbumin (OA) or Japanese Cedar Pollen (JCP)). BALB/c mice were injected with DEP plus OA or OA alone three times with a 3-week interval. After the last instillation, proliferative response and lymphokine-producing activity of mediastinal lymph node cells (LNC) were examined in vitro. Proliferative response to OA in mediastinal LNC from mice injected with DEP plus OA was enhanced 4-17 times of that from control mice. IL-4-producing activity by OA stimulation also enhanced in mediastinal LNC from mice injected with DEP plus OA. A significantly larger amount of anti-OA IgE antibody was detected in sera from DEP- and OA-injected mice compared with those from control mice. The levels of IL-4, estimated by JCP antigen in mediastinal LNC, from mice injected with DEP plus JCP were two-fold higher than those from mice injected with JCP alone. These results suggest that intratracheal instillation of DEP affects antigen-specific IgE antibody responses via local T-cell activation, especially enhanced IL-4 production.

Animals↗