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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 523 records · Page 29Linked to original sources
PubMed1996

Scintigraphic study of malignant melanoma with 123I-iodoamphetamine.

N-isopropyl-p-I-123-iodoamphetamine (123I-IMP) is extracted by the brain in proportion to regional blood flow. It is particularly useful in the clinical assessment of various pathological conditions related to altered cerebral flow. Moreover, it has been reported that 123I-IMP is avidly incorporated into melanin and melanotic melanoma. We evaluated 123I-IMP scintigraphy using either planar or single photon emission tomography (SPET) studies in 10 patients with malignant melanoma. The patients were classified into two groups according to the tumour site: Group A, six patients with primary or metastatic cutaneous malignant melanoma of the extremity with planar scintigraphy; Group B, four patients with primary malignant melanoma of other organs with planar scintigraphy and SPET. In Group A, tumour uptake was demonstrated in four of six patients; in Group B, three of four patients had tumour accumulation on SPET and planar scintigraphy. SPET revealed the exact tumour localization, even in the case of a tumour located in the lung. These results suggest that planar scintigraphy using 123I-IMP is useful in the detection of malignant melanoma. Furthermore, more clear tumour localization is possible with SPET, even in the case of a tumour located in the lung.

Aged↗
PubMed1996

Effects of MCI-727 on pancreatic exocrine secretion and acute pancreatitis in two experimental rat models.

The effects of a newly developed compound having antiulcer action, (Z)-2-(4-methylpiperazin-1-yl)-1-[4-(2-phenyl-ethyl)phenyl]-eth anone oxime hydrochloride monohydrate (MCI-727), on pancreatic exocrine secretion were studied in anesthetized rats and evaluated its preventive and therapeutic effects on acute pancreatitis in two experimental rat models. Intraduodenal administration of MCI-727 [25, 50, or 100 mg/kg body weight (wt)] stimulated a dose-dependent increase in pancreatic juice and bicarbonate output without increasing the protein output or plasma cholecystokinin concentration. MCI-727-stimulated pancreatic exocrine secretion was completely abolished by antisecretin serum but not by the cholecystokinin receptor antagonist loxiglumide (50 mg/kg body wt/h) or cholinergic receptor antagonist atropine (100 mu g/kg body wt/h). In rats with acute pancreatitis induced by four subcutaneous injections of 20 mu g/kg body wt cerulein at hourly intervals over 3 h, MCI-727 administered orally at a dose of 100 mg/kg body wt 30 min before the first cerulein injection significantly reduced the increases in serum amylase and lipase activity and pancreatic wet weight and induced improvements in the results of histologic examination. Moreover, when given 30 min before and 90 min after the first cerulein injection, MCI-727 had even more dramatic protective effects on all these parameters. In addition, even when administered immediately after the last cerulein injection, MCI-727 effectively ameliorated all these alterations of acute pancreatitis. However, MCI-727 had no apparent beneficial effects on the biochemical and histologic alterations of acute pancreatitis in the severe form induced by retrograde intraductal injection of 1.0 ml/kg body wt of 4% sodium taurocholate. These findings suggest that oral administration of MCI-727 stimulates pancreatic exocrine secretion by endogenous secretin release and that it has therapeutic as well as preventive effects on mild forms of acute pancreatitis in rats.

Acute Disease↗
PubMed1996

Endogenous tumor necrosis factor inhibits the cytotoxicity of exogenous tumor necrosis factor and adriamycin in pancreatic carcinoma cells.

Pancreatic carcinoma is one of the most devastating neoplasms with regard to its resistance to conventional therapy. In a previous report, we found that endogenous tumor necrosis factor (enTNF) exerts an intracellular protective effect against exogenous TNF- and Adriamycin (ADM)-induced cytotoxicity by scavenging oxygen free radicals (OFR) with induced manganous superoxide dismutase (MnSOD). We also know that glutathione S-transferase pi (GST-pi) and glutathione (GSH) also scavenge OFR. It remains unclear to what extent enTNF and MnSOD induced by enTNF regulate the sensitivity to ADM and exogenous TNF among different carcinoma cells. In this study, we examined the relationship between ADM and exogenous TNF sensitivity and en-TNF expression and MnSOD activity in four pancreatic carcinoma lines. We determined whether ADM and exogenous TNF sensitivity could be predicted by measuring enTNF expression and MnSOD activity in the carcinoma cells. The sensitivity to TNF and ADM varied with the cell lines, and TNF sensitivity correlated well with Adriamycin sensitivity. Moreover, enTNF expression and Mn-SOD activity correlated positively with resistance to ADM and exogenous TNF. When MIAPaCa-2 cells, which had the lowest enTNF expression and the highest sensitivity to exogenous TNF and ADM, were transfected with the nonsecretory-type human TNF gene (pTNF delta pro) to increase enTNF synthesis, their intracellular MnSOD activity and exogenous TNF and ADM resistance were increased. These findings suggest that MnSOD plays a critical role in scavenging OFR induced by ADM and exogenous TNF. enTNF is the most important factor that regulates the production of MnSOD. Therefore, it is plausible that inhibition of enTNF expression or MnSOD activity in pancreatic carcinoma would improve the efficacy of therapies for pancreatic carcinoma.

Doxorubicin↗
PubMed1996

Interaction between nucleocapsid protein (NP) and phosphoprotein (P) of human parainfluenza virus type 2: one of the two NP binding sites on P is essential for granule formation.

The paramyxovirus phospho- (P) and nucleocapsid (NP) proteins are involved in transcription and replication of the viral genome. To study the interaction between NP and P proteins, we established HeLa cell lines that constitutively expressed the NP and/or P proteins of human parainfluenza virus type 2 (hPIV-2). Co-immunoprecipitation assays revealed that the NP and P proteins can form complexes in HeLa cells expressing both proteins (HeLa-NP+P cells) and in mixed cell lysates of HeLa-NP and HeLa-P cells. Deletion mutant analysis of the P protein was performed to identify the regions of P protein that interact with NP protein. The results indicate that two independent NP-binding sites exist on P protein: one is located in the N-terminal part of the protein, aa 1-47, and the other in the C-terminal part, aa 357-395. In addition, cells co-expressing NP and P proteins with N-terminal deletions showed immunofluorescence staining patterns (granular pattern) similar to those found in hPIV-2-infected cells. However, cells co-expressing NP and P proteins with C-terminal deletions showed a different immunofluorescence staining pattern (diffuse pattern), indicating that the C-terminal region is required for granule formation.

Animals↗
PubMed1996

Regulation of human immunodeficiency virus gp160-mediated cell fusion by antibodies against fusion regulatory protein 1.

We have isolated new MAbs directed against the human fusion regulatory protein 1 (FRP-1; CD98) molecule using human FRP-1-expressing L929 cells as antigens. The biological activities, and in particular the human immunodeficiency virus (HIV)-mediated fusion regulatory activity of seven anti-FRP-1/CD98 MAbs were analysed using the U937/gp160 cell line, which is a CD4+ U937 cell line expressing HIV gp160. Two MAbs induced multinucleated giant cell formation in U937/gp160 cells and the other five MAbs showed no fusion-inducing ability. However, four of these MAbs suppressed multinucleated giant cell formation of U937/gp160 cells induced by the activating anti-FRP-1 MAbs. Interestingly, five of the MAbs induced multinucleated giant cells in peripheral blood monocytes and one MAb showing fusion-inducing ability in U937/gp160 cells suppressed multinucleated giant cell formation of monocytes induced by anti-FRP-1 MAbs. Furthermore, four of the anti-FRP-1 MAbs suppressed cell fusion of Jurkat/gp160 cells, which are Jurkat cells expressing HIV gp160. Thus, FRP-1/CD98 is capable of either activating or inhibiting HIV-mediated cell fusion depending on whether an enhancing or inhibiting antibody is used, indicating that FRP-1/CD98 is a multipotential molecule. Thus, HIV-mediated cell fusion can be regulated by modification of the FRP-1 system. Furthermore, the present study demonstrates that the FRP-1 and FRP-2 systems are interdependent.

Animals↗
PubMed1996

Identification of the sequences responsible for nuclear targeting of the V protein of human parainfluenza virus type 2.

In human parainfluenza virus type 2 (hPIV-2)-infected cells, anti-phosphoprotein (P)-specific monoclonal antibody (MAb) densely stained the perinuclear regions of infected cells throughout infection, indicating that the P protein was localized exclusively in the cell cytoplasm. By contrast, antigens recognized by MAbs directed against the P-V-common domain of hPIV-2 were located predominantly in the cytoplasm, but in some hPIV-2-infected cells they were also found in the nuclei, suggesting that a fraction of hPIV-2 V protein is localized there. hPIV-2 V protein expressed from a cDNA clone was localized in the nuclei of transfected cells. By using indirect immunofluorescence analyses, we examined the intracellular localization of various sequentially deleted V proteins, to determine the nuclear localization signals (NLS) of the V protein. Two noncontiguous regions in the V protein were required for nuclear localization and retention, since deletion of these regions [region I (aa 1-46) and region II (aa 175-196)] resulted in cytoplasmic localization. Both regions resulted in nuclear localization independently. A nucleoplasmin-like NLS was identified in region II but no consensus targeting sequence could be found in region I. When NP protein was co-expressed with V protein or the N-terminal fragment (aa 1-46) of V protein, a fraction of the NP protein was translocated into cell nuclei.

Amino Acid Sequence↗
PubMed1996

[Rapid detection of the hemolysin genes in Aeromonas sobria by the polymerase chain reaction].

The hemolysin of Aeromonas sobria is one of the important virulence factors in this organism. Rapid detection and identification test for A. sobria is important for early and specific diagnosis of this infectious disease. We evaluated the polymerase chain reaction (PCR) for the rapid detection of A. sobria. Two pairs of synthetic oligonucleotide primers (ASA1-s and a; AerAAS-s and a) were used in PCR technique to detect the different hemolysin genes (ASA1 and aerAAS) in A. sobria. The PCR identified 91% of ASA1-positive and 23.4% of aerAAS-positive strains in beta-hemolytic A. sobria. Other species of Aeromonas, Plesiomonas shigelloides, Vibrio cholerae O1 and V. parahaemolyticus tested were negative in the PCR with two pairs of primers. The PCR technique for detection of two hemolysin genes suggested the possibility of application of this method for detection of A. sobria in A. sobria-associated infections.

Aeromonas↗
PubMed1996

Defect in pancreatic exocrine and endocrine response to CCK in genetically diabetic OLETF rats.

Clinical as well as experimental studies in insulinopenic diabetes mellitus have demonstrated abnormal pancreatic exocrine responses to cholecystokinin (CCK). In the present study, we examined pancreatic exocrine and endocrine function in the recently developed genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and compared them with those in the control Long-Evans Tokushima Otsuka (LETO) rats of the same age. Stepwise increasing doses of CCK octapeptide (CCK-8; 0.027-7.0 nmol.kg-1.h-1) evoked a characteristic biphasic dose-response curve for pancreatic juice and protein output in the LETO rats, whereas the OLETF rats were totally insensitive to CCK-8 stimulation. However, the responsiveness and the sensitivity to both carbamylcholine and secretin were similar in the two groups. Intraduodenal infusion of casein (500 mg/h) failed to stimulate pancreatic exocrine secretion in the OLETF rats despite a greater CCK response than in the LETO rats (peak response: 8.43 +/- 0.97 vs 5.12 +/- 0.30 pmol/l in LETO, P < 0.01). Intravenous infusion of CCK-8 (4.4 nmol.kg-1.20 min-1) caused a significant increase in serum insulin concentrations and a concomitant decrease in glucose levels in the LETO rats but not in the OLETF rats. On the other hand, an intravenous bolus injection of 1.1 mmol/kg glucose caused a greater insulin release in the OLETF rats than in the LETO rats. In contrast, gastric acid secretion in the OLETF rats was significantly high in basal and in response to intravenous infusion of CCK-8 compared with that in the LETO rats. Four subcutaneous injections of 20 micrograms/kg caerulein at hourly intervals over 3 h induced acute pancreatitis in the LETO rats but did not elicit any significant increase in serum amylase or lipase activities and pancreatic wet weight or histological evidence of acute pancreatitis in the OLETF rats. These results indicate that the exocrine and endocrine pancreas of the recently developed genetically diabetic OLETF rats are totally and specifically insensitive to exogenous and endogenous CCK stimulation, whereas parietal cells in these rats are sensitive to CCK stimulation.

Acute Disease↗
PubMed1996

Regulation of the C3 production by gamma interferon from peripheral blood T cells in patients with membranoproliferative glomerulonephritis and poststreptococcal acute glomerulonephritis.

This study assessed the regulatory role of peripheral blood T cells in the C3 production in patients with poststreptococcal glomerulonephritis and branoproliferative glomerulonephritis. Peripheral blood T cells from patients at various stages of disease were cultured and the supernatants tested for gamma interferon (IFN-gamma) content and the capacity to stimulate C3 production by HuH-7 cells. Supernatants from patients with membranoproliferative glomerulonephritis and from convalescent patients with poststreptococcal glomerulonephritis significantly stimulated the C3 production; the degree of stimulation correlated with the IFN-gamma content of the supernatants. Similar results were obtained using recombinant IFN-gamma. In both cases, the effect was blocked by the addition of anti-IFN-gamma monoclonal antibody to the cultures. Interleukin 2 and interleukin 6 levels in supernatants from T cell cultures of patients and controls were essentially the same. In summary, IFN-gamma plays a regulatory role in C3 production by human hepatoma cell lines.

Acute Disease↗
PubMed1996

Brugia malayi infection in mice with selective suppression of IgE production.

For the purpose of evaluating the roles of IgE in helminth infections in vivo, IgE-suppressed mice provide useful models. After infection with 50 third-stage larvae of the filarial parasite Brugia malayi, total IgE in BALB/c mice increased to five times higher than uninfected levels. However, anti-B. malayi IgE antibody was not detected, indicating polyclonal IgE B cell activation by the infection. In BALB/c mice which had received repeated injections of anti-mouse epsilon monoclonal antibody from birth and which were subsequently infected, total IgE levels were less than 10 ng/ml, but anti-B. malayi IgG antibody and total IgA were produced similar to the control. Therefore, IgE-isotype-specific suppression was attained. Concerning the protection against B. malayi, the numbers of fourth-stage larvae and adult worms at 2 and 5 weeks after primary infection, respectively, and fourth-stage larvae at 2 weeks after secondary infection were not significantly different between control and IgE-suppressed mice.

Animals↗
PubMed1996

Preferential differentiation of P19 mouse embryonal carcinoma cells into smooth muscle cells. Use of retinoic acid and antisense against the central nervous system-specific POU transcription factor Brn-2.

Investigation of the molecular mechanisms that control smooth muscle cell (SMC) development and differentiation is a prerequisite in understanding the regulatory mechanisms of physiological and pathological SMC-associated vascular processes. The pluripotent murine embryonal carcinoma P19 cell, whose developmental potential resembles that of early embryonic cells, can develop into cell types derived from the neuroectoderm, mesoderm, and endoderm. In the present study, we have shown a unique strategy to enhance SMC differentiation in P19 cells. Under chemical induction of high concentrations of retinoic acid (1 micromol/L), P19 cells showed optimum differentiation into SMCs. Because the P19 cells thus induced also showed differentiation into neuronal cells, a strategy to block neuronal lineage differentiation was developed using a stable transformant antisense RNA construct against Brn-2, a neuronal lineage-specific POU-domain transcription factor; thus, by specifically inhibiting neuronal differentiation, enhanced SMC differentiation by P19 cells was attained. SMC expression was confirmed by immunohistochemical staining, RNA analysis (RNase protection assay), and protein analysis (Western blot) using SMC-specific markers (eg, SM1 and calponin) and alpha-smooth muscle actin. Our results show that the pathway of SMC differentiation may provide an in vitro system useful in the investigation of SMC regulatory mechanisms (eg, transcriptional regulation) and in the further understanding of SMC development and differentiation.

Amino Acid Sequence↗
PubMed1996

Nocturnal blood pressure and silent cerebrovascular lesions in elderly Japanese.

BACKGROUND AND PURPOSE: We conducted a cross-sectional epidemiological survey using ambulatory blood pressure monitoring and brain MRI in a cohort from northern Japan to determine whether an inappropriately low nocturnal blood pressure, or an excess fall in nocturnal blood pressure, might be responsible for silent cerebrovascular lesions in the elderly. METHODS: Untreated subjects over 55 years and under 64 years of age (late middle age; 24 men and 46 women, 60% of eligible people) and over 65 years and under 75 years of age (elderly; 29 men and 52 women, 91% of eligible people) participated in the study. We evaluated the relationship between the amplitude (Daytime Average-Nighttime Average) or the rate ([Daytime Average-Nighttime Average]/Daytime Average) of the fall in nocturnal blood pressure and the incidence of silent cerebrovascular lesions on MRI (number of lacunar infarctions or extent of periventricular hyperintensity). RESULTS: The amplitude or the rate of the fall in nocturnal blood pressure in elderly women with one or two lacunar infarctions was significantly higher than that in those without such infarctions. There was a significant positive correlation between the amplitude or the rate of the fall in nocturnal blood pressure and the extent of periventricular hyperintensity in the elderly women. This relationship was observed in women, but not in men, of late middle age; this was not seen in elderly men. CONCLUSIONS: Results indicate that an inappropriately low nocturnal blood pressure, or an excessive fall in nocturnal blood pressure, is associated with ischemic silent cerebrovascular lesions, at least in elderly women. Treatment of hypertension in such women should be administered with care and with regard to nocturnal blood pressure.

Age Distribution↗
PubMed1996

Study on adhesion factors in lymphocyte migration to the middle ear mucosa.

We investigated influences of adhesion factors on the migration of antigen-specific IgA-forming cells (ASAFCs) to the middle ear mucosa by means of an in vitro lymphocyte binding assay. Peyer's patch (PP) lymphocytes from guinea pigs with mucosal immunization, which are rich in ASAFCs, more frequently bound with the inflamed middle ear mucosa than those of PP and spleen cells from animals with systemic immunization, in which antigen-specific IgG-forming cells (ASGFCs) were induced (p > .001). The bindings were not affected by antigenic and nonantigenic stimuli to the middle ear mucosa for producing otitis media. On human middle ear mucosa from 10 patients with acute mastoiditis and chronic otitis media, endothelial cells of newly grown vessels were stained strongly with intercellular adhesion molecule (ICAM)-1, and weakly with vascular cell adhesion molecule (VCAM)-1, platelet endothelial cell adhesion molecule (PECAM), and endothelial leukocyte adhesion molecule (ELAM)-1. Many lymphocytes bound mainly to these endothelial cells, and a few cells were observed bound to the basal portion of epithelial cells. The binding of lymphocytes was significantly, but not completely, inhibited by anti-ICAM-1 antibody (p < .001). These findings suggest that PP lymphocytes with activated mucosal immunity more frequently migrate to the inflamed middle ear mucosa, and that those migrations, after extravasation, may be regulated by the interaction between various binding factors and their receptors on lymphocytes, which is different from that of adhesion molecules and their ligands in the extravasation.

Animals↗
PubMed1996

Cis- and trans-linalool 3,7-oxides and methyl salicylate glycosides and (Z)-3-hexenyl beta-D-glucopyranoside as aroma precursors from tea leaves for oolong tea.

Two new alcoholic aroma precursors, cis- and trans-linalool, 3,7-oxides 6-O-beta-D-apiofuranosyl-beta-D-glucopyranosides (1 and 2), as well as two already known compounds, (Z)-3-hexenyl beta-D-glucopyranoside (3) and methyl salicylate 6-O-beta-D-xylopyranosyl-beta-D-glucopyranoside (beta-primeveroside: 4), and another new monoterpendiol glycoside, 8-hydroxygeranyl beta-primeveroside (5) have recently been isolated as aroma precursors in tea leaves (Camellia sinensis var. sinensis cv. Maoxie) ready for oolong tea processing.

Carbohydrate Sequence↗
PubMed1996

Ambulatory blood pressure monitoring in evaluating the prevalence of hypertension in adults in Ohasama, a rural Japanese community.

We estimated the prevalence of hypertension and evaluated the degree of blood pressure control on the basis of ambulatory blood pressure monitoring in patients receiving antihypertensive medication. A total of 969 adults (mean age +/- SD, 59.3 +/- 12.1 years old range: 20-79 yr) among 1,575 eligible persons (65.1%) recruited from a total adult population of 2,789 people living in a rural region of northern Japan underwent measurement of initial screening blood pressure; ambulatory blood pressure was measured subsequently. A total of 285 subjects (66.5 +/- 9.2 years old) were taking antihypertensive medication (treated group), while 684 (56.3 +/- 12.0 years old) were not (untreated group). The WHO criteria were used to categorize screening blood pressure. Ambulatory blood pressure levels were classified as follows: hypertension, systolic blood pressure > or = 144 mmHg and/or diastolic blood pressure > or = 85 mmHg; and normotension, systolic blood pressure < or = 133 and diastolic blood pressure < or = 78 mmHg. Of the 285 treated subjects, 49 (17.2%) were classified as hypertensive by screening measurements, while 36 (12.6%) were classified as such by ambulatory blood pressure monitoring. Only 12 (24.5%) of the former 49 subjects were also classified as hypertensive, while 20 (40.8%) were classified as normotensive by ambulatory blood pressure monitoring. Of the 684 untreated subjects, 34 (5.0%) were hypertensive by screening measurements and 43 (6.3%) were hypertensive by ambulatory blood pressure monitoring. Only 14 (41.2%) of the former 34 subjects were classified as hypertensive by ambulatory blood pressure monitoring. Of the 34 untreated subjects classified as hypertensive by screening measurements, ambulatory blood pressure monitoring showed 12 (35.3%) to be normotensive, suggesting that they were cases of "white coat" hypertension. The study first confirmed, based on community-derived data, that there are large discrepancies between screening (casual) blood pressure measurements and ambulatory blood pressure monitoring with respect to the recognition of hypertension and normotension. The determination of blood pressure levels by ambulatory blood pressure monitoring may result in a different prognosis of hypertension from that made on the basis of screening blood pressure measurements. The prognostic value of ambulatory blood pressure has to be further investigated.

Adult↗
PubMed1996

Bilateral aldosterone-producing adenomas in two patients diagnosed by immunohistochemical analysis of steroidogenic enzymes.

Bilateral adrenal aldosterone-producing adenomas (APA) are rare. It is important to distinguish bilateral APA from idiopathic hyperaldosteronism (IHA) which is due to bilateral hyperplasia of the adrenal cortex. We present two patients with bilateral APA in whom the diagnosis was made histochemically by analyzing steroidogenic enzymes. They showed hypokalemia, high plasma aldosterone concentration (PAC) and suppressed plasma renin activity (PRA). Bilateral adrenal tumors were represented by computed tomography, and surgical resection was performed. In both cases, cytochrome P-450 and other enzymes that were involved in aldosterone synthesis were found mainly in tumor, but little in the zona glomerulosa of the adjacent adrenals, which showed paradoxical hyperplasia. Such cases are difficult to distinguish from IHA. The two disorders were differentiated by immunohistochemical analysis of steroidogenic enzymes.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

"Web-like obstruction"--a sign of regional complete remission after concurrent chemoradiotherapy in small cell lung cancer.

Two patients with small cell lung cancer (SCLC) developed "web-like" mucosa that obstructed bronchi after concurrent chemoradiotherapy. It seemed that the orifice of the bronchi had disappeared. Since the patients were free of local recurrence and the histologic findings of "web-like" mucosa were negative for malignancy, we believe that "web-like obstruction" was additional sign of regional complete remission of SCLC after concurrent chemoradiotherapy.

Aged↗