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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 721 records · Page 40Linked to original sources

Intravital and electron microscopic observation of Ito cells in rat hepatic microcirculation.

Intralobular distribution of Ito cells (fat-storing cells) in hepatic microcirculatory units was investigated through intravital fluorescence microscopy. By using a low-level ultraviolet epi-illumination and a sensitive silicon intensified target camera, the intrahepatic autofluorescence was visualized and digitally processed. In rats fed an ordinary diet, the ultraviolet-excited autofluorescence was composed of at least two different origins that could not be spectrophotometrically distinguished, namely, multiple patchy autofluorescence activities along the sinusoids and terminal hepatic venules and diffuse parenchymal autofluorescence. Multiple patchy activities showed a rapid photobleaching phenomenon under the continuous ultraviolet excitation. These fluorescent activities were completely eliminated by depleting the intrahepatic retinoid contents using a vitamin A-deficient diet for 4 weeks. Furthermore repeated administration of vitamin A significantly enhanced the patchy fluorescent activities. Electron microscopy revealed that these vitamin A fluorescent activities are colocalized with the fat droplets in Ito cells, providing evidence that Ito cells exist not only in perisinusoidal spaces but also in the perivascular spaces of the terminal hepatic and portal venules. The current intravital technique thus provides a new method to observe Ito cells in hepatic microcirculatory units in vivo.

Animals↗

Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthritis and rheumatoid arthritis by oligonucleotide DNA typing.

HLA-DR gene frequencies in 59 Japanese children with juvenile rheumatoid arthritis (JRA) and 62 Japanese adults with rheumatoid arthritis (RA) were analyzed by oligonucleotide DNA typing. As in other studies, the frequency of DRB1*0405 in RA patients was significantly higher than in the Japanese controls. In a comparison of non-classified JRA patients with Japanese controls, no significant differences were observed in the frequency of DR types. However, when the JRA patients were classified into four clinical types, i.e., a rheumatoid factor-positive [RF(+)] polyarticular type, a rheumatoid factor-negative [RF(-)] polyarticular type, a pauciarticular type, and a systemic onset type, DRB1*0405 was found to be significantly higher in the RF(+) polyarticular JRA patients than in the controls (P < 0.05). Thus, the RF(+) polyarticular type of JRA had the same HLA association as RA. This result is consistent with the fact that both RF(+) polyarticular JRA and RA cases have a similar clinical course.

Adolescent↗

Immune defense and eosinophilia in congenitally IgE-deficient SJA/9 mice infected with Angiostrongylus costaricensis.

The roles of IgE in protective immunity and eosinophilia in Angiostrongylus costaricensis infection were examined by comparing IgE-deficient SJA/9 mice and IgE-producing SJL/J mice. In primary infection, mean total IgE levels increased to a maximum of 390 ng/ml, which was more than 10 times greater than the 29 ng/ml measured preinfection in SJL/J mice but less than the 10 ng/ml found in SJA/9 mice throughout the experiment. Immune defense as determined by recovery of adult worms and eosinophilia were similar in SJL/J and SJA/9 mice. Protective immunity was induced by infection with A. costaricensis followed by treatment with levamisole for 4-6 days postinfection. After the challenge infection, the numbers of adult worms and eosinophils in SJA/9 mice were not significantly different from those in SJL/J mice. Anti-A. costaricensis IgE antibody was not detected in either strain of mice during the experiment. These results indicate that A. costaricensis infection induced the production of IgE not specific for parasite antigens in IgE-producing mice. Potentiated nonspecific IgE played no significant role in immune defense and eosinophilia.

Angiostrongylus↗

Duration and potency of anticholecystokinin action of subcutaneous and oral loxiglumide on cerulein-stimulated pancreatic exocrine secretion.

The duration and the potency of the antiCCK activities of loxiglumide given by sc and oral routes were examined in rats. Pancreatic juice flow and protein output in response to an iv bolus injection of cerulein (100 ng/kg body wt) were measured at specified time intervals from 1-12 h after loxiglumide administration. Subcutaneous loxiglumide (10 g/kg body wt) effectively suppressed cerulein-stimulated protein output for 4 h and pancreatic juice volume for 6 h, when total outputs during a 60-min period after cerulein stimulation were compared with the control value without loxiglumide pretreatment. Oral dose of loxiglumide exerted longer-term anti-CCK activity (protein output: 6 h, pancreatic juice: 8 h) than the same sc dose. In addition, oral loxiglumide showed more potent suppression of protein output than the same sc dose at the corresponding time interval. Higher oral dose of loxiglumide (50 mg/kg body wt) caused longer inhibition on both protein (8 h) and pancreatic juice secretion (12 h). These results suggest that the half-life of loxiglumide given by oral route is longer than that by sc route or that the bioavailability of oral loxiglumide is higher than that of sc dose. The present study demonstrates that loxiglumide, given either by sc or by oral route, has long duration of action in antagonizing responses to exogenously administered cerulein.

Administration, Oral↗

Colloid liver SPECT of hepatic alveolar echinococcosis.

Seventy-one-year-old man had a liver mass. He lived in Hokkaido, where there is an epidemic of hydatic disease. Abdominal US image showed an echogenic mass. CT revealed a low density mass with an unclear margin. A 99mTc-Sulfur colloid liver SPECT study was performed to detect the liver mass. The SPECT scan was done after intravenous administration of 5 mCi of 99mTc-sulfur colloid, and it revealed a lack of uptake in the liver mass. The liver SPECT findings were correlated with subsequent CT and US imaging. Echo-guided biopsy showed a PAS-positive cuticle layer of echinococcosis in the necrotic tissue. This is the first report of a case of detection of hepatic alveolar echinococcosis by means of a colloid liver SPECT imaging procedure.

Aged↗

The practice of consultation-liaison psychiatry in Japan.

Consultation-liaison (C-L) psychiatry has been developing for the past 10 years as a new clinical service field in Japan. Although this kind of service had been practiced previously, it was not recognized as an independent clinical field. Still in the developing phase, clinical research in C-L psychiatry has been reported, although its quality has been variable. The authors describe the development and a typology of C-L psychiatry (seven types) in Japan. This article reports time spent on C-L psychiatry activity in a general hospital. Although C-L psychiatry requires much time and labor, hardly any of the C-L psychiatry services are reimbursed in the Japanese insurance system. The authors propose a "new department" as one option to continue providing C-L psychiatry service to general hospital patients and for further development of C-L psychiatry in Japan.

Ambulatory Care↗

Labeling of fractured human skin with antibodies to BM 600/nicein, epiligrin, kalinin and other matrix components.

A variety of methods were used to fracture the dermal-epidermal junction (DEJ) of human skin. These included warm and hot phosphate buffered saline, trypsin, cold 1 M salt, potassium bromide and proteolytic digestion with dispase. The localization and sensitivity of basement membrane components (bullous pemphigoid antigen, BM 600/nicein, epiligrin, kalinin, laminin, collagens IV and VII (EBA antigen) and linkin) were determined after the DEJ was fractured by each method. We found that the basement membrane zone proteins, BM 600/nicein, epiligrin and kalinin remained with the dermal side of the DEJ fractured through the lamina lucida by cold salt, phosphate buffered saline and potassium bromide. BM 600/nicein, epiligrin and kalinin were not detected after treatment with trypsin. In contrast, laminin, another glycoprotein in the lamina lucida, was insensitive to all of the procedures, but co-localized to the dermal side of DEJ-fractured skin. We also found that separation of the DEJ with brief exposure of skin to 56 degrees C provided a useful substrate for testing the autoantibodies in the sera of patients with epidermolysis bullosa acquisita (EBA). Heat-separated skin can be prepared in a significantly shorter period of time than salt-separated skin.

Antibodies↗

Age-specific characteristics of nocturnal blood pressure in a general population in a community of northern Japan.

The age- and gender-specific profile of circadian blood pressure variation was examined by monitoring ambulatory blood pressure (ABP) in 477 untreated subjects in a rural community of northern Japan. Autoregressive spectral analysis demonstrated three major peaks at around 24, 12, and 8 h. We fitted a truncated Fourier series with three harmonics to the blood pressure (BP) data using least squares regression. More than half of the BP and pulse rate periodic curves were bimodal, one-third were trimodal, and the remainder were unimodal. The nadir of BP appeared between 00:00 and 01:30, and that of pulse rate occurred between 00:30 and 02:00. The nadir of systolic and diastolic BP, as well as pulse rate, appeared earlier with increasing age, and the difference between subjects in their 20s and those in their 70s was about 1 h. The amplitude of 24 h BP decreased with increasing age in men, but not in women. This type of information on the circadian BP profile of a general population is useful for the diagnosis and treatment of hypertension.

Adult↗

Characteristics of a community-based distribution of home blood pressure in Ohasama in northern Japan.

OBJECTIVE: To evaluate the distribution, reference values and day-to-day variation of blood pressure of untreated subjects measured at home. DESIGN: Cross-sectional study of a cohort. SETTING: General community in northern Japan. SUBJECTS: Blood pressure was measured in 871 subjects (mean +/- SD age 46.0 +/- 19.5 years, range 7-98, constituting 38.7% of the local population of Uchikawama region, Ohasama) who were not receiving antihypertensive medication. METHODS: Subjects measured their own blood pressure at home at least three times (mean +/- SD 19.7 +/- 8.4) each morning using a semi-automatic oscillometric blood pressure measuring device. Screening blood pressure was measured once. MAIN OUTCOME MEASURES: Distribution of home blood pressure in the study population as a whole and with respect to age and sex, and the distribution of day-to-day variation of home blood pressure were determined. RESULTS: Mean home blood pressure was 117.3 +/- 13.4/69.3 +/- 9.7 mmHg (95% confidence interval 116.4-118.2/68.7-70.0). The 95th centile value was 143/85 mmHg, mean+SD 131/79 mmHg and mean + 2SD 144/89 mmHg. Mean screening blood pressure was 126.2 +/- 18.9/72.1 +/- 11.7 mmHg (95th centile 159/92 mmHg). Age- and sex-specific 95th centile values as well as mean +/- SD were obtained. Mean+SD, mean + 2SD and the 95th centile values obtained as reference upper limits of home blood pressure from subjects identified as normotensive by screening blood pressure (n = 707) were 125/77, 137/86 and 134/83 mmHg, respectively. Home blood pressure increased gradually with increasing age in both men and women, although blood pressure was significantly higher in men until 50 years of age. Day-to-day variation of home systolic blood pressure also increased with age. CONCLUSION: Since the distribution of home blood pressure values was affected by age and sex, age- and sex-matched reference values for home blood pressure should be established. Home blood pressure values in elderly subjects should be evaluated carefully, since these exhibit greater day-to-day variation.

Adolescent↗

Regional distribution of 201Tl during one-leg exercise: comparison with leg blood flow by plethysmography.

To validate the use of 201Tl distribution as an estimate of regional blood flow in the legs, 201Tl leg uptake was compared by whole body scintigraphy and simultaneously measured leg blood flow by plethysmography during one-leg exercise in 11 male subjects. 201Tl leg uptake ratio and leg blood flow ratio were also compared to exclude the effect of cardiac output variation in each subject. There was a good correlation between 201Tl leg uptake and leg blood flow (r = 0.85, P < 0.01, y = 0.28x + 1.00). Moreover, there was a highly linear correlation between these ratios (r = 0.98, P < 0.01, y = 0.75x + 0.13), although the 201Tl leg uptake ratio somewhat underestimated the leg blood flow ratio as exercise became strenuous. It is concluded that 201Tl leg uptake reflects regional blood flow in the legs during exercise.

Aged↗

Lysosome labilizers potentiate the antitumor effects of tumor necrosis factor-alpha.

Enhancement of in vitro cytotoxic activity of tumor necrosis factor-alpha (TNF-alpha) was observed in combination with lysosome labilizers, particularly with urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and lipoprotein lipase (LPL). The concentration of TNF-alpha resulting in 50% cytotoxicity to L929 cells was only 20-30% of the value for TNF-alpha alone, when used in combination with a nontoxic dose of u-PA, t-PA or LPL. Furthermore, combined intravenous (i.v.) administration of TNF-alpha (3.5 x 10(5) U/mouse) and u-PA (300 IU/mouse) markedly increased the in vivo antitumor activity of TNF-alpha to Meth A tumors transplanted into BALB/c mice; the tumor weight in co-administered mice was about 40% of that in mice given TNF-alpha alone on day 6. The combination therapy of TNF-alpha (7.0 x 10(4) U/mouse, i.v.) and u-PA (300 IU/mouse, i.v.) was also effective for L929 tumors in Crj:CD-1(1CR)-nu nude mice compared with the conventional therapy with TNF-alpha alone. These results suggest that the combination of TNF-alpha and lysosome labilizers is a promising antitumor therapeutic regimen with clinical potential.

Animals↗

Changes of proliferative activity and phenotypes in spontaneous differentiation of a colon cancer cell line.

We examined the alterations of proliferative activity and c-myc expression of a colon cancer cell line (Caco-2) during its spontaneous differentiation. Caco-2 cells were cultured in various types of media and the degree of differentiation was monitored in terms of dome formation in cell monolayers and expression of alkaline phosphatase (ALP) activity. In Caco-2 cells cultured with Eagle's minimum essential medium (EMEM) containing 10% fetal calf serum (FCS), dome formation was demonstrated and ALP activity was markedly increased after the cells reached confluence. Five-fold reduction of c-myc mRNA and a marked decrease in S-phase cells were observed in the differentiated cells. These changes were not induced in FCS-free EMEM. The addition of insulin and transferrin to FCS-free EMEM did not induce cell differentiation or reduction of c-myc mRNA expression. When Caco-2 cells were cultured with three different serum-free media, the induction of dome formation and the increase of ALP activity were observed to varying degrees. Expression of c-myc mRNA in the cells cultured with one serum-free medium decreased to a level similar to that in fully differentiated cells cultured with EMEM containing 10% FCS. These results suggest that a spontaneous switch from a proliferative state with high c-myc expression to differentiated phenotype occurs after cells reach confluence and depends on the culture conditions.

Cell Differentiation↗

Enhanced antitumor effect of recombinant human tumor necrosis factor in combination with recombinant human granulocyte colony-stimulating factor in BALB/c mice.

The synergistic antitumor effect of tumor necrosis factor (TNF) and granulocyte colony-stimulating factor (G-CSF) was investigated. G-CSF was administered subcutaneously to BALB/c mice inoculated with Meth-A cells at a dose of 2.5 micrograms/day for 5 consecutive days. When TNF (1 x 10(3) U) was administered intravenously to mice which had been pretreated with G-CSF, tumor growth showed a 74.1% inhibition 17 days after the tumor cell inoculation, compared to that of untreated mice. In this experiment, G-CSF significantly (P < 0.025) enhanced the antitumor effect of TNF. The in vitro cytotoxicity of TNF (10 U/ml) towards Meth-A cells was increased about 5.2-fold in the presence of neutrophils (E/T = 50) as compared to the cytotoxicity obtained with TNF alone. A combination of TNF and G-CSF (50 ng/ml) in the presence of neutrophils, resulted in a 2.1 times greater cytotoxicity against Meth-A cells as compared to that obtained without G-CSF. Significant augmenting effects of G-CSF on superoxide (O2-) production by TNF-stimulated neutrophils were observed. These observation suggest that the neutrophil plays an important role in the antitumor action of TNF on Meth-A cells, and that the antitumor effect of TNF is enhanced by combination with G-CSF.

Animals↗

Two chronic myelogenous leukaemia cell lines which represent different stages of erythroid differentiation.

We established two cell lines, YN-1 and Y-1K, from the peripheral blood of two chronic myelogenous leukaemia patients in blastic crisis. Characterization of the YN-1 and Y-1K cells revealed that these cells expressed erythroid lineage markers. However, there was a marked difference in the level of gamma-globin mRNA and haemoglobin in YN-1 and Y-1K cells. YN-1 contained approximately 1-5% benzidine-positive staining cells, whereas no benzidine-positive cells were observed in Y-1K cells. Haemoglobin production in YN-1 cells was markedly increased with various chemical inducers of erythroid differentiation, but was not in Y-1K cells. In contrast, Y-1K cells expressed CD34 stem cell antigen and CD41 megakaryocyte-specific antigen. These observations suggested that, although both cell lines were committed to the erythroid lineage, each cell line represented a distinct differentiation stage in the erythroid differentiation programme. Y-1K seemed to correspond to an early stage of cells in erythroid lineage, whereas YN-1 represented a more advanced stage in human erythropoiesis.

Adult↗