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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 793 records · Page 44Linked to original sources

[Seasonal fluctuations of substance P and vasoactive intestinal peptide concentrations in nasal secretions of patients with nasal allergy to Japanese cedar pollen].

Substance P (SP) and vasoactive intestinal peptide (VIP) concentrations in nasal secretions and plasma from patients with nasal allergy to Japanese cedar pollen and healthy volunteers were measured from Jan to Dec, 1991 using EIA established by us. Simultaneously, the numbers of airborne pollens of Japanese cedar and cypress were counted, and the relation to the SP and VIP concentrations in nasal secretions from the patients with nasal allergy to Japanese cedar pollen was studied. The mean SP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 81.9 +/- 48.4 fmol/mg protein, which was significantly higher than that in the non-pollination season (30.4 +/- 14.7 fmol/mg protein) (p < 0.01). Likewise, the mean VIP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 14.2 +/- 10.4 fmol/ml protein, which was significantly higher than that in the non-pollination season (4.2 +/- 3.0 fmol/mg protein) (p < 0.01). The SP and VIP concentrations in nasal secretions from the healthy volunteers were not affected by the scattering of pollens. The SP and VIP concentrations in plasma from the patients and the healthy volunteers were not affected by the scattering of pollens.

Adult↗

Effect of slow release nifedipine tablets in patients with essential hypertension.

The antihypertensive effect of slow release nifedipine (CAS 21829-25-4) tablets (20 mg, Adalat) administered once or twice daily was studied in patients with essential hypertension of WHO stage I or II. Ambulatory blood pressure was monitored by a finger volume oscillometric device every 5 min for 24 h before and during the treatment with nifedipine. Whether administered once or twice daily, nifedipine tablets dit not change the pattern of circadian blood pressure variation; i.e. diurnal rise and nocturnal fall. Twice daily administration induced a significant downward shift in the blood pressure pattern. In other words, further hypotensive effect was observed during the night when the blood pressure was already low. On the other hand, administration once daily in the morning lowered daytime blood pressure without affecting blood pressure during the night. The duration of action of nifedipine tablets administered once daily was 12 h or more. In the acute experiment using 20 mg tablets of nifedipine, plasma concentration of nifedipine was well correlated with the percentage change in mean blood pressure. The minimal effective plasma concentration of nifedipine was estimated to be 13.4 ng/ml. However, in chronic treatment, nifedipine lowered blood pressure at the plasma concentration of 10 ng/ml. The results indicate that nifedipine tablets administered once daily provide an effective antihypertensive regimen for controlling daytime hypertension with minimal antihypertensive effect during the night.

Adult↗

[Pulmonary clearance of 99mTc-DTPA aerosol in patients with progressive systemic scleroderma].

Alveolar epithelial permeability was assessed in 32 patients with progressive systemic scleroderma (PSS), using 99mTc-DTPA aerosol. Immediately after the inhalation of 99mTc-DTPA aerosol for 3 to 6 minutes under normal tidal breathing, lung was imaged sequentially for 30 minutes from the posterior by a gamma camera and exponential fitting was processed on the time activity curve. T1/2 (min) was used as a parameter for the evaluation of permeability of alveolar epithelium. Patients with collagen disease showed shorter T1/2 (T1/2 = 43.7 +/- 23.8 min) than the normal volunteers (T1/2 = 76.8 +/- 8.7 min). No significant difference was observed between patients with or without interstitial changes on the chest CT. Significant correlation was not observed between T1/2 and %VC or %DLco. In 8 cases, studies were repeated in the interval of 3 to 19 months. Improvement of T1/2 was seen in 4 cases, independent of CT findings. These results suggest that 99mTc-DTPA aerosol clearance study provides information independent from other lung examinations, and may be useful for the assessment of lung interstitial changes in patients with PSS.

Administration, Inhalation↗

[Clinical evaluation of meropenem in the pediatric field].

We studied the clinical efficacy of meropenem (SM-7338, MEPM), a new parenteral carbapenem beta-lactam antibiotic, in pediatric field. Thirteen patients with 2 months to 8 years and 8 months of ages, with acute infectious diseases were administered with doses at 39.3 to 76.7 mg/kg/day of MEPM intravenously. The diagnoses consisted of 7 respiratory tract infections, 1 sepsis, 2 orbital cellulitis, 1 parotid abscess, 1 lymphadenitis and 1 pyoderma. The clinical efficacy rate was 84.6% (11/13), and the bacteriological eradication rate was 71.4% (5/7). Clinical laboratory examinations revealed 1 patient with eosinophilia and another with anemia. No other side effects attributable to this drug were observed. It appears that MEPM is a useful antibiotic for moderate to severe acute bacterial infections in children.

Bacterial Infections↗

[Effect of cefclidin and E1077, new cephalosporins, on the alcohol-metabolizing system in rats].

Administration of latamoxef and cefoperazone, reported to act like disulfiram in humans, caused a depression of mitochondrial low Km aldehyde dehydrogenase (low Km ALDH) activity in rats. In addition, a marked increase of blood acetaldehyde concentration was observed when rats were given alcohol orally at 18 hours after administration of these cephalosporins. However, mitochondrial low Km ALDH activity and blood acetaldehyde level were not altered by repeated administration of 300 mg and 1,000 mg of cefclidin (CFCL, E1040) or E1077 per kg. From these results, it was concluded that neither CFCLn or E1077 affected the alcohol metabolizing-system.

Acetaldehyde↗

[A case of bronchial actinomycosis associated with bronchoscopically removed broncholith].

A 57-year-old woman with bronchial actinomycosis associated with broncholith is presented. She had suffered from fever and productive cough for 7 years. Her chest roentgenograms showed atelectasis of the middle lobe and calcification in the middle lobe bronchus. Bronchoscopic examination revealed a broncholith covered with pus and granulomatous tissue. The biopsy specimen revealed sulfur granules containing a partially calcified lesion, and it was diagnosed as actinomycosis. After treatment with antibiotics, the broncholith became movable, and it was removed bronchoscopically. Its shape was like a molding of the right middle lobe bronchus. We speculate that the growth of this broncholith partially resulted from chronic inflammation associated with actinomycelial infection.

Actinomycosis↗

[Effect of serum factors on the differentiation of a colon cancer cell line Caco-2].

A human colon cancer cell line Caco-2 undergoes spontaneous enterocytic differentiation under the standard culture condition. We examined the changes in the proliferative activity of Caco-2 cells during the differentiation, and the effect of serum factors on this spontaneous differentiation. Caco-2 cells cultured in FCS-containing media exhibited the differentiation phenotypes such as dome formation and increase of ALP activity after the 6th day of culture. Cell cycle analysis showed a marked decrease in S phase cell population during the cell differentiation. When Caco-2 cells were cultured in FCS free media, the cell population of S phase remained unchanged during culture period and the differentiation phenotypes were not induced. The addition of FCS to Caco-2 cell cultured in the absence of FCS resulted in the rapid induction of the differentiation phenotypes. These results suggest that differentiation of Caco-2 cells is closely related to the reduction of cell proliferation and requires some factors in FCS.

Animals↗

[A case of occult breast carcinoma with micronodular shadows on chest x-ray film].

A 57-year-old woman was admitted to our hospital for the evaluation of roentgenological micronodular shadows of the bilateral middle and lower lung fields. Physical findings were normal except for left axillary lymph adenopathy. The level of tumor marker NCC-ST-439 was markedly elevated (2800 U/ml). Histological examination of the transbronchial biopsy and the swollen lymph node biopsy specimens showed proliferation of identical tumor cells. Breast or lung carcinoma was suspected as the primary site. Echogram of the left breast showed microcalcification without a mass. The biopsy specimen obtained from the calcified lesion indicated occult breast carcinoma. From these findings the diffuse micronodular shadows on the chest roentgenogram were considered to be the metastatic lesions of occult breast carcinoma. This case indicates that occult breast carcinoma should be considered as a possible primary site for diffuse pulmonary metastatic lesions.

Antigens, Tumor-Associated, Carbohydrate↗

Lymphocyte-mucosal interaction of the middle ear mucosa.

The middle ear mucosa possesses immunologic features similar to those of the peripheral mucosa sites in the common mucosal immune system and after mucosal immunization, antigenspecific IgA-forming cells appear in the inflamed mucosa of the tympanic cavity. Recent investigations suggest that lymphocyte migration to lymphoid tissues is regulated by lymphocyte-high endothelial venules (HEV) interaction. However, the lymphocyte migration mechanism to the middle ear mucosa is still unclear. We investigated whether or not organ-specific determinants which lymphocytes bind with are present on the middle ear mucosa by in vivo and in vitro lymphocyte adherence assays by using fluorescein-labeled lymphocytes from various lymphoid tissues. Many lymphocytes from Peyer's patches and hilar lymphnodes adhered on the inflamed middle ear mucosa with or without mucosal immunization, while these cells were not found on the normal tympanic mucosa. The number of the cells was smaller than that in the gastrointestinal mucosa. Lymphocyte adherence to the middle ear mucosa was not suppressed by anti-T cell antibody. These findings suggest that the middle ear mucosa possesses organ-specific mucosal determinants which B-lymphocytes selectively bind with, and that those determinants which regulate lymphocyte migration to the middle ear mucosa differ from those of other mucosae in the gastrointestinal tract.

Animals↗

[Clinical evaluation of 99mTc ethyl cysteinate dimer SPECT in patients with spinocerebellar degeneration; comparison with cerebral blood flow determined by PET].

Technetium-99m ethyl cysteinate dimer (99mTc-ECD) is regarded as a promising radiopharmaceutical for imaging regional cerebral blood flow (rCBF). We evaluated 99mTc-ECD SPECT comparing with rCBF images obtained by PET in 12 patients with spinocerebellar degeneration (SCD). SPECT images of 99mTc-ECD demonstrated characteristic findings of decreased rCBF in bilateral cerebellar hemisphere and almost identical with PET rCBF images in all patients based on the visual inspection. Semiquantitative analysis by drawing 14 intracranial regions of interest on SPECT and PET images revealed linear correlation between 99mTc-ECD count and rCBF measured by PET even in relatively high rCBF regions. In summary, 99mTc-ECD is a promising tracer for evaluating rCBF in patients with SCD and distribution of it correlates well with rCBF measured by PET.

Adult↗

Does superoxide underlie the pathogenesis of hypertension?

Although active oxygen species play important roles in the pathogenesis of various diseases, the molecular mechanism for oxygen toxicity in vascular diseases remains to be elucidated. Since endothelium-derived relaxing factor (EDRF) is inactivated by superoxide radicals in vitro, oxidative stress in and around vascular endothelial cells may affect the circulatory status of animals. To study the role of superoxide radicals and related enzymes, such as superoxide dismutase (SOD), in vascular diseases, we have developed a fusion protein (HB-SOD) consisting of human Cu/Zn-type SOD and a C-terminal basic peptide with high affinity for heparan sulfate on endothelial cells. When injected intravenously, HB-SOD bound to vascular endothelial cells, underwent transcellular transport, and localized within vascular walls by a heparin-inhibitable mechanism. The blood pressure of spontaneously hypertensive rats (SHR) but not normal animals was decreased significantly by HB-SOD. Heparin inhibited the depressor effect of HB-SOD. In contrast, native SOD had no effect on blood pressure of either SHR or normal rats. Neither H2O2-inactivated HB-SOD nor the C-terminal heparin-binding peptide showed such a depressor effect, suggesting that the catalytic function of HB-SOD is responsible for its depressor action. To know the source of superoxide radicals, we determined xanthine oxidase activity in the aorta and uric acid levels in the plasma. Although no appreciable difference in xanthine oxidase activity was found between the two animal groups, uric acid levels were significantly higher in SHR than in normal rats. Oxypurinol, a potent inhibitor of xanthine oxidase, also decreased the blood pressure of SHR but not of normal rats. These findings indicate that superoxide radicals in and around vascular endothelial cells play critical roles in the pathogenesis of hypertension of SHR.

Amino Acid Sequence↗

Expression of a hybrid Cu/Zn-type superoxide dismutase which has high affinity for heparin-like proteoglycans on vascular endothelial cells.

Since plasma levels of enzymes, such as superoxide dismutase (SOD), that scavenge reactive oxygen species are low, surface membranes of endothelial and parenchymal cells of various tissues are often exposed to oxidative stress. To dismutase superoxide radicals efficiently in and around vascular endothelial cells, we constructed a fusion gene encoding a hybrid SOD (HB-SOD) consisting of human Cu/Zn-SOD and a C-terminal basic peptide that binds to heparin-like proteoglycans. The fusion gene was expressed in yeast, and the resulting HB-SOD was highly purified. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, HB-SOD revealed a protein band with an apparent molecular weight of 20,000. HB-SOD bound to endothelial cells of aortic segments by a mechanism which was inhibited by heparin but not by antithrombin III. When injected intravenously to rats, 125I-labeled HB-SOD rapidly disappeared from the circulation; the rate of disappearance was decreased by heparin. Less than 1% of the injected HB-SOD was found in the urine 20 min after administration at which time more than 70% of SOD was excreted in its intact form. Immunohistochemical studies revealed that HB-SOD predominantly bound to heparin-like proteoglycans on endothelial cells of the artery and other tissues. HB-SOD might permit studies on pathophysiological roles of superoxide radicals in and around vascular endothelial cells in vivo.

Amino Acid Sequence↗

Activation of IFN-beta element by IRF-1 requires a posttranslational event in addition to IRF-1 synthesis.

Expression of the Type I IFN (i.e., IFN-alpha s and IFN-beta) genes is efficiently induced by viruses at the transcriptional level. This induction is mediated by at least two types of positive regulatory elements located in the human IFN-beta gene promoter: (1) the repeated elements which bind both the transcriptional activator IRF-1 and the repressor IRF-2 (IRF-elements; IRF-Es), and (2) the kappa B element (kappa B-E), which binds NF kappa B and is located between the IRF-Es and the TATA box. In this study we demonstrate that a promoter containing synthetic IRF-E, which displays high affinity for the IRFs can be efficiently activated by Newcastle disease virus (NDV). In contrast, such activation was either very weak or nil when cells were treated by IFN-beta or tumor necrosis factor-alpha (TNF-alpha), despite the fact they both efficiently induce de novo synthesis of the short-lived IRF-1 in L929 cells. In fact, efficient activation of the IRF-E apparently requires an event in addition to de novo IRF-1 induction, which can be elicited by NDV even in the presence of protein synthesis inhibitor, cycloheximide. Moreover, efficient activation of the IRF-E by NDV is specifically inhibited by the protein kinase inhibitor, Staurosporin. Hence our results suggest the importance of IRF-1 synthesis and post-translational modification event(s), possibly phosphorylation for the efficient activation of IRF-Es, which are otherwise under negative regulation by IRF-2.

Alkaloids↗

Independent inactivation of MPF and cytostatic factor (Mos) upon fertilization of Xenopus eggs.

In vertebrates, mature eggs are arrested at the second meiotic metaphase by the cytostatic factor (CSF), now known to be the c-mos proto-oncogene product (Mos). Fertilization or egg activation triggers a transient increase in the cytoplasmic free calcium and releases the meiotic arrest by inactivating maturation/mitosis-promoting factor (MPF). CSF or Mos, which is also inactivated by the calcium transient, seems to stabilize MPF in mature eggs and CSF-injected embryos. Thus, it was assumed that CSF inactivation is the primary cause of MPF inactivation on meiotic release. We have directly compared the degradation kinetics of CSF (Mos) and MPF during meiotic release, using the same batch of Xenopus eggs. We report here that, at the molecular level, cyclin subunits of MPF are degraded before Mos is degraded and, at the physiological level, that MPF activity is inactivated before CSF activity during activation of Xenopus eggs. These results, in conjunction with circumstantial evidence, support the novel view that a calcium transient on fertilization induces a CSF-independent pathway for MPF inactivation, whereas CSF inactivation during meiotic release serves only to allow the fertilized egg to enter mitosis.

Animals↗