Biomedical subjects

F Sato

Publications and source records attributed to F Sato.

At least 199 records · Page 11Linked to original sources

PubMed1995

[Two patients with far advanced gastric cancer responding to combination chemotherapy with 5-FU and CDDP].

Combination chemotherapy with 5-FU and CDDP was given to two patients with far advanced gastric cancer. One patient was associated with metastases of lung, liver, pancreas and Virchow and periaortic lymph nodes, and the other was associated with metastases of periaortic lymph nodes and malignant ascitis. The regimen consisted of 5-FU 1,000 mg/m2 (day 1-5, continuous infusion) and CDDP 100 mg/m2 (day 3, 1 hr drip infusion). The interval was from the 6th to the 21st day. The response to chemotherapy showed shrinking of primary gastric lesions and metastases of liver, pancreas and periaortic lymph nodes, and disappearance of Virchow lymph nodes and malignant ascitis. Adverse reactions were thrombocytopenia (Grade 4), leukocytopenia (Grade 3), stomatitis (Grade 1, 3), vomiting (Grade 1, 2) and peripheral neuropathy (Grade 3). This therapy is thought to be effective against far advanced gastric cancer.

Adenocarcinoma↗

PubMed1995

[Effects of inhaled oxitropium bromide, an anticholinergic drug, on pulmonary hemodynamics in patients with chronic obstructive pulmonary diseases].

We studied the effects of the inhaled anticholinergic agent oxitropium bromide (Ox) on pulmonary hemodynamics in eleven patients with chronic obstructive pulmonary disease. All the patients underwent right heart catheterization and seven of them underwent an incremental ergometer exercise test while in the supine position. Pulmonary hemodynamics and arterial blood gases were measured at rest and during maximal exercise, before and 30 minutes after inhalation of 2 puffs (200 micrograms) of Ox. Inhalation of Ox did not significantly change pulmonary hemodynamics at rest. The mean pulmonary arterial pressure and the mean pulmonary capillary wedge pressure during exercise decreased significantly (from 40.3 +/- 4.6 to 37.7 +/- 3.9 mmHg, and from 20.4 +/- 3.5 to 17.1 +/- 2.7 mmHg, respectively, mean +/- SE). However, neither cardiac output nor pulmonary vascular resistance changed with inhalation of the drug, at rest or during exercise. We therefore conclude that this commonly used dose of Ox does not directly affect the pulmonary vascular system. The small but significant decreases in pulmonary arterial pressure and pulmonary capillary wedge pressure with Ox may have been indirect effects, caused by bronchodilation.

Administration, Inhalation↗

PubMed1995

Studies on calcium antagonistic and alpha 1-adrenergic receptor blocking activities of monatepil maleate, its metabolites and their enantiomers.

The calcium antagonistic and alpha 1-adrenergic receptor blocking activities of monatepil maleate (CAS 103377-41-9, (+/-)-N-(6,11-dihydrodibenzo [b, e] thiepin-11-yl) -4-(4-fluorophenyl)-1-piperazinebutanamide monomaleate, AJ-2615), a novel calcium antagonist, its metabolites and their enantiomers were studied in vitro. Monatepil maleate inhibited calcium-induced contractions of rat thoracic aorta (pA2 = 8.71) and l-phenylephrine-induced contractions of rabbit superior mesenteric artery (IC50 = 56.6 nmol/l). The calcium antagonistic activities of the metabolites of monatepil maleate (AJ-2615-sulfoxide A, AJ-2615-sulfoxide B and AJ-2615-sulfone) were 1/10 of that of monatepil maleate. However, their alpha 1-adrenergic receptor blocking activities were similar to or slightly more potent than that of monatepil maleate. The potencies of the calcium antagonistic activities of monatepil maleate and its enantiomers [(S)-AJ-2615 and (R)-AJ-2615] were in the order of (S)-AJ-2615 > monatepil maleate > (R)-AJ-2615 whereas no difference was observed among them in alpha 1-adrenergic receptor blocking activity. In calcium antagonistic and alpha 1-adrenergic receptor blocking activities, there was no difference between the enantiomers of monatepil maleate metabolites. In conclusion, there was a difference with several times in calcium antagonistic activity between the two enantiomers of monatepil maleate but not in their alpha 1-adrenergic receptor blocking activity.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1995

Immunolocalization of dehydroepiandrosterone sulfotransferase in normal and pathologic human adrenal gland.

Dehydroepiandrosterone sulfotransferase (DHEA-ST) catalyzes the conversion of dehydroepiandrosterone (DHEA) to dehydroepiandrosterone sulfate (DHEA-S) in the adrenals. Both DHEA and DHEA-S are quantitatively the most important corticosteroids in human. In this study, DHEA-ST was immunolocalized in normal (5 cases) and neoplastic human adrenal glands (33 cases), using a specific IgG fraction raised against the enzyme. DHEA-ST was present in almost all the zona reticularis cells and some cortical cells demonstrating lipid depletion in the zona fasciculata but not in the zona glomerulosa of the normal adrenal. This finding is consistent with adrenocorticotrophic hormone dependency of the enzyme expression. In adrenocortical adenoma, DHEA-ST immunoreactivity was observed in all the cases of Cushing's adenoma, adenoma associated with pre-Cushing's syndrome, nonfunctioning, hormonally inactive adenoma, and two of seven cases of aldosteronoma, but distribution of immunoreactivity was markedly heterogeneous among the adenoma cases. In attached non-neoplastic adrenal glands of the adenoma, intense and diffuse immunoreactivity was observed in the zona reticularis cells in all the cases of aldosteronoma and five of six of the nonfunctioning hormonally inactive adenoma, but DHEA-ST immunoreactivity was not observed or sporadic in the attached adrenal glands of Cushing's adenoma and adenoma with pre-Cushing's syndrome. These results in the attached adrenal gland may be correlated with decreased DHEA-ST expression due to autonomous neoplastic cortisol secretion and subsequent adrenocorticotrophic hormone suppression. In adrenocortical carcinoma, DHEA-ST was observed in all the cases, but the relative immunointensity of carcinoma cells was weak compared to that of the zona reticularis of the normal adrenal and adenoma.

Adrenal Cortex Neoplasms↗

PubMed1995

Expression of the endogenous Marek's disease virus ICP4 homolog (MDV ICP4) gene is enhanced in latently infected cells by transient transfection with the recombinant MDV ICP4 gene.

The ICP4 homolog of Marek's disease virus (MDV ICP4) is a possible candidate for the transactivator of the early genes. We transfected MDCC-MSB-1 (MSB-1) tumor cells with plasmid including a coding region of MDV ICP4 using cationic liposome. As carriers for intranuclear transport, high mobility group -1 and -2 proteins were bound to the plasmid DNA before forming liposomes. We detected transcripts from the plasmid 2 hr after transfection by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. We also detected abundant transcripts of endogenous ICP4 2-96 hr after transfection. These data suggested that expression of introduced MDV ICP4 gene enhanced the expression of endogenous MDV ICP4. On the other hand, quantitative PCR analysis for virus genome DNA indicated no significant alteration of copy number of virus genome in transfected MSB-1 cells, suggesting that reactivation of virus requires more than turning on MDV ICP4 gene.

Animals↗

PubMed1994

Important contribution of the methylene part of LTB4 toward binding affinity to the LTB4 receptors and rise in intracellular-free calcium concentration.

In order to examine a role of the C(16)-C(20) methylene part of leukotriene B4 (LTB4) toward the activation of leukocytes, we synthesized the LTB4-analogues in which the length of the C(16)-C(20) part of LTB4 is varied systematically while the two hydroxyl groups at C(5) and C(12) positions and the 6(Z), 8(E), 10(E) conjugated triene unit remained untouched. We examined their binding affinity to the LTB4 receptors present in the rat polymorphonuclear leukocytes (PMNLs) and their ability to raise intracellular-free calcium concentration ([Ca2+]i) in the rat PMNLs loaded with fura-2. As the length of the chain of LTB4 was increased or decreased one by one, the binding affinity to the LTB4 receptors diminished, and the analogues of more than three carbon atoms shorter chain were of about three log order less activity than LTB4. The biological potency as assessed in [Ca2+]i rises pararelled that of the binding affinity to the PMNL membrane. These results indicate that the C(16)-C(20) part of LTB4 plays important role for the activity. In a similar way we prepared the LTB4-analogues of a different chain length between C(2)-C(4) of LTB4 and tested their biological activity. We found that the C(2)-C(4) part of LTB4 also affects the activity.

Animals↗

PubMed1994

Apigenin induces morphological differentiation and G2-M arrest in rat neuronal cells.

Flavonoids are pigments of edible plants. We have recently reported that most flavonoids induce G1 arrest in human cancer cells, and that genistein (an isoflavone) specifically inhibits their cell cycle at G2-M phase. In the present study, apigenin (a flavone) was found to inhibit the proliferation of B104 rat neuronal cells, and flow-cytometric analysis showed that apigenin arrested their cell cycle at G2-M phase. This effect was dose-dependent and reversible when apigenin was removed from the culture medium. Microscopic observation showed that apigenin did not significantly increase the mitotic index compared with the control. Further, apigenin induced morphological differentiation, that is, elongation and arborization of neurites in B104 cells. This is the first report to show that apigenin inhibited the proliferation of malignant tumor cells by G2-M arrest and induced morphological differentiation.

Animals↗

PubMed1994

Purification and characterization of S-adenosyl-L-methionine: norcoclaurine 6-O-methyltransferase from cultured Coptis japonica cells.

S-adenosyl-L-methionine:norcoclaurine 6-O-methyltransferase (norcoclaurine 6-O-methyltransferase), which catalyzes the transfer of the S-methyl group of S-adenosyl-L-methionine to the 6-hydroxyl group of 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-6,7- isoquinolinediol (norcoclaurine), was purified from cultured Coptis japonica cells and its enzymic properties were characterized. Purified norcoclaurine 6-O-methyltransferase had apparent pI 4.7, a native molecular mass of 95 kDa (determined by gel filtration) and subunit molecular mass of 40 kDa (SDS/PAGE). The enzyme did not require a divalent cation for activity, and the addition of Fe2+, Cu2+, Co2+, Zn2+, Mn2+, or Ni2+ at 5 mM severely inhibited enzyme activity. Neither p-chloromercuribenzoate, N-methylmaleimide nor iodoacetamide inhibited enzyme activity at 1 mM. 5,6-Dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]qu inolizinium (berberine, the end-product of the biosynthetic pathway in which norcoclurine 6-O-methyltransferase catalyzes an intermediate step) also inhibited the activity by 50% at 10 mM. Norcoclaurine 6-O-methyltransferase methylated both (S)-norcoclaurine and (R)-norcoclaurine and (R,S)-norlaudanosoline. Further characterization of substrate-saturation kinetics and product inhibition of the purified enzyme indicated that norcoclaurine 6-O-methyltransferase follows a bi-bi ping-pong mechanism with Km values of 2.23 mM and 3.95 mM for (R,S)-norlaudanosoline and S-adenosyl-L-methionine, respectively, while Ki values for S-adenosylhomocysteine versus S-adenosyl-L-methionine and (R,S)-norlaudanosoline were 2.1 mM and 0.18 mM, respectively.

Amino Acid Sequence↗

PubMed1994

Changes in morphology of elastin fibers during development of the tunica intima of monkey aorta.

The normal development of elastin fibers in the thoracic aorta was studied in fetal, young, and adult monkeys. Tissue was examined by scanning electron microscopy (SEM) after NaOH treatment and by transmission electron microscopy (TEM). The NaOH treatment of fixed tissues effectively removed collagen fibers and enabled three-dimensional visualization of the elastin fibers. In intact fetal aortae, the internal elastic lamina (IEL) was situated immediately beneath the endothelium. This IEL consisted of superficial, longitudinally arranged bundles of elastin fibrils and an underlying solid sheet containing round fenestrations. In neonates, diffuse intimal thickening was observed. In the young and young-adult monkeys, the aortae exhibited intimal thickening with slender but split IEL. One of the most important findings of this study was that elastin fibers in the intimal thickening, as well as smooth muscle cells, ran in a longitudinal fashion. This was in contrast with the elastic laminae of the media which were mainly oriented circumferentially. Subendothelial elastin fibers in this intimal thickening combined with longitudinally arranged microfibrils which formed close associations with endothelial stress fibers. In some adult monkey aortae with well-developed intimal thickening, a complex meshwork of slender elastin fibers was also found beneath the endothelium. The development of the intimal elastin fibers is discussed in relation to hemodynamic forces.

Actin Cytoskeleton↗

PubMed1994

A high frequency of induction of chromosome aberrations in the bone marrow cells of LEC strain rats by X-irradiation.

LEC strain rats, which have been known to develop hereditarily spontaneous fulminant hepatitis 4 to 5 months after birth, are highly sensitive to whole-body X-irradiation when compared to WKAH strain rats. The present results showed that the frequencies of all types of chromosome aberrations induced by X-irradiation in the bone marrow cells of LEC rats were approximately 2- to 3-fold higher than those of WKAH rats, though no significant difference was observed in the frequency of spontaneous chromosome aberrations between LEC and WKAH rats.

Animals↗

PubMed1994

Radiation hypersensitivity of LEC strain rats controlled by a single autosomal recessive gene.

LEC strain rats (LEC rats), which are known to develop hereditarily spontaneous fulminant hepatitis 4-5 months after birth, were highly sensitive to whole-body X-irradiation when compared to WKAH strain rats. The radiosensitivity of F1 hybrids of LEC and WKAH rats was similar to that of WKAH rats and significantly lower than that of LEC rats. Segregation data of backcross hybrids (F1 x LEC and LEC x F1) suggested that the hypersensitivity of LEC rats to whole-body irradiation is controlled by a single autosomal recessive gene. The radiosensitivity of fibroblasts from LEC rats was higher than that of fibroblasts from WKAH rats. The repair process of DNA double-strand breaks in LEC cells was slower than that in WKAH cells. LEC rats could provide a useful animal model to assist in understanding the mechanism of radiation-induced DNA damage and repair.

Animals↗

PubMed1994

Secretion of ions and pharmacological responsiveness in the mouse paw sweat gland.

1. Some of the basic functional features of the mouse paw eccrine sweat gland were delineated to allow comparison with those of transgenic mice in the future. 2. The mouse sweat secretory coil responds to methacholine, elaborating a K(+)-rich (> 120 mmol/l), Na(+)-poor (< 70 mmol/l) primary fluid as does the rat paw sweat gland, as previously reported. The methacholine-induced sweat rate increases with age in parallel with the growth of the sweat gland over the first 6 weeks of life. 3. The sweating response to cyclic AMP-elevating agents, such as isoprenaline or forskolin, is as much as 40% of the methacholine-induced sweat rate at 1 week of age, but falls to 10% by 6 weeks of age despite the fact that the agonist-induced tissue accumulation of cyclic AMP expressed on a per microgram of protein basis triples with age over the same period. 4. A marked K+ outflux was also noted in response to methacholine and a small K+ outflux was seen in response to cyclic AMP-elevating agonists in superfused adult mouse secretory coils in vitro. 5. Since sweat secretion is usually associated with activation of either K+ channels or Cl- channels or both, and since the sweating occurred in response to cyclic AMP-elevating agonists, we speculate that the cyclic AMP-activated Cl- channels (the mouse version of the cystic fibrosis transmembrane conductance regulator) may also occur in the mouse sweat gland, but that the degree of their expression may be influenced by the age of the mice.

Aging↗

PubMed1994

beta-Mercaptoethanol differentially acts on the rat somatotrophs and lactotrophs in primary culture to suppress the secretion of immunoreactive hormones.

We previously reported that beta-mercaptoethanol (ME) reduced the content of immunoreactive prolactin (iPRL) within the adenohypophyseal cells, primarily through its direct effect on the disulfide bonding of the PRL molecule. Because of the structural similarities between PRL and growth hormone (GH), the effects of ME on the hormonal dynamics of iGH were compared to those of iPRL. ME reduced secretion and intracellular content of both iGH and iPRL in the cultured rat adenohypophyseal cells. However, iGH was more resistant to the suppressive effects of ME than iPRL. This was particularly so with regard to the intracellular hormonal contents. While 0.01% ME caused approximately 90% reduction in the iPRL content of the lactotrophic cells, the highest tested dose of ME, i.e. 0.1%, showed only 20% reduction in the iGH content of the somatotrophic cells. Also, the minimum effective dose of ME to suppress iGH secretion was 10-fold higher than that required for the suppression of iPRL secretion. Significant suppression of iGH secretion was not observed until 120 min after the onset of ME incubation as opposed to 2-9 min for the suppression of iPRL. These findings, together with the lack of any direct effects of ME on the iGH molecule itself, strongly suggested that ME acted via different mechanisms and/or pathways in the somatotrophs and lactotrophs to suppress respective hormonal dynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Characterization of accumulation of tobacco PR-5 proteins by IEF-immunoblot analysis.

Accumulation of group 5 pathogenesis-related (PR) proteins in tobacco was characterized by immunological analysis combined with isoelectric focusing. This method clearly distinguished 3 subclasses of PR-5 proteins; basic (osmotin), neutral (osmotin-like protein: OLP) and acidic (PR-S). A high accumulation of PR-5 proteins was detected only in root tissues in which neutral osmotin-like protein was mainly accumulated, in addition to a small amount of osmotin. Immunohistochemical analysis revealed that OLP accumulated in the cortex of the root. Cultured tobacco cells accumulated large amounts of neutral PR-5 proteins (OLP) in cells and the acidic form (PR-S) in the medium. Adaptation to salt stress was associated with a higher accumulation of basic PR-5 (osmotin) and less neutral PR-5. In an analysis of the effect of biotic and abiotic stimuli on the synthesis of PR-5 proteins in leaf tissues, ethylene was found to induce a high accumulation of basic and neutral PR-5 proteins. Tobacco mosaic virus (TMV) infection induced accumulation of all major PR-5 proteins, but induction of OLP was less than that of the other isoforms. Systemic induction of PR-5 proteins in upper non-infected leaves was not observed. Salicylate induced only a small accumulation of PR-S. These results indicate that each PR-5 protein has an independent regulatory pathway for its gene expression.

Amino Acid Sequence↗

PubMed1994

Interleukin-1 alpha in human sweat is functionally active and derived from the eccrine sweat gland.

We wished to establish the presence of interleukin-1 (IL-1) in human sweat (5) and clarify its origin and mechanism of secretion. IL-1 alpha concentration ([IL-1 alpha]) in clean sweat from the back increased with the sweat rate, plateauing at the maximal sweat rate ([IL-1 alpha]max). The mean [IL-1 alpha]max was 545 pg/ml (n = 17) for men and 1,324 pg/ml for women in back sweat. The mean [IL-1 alpha]max for axillary sweat in men was 1,568 (n = 6). Palmar sweat was 9.2 ng/ml (n = 5) for IL-1 alpha and 7.9 ng/ml for IL-1 beta. [IL-1 alpha]max decreased to one-third that of the first sweat test, when second sauna sweat tests were conducted after 2 h of continuous sweating on the same day. Western blot analysis of the purified sweat IL-1 alpha fraction revealed bands at 17, 29, and 33 kDa. Immunoreactive IL-1 alpha was localized mainly in the secretory coil lumen, intercellular canaliculi, cytoplasm, mitochondria, and near plasma membranes. Polymerase chain reaction revealed the presence of IL-1 alpha mRNA in the sweat gland and in cultured human eccrine secretory coil cells. Both sweat IL-1 alpha and human recombinant IL-1 alpha at 500 pg/ml strongly stimulated interleukin-6 and interleukin-8 production in cultured fibroblasts. We conclude that the IL-1 alpha-like immunoreactive substance in sweat is IL-1 alpha itself, is derived from the sweat gland, and is biologically active at concentrations normally present in fresh sweat.

Adolescent↗

PubMed1994

Induction of lung tumors in C3H strain mice after single or fractionated irradiation with X-rays.

Murine model for lung tumor induction was studied in C3H/He male mice, a strain with low spontaneous incidence of lung tumors. Dose-response relationships in lung tumor induction were compared following irradiation with single doses and split doses of X-rays to the thorax either at night or in the daytime. The tumor incidence after a single 1.25 Gy dose at night during the period of nocturnal activity almost reached the maximum level after a 5 Gy dose in the daytime. Proliferative activity determined by observing the labeling index with tritiated thymidine in the normal lung was low as a whole, but tended to decrease in the daytime. When the proliferative response was induced by X-irradiation, significantly higher activity was observed at night. These circadian fluctuations were thought to affect radiosensitivity and lung tumor induction in mice. When split doses or fractionated doses of X-rays were applied to the thorax, lung tumor incidence definitely increased. The incidence after two 7.5 Gy doses with a 12 hr-interval was 41%, 3-fold higher than that after a single 15 Gy dose. Moreover, fractionated whole body irradiations (three times at 3 Gy with 3-month-interval) after a single 7.5 Gy thoracic irradiation was most effective in increasing not only the incidence (47%) but also the multiplicity of the lung tumor. More than 30% of tumor-bearing mice had two or more tumors following thoracic and whole body irradiations, while only 10% of tumor-bearers had multiple tumors after single or fractionated thoracic irradiation alone.

Animals↗

PubMed1994

Expression and purification of recombinant Marek's disease virus serotype 1 specific phosphorylated protein pp38 in E. coli.

Phosphorylated protein pp38 is the only protein that is detected in the Marek's disease (MD) lymphoma caused by MD virus serotype 1 (MDV-1) and lymphoblastoid cell lines. In this study, a recombinant protein coded for by the almost entire open reading frame of the MDV-1 pp38 cDNA was produced in E. coli and purified by affinity chromatography. Prior to the expression and purification of the protein, cDNA containing the entire coding region for pp38 was cloned and its nucleotide sequence was determined. Immunoblot analysis indicated that the expressed recombinant protein electrophoresed close to that of the pp38 in infected cells. The difference in mobility of the purified recombinant and the pp38 in infected cells corresponded to a fusion peptide. The recombinant pp38 may be of interest for function analyses and the diagnotic use of pp38.

Amino Acid Sequence↗

PubMed1994

Magnetic resonance imaging of young and aged rat brains under a magnetic field of 7.05 T.

Using a homemade MR imaging probe (Helmoholtz coil), MR images of brains of 5-week-old and 23- or 24-month-old Wistar rats were taken under a magnetic field of 7.05 T (Tesla). The probe was designed to fit the rat head and made by winding thin copper film round an acrylic tube with a 5-cm i.d., 10-cm length and 2-mm thickness. This was adjusted to resonate with the 300 MHz radiofrequency corresponding to the resonance frequency of 1H under a magnetic field of 7.05 T. MR images were obtained by T1-weighted and two-dimensional Fourier transformation techniques. The sagittal and coronal sections were imaged in 1-mm-thick slices. The size of the data matrix was 128 phase-encoded steps. Each image was obtained through eight acquisitions. A comparison of the MR images with those semi-microscopically taken at the same position of the coronal section revealed that the cerebral cortex, hippocampus, hypothalamus and thalamus were clearly imaged by this probe. With aging, MR images of cerebral cortices were observed with decreased signal intensities. Enlargement of the third ventricles and hypertrophy of cranical parietal bones were also recognized in sagittal MR images of aged rats. These observations were more marked in males than in females. From these observations it was concluded that this probe was applicable for MR imaging of rat brains under a magnetic field of 7.05 T.

Aging↗