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M Okamoto

Publications and source records attributed to M Okamoto.

At least 685 records · Page 38Linked to original sources
PubMed1992

[Nicotine-induced ambulatory stimulant effect and its reverse tolerance].

Nicotine-induced ambulatory stimulant effect and its reverse tolerance produced by daily administration of nicotine in rats were investigated. Nicotine (0.5 and 1.0 mg/kg, sc) increased the ambulatory activity, which was enhanced by the daily administration of nicotine. Although total ambulatory activity and drinking behavior during 20 h (from 13:00 to 9:00) following daily administration of nicotine (1.0 mg/kg, sc) for 7 successive days decreased, these behaviors returned to the control levels after the nicotine-treatment period. Moreover the periods (tau s) of the ambulatory activity and drinking were not changed by daily injections of nicotine (1.0 mg/kg, sc) for 6 successive days. The enhancement of the ambulatory stimulant effect produced by daily injections of nicotine (0.5 mg/kg) was antagonized by mecamylamine (0.2 mg/kg) and haloperidol (0.05, 0.1 and 0.2 mg/kg), which were subcutaneously administered at 20 min before injections of nicotine. These results suggest that the enhancement of nicotine-induced ambulatory stimulant effect by the daily administration of nicotine is concerned with central dopaminergic stimulation through the nicotinic acetylcholine receptor in the rat brain.

Animals↗
PubMed1992

[A case of renal cell carcinoma in childhood].

We report a case of renal cell carcinoma in a 6-year-old girl. The child had the chief complaints of gross hematuria and abdominal pain. An examination using ultrasound, computerized tomography scans and angiography showed a left renal tumor. Left side radical nephrectomy with lymphadenectomy was performed. Histopathological examination revealed renal cell carcinoma of clear cell type with metastasis to the hilar lymph node. She received postoperative therapy with interferon. Now, 3 years since the operation, she is living without evident recurrence. We reviewed 89 Japanese cases of renal cell carcinoma in children including this case and have discussed symptoms, differential diagnosis and treatments.

Carcinoma, Renal Cell↗
PubMed1992

[Inhibition of Cls activity by methylprednisolone].

From a clinical study it was found that serum ClINH activity increased 6 hours after methylprednisolone (MP) pulse therapy in all the patients we studied with connective tissue diseases. Furthermore plasma ClINH-Cls complex decreased after pulse therapy. These phenomena lead us to investigate the effect of MP on Cls. 1) When a constant amount of Cls (8 micrograms/ml) was incubated with several concentrations of MP (2-50 mg/ml), the Cls activity of consuming C4 hemolysis was inhibited by MP in a dose-dependent manner. 2) MP inhibited consumption of C2 as well as C4 by Cls in a dose-dependent manner, even when MP had been removed by dialysis following incubation with Cls. These experimental data suggested that the trace amounts of Cls generated by immune complexes could be inhibited by long circulation of MP even at low concentrations in vivo, and resulted in a decrease of ClINH consumption and ClINH-Cls complex formation. These results indicated that the inhibition of Cls activity is one of the most important mechanisms in the process of the anti-inflammatory effect of MP in vivo.

Complement C1 Inactivator Proteins↗
PubMed1992

[Complement system in status asthmatics--analysis of anti-complementary effects induced by methylprendisolone].

Complement system was investigated in 7 patients with status asthmatics treated with large doses of methylprednisolone (MPS). Complement hemolytic activities, complement protein profile, complement fragments and circulating immune complexes were measured before, 3 and 8 hours after and 14 days after MPS administration. MPS normalized C4 and C1INH activities 6 hours after administration. MPS also decreased ACH50 6 hours after administration and D activity 3 and 6 hours after, but these activities recovered to their previous normal range within 14 days. P and H were decreased at each measurement time, and C1s was transiently decreased 6 hours after MPS administration. Complement fragment iC3b was increased at each measurement time, but fragment Bb tended to be decreased 14 days after MPS administration. The increment of anaphylatoxin C3a recovered to normal 14 days after MPS administration. In vitro experiments, MPS inhibited D and C1s activation directly, and decreased the decay of B and C4. Inhibition of C1s might also increase C1INH activity clinically. These results clarified that the alternative complement pathway was activated, and suggested that the C1 bypass pathway might be also activated in status asthmatics. It was further considered that these anti-complementary effects induced by MPS, brought about an improvement in asthmatic symptoms. Studies to identify the complement activators continued, and circulating immune complexes may possibly be one of those agents activating complement cascade.

Adult↗
PubMed1992

Left main coronary trunk compression by dilated main pulmonary artery in atrial septal defect. Report of three cases.

Narrowing of the left main coronary trunk, which was compressed by the dilated pulmonary artery, was associated with atrial septal defect in three adults. One of them had severe pulmonary hypertension. Coronary angiograms revealed localized narrowing of the left main coronary trunk, and the left main coronary trunk had a concave shape. No stenosis of other coronary arteries was observed. In all patients the atrial septal defect was closed with a polytetrafluoroethylene patch. In the patient with 75% narrowing of the left main coronary trunk, aorta-coronary bypass was performed; it was not performed in the two with 50% narrowing. In two survivors postoperative coronary angiograms showed that the narrowing of the left main coronary trunk improved or disappeared. These results suggest that markedly dilated pulmonary arteries easily compress the left main coronary trunk and cause narrowing, which improves after atrial septal defect closure.

Constriction, Pathologic↗
PubMed1992

[Rearrangement of immunoglobulin light chain and heavy chain constant region genes in multiple myeloma].

We analysed immunoglobulin (Ig) gene rearrangements in 28 patients with multiple myeloma by Southern hybridization method. We used 5 probes which cover C kappa and kappa de loci of Ig light chain kappa gene, and JH, 5'S mu and S gamma 3 loci of Ig heavy chain gene. In 11 out of 12 patients with kappa-producing myeloma, DNA rearrangements were observed using C kappa probe. Among them, kappa de region was rearranged in 7 patients and kept germline configuration in 4 patients. In all of 14 patients with lambda-producing myeloma, C kappa region was deleted and kappa de region was rearranged. 5'S mu-probe was very useful for detecting class switch recombination, and furthermore by using S gamma-probe together, S mu-S gamma joining could be detected. In all of 10 patients with gamma-producing myeloma, 5'S mu and S gamma-probes detected the rearranged band of the same size on at least 1 allele, which suggested the presence of S mu-S gamma joinings. In 8 of 10 patients with Bence-Jones myeloma, 5'S mu-probe detected rearranged bands and the presence of class switch recombinations were suggested as observed in other Ig secretory myelomas. In other 2 patients with Bence-Jones myeloma, non-functional class switch recombinations were detected. The results of this study indicated that genotypes corresponded well to phenotypes in multiple myeloma, and further analysis in other types of B cell malignancies will be interesting.

Gene Rearrangement, B-Lymphocyte, Heavy Chain↗
PubMed1992

[Pharmacokinetic studies of dFdC (2',2'-difluorodeoxycytidine), ara-C and BH-AC (N4-behenoyl ara-C) in experimental animals].

dFdC (2',2'-difluorodeoxycytidine; LY 188011), a new analogue of ara-C, which contains fluorines in the sugar moiety, has shown a wider antitumor spectrum and has effective to solid tumors, as compared with ara-C. The pharmacokinetic behavior of dFdC was compared with that of sera-C or BH-AC (N4-behenoyl ara-C) using experimental animals. The results were as follows. 1. Plasma levels (rabbits): The half-lives of dFdC were longer than those of ara-C. The peak level of ara-C, which derived from BH-AC, was not so high but continued for relatively a long time. 2. Tissue levels (S.180 tumor bearing mice): dFdC levels were high in the spleen and thymus, tumor, testis and muscle, and persisted longer than ara-C. The levels of ara-C derived from BH-AC were low, but persisted for a long time. 3. Inactivation: The grade of inactivation of dFdC to dFdU was observed as same as that of ara-C to ara-U. dFdC was rapidly phosphorylated to dFdCTP in tumor cells, and dFdCTP accumulated higher, when compared with ara-CTP. Clinically, the determinations of unchanged drug levels in the plasma, and the dFdCTP, ara-CTP and dCTP levels in tumor tissue seemed to be important.

Animals↗
PubMed1992

[A case of infected caliceal diverticulum].

A 60-year-old woman was admitted to our clinic with the chief complaint of high fever. Antibiotic therapy had produced no improvement in another hospital and she was referred to our hospital for further examination and treatment. Intravenous pyelography showed left non visualized kidney and a stone shadow in left ureter. Computed tomography showed a cystic lesion, 9 x 9 x 8 cm, in the upper pole of the left kidney. We punctured and drained 400 cc of turbid yellowish fluid by a transcutaneous route. The nephrostogram clearly showed a communication with infundibulum. A diagnosis of infected caliceal diverticulum was made. Further examination demonstrated no function of left kidney and we performed nephrectomy. She has reported no symptoms for 6 months after the operation.

Diverticulum↗
PubMed1992

[A case of infective endocarditis of the tricuspid valve repaired by vegetectomy and annuloplasty].

A successful repair of infective endocarditis of the tricuspid valve in a drug abuser is reported. A 25-year-old woman with a history of drug addiction was referred to our hospital complaining of high fever despite antibiotic therapy. Blood cultures showed staphylococcal septicemia, and echocardiography revealed large vegetations attached to the tricuspid annulus and massive regurgitation of the tricuspid valve. Blood studies showed renal failure and hematological abnormalities due to septicemia and right ventricular failure. Excision of the vegetation and the posterior leaflet was performed along with annuloplasty (Kay's procedure). The patient's postoperative course was uneventful and subsequent echocardiographic examination disclosed no evidence of recurrence, and insignificant tricuspid valvular regurgitation. Local excision of vegetation and leaflet repair by annuloplasty may be performed in cases with well-circumscribed vegetation and minor leaflet damage.

Adult↗
PubMed1991

Functional expression of the cDNAs encoding rat 11 beta-hydroxylase [cytochrome P450(11 beta)] and aldosterone synthase [cytochrome P450(11 beta, aldo)].

Expression plasmids containing two cDNAs of a rat cytochrome P450(11 beta) family, pcP450(11 beta)-62 [Nonaka, Y., Matsukawa, N., Morohashi, K., Omura, T., Ogihara, T., Teraoka, H. & Okamoto, M. (1989) FEBS Lett. 255, 21-26] and pcP450(11 beta, aldo)-46 [Matsukawa, N., Nonaka, Y., Ying, Z., Higaki, J., Ogihara, T. & Okamoto, M. (1990) Biochem. Biophys. Res. Commun. 169, 245-252], were constructed and introduced into COS-7 cells by electroporation. Enzymatic activities of the expressed cytochromes P450(11 beta) and P450(11 beta, aldo) were determined by using 11-deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone, 18-hydroxycorticosterone, or 19-hydroxy-11-deoxycorticosterone as a substrate. Cytochrome P450(11 beta) catalyzed 11 beta-, 18- and 19-hydroxylations of 11-deoxycorticosterone and 19-oxidation or 19-hydroxy-11-deoxycorticosterone at substantial rates, 18-hydroxylation of corticosterone at a very low rate, but no aldosterone production. Cytochrome P450(11 beta, aldo) catalyzed 11 beta- and 18-hydroxylations of 11-deoxycorticosterone, 18-hydroxylation of corticosterone and aldosterone production from 11-deoxycorticosterone or corticosterone. But neither 19-hydroxylation of 11-deoxycorticosterone nor 19-oxidation of 19-hydroxy-11-deoxycorticosterone was catalyzed by cytochrome P450(11 beta, aldo).

Adrenodoxin↗
PubMed1991

Purification and characterization of three forms of differently glycosylated recombinant human granulocyte-macrophage colony-stimulating factor.

We have purified recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF) produced in human lymphoblastoid Namalwa cells. From the results of tunicamycin treatment and N-glycosidase F digestion, it was demonstrated that Namalwa-derived hGM-CSF was highly glycosylated at two potential N-glycosylation sites and several O-glycosylation sites as previously shown for naturally occurring hGM-CSF. We classified the hGM-CSF molecules into three groups according to the molecular weight corresponding to the degree of N-glycosylation: the molecules with two N-glycosylation sites occupied (designated 2N), the molecules with either site glycosylated (1N), and the molecules lacking N-glycosylation (0N). Despite such varied degrees of N-glycosylation, almost all molecules were O-glycosylated. To investigate the role of carbohydrate moieties of hGM-CSF, we isolated each form of hGM-CSF and examined its biological properties. The 2N-type showed 200-fold less in vitro specific activity compared with unglycosylated Escherichia coli-derived hGM-CSF, although the activity of the 0N-type was equivalent to that of the E. coli-derived material. The 1N-type showed an intermediate level of activity. However, in terms of clearance from blood circulation in the rat, the 2N-type showed a half-life five times longer than that of the 0N-type and E. coli-derived hGM-CSF. From these findings, we concluded that N-linked carbohydrate moieties of hGM-CSF play conflicting physiological roles in the efficacy of the protein in vivo but that O-linked carbohydrate moieties do not have such effects.

Animals↗
PubMed1991

Preferential distribution of group-II-like phospholipase A2 in mononuclear phagocytic cells in rat spleen and liver.

The localization of calcium-dependent phospholipase A2, (PLA2) immunochemically closely related to the enzyme of the viperid and crotalid type (group II), in cells isolated from rat spleen and liver was examined using a polyclonal antibody directed against rat spleen group II, PLA2 (PLA2M). In isolated spleen cells, the monocyte/macrophage fraction had the highest PLA2 activity (1.28 +/- 0.35.min-1.10(6) cells-1) which was almost completely inhibited by the anti-PLA2M antibody. An immunoblot analysis confirmed the presence of the enzyme in this fraction. An immunocytochemical study revealed that the PLA2 was present in spleen macrophages. In the isolated liver cells, Kupffer cells (0.92 +/- 0.22 nmol.min-1.10(6) cells-1) contained higher anti-PLA2M-antibody-inhibitable PLA2 activity than parenchymal cells (0.26 +/- 0.06.min-1.10(6) cells-1). The immunocytochemical study showed that cells immunopositive with anti PLA2M antibody were Kupffer cells. These results suggest that the mononuclear phagocytic cells in rat spleen and liver have relatively high activity of group-II-like PLA2. Subcellular distribution patterns of the anti-PLA2M-antibody-inhibitable phospholipase A2 activity in different cell populations from spleen and liver were compared. A mode of the distribution of the enzyme in the spleen macrophages was essentially similar to that in the spleen lymphocytes. The distribution in Kupffer cells was similar to that in parenchymal cells.

Animals↗
PubMed1991

Induction of group II-like phospholipase A2 by lipopolysaccharide in the liver of BCG-primed rat.

The specific activity of phospholipase A2 (PLA2) in the liver homogenate was elevated 1.7-fold in bacillus Calmette-Guerin (BCG)-treated rats, 1.6-fold in lipopolysaccharide (LPS)-treated rats, and 2.4-fold in BCG-infected rats treated with LPS, compared with that of control rats. These increased activities were almost completely inhibited by the antibody directed against rat splenic group II PLA2 (PLA2M) but not by anti-pancreatic PLA2 antibody. The results of immunoblot analysis confirmed that the PLA2 immunochemically related to the group II enzyme was induced by treatment with BCG and/or LPS. The anti-PLA2M antibody-inhibitable PLA2 activity per a single cell was elevated not only in nonparenchymal cell fraction but also in hepatocyte fraction, as in the case of whole liver. On the contrary, the PLA2 concentration and its specific activity did not change by the same treatment both in spleen homogenate and in isolated spleen cell fractions although a 3-fold increase in spleen mass occurred by BCG treatment. These results suggested that a tissue-specific mechanism of the PLA2 induction by these inflammatory mediators may operate in liver.

Animals↗
PubMed1991

Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin.

During B cell differentiation, at least three stages can be defined in terms of their growth signal requirement by using two different growth signals, which are recombinant interleukin 7 (IL-7) and a stromal cell clone PA6 which does not produce IL-7; first a PA6 dependent stage, second a PA6 + IL-7 dependent stage and third an IL-7 dependent stage. In order to test the possibility that this differentiation of growth signal requirement is controlled by the expression of functional immunoglobulin molecules, we have investigated the frequencies of PA6 + IL-7 dependent and IL-7 dependent cells which are present in the bone marrow of either mu-chain or kappa-chain gene transgenic mice. In a mu-chain gene transgenic mouse, the frequency of PA6 + IL-7 dependent cells is selectively reduced, while that of IL-7 dependent cells is selectively reduced in a kappa-chain gene transgenic mouse. This result suggests that expression of a functional mu-chain gene drives PA6 + IL-7 dependent cells to differentiate into the subsequent IL-7 dependent stage. Likewise, when mu-chain positive IL-7 dependent cells express a functional light-chain gene, their growth signal requirement changes into an IL-7 unreactive stage.

Animals↗
PubMed1991

Effects of volume loading on left atrial systolic time intervals.

The effects of volume loading on the left atrial preejection period (LAPEP) and left atrial ejection time (LAET) were examined in 24 patients with various heart diseases using pulsed Doppler echocardiography. In response to volume loading, the left atrial dimension before atrial contraction significantly increased from 30.6 mm +/- 5.8 mm to 32.4 mm +/- 5.4 mm and the change in the left atrial dimension during atrial contraction tended to increase. The peak velocity in the atrial contraction phase significantly increased from 58 cm/s +/- 14 cm/s to 63 cm/s +/- 13 cm/s, and the integral of the atrial contraction phase tended to increase. LAPEP significantly decreased from 114 ms +/- 16 ms to 104 ms +/- 14 ms and LAET significantly decreased from 128 ms +/- 15 ms to 124 +/- 12 ms. The relation between LAET and left ventricular end-diastolic pressure, and that between LAPEP and mean pulmonary capillary wedge pressure, shifted downward to the right after volume loading. Thus, left atrial ejection is augmented by volume loading according to the Frank-Starling mechanism, while LAPEP decreases due to an increase in preload and LAET decreases due to an increase in afterload.

Atrial Function, Left↗
PubMed1991

Localization of the gene transcripts of 11 beta-hydroxylase and aldosterone synthase in the rat adrenal cortex by in situ hybridization.

Using in situ hybridization, localization of the gene transcripts of 11 beta-hydroxylase and aldosterone synthase was investigated in order to clarify the sites for the synthesis of corticosterone (glucocorticoid) and aldosterone (mineralocorticoid) in the rat adrenal cortex. The gene transcript of 11 beta-hydroxylase was localized in all the endocrine cells of the entire adrenal cortex, while that of aldosterone synthase was exclusively confined in zona glomerulosa cells. These results represent that every endocrine cell of all the cortical zones synthesizes 11 beta-hydroxylase which converts 11-deoxycorticosterone to corticosterone, and only glomerulosa cells synthesize aldosterone synthase which produces aldosterone from corticosterone. Thus it is clearly shown that zona glomerulosa cells synthesize mineralocorticoid, while zona fasciculata as well as reticularis cells produce glucocorticoid.

Adrenal Cortex↗
PubMed1991

PAF inhibitory activity of diketopiperazines: structure-activity relationships.

FR900452, a natural product isolated from the culture broth of Streptomyces phaeofaciens No. 7739, was found to inhibit PAF-induced rabbit platelet aggregation with an IC50 of 3.7 x 10(-7)M. FR900452, 1-methyl-3-[1-[5- methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-yli- dene)-2-piperazinyl]ethyl]-2-indoline, has an oxocylopentylidene group incorporated as a vinylogous amide in a diketopiperazine skeleton. This unique structure led us to synthesize diketopiperazine derivatives, 3-arylalkyl- 6-substituted-piperazine-2,5-diones. Their observed PAF inhibitory activity suggest that the D-D configuration of diketopiperazine is an important factor for anti-PAF activity and that the hydrophobic aromatic portion may play a specific role in the binding of the diketopiperazine to the PAF receptor.

Animals↗