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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 577 records · Page 32Linked to original sources
PubMed1993

Different effects of various hematopoietic growth factors on myelomonocytic cell line (KY-821) and its drug-resistant sublines.

Human myelomonocytic leukemic cell line, designated as KY-821, and its sublines KY-Ra, KY-VCR, and KY-MTX, which were resistant to cytosine arabinoside, vincristine, and methotrexate, respectively, were compared for response to various hematopoietic growth factors. Cells of KY-Ra and KY-VCR proliferated in response to natural interleukin-1 (nIL-1), whereas the proliferation of KY-821 and KY-MTX was inhibited. Unexpectedly, recombinant IL-1 alpha and IL-1 beta had no effect on the proliferation of each cell line. The effect of nIL-1 was partially deleted by an addition of optimal anti-IL-1. Supernatants of each cell line had no IL-1 activity. Interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) also had an inhibitory effect for KY-821 and KY-MTX, but lacked such effect in KY-RA and KY-VCR. nIL-1, IFN gamma and TNF alpha could not differentiate between any of the cell lines but IFN gamma and TNF alpha induced monocytic surface antigens. In addition, there was no difference in the number of IL-1 and TNF alpha receptors in each cell line. These results indicate that there is a difference in biological effects between nIL-1 and recombinant IL-1 species and acquirement of resistance for some types of drugs may associate closely with different responses to hematopoietic growth factors, probably through altered postmembranous transduction.

Animals↗
PubMed1993

Induction of surface antigen recognized by new monoclonal antibody, YU311, on 1-beta-D-arabinofuranosylcytosine-resistant human leukemic cell line.

A new monoclonal antibody, YU311, against an antigen expressed on 1-beta-D-arabinofuranosylcytosine(ara-C)-resistant human leukemic cell line with decreased deoxycytidine kinase activity was generated. YU311 reacted with ara-C-resistant human leukemic cell line (KY-Ra), but not with its parental cell line (KY-821) which was sensitive to ara-C. YU311 recognized the 92-kDa membrane protein. Furthermore, YU311 inhibited the growth of KY-Ra in suspension medium with and without ara-C. In immunocytochemistry, there was no difference in expression of usual differentiation antigens between KY-Ra and KY-821. These findings indicate that antigenic change could occur in ara-C-resistant human leukemic cells with stable expression of differentiation antigens and that the 92-kDa membrane protein may be one of the membrane proteins which regulate cell growth of KY-Ra.

Animals↗
PubMed1993

Persistent degenerative state of non-pyramidal neurons in the CA1 region of the gerbil hippocampus following transient forebrain ischemia.

Morphological changes in the neurons of the gerbil hippocampus following 5 min of forebrain ischemia were examined using light and electron microscopy. Although non-pyramidal neurons in the CA1 region of the hippocampus survived through the full length of the observation period, up to six weeks after ischemia, they consistently demonstrated degenerative changes distinct from those of the well-known "delayed neuronal death" of CA1 pyramidal cells. When examined with the light microscope, CA1 non-pyramidal neurons were found to be shrunken and their nuclei and cytoplasm were hyperchromatic between seven days and six weeks after ischemia. When examined with the electron microscope, postischemic non-pyramidal neurons were found to have markedly electron-dense profiles; their cytoplasm contained numerous free ribosomes and heterogeneous smaller granular substances, the latter also filling the nuclei. However, there was no loss of ribosomes from the rough endoplasmic reticulum, and mitochondrial cristae were preserved, suggesting that these neurons were viable. CA1 non-pyramidal neurons were studied immunohistochemically using three types of monoclonal antibodies, one each against parvalbumin, a nonphosphorylated epitope on the 168,000 mol. wt and 200,000 mol. wt subunits of neurofilament proteins, and microtubule-associated protein 2. CA1 non-pyramidal neurons lost immunoreactivity to these neuron-specific substances six weeks after ischemia, suggesting that these degenerating cells lacked certain types of normal neuronal activity. We conclude that non-pyramidal neurons in the hippocampal CA1 region survive transient ischemia but undergo degenerative changes following complete loss of CA1 pyramidal cells. These changes may be due to depletion of presumptive target-derived trophic factors within the non-pyramidal neurons.

Animals↗
PubMed1993

Primary collision neoplasm of malignant melanoma and adenocarcinoma in the lung. A case report.

We report an extremely rare case of a primary collision neoplasm in the lung consisting of malignant melanoma and adenocarcinoma. A malignant melanoma was histologically diagnosed by a transbronchial lung biopsy of the lung nodule in a 61-year-old woman, in whom there was no demonstrable primary malignant melanoma found elsewhere. However, at autopsy the above two components of the pulmonary tumor were both histologically and immunohistochemically confirmed. There was little intermingling of the two tumors. The malignant melanoma was positive for monoclonal antibody specific for melanotic tumor (HMB45) and S-100 protein but was negative for epithelial membrane antigen (EMA), while it was the opposite in the adenocarcinoma. This case is, to our knowledge, the first reported collision tumor of the above two components.

Adenocarcinoma↗
PubMed1993

Replacement of Thr-303 of P450 2E1 with serine modifies the regioselectivity of its fatty acid hydroxylase activity.

Threonine-303 of rabbit P450 2E1, which is putatively located at the distal heme surface, was replaced by serine and valine via site-directed mutagenesis. In the oxidized state, the Ser-mutated P450 exhibited a low- and high-spin mixed-type (low > high) absorption spectrum, whereas the Val-mutated P450, like the wild-type P450, exhibited a nearly high-spin type spectrum. The reduced CO complexes of the Ser- and Val-mutated P450s, as well as that of the wild-type P450, showed a Soret absorption maximum at 452 nm. Both mutated P450s were active in the hydroxylation of C10 to C18 fatty acids at somewhat lower rates than the wild-type P450. The Val-mutated P450 gave the same two products (the major one is probably the omega-1 hydroxy analog) as the wild-type P450, while additional products were formed on incubation with C11 to C17 fatty acids as substrates of the Ser-mutated P450; a total of four products was detected for each of the C12 to C15 fatty acids, and three for each of the C11, C16, and C17 homologues. The metabolites of laurate were determined by GC-MS analysis to be the omega-1, omega-2, omega-3, and omega-4 hydroxy counterparts. The Ser-mutated P450 hydroxylated drug substrates at almost the same rates as the wild-type P450, while the mutation to valine significantly lowered the drug hydroxylase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Importance of successive prolines in the carboxy-terminal region of P450 2C2 and P450 2C14 for the hydroxylase activities.

Proline-480 and proline-481 are highly conserved in the P450 2 family. When these successive prolines of P450 2C2 were replaced by Ala-Thr, its activities of laurate (omega-1)-hydroxylation and benzphetamine N-demethylation were lost. On the other hand, the mutated P450 which retained one of the proline residues was 60-100% active in the (omega-1)-hydroxylation and 100-120% active in the N-demethylation. Pro-Pro (480, 481) to Ala-Thr mutated P450 2C14 was also inactive in testosterone 16 alpha-hydroxylation and benzphetamine N-demethylation, the activities of the wild-type P450 2C14. In the carboxyterminal region of the P450 2C subfamily, the sequence of P450 2C2 from residues 469-473 is noticeably different from those of the other members of this subfamily. The Ser-473 to Val mutation of P450 2C2 caused a decrease in the (omega-1)-hydroxylase activity to one-fifth but the N-demethylase activity was not much affected. When the sequence of P450 2C2 from residues 469-473 was replaced by that of P450 2C14 (mutation at four residues), the 16 alpha-hydroxylase and N-demethylase activities were increased by seven- and three-fold, respectively, and the (omega-1)-hydroxylase activity was decreased to one-third. The mutated P450 2C2, in which the carboxy-terminal four residue sequence or the proline cluster adjacent to the amino-terminal membrane-anchor signal sequences was deleted, was not accumulated in yeast cells transformed with plasmids directing the synthesis of such P450s.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Structural requirements for the induction of hepatic microsomal cytochrome P450 by imidazole- and pyridine-containing compounds in rats.

We investigated the structural requirements for the induction of hepatic microsomal cytochrome P450 2B1/2 (P450 2B1/2) and cytochrome P450 1A1/2 (P450 1A1/2) by imidazole- and pyridine-containing compounds in rats. Clotrimazole, an azole antifungal drug, and 1-diphenylmethylimidazole preferentially induced P450 2B1/2 in a dose-dependent manner, and slightly induced P450 1A1/2. 1-Benzylimidazole preferentially induced P450 1A1/2. 1-Phenylimidazole, which lacks the methylene bridge of 1-benzylimidazole, only induced P450 1A1/2. In turn, loss of aromaticity of the N-substituted moiety of imidazole, as in 1-cyclohexylmethylimidazole and 1-tert-butylimidazole, resulted in a preferential induction of P450 2B1/2. Likewise, various pyridine-containing compounds showed structure-dependent induction of P450 species. Namely, 4-diphenylmethylpyridine induced P450 2B1/2. 4-Benzylpyridine induced both P450 2B1/2 and P450 1A1/2. 4-Cyclohexylmethylpyridine and 4-tert-butylpyridine predominantly induced P450 2B1/2. 4-Phenylpyridine preferentially induced P450 1A1/2 rather than P450 2B1/2. Oxygenation products at the methylene bridge, 4-benzoylpyridine and phenyl-4-pyridylmethanol, could not induce P450 1A1/2. In turn, 2,4'-dipyridyl induced both P450 2B1/2 and P450 1A1/2, but not 2,2'-dipyridyl. 4,4'-Trimethylenedipyridine preferentially induced P450 1A1/2 at very low doses. These findings indicate that imidazole- and pyridine-containing compounds having lipophilic groups are inducers of hepatic P450, and that such compounds having aromatic groups and taking coplanar conformational structures are potent inducers of P450 1A1/2.

2,2'-Dipyridyl↗
PubMed1993

Role of leukotrienes in indomethacin-induced mucosal damage in rats.

The role of leukotriene (LT) in the pathogenesis of indomethacin-induced gastric mucosal damage was investigated in rats. After administration of indomethacin, LTB4 and sulfidopeptide LT (SPLT) content in gastric mucosa were assessed by radioimmunoassay and mucosal blood flow was measured by laser-Doppler flowmetry. Indomethacin (20 mg/kg) caused visible gastric mucosal damage. Indomethacin at this dose caused marked reduction of gastric mucosal blood flow but did not affect gastric mucosal content of LTB4 and SPLT. AA-861, a selective 5-lipoxygenase, and DS-4575 and YM-683, two different SPLT receptor antagonists, inhibited both mucosal damage and reduction of mucosal blood flow. These results suggested that endogenous LT, especially SPLT, may be involved in the indomethacin-induced mucosal damage via the reduction of gastric mucosal blood flow.

Animals↗
PubMed1993

Immunohistochemistry of neuronal inclusions in the cerebral cortex and brain-stem in Lewy body disease.

Three cases of Lewy body disease were investigated in order to compare the morphological and immunohistochemical characteristics of the neuronal inclusions in the cerebral cortex (CC) and brain-stem (BS). Ultrastructurally, the CC contained intermediate-sized filaments with variable amounts of granular material and other organelles, whereas the BS consisted of an electron-dense core and an outer area with radially oriented filaments. The cerebral cortex was immuno-reactive with antibodies against tyrosine hydroxylase (TH) and tau protein, and differed from BS. In addition, although the CC were antigenically similar to BS in their neurofilament (70, 160 and 200 kDa) and ubiquitin contents, the localization of neurofilament immunoreactivity differed between them, being confined positively to the core of CC, but to the periphery of the BS. Although Lewy bodies (LB) in idiopathic Parkinson's disease are morphologically similar to BS, they have been reported to differ in their immunoreactivity with antibodies against tau. It has been reported that CC differ from LB with regard to immunoreactivity with antibodies against TH and tropomyosin. It is inferred that these inclusions (CC, BS and LB) differ in morphogenesis.

Aged↗
PubMed1993

Small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features of the thoracic wall: a case report with histological, immunohistochemical and ultrastructural examinations.

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.

Adult↗
PubMed1993

GM-CSF and eosinophil chemotactic factors in an acute lymphoblastic leukemia patient with eosinophilia.

We describe a patient with common acute lymphoblastic leukemia associated with blood and cerebrospinal fluid (CSF) eosinophilia. Serum obtained at onset and conditioned medium prepared from T cells obtained at remission stimulated with interleukin-2 contained eosinophil colony stimulating activity (Eo-CSA), which was confirmed to be predominantly GM-CSF. Leukemic cell conditioned medium and serum obtained at remission contained no Eo-CSA. The CSF contained increased eosinophil chemotactic activity, however, this factor was not identified.

Adult↗
PubMed1993

Syntheses and biological activities of optical isomers of 3-chloro-5-[3-(2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2-a]pyridine- 3-spiro-4'-piperidino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine (mosapramine) dihydrochloride.

Mosapramine (1) is a new neuroleptic drug with an asymmetric carbon atom (8a) in its imidazopyridine ring. The enantiomers of this agent were synthesized to compare their biological activities, such as antiapomorphine activity, affinity for dopamine D2 receptor and acute toxicity. The key intermediates, (R)-(-)- and (S)-(+)-2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2-a]pyridine- 3-spiro-4'-piperidines, were prepared by optical resolution of the corresponding (+/-)-compound and were treated with 3-chloro-5-(3-methanesulfonyloxypropyl)-10,11-dihydro-5H-dibenz[b, f]azepine to afford (R)-(-)-1 and (S)-(+)-1, respectively. There were few differences in the examined biological activities of the two enantiomers as their dihydrochlorides.

Animals↗
PubMed1993

NC-1300, a proton-pump inhibitor, requires gastric acid to exert cytoprotection in rat gastric mucosa.

Effect of gastric acid suppression on the cytoprotective effect of a single dose of NC-1300 given intragastrically was studied. NC-1300 given intragastrically prevented gastric mucosal damage caused by absolute ethanol in rats in a dose-related manner, while the drug given subcutaneously did not. Pretreatment with NC-1300 given subcutaneously to suppress acid secretion abolished the protective effect of NC-1300 given intragastrically, but not in the presence of 0.1 N HCl. Repeated intragastric administration of NC-1300 for 7 days failed to prevent the ethanol damage. These results suggest that NC-1300 requires gastric acid to exert a protective effect against ethanol in rat gastric mucosa.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

The effects of orally administered Y-25130, a selective serotonin3-receptor antagonist, on chemotherapeutic agent-induced emesis.

The antiemetic effects of orally administered Y-25130, a potent and selective 5-HT3-receptor antagonist, were compared with those of ondansetron, granisetron, metoclopramide and domperidone. Y-25130 (0.1-1.0 mg/kg) dose-dependently prolonged the latency to the first vomiting and decreased the number of vomitings induced by cisplatin in dogs. The antiemetic effect of Y-25130 against cisplatin-induced vomiting was more potent than that of metoclopramide and ondansetron, but it showed little difference from that of granisetron. The emesis induced by the combined treatment of doxorubicin and cyclophosphamide was also inhibited by Y-25130 (0.1-1 mg/kg) in ferrets. The antiemetic effect of Y-25130 was more potent than that of metoclopramide, almost the same as that of granisetron and less potent than that of ondansetron. Because of a notable difference of potency ranking between Y-25130 and ondansetron in these two tests, a third test was performed to evaluate the inhibitory effect of Y-25130 in ferrets on cisplatin-induced emesis in comparison with that of ondansetron. The antiemetic effect of Y-25130 on cisplatin-induced emesis in ferrets was very similar to that of ondansetron. Domperidone did not inhibit these cytotoxic agents-induced emeses. These results suggest that Y-25130 is an orally active antiemetic compound against cisplatin and doxorubicin/cyclophosphamide-induced emeses; and its the antiemetic potency is similar to those of granisetron and ondansetron, but superior to those of metoclopramide and domperidone.

Administration, Oral↗
PubMed1993

Stimulation of mitogenesis in human thyroid epithelial cells by endothelin.

We investigated whether a potent vasoconstrictor, endothelin, stimulated the proliferation of human thyroid epithelial cells (thyrocytes). [3H]-thymidine incorporation into normal thyrocytes and thyrocytes from patients with Graves' disease was significantly increased at 10(-9) mol/l endothelin, reaching a plateau at 10(-8) mol/l. The proliferative responses of the thyrocytes obtained from patients with Graves' disease were similar to those of normal thyrocytes. Furthermore, the cell number of thyrocytes stimulated by endothelin was increased as compared with that of unstimulated thyrocytes. Neither indomethacin nor heparin affected this endothelin-stimulated thyrocyte proliferation. When thyrocytes were cultured with both endothelin and recombinant interleukin 1 beta, there was an additive effect on thyrocyte proliferation. The Ca2+ entry blocker, verapamil, inhibited both the proliferative responses of thyrocytes to endothelin and the additive effect of endothelin and recombinant interleukin 1 beta on thyrocyte proliferation. These results suggest that endothelin functions as a growth-promoting factor for human thyrocytes, presumably through intracellular calcium influx.

Calcium↗
PubMed1993

Immune complex type crescentic glomerulonephritis accompanied with perinuclear anti-neutrophil cytoplasmic antibodies.

A 70-year-old male developed rapidly progressive glomerulonephritis syndrome with serum perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). A renal biopsy showed diffuse crescentic glomerulonephritis. Immunofluorescence microscopy revealed 2+ granular staining of IgG over the mesangial area and along glomerular capillary walls. Electron microscopy showed scattered deposits in the paramesangial area. These morphologic findings were consistent with those of immune complex type crescentic glomerulonephritis (IC-CGN). Serum C3, C4, and CH50 were within normal limits, and circulating immune complexes were not detected by C1q-binding assay, but both P-ANCA and anti-myeloperoxidase antibodies were positive. A possible relation of P-ANCA to IC-CGN is discussed.

Aged↗
PubMed1993

Rheumatoid arthritis in a patient with pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a rare, inherited disorder of the connective tissue. Possible association of autoimmune thyroiditis and PXE has been suggested, but reports of other autoimmune diseases complicating PXE are rare. We report a case of rheumatoid arthritis (RA) in a patient with PXE. Since the frequency of PXE is likely to be underdiagnosed, further studies to elucidate the true incidence and significance of the association of RA and PXE will be needed.

Adult↗