[Structure of esophageal Auerbach's plexus and distribution of nitric oxide neurons in guinea pigs].
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Animals↗
Biomedical subjects
T Morikawa
Publications and source records attributed to T Morikawa.
Enzymic O-sulfation of tyrosine residues in hirudins by sulfotransferase from Eubacterium A-44.
The enzymic O-sulfation of Tyr residues in a recombinant hirudin variant-1 (rHV-1) and its analog in which Glu61 and Glu62 were replaced by Tyr, [E61Y, E62Y]rHV-1, was carried out by use of sulfotransferase isolated from an anaerobic bacterium from the human intestine, Eubacterium A-44. Although rHV-1 was not sulfated by this enzyme, the sulfation of [E61Y, E62Y]rHV-1 was observed, and three kinds of sulfated analog, whose C-terminal six amino acid residues were -PYY(SO3H)YLQ, -PYYY(SO3H)LQ, and -PYY(SO3H)Y(SO3H)LQ, were obtained. Among the sulfated hirudin analogs tested here, the Tyr62 and Tyr63 bisulfated [E61Y, E62Y]rHV-1 showed the strongest thrombin inhibition with the inhibition constant (Ki) of 0.0430 pM, followed by the Tyr63 monosulfated analog (Ki = 0.0593 pM) and the Tyr62 monosulfated one (Ki = 0.158 pM). The Tyr63 monosulfated analog and Tyr62 and Tyr63 bisulfated one were more potent inhibitors of thrombin than unsulfated rHV-1. The increase in affinity caused by sulfation was predominantly due to an increase in the association-rate constant.
Amino Acid Sequence↗
Inhibition of matrix metalloproteinases by peptidyl hydroxamic acids.
Synthetic inhibitors of interstitial collagenase, tri- and tetrapeptidyl hydroxamic acids, have been developed and tested for their inhibitory activities against human matrix metalloproteinases. A water soluble inhibitor, p-NH2-Bz-Gly-Pro-D-Leu-D-Ala-NHOH (FN-439) inhibited interstitial and granulocyte collagenases, granulocyte gelatinase and skin fibroblast stromelysin with IC50 of 1 x 10(-6) M, 3.0 x 10(-5) M and 1.5 x 10(-4), respectively, but not thermolysin and serine proteinases. FN-439 was found to retain its inhibitory activity against matrix metalloproteinases even after prolonged incubation with pronase or human granulocyte elastase, indicating a favorite candidate of the inhibitor to modulate metalloproteinase activities in vivo.
Amino Acid Sequence↗
Cluster a personality disorder: a marker of worse treatment outcome of major depression?
This study attempted to identify a specific personality disorder (PD) cluster associated with poor outcome after a 4-month course of antidepressant therapy. Subjects were 96 consecutive outpatients with major depression. The Structured Clinical Interview for DSM-III-R (SCID) was used to make Axis I and Axis II diagnoses. To evaluate the net effect of each PD cluster on the outcome of depression, a log-linear model was applied. The analysis showed that the presence of a PD from cluster A was significantly correlated with the 4-month outcome of depression.
Adult↗
Constitutive production of multiple colony-stimulating factors in patients with lung cancer associated with neutrophilia.
Production of colony-stimulating factor (CSF) was examined in three patients with lung cancer associated with neutrophilia. All three patients presented a marked increase in neutrophil count (26,000-39,000 microliters-1) that continued at least for 3 weeks and rapidly disappeared after surgical removal of the tumours. Culture media (CM) incubated with the excised tumour tissues stimulated the colony formation of bone marrow myeloid progenitor cells in vitro. Northern blot analysis of poly(A)+ RNA from the tumour tissues revealed a constitutive expression of granulocyte (G), macrophage (M), and granulocyte-macrophage (GM) CSF genes in all tumours. Immunoassay specific for these CSFs revealed that G- and M-CSF immunoreactivity was detected in all CM and GM-CSF protein in two out of three CM. The plasma CSF levels also increased before operation and decreased to normal or near-normal range after operation. In contrast, tumour cell CM obtained from two lung cancer patients without leucocytosis neither stimulated haematopoietic colony formation nor contained immunoreactive CSFs. These results indicated that the neutrophilia found in the three patients was probably caused by constitutive production of multiple CSFs by lung cancer cells.
Aged↗
[Roxithromycin treatment in patients with chronic lower respiratory tract disease--its clinical efficacy and effect on cytokine].
We demonstrated the efficacy of "long term" roxithromycin (RXM) treatment in 15 patients with chronic lower respiratory tract disease (11 with diffuse panbronchiolitis and 4 with sinobronchial syndrome). (1) Fourteen (93.3%) of the 15 patients showed improvement when assessed by the comprehensive improvement score, and they showed significant improvements in PaO2 (74.2 +/- 10.4 Torr to 84.3 +/- 10.9 Torr, p < 0.01), %VC (86.9 +/- 20.2% to 96.0 +/- 21.9%, p < 0.001) and FEV1 (1.81 +/- 0.87 L to 2.14 +/- 1.08 L, p < 0.01) after RXM treatment. (2) Neutrophils accumulated in the pre-RXM treatment bronchoalveolar lavage (BAL) fluid and decreased in BAL fluid of patients responding to RXM treatment (49.8 +/- 28.3% to 17.1 +/- 15.7%, p < 0.01). Additionally, the levels of interleukin 1 beta and interleukin 8 were significantly higher in BAL fluid of these patients than those in the healthy volunteers (p < 0.025, p < 0.01 respectively), and correlated with the neutrophil accumulation (r = 0.619, p < 0.05). These cytokines showed a decrease after RXM treatment. These results indicated that RXM acts by reducing pulmonary inflammation through reduction of neutrophil migration to inflammatory sites, and is effective on chronic lower respiratory tract disease.
Adult↗
Chronic eosinophilic pneumonia progressing to lung fibrosis.
A 65 year old Japanese man was hospitalized with fever. Opacities distributed mainly in the subpleural regions were found on chest computed tomographic scan (CT), and these promptly cleared with corticosteroid therapy. Four years later, he presented with severe eosinophilia. Both chest X-ray and high resolution CT scan showed ground-glass opacities and honeycombing, suggesting lung fibrosis. A lung biopsy demonstrated intra-alveolar eosinophil infiltration, interstitial thickening with eosinophil infiltration, and a widely-distributed desquamative interstitial pneumonia-like reaction. With corticosteroid therapy, the ground-glass opacities decreased with a corresponding clinical improvement, although lung honeycombing and blood eosinophilia remained. In this case, circulating intercellular adhesion molecule-1 and circulating and bronchoalveolar lavage fluid eosinophil granule proteins were felt to be more effective markers for evaluating disease activity than the blood eosinophil number.
Aged↗
Age-dependent decrease in platelet aggregation in rats.
The degree of platelet aggregation induced by ADP and collagen was examined in platelet-rich plasma from 7- to 90-week-old rats. The aggregation induced by ADP was unchanged at 90 weeks. Collagen-induced aggregation decreased remarkably at 60 and 90 weeks. Therefore, collagen-induced platelet activation is highly age-dependent, with rats of advanced age showing a lower response than younger rats.
Adenosine Diphosphate↗
Inhibition of Helicobacter pylori urease activity by hydroxamic acid derivatives.
Helicobacter pylori (HP) produces strong urease [EC 3.5.1.5], which is considered to play a role in the pathogenesis of gastritis and peptic ulcers. Inhibitions against this enzyme have been studied with hydroxamic acid (HXA) derivatives of aliphatic or aromatic carboxylic acids, amino acids and dipeptides. A number of HXAs potently inhibited the urease (I50 values were near the order of 10(-6)M), and H-Ile-Gly-NHOH (I50 = 0.20 x 10(-6)M) was the most potent inhibitor among the derivatives. HP urease was inhibited more potently, in general, than Jack bean (JB) urease by HXAs, and a correlation between the chemical structures of HXA derivatives and their inhibitory effects on HP urease was observed, in comparison with JB urease.
Amino Acids↗
Synthetic dipeptide, N-stearoyl-D-Ser-L-Pro-OEt, induces release of tissue-type plasminogen activator in cultured cells and in experimental animals.
The tissue-type plasminogen activator (t-PA)-releasing action of synthetic dipeptides containing Gly, Ser or Pro was investigated. Among 10 dipeptides, Boc-L-Ser-L-Pro-OH and H-L-Ser-L-Pro-OH induced t-PA release in vitro, but the others were inactive. Since Boc-L-Ser-L-Pro-OH was more effective than H-L-Ser-L-Pro-OH, 7 related dipeptides with N-acylation were synthesized. Five of them enhanced the release of t-PA; N-stearoyl-L-Ser-L-Pro-OH (FK-5) had the greatest effect. Four compounds were further examined for activity to enhance the release of t-PA in rats. FK-5 produced a two-fold increase in fibrinolytic activity, and N-palmitoyl-L-Ser-L-Pro-OH (FK-4) also markedly enhanced the release of t-PA. Since FK-5 caused severe hemolysis, 7 analogues of FK-5 were synthesized. All of them enhanced the release of t-PA from melanoma (Bowes) cells. In rats, FK-5, N-stearoyl-D-Ser-L-Pro-OH (FK-8) and N-stearoyl-D-Ser-L-Pro-OEt (FK-10) enhanced the fibrinolytic activity two-fold. FK-5 and FK-8 also exhibited strong hemolytic activity, but FK-10 did not induce hemolysis. Therefore, FK-10 was examined in rabbits. After the injection of this compound, the fibrinolytic activity in the euglobulin fraction was markedly enhanced without accompanying hemolysis. Thus, FK-10 potently enhances fibrinolytic activity both in vitro and in vivo.
Amino Acid Sequence↗
Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase inhibitors: 2-oxetanones with a side chain mimicking the extended structure of 1233A.
Structural analogs of 1233A, a microbial metabolite inhibiting 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) synthase, were designed and synthesized. The 2-oxetanone moiety was left intact. All analogs prepared were tested for inhibition of HMG-CoA synthase activity and sterol synthesis in mouse liver and for effect on serum triglyceride levels. Of these analogs, trans-4-[2-[3-(7-carboxy-2- naphthyl)phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (4a) showed the highest inhibitory activity in vitro, and also had in vivo inhibitory activity without causing any increase in triglyceride level.
Animals↗
Two-color analysis of lymphocyte subsets of bronchoalveolar lavage fluid and peripheral blood in Japanese patients with sarcoidosis.
Analysis of T-cell surface markers was carried out in peripheral blood and bronchoalveolar lavage (BAL) fluid of Japanese patients with sarcoidosis to examine the influence of differing racial background. The subjects were 26 untreated patients in whom a diagnosis of active sarcoidosis had recently been established and 9 healthy volunteers, and two-color immunofluorescence analysis was performed. CD3+HLA-DR+ cells, CD4+HLA-DR+ cells, and CD4+CD29+ cells in peripheral blood and BAL fluid were significantly increased in the patients compared with the healthy volunteers, and the mean percentages increased in parallel with the extent of the radiologic stage. The percentage of CD3+HLF-DR+ cells in peripheral blood and lavage fluid also significantly correlated with serum activity of angiotensin-converting enzyme (r = 0.69, p < 0.001; r = 0.61, p < 0.001, respectively). Thus, the evaluation of these antigens' expression is an important clinical approach for the staging of the disease. However, no significant differences were found in CD3+CD25+, CD4+CD45RA+, or CD8+CD11+ cells in either peripheral blood or BAL fluid between the patients and volunteers. Our results indicated that in Japanese patients with sarcoidosis, circulating T cells are activated but CD25+ cells are not increased in peripheral blood and BAL fluid, but there is not a significant association with racial background.
Adult↗
Three cases of extrapulmonary small cell carcinoma occurring in the prostate, stomach, and pancreas.
Small cell carcinomas are fairly common neoplasms in the lung, but tumors featuring similar histological profiles may occur in extrapulmonary organs. Three cases of small cell carcinomas occurring in the prostate (case 1), stomach (case 2), and pancreas (case 3) are presented. Production of hormones was demonstrated immunohistochemically in all cases. In case 2 alpha-fetoprotein (AFP) was elevated in the serum and observed immunohistochemically in tumor cells. Production of AFP is a distinctive feature, which has not been reported in the pulmonary and extrapulmonary cases of small cell carcinoma. Amplification and/or expression of myc gene family have been suggested to be related to the prognosis of pulmonary small cell carcinoma. Amplification of myc genes was not detected in any of our cases, but c-myc protein was demonstrated immunohistochemically in tumor cells of case 1.
Adult↗
[Atypical chronic myeloproliferative disorder with translocation (12;13) (p13;q12) and tumor formation].
A 49 year-old man was admitted to our hospital in May 1989, with a cervical tumor and leukocytosis. He had been pointed out leukocytosis for last two years. Peripheral blood examinations demonstrated an increase of leukocytes (39,500/microliters) with low neutrophil alkaline phosphatase, eosinophilia and immature cells. Examination of bone marrow revealed normoplasia with 5.6% eosinophils, 1.4% myeloblasts, 2.6% promyelocytes and 250/microliters megakaryocytes. Cytogenetic analysis disclosed 46, XY, t (12;13) (p13;q12). Southern blot analysis showed no BCR rearrangement. The tumor cells had infiltrated the lymph nodes. Pathological finding agreed with the specimen of the lymph node as in the clot section of bone marrow. He was diagnosed as having a chronic myeloproliferative disorder with tumor formation and was treated with anti-leukemia drugs, including BH-AC, THP, VDS, MTX, VP-16, BUS, 6MP and uvenimex. He showed hematological remission, temporary, but he did not reach cytogenetical remission and died in April 1990. Further study in a large series is necessary to define whether the abnormality of the chromosome with t(12;13) (p13;q12) is characteristic in cases with tumor formation.
Chromosomes, Human, Pair 12↗
[Small cell lung cancer].
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Antineoplastic Combined Chemotherapy Protocols↗
[Association between diffuse panbronchiolitis and HTLV-I infection].
To determine whether HTLV-I infection is associated with diffuse panbronchiolitis (DPB), we investigated T-cell surface markers of peripheral blood and bronchoalveolar lavage fluid (BALF) in 9 healthy volunteers, 6 HTLV-I seronegative DPB patients (HTLV-I(-)DPB) and 8 HTLV-I seropositive DPB patients (HTLV-I(+)DPB). In peripheral blood, no significant difference was observed between HTLV-I(-)DBP and healthy volunteers. However, in BALF, HTLV-I(-)DPB showed a significant decrease of the CD4/CD8 ratio and an increase of CD8+HLA-DR+ cells compared with healthy volunteers. CD3+CD25+ and CD4+HLA-DR+ cells in peripheral blood were significantly increased in HTLV-I(+)DPB compared with those in HTLV-I(-)DPB. No significant difference was observed in BALF cells between HTLV-I(-) and HTLV-I(+)DPB with the exception of CD3+CD25+ cells. The most striking result was a marked elevation of CD3+CD25+ cells in 2 of 8 HTLV-I seropositive patients. Microscopic findings of open lung biopsy specimens obtained from the 2 patients differed from the typical microscopic findings in DPB. From these findings, we consider that HTLV-I infection may be associated with pulmonary lesions like DPB, but of a different, pathologically distinct, type.
Adult↗
Ultraviolet photoelectron spectra of C82 and KxC82.
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Journal Article↗
[Effect of erythromycin on neutrophil chemotactic activity from human monocytes].
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Cells, Cultured↗