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Biomedical subjects

H Takami

Publications and source records attributed to H Takami.

At least 19 recordsLinked to original sources
PubMed1992

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 1.

A series of 11-[[2-[(arylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acids and related derivatives were synthesized. The compounds were tested for their antagonizing effects on guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationships are discussed. (+/-)-11-[[2-[(Styrylsulfonyl)amino]ethyl]-thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acid (41) and (+/-)-11-[[2-[(phenylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]thiepin-2-carboxylic acid (4af) were the most promising compounds with K(i) values of 6.5 +/- 0.29 and 3.7 +/- 0.31 nM, respectively, for the TXA2/PGH2 receptor. These compounds also significantly inhibited U-46619-induced guinea pig platelet aggregation ex vivo (10 mg/kg po). Compound 41 was resolved into its optically active form. The (-)-isomer was 60-fold more potent than the (+)-isomer in the TXA2/PGH2 receptor binding assay. Some compounds tested in this study showed both TXA2/PGH2 receptor antagonizing and TXA2 synthase inhibitory effects.

Animals↗
PubMed1992

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 2.

A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Molecular cloning, nucleotide sequence and expression of the structural gene for a thermostable alkaline protease from Bacillus sp. no. AH-101.

Alkaliphilic Bacillus sp. no. AH-101 produces an extremely thermostable alkaline serine protease that has a high optimum pH (pH 12-13) and shows keratinolytic activity. The gene encoding this protease was cloned in Escherichia coli and expressed in B. subtilis. The cloned protease was identical to the AH-101 protease in its optimum pH and thermostability at high alkaline pH. An open reading frame of 1083 bases, identified as the protease gene, was preceded by a putative Shine-Dalgarno sequence (AAAGGAGG) with a spacing of 11 bases. The deduced amino acid sequence revealed a pre-pro-peptide of 93 residues followed by the mature protease comprising 268 residues. AH-101 protease showed slightly higher homology to alkaline proteases from alkaliphilic bacilli (61.2% and 65.3%) than to those from neutrophilic bacilli (54.9-56.7%). Also AH-101 protease and other proteases from alkaliphilic bacilli shared common amino acid changes and a four amino acid deletion when compared to the proteases from neutrophilic bacilli. AH-101 protease, however, was distinct among the proteases from alkaliphilic bacilli in showing the lowest homology to the others.

Amino Acid Sequence↗
PubMed1992

Transaortic patch angioplasty for left coronary ostial stenosis in a patient with Takayasu's aortitis.

A 35-year-old woman who had left coronary ostial stenosis and aortic valve regurgitation due to Takayasu's aortitis underwent transaortic patch enlargement of the stenosed left coronary ostium in combination with aortic valve replacement. This technique may be suitable and recommendable as an alternative to aortocoronary bypass grafting or endarterectomy for coronary ostial stenosis in Takayasu's aortitis.

Adult↗
PubMed1992

Coronal fracture of the body of the hamate: case reports.

Coronal fracture of the body of the hamate with associated dorsal subluxation of the bases of the fourth and fifth metacarpals is rare. Two cases of this injury with and without disruption of the dorsal carpometacarpal ligaments treated with open reduction and internal fixation are reported. Oblique roentgenographic views with the hand pronated 30 degrees from the true lateral were helpful in the assessment of the fracture.

Adult↗
PubMed1992

Comminuted intra-articular fracture of the distal radius with rotation of the palmar medial articular fragment: case reports.

Two cases of comminuted intra-articular fracture of the distal radius with rotation of the palmar medial articular fragment are reported. In both cases the palmar medial articular fragment pivoted on the intact volar capsular attachments. This rare injury appears to be a variant of Barton's fracture and requires open reduction and internal fixation for accurate repair of the disrupted distal radial articular surfaces.

Adult↗
PubMed1992

Rupture of the extensor pollicis longus tendon without fracture after wrist trauma: case reports.

Four cases of rupture of the tendon of the extensor pollicis longus without detectable fracture after wrist injury are reported. The clinical features of this condition did not differ materially from those of rupture occurring after a Colles fracture. All patients were rather young, the average age being 40 years. In one patient rupture occurred a day after injury. In all patients satisfactory thumb function was restored with extensor indicis proprius tendon transfer.

Adult↗
PubMed1992

Dislocation of the carpal scaphoid associated with median nerve compression: case report.

Dislocation of the carpal scaphoid is a rare injury. A case of delayed diagnosis of scaphoid dislocation necessitating late treatment is described. The scaphoid was displaced anteromedially, causing compression of the median nerve in the carpal canal. Treatment consisted of carpal tunnel decompression and scapho-trapezium trapezoid fusion. Useful wrist motion without significant pain was restored.

Carpal Bones↗
PubMed1992

Myocardial energy metabolism in asphyxiated canine hearts preserved for 24 hours.

Myocardial energy metabolism in asphyxiated cadaver hearts preserved in UW solution (UWS; group 1, n = 6) or modified Collins' solution (MCS; group 2, n = 6) was compared with that in cardioplegic arrested hearts immersed in ice-cold MCS with (group 3, n = 6) or without myoprotective drugs (group 4, n = 5). All hearts were stored for 24 hr. The hearts in groups 1 and 2 were pretreated with prostacyclin, verapamil, and propranolol; asphyxiated for 10 min, reversed by coronary perfusion with warm blood cardioplegia (WBCP); perfused with ice-cold crystalloid cardioplegia for 2 hr; excised and immersed in cold storage solution for 22 hr; and perfused again with WBCP before reperfusion. ATP contents were measured in biopsy specimens by HPLC. Myocardial ATP level decreased significantly from 23.7 +/- 1.7 to 15.9 +/- 2.5 mumol/g dry wt. (P less than 0.0001) by asphyxia, but recovered to within normal limits by WBCP in group 1. The ATP level again decreased to 15.8 +/- 2.4 mumol/g dry wt. during 24-hr storage, but finally rose to 22.4 +/- 3.5 mumol/g dry wt. by terminal WBCP. The ATP metabolism in group 2 was similar to that in group 1. The ATP content in group 4 was significantly lower than that in other groups (P less than 0.01) after 24-hr preservation. The study shows that damage to cadaver hearts can be reversed and the hearts maintained satisfactorily viable for 24 hr.

Adenosine Triphosphate↗
PubMed1992

Immune deposits in the glomerular extracellular matrix detected by the quick-freezing and deep-etching method.

Chronic serum sickness nephritis was induced in rats by sensitization with egg albumin. The glomeruli were then examined by the quick-freezing and deep-etching method with immunohistochemical identification of immune complex deposits on replica membranes. In control rats, the glomerular basement membrane showed a three-layered structure. The middle layer was composed of a compact meshwork of fine fibrils that was connected to adjacent endothelial and epithelial cells by perpendicular fibrils in the inner and outer layers. The mesangial matrix contained a similar but looser meshwork structure. In the nephritic rats, small granular deposits were observed within the meshwork, distorting its fine structure. Larger nodular aggregates extended continuously from the middle layer to the epithelial side. Disruption of the connecting fibrils overlying these larger aggregates was noted. The deposits were stained by antiegg albumin or antirat IgG antibodies. Gold particles immunostaining for the sensitizing antigen were also localized within the deposits. These findings suggest that the deposition of immune complexes occurs in the fibrillary meshworks of the mesangium and lamina densa in this experimental model, with the resultant distortion of their meshwork structures and the formation of nodular aggregates.

Animals↗
PubMed1992

Effects of KW-3635, a novel dibenzoxepin derivative of a selective thromboxane A2 antagonist, on human, guinea pig and rat platelets.

We examined the binding of [3H]U-46619, a thromboxane A2 agonist, to human and guinea pig platelets and the binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to human, rat and guinea pig platelets. KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1- benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxepin-2-c arboxylate monohydrate) concentration-dependently inhibited the [3H]U-46619 binding to human and guinea pig platelets with inhibition constants of 1.2 nM and 2.7 nM, respectively. KW-3635 also potently inhibited the [3H]SQ 29,548 binding to human and guinea pig platelets with inhibition constants of 1.9 nM and 3.2 nM, respectively. In contrast, KW-3635 was less active against thromboxane A2/prostaglandin H2 receptors in rat platelets with an inhibition constant of 97 nM. KW-3635 at 10(-5) M did not antagonize various receptors including prostaglandin E2, prostaglandin I2 and neurotransmitters. In addition, 10(-5) M KW-3635 did not alter the prostaglandin D2-induced cAMP accumulation in EBTr cells. KW-3635 was inactive towards thromboxane synthase, cyclooxygenase and prostaglandin I2 synthase up to 10(-5) M. KW-3635 slightly inhibited 5-lipoxygenase with an IC50 value of 71 microM. These data indicate that KW-3635 is a potent and selective non-prostanoic thromboxane A2 antagonist, and it can recognize the species differences in thromboxane A2/prostaglandin H2 receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Molecular cloning, nucleotide sequence, and expression of the structural gene for alkaline serine protease from alkaliphilic Bacillus sp. 221.

The gene encoding an alkaline serine protease from alkaliphilic Bacillus sp. 221 was cloned in Escherichia coli and expressed in Bacillus subtilis. An open reading frame of 1,140 bases, identified as the protease gene was preceded by a putative Shine-Dalgarno sequence (AGGAGG) with a spacing of 7 bases. The deduced amino acid sequence had a pre-pro-peptide of 111 residues followed by the mature protease comprising 269 residues. The alkaline protease from alkaliphilic Bacillus sp. 221 had higher homology to the protease from alkaliphilic bacilli (82.1% and 99.6%) than to those from neutrophilic bacilli (60.6-61.7%). Also Bacillus sp. 221 protease and other protease from alkaliphilic bacilli shared common amino acid changes and 4 amino acid deletions that seemed to be related to characteristics of the enzyme of alkaliphilic bacilli when compared to the proteases from neutrophilic bacilli.

Amino Acid Sequence↗
PubMed1992

[A randomized controlled study on imipenem/cilastatin sodium in comparison to aztreonam + lincomycin in treating severe infections in patients with malignant tumors or hematological diseases].

A randomized controlled study was conducted to compare effects of imipenem (IPM) (1.0-1.5 g/day) with those of aztreonam (AZT) (4 g/day) +lincomycin (LCM) (1,200-2,400 mg/day) in patients with malignant tumors or hematological diseases and severe infections. A total of 95 patients entered the study between October 1989 and March 1991. Forty-seven patients were treated with IPM and the remaining 48 patients were given AZT+LCM. No statistically significant differences existed in age, sex or underlying diseases between the 2 groups. Overall, the clinical cure rate of the IPM group was 53%; This was significantly higher than the 31% cure rate obtained in the AZT+LCM group (P less than 0.05). The difference was significant in patients whose granulocyte counts were less than 1,000/microliters, but not in those whose granulocyte counts were 1,000/microliters or higher. Side effects were observed in 5 patients given IPM and one given AZT+LCM. In conclusion, no significant differences appeared to exist regarding clinical efficacy and safety between the 2 treatment regimens.

Adolescent↗
PubMed1992

[Investigation on central venous catheter related sepsis].

We made an investigation on central venous catheter related sepsis (CRS) in recent 5 years (1987-1991). The incidence of CRS was high; 16.0% (125 out of 782 cases) or 13.1% (135 out of 1029 catheters). CRS occurred frequently during 2-3 weeks after catheter insertion. The incidence of CRS was not affected by the kind of disease (malignant or benign), complication (diabetes, liver cirrhosis, collagen disease) operation or administration of antibiotics. Eight percent out of 91 organisms isolated from culture of catheter tips were so-called resistant strains; multi-drug resistant Staphylococci (16), Pseudomonas aeruginosa (5), fungi (49), etc. Complications (shock, acute renal failure, secondary pneumonia, fungal endophthalmitis) broken out in 18 patients (14.4% out of 125 CRS). Fungi were isolated from 14 out of 18 complicated cases, furthermore fungi were isolated alone in 11 cases. No complication were seen among cases from which gram positive cocci were isolated alone. Body temperature and white blood cell count of complicated cases were significantly higher than those of uncomplicated cases. The duration until removal of catheter from outbreak of fever in complicated cases was significantly longer than that in uncomplicated cases.

Candida↗
PubMed1992

[Favorable prognoses in 24 adult patients with acute leukemia, surviving over five years since 1985].

Since 1985 we have experienced 24 leukemia cases with long-term survival, who were treated with one of three types of postremission therapy. Of them, 20 patients were physically fit for ordinary work and returned to their work as workers or housewives during long-term follow-up period. Two housewives gave birth. We have devised three types of postremission therapy; 1) multidrug combination therapy with gradually longer intermissions (January 1980-March 1983); 2) controlled randomized clinical trial by the Japanese Foundation for the Multidisciplinary Treatment of Cancer, April 1983-March 1985-March 1988). In a group who underwent multidrug combination therapy without prednisolone, 12 of 20 patients who achieved complete remission have shown continued complete remission, as of November 1991, including seven 5-year survivors. These results indicate that improvement of postremission therapy makes it possible for adult patients with acute leukemia to survive 5 years or longer.

Adolescent↗
PubMed1992

[Bleeding time].

Bleeding time indicates the interaction of the platelets with the damaged vessel wall and the subsequent formation of the primary hemostatic plug. Bleeding time has been widely used in the diagnosis of bleeding disorders, especially thrombocytopenia, abnormalities in platelet function, vascular disorders, and von Willebrand's disease. There are a number of methods to perform the bleeding time test, but there are significant problems concerning sensitivity, specificity, and reproducibility. To study the inhibitory effects of monoclonal antibodies (anti-vWF, anti-GPIb, and anti-GPIIb/IIIa) on primary hemostasis, these antibodies were infused to normal pigs. Anti-vWF and anti-GPIb antibodies markedly prolonged the bleeding time and inhibited hemostatic plug formation. The anti-GPIIb/IIIa antibody completely inhibited ADP-and collagen-induced platelet aggregation, but no or only mild prolongation of bleeding time was observed. The quantitative bleeding time which measures both the time and the amount of blood loss is useful in the diagnosis of hemorrhagic disorders and in judging the efficacy of the treatment. It will provide important information to understand the mechanism of primary hemostasis.

Animals↗