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Biomedical subjects

H Ohkubo

Publications and source records attributed to H Ohkubo.

At least 145 records · Page 8Linked to original sources

Amino acid sequence of mammalian elongation factor 2 deduced from the cDNA sequence: homology with GTP-binding proteins.

Complementary DNA clones, pHEW1 and pRE2, coding for hamster and rat polypeptide chain elongation factor 2 (EF-2), respectively, were isolated and sequenced. It was shown that the cDNA insert in pHEW1 contains a 2574-base-pair open reading frame coding for an 857-amino acid polypeptide with Mr 95,192, excluding the initiation methionine. Comparative studies of sequence homology among EF-2 and several GTP-binding proteins show that five regions in the amino-terminal position of EF-2, corresponding to about 160 amino acids, show homology with GTP-binding proteins, including protein synthesis elongation and initiation factors, mammalian ras proteins, and transducin. The carboxyl-terminal half of EF-2 contains several regions that have 34-75% homology with bacterial elongation factor G. These results suggest that the amino-terminal region of EF-2 participates in the GTP-binding and GTPase activity whereas the carboxyl-terminal region interacts with ribosomes. Finally, the sequence provides direct evidence that diphthamide (2-[3-carboxy-amido-3-(trimethylammonio)propyl]histidine), the site of ADP-ribosylation by diphtheria toxin, is produced by post-translational modification of a histidine residue in the primary translational product.

Amino Acid Sequence↗

A new vasodilator 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (KC-404) has a dual mechanism of action on platelet aggregation.

3-Isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (KC-404) at a concentration of greater than or equal to 4.34 X 10(-5) M inhibited adenosine diphosphate-, arachidonic acid- and collagen-induced aggregation of rabbit platelets. In rabbit, KC-404 (0.5 and 2 mg/kg, i.v.) caused a decrease in weight of collagen strip extracorporeally superfused with arterial blood, because of a disaggregation of deposited platelet aggregates. This disaggregatory effect of KC-404 was markedly diminished by the pretreatment of animals with aspirin. KC-404 (greater than or equal to 4.34 X 10(-6) M) and its major metabolite diOH-KD-404 (greater than or equal to 3.78 X 10(-7) M) significantly potentiated the anti-aggregatory action of prostacyclin on rabbit platelets. KC-404 (greater than or equal to (4.34 X 10(-8) M) exerted a similar effect in rat platelets. KC-404 had no significant effect on 6-keto-PGF1 alpha and thromboxane A2 formation by rat aortic segment and rabbit platelets, respectively. KC-404 inhibited cyclic AMP phosphodiesterase (Ki = 91 microM). The present results indicate that KC-404 exhibits its anti-platelet effect via the inhibition of cyclic AMP phosphodiesterase activity in platelets and via the potentiation of anti-aggregatory activity of prostacyclin on platelets.

3',5'-Cyclic-AMP Phosphodiesterases↗

Differential expression of the multiple forms of rat prekininogen mRNAs after acute inflammation.

Responses of the rat liver prekininogen mRNAs after induction of acute inflammation were examined by blot-hybridization and S1 nuclease protection analyses with the aid of cDNA probes specific for rat kininogens. Marked changes in the relative levels of the low molecular weight (LMW) prekininogen mRNAs were observed after administration of Escherichia coli lipopolysaccharide, and the mRNA levels increased with a half-maximal dose of approximately 100 ng of lipopolysaccharide/100 g body weight. At maximum level of induction, the LMW prekininogen mRNAs comprised about 1% of total liver mRNA, thus representing a major component of the liver mRNA in the acutely inflamed rat. Differences in the inflammatory responses of various forms of the prekininogen mRNAs were then investigated by S1 nuclease protection analysis with the use of three different cDNA probes, each specific for either K-prekininogen or two types of T-prekininogens. Both of the T-prekininogen mRNAs increased progressively during the first 24 h after induction of inflammation, and at maximum level of induction, these two mRNAs increased about 10- and 13-fold over their normal level. In contrast, neither of the high molecular weight and LMW K-prekininogen mRNAs exhibited such an increase after induction of inflammation. Thus, the expressions of the rat T- and K-prekininogen mRNAs are differentially regulated in response to the induction of acute inflammation.

Acute Disease↗

Induction of rat liver angiotensinogen mRNA following acute inflammation.

Inflammatory responses of the angiotensinogen mRNA in rat liver and brain were examined by RNA blot-hybridization analysis with use of a cDNA probe specific for rat angiotensinogen. The angiotensinogen mRNA in the liver increased rapidly during the first 5 h following the administration of Escherichia coli lipopolysaccharide, and at maximum level of induction, the mRNA increased approximately 5-fold over its normal level. The levels of the mRNA increased with increasing doses of lipopolysaccharide, the half-maximal dose being approximately 1 microgram/100 g body weight. In contrast, no such increase was observed in the brain angiotensinogen mRNA. Thus, the expression of the rat angiotensinogen mRNA is regulated in a tissue-specific manner in response to induction of acute inflammation.

Angiotensinogen↗

CO2 laser in treating carcinoma of the tongue.

Since 1980, we have been using CO2 laser in treating carcinomas of the tongue. Carcinomas confined to the mucosa have been treated with laser excision alone. Five patients were treated in this way and they are all alive with no evidence of disease. Follow-up ranges from 11 months to 3 years. Carcinomas with a superficial muscular invasion have been treated with mass reduction laser surgery followed by chemoradiotherapy. There were 19 patients which fell in this category. Of these 19, 17 are alive with no evidence of disease, 1 died of an intercurrent disease, and 1 died of cervical metastasis. Follow-up ranges from 9 months to 5 years and 1 month. For carcinomas with a deep muscular invasion, we first attempted an induction chemotherapy consisting of cisplatin and pepleomycin. When the chemotherapy was effective, we applied mass reduction laser surgery followed by chemoradiotherapy. Two patients were treated in this way. One is alive with no evidence of disease (11-month follow-up) whereas the other died of pulmonary metastasis. Following the treatments using laser, speech intelligibility is much better than after extensive surgeries.

Adult↗

[Clinical evaluation of aspoxicillin in children].

Aspoxicillin (ASPC), a new penicillin for injection, was evaluated for its efficacy and safety in 29 children with bacterial infection (Table 1), and the following results were obtained. MICs of ASPC to 26 strains of isolated organisms are shown in Table 2. MICs to 4 out of 13 strains of H. influenzae were higher than 6.25 micrograms/ml. MICs to 5 strains of S. pneumoniae were lower than 0.78 microgram/ml and 1 out of 3 strains of S. aureus and 1 strain of E. coli showed higher MICs than 100 micrograms/ml. ASPC was administered in 3 or 4 divided doses at a daily dosage ranging from 21 to 98 mg/kg by 30 minutes drip infusion or intravenous injection to 29 patients (16 cases of pneumonia, 8 cases of tonsillitis, 3 cases of bronchitis, 1 case of urinary tract infection, 1 case of impetigo) and the following clinical results were obtained: excellent; 11 cases, good; 11 cases, fair; 3 cases, poor; 1 case. The overall efficacy rate was 85% (Table 3, 4). No clinical side-effects were observed in any of the patients. Leukopenia was noted in 1 case. Slight elevation of GOT and GPT was noted in 2 cases, and minimal elevation of GOT was observed in other 2 cases (Table 5). These data suggest that ASPC is an useful new antibiotic in the treatment of children with susceptible bacterial infection and may be used as the first choice antibiotic for the treatment of respiratory tract infection in children.

Amoxicillin↗