Biomedical subjects
Publications and source records attributed to S Kudo.
The authors review the anatomy of the middle sacral artery and its relationship to the lower lumbar and internal iliac arteries. Middle sacral arteriography was performed in 8 patients, transcatheter tumor embolization in 6, and infusion chemotherapy in 1. There were no complications. The authors consider selective middle sacral arteriography beneficial in the diagnosis and treatment of sacral tumors.
Intraarterial occlusion-infusion of vincristine and Adriamycin was performed in six dogs using balloon infusion catheters. Tissue toxicity was compared with that obtained when the same drugs were administered by simple arterial infusion. Balloon occlusion of the external iliac artery produced reversed blood flow in the deep femoral, caudal femoral, and superficial circumflex iliac arteries, potentially altering the distribution of the drugs. Thrombosis of arterial branches occurred in three dogs, sooner but no more often in the groups receiving occlusion-infusion chemotherapy. Skin ulceration and dilatation of peripheral small vessels were significantly more frequent and extensive in the groups receiving occlusion-infusion. One infusion dog developed a single small ulcer on the hind paw; five of the six occlusion-infusion dogs developed multiple skin ulcers on the thigh and/or distal extremity. These findings suggest that even though intraarterial occlusion-infusion chemotherapy is not applicable in all instances, the technique does produce significantly greater drug-related effects than simple intraarterial infusion.
A highly purified preparation of Tetrahymena calmodulin activated a membrane-bound guanylate cyclase by more than 40-fold. This activation of guanylate cyclase by calmodulin was inhibited completely by local anesthetics such as dibucaine, tetracaine, lidocaine and procaine at concentrations that had no appreciable effect on the activities of basal guanylate cyclase (without calmodulin) and adenylate cyclase. The inhibition by dibucaine of calmodulin-mediated activation of the enzyme activity was not reversed by calcium but was partially overcome by increasing the concentration of calmodulin. Kinetic analysis of local anesthetic-induced inhibition of activation of guanylate cyclase demonstrated a mixed type of antagonism. These results suggest the possibility that the inhibition of calmodulin-dependent guanylate cyclase resulted, in part, from interaction of the drugs with calmodulin.
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Trifluoperazine was shown previously to inhibit the activation of Tetrahymena guanylate cyclase activity by calmodulin [S. Nagao, S. Kudo and Y Nozawa, Biochem. Pharmac. 19, 2709 (1981)]. The present paper reports that N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), another representative calmodulin inhibitor, inhibited the calmodulin-induced activation of the guanylate cyclase, and that trifluoperazine and W-7 also inhibited Tetrahymena adenylate cyclase. The adenylate cyclase activity was found to be present in a membrane-bound form and not to be influenced by calmodulin. The inhibitions of the adenylate cyclase activity by these agents were dose-dependent and not Ca2+-dependent. These findings suggest that the inhibitory actions of these drugs may not necessarily be specific for calmodulin-dependent enzymes in T. pyriformis.
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The possible role of Mg2+-HCO3-ATPase, carbonic anhydrase and several other enzymes in rat intestinal mucosa as mediators of the action of aldosterone has been examined. The small-intestinal tract was cut into seven segments, 15 cm each in length and the mucosa was scraped off, homogenized in 50 mM D-mannitol-2 mM Tris-HCl buffer (pH 7.1), differentially fractionated and a crude brush border was obtained. The mucosa from the colon and rectum was combined and used as the large-intestinal sample. Five days after the adrenalectomy, activities of brush border Mg2+-HCO3-ATPase and supernatant carbonic anhydrase from the upper small intestine decreased to about 60 and 40% of normal values, respectively. Activities of Na+-K+-ATPase, beta-glycerophosphatase and succinate dehydrogenase were all decreased. Two and 4 h after i.p. injection of aldosterone (40 micrograms/kg) to adrenalectomized rats, all enzyme activities increased except for Na+-K+-ATPase in the upper small intestine. In contrast, Mg2+-HCO-3-ATPase and carbonic anhydrase activities were unchanged 3 h after i.p. injection of dexamethasone (200 micrograms and 1 mg/kg). The activation of both Mg2+-HCO3-ATPase and carbonic anhydrase by a single injection of aldosterone was blocked by pretreatment with cycloheximide (1 mg/kg). These results suggest that aldosterone may induce the synthesis of enzyme proteins in the intestinal mucosa.
Although ligamentum flavum ossification (LFO) often occurs in normal persons, there are no reports of its detection on lateral chest radiographs made during screening examinations. Review of 1,744 consecutive lateral chest radiographs identified LFO in 6.2% of males and 4.8% of females. LFO occurred mainly at the intervertebral segments from T9-T10 through T12-L1. Most prevalent was the hook-shaped LFO, protruding inferiorly from the inferior facets into the projections of the intervertebral foramina. Though LFO can cause severe neurologic symptoms, none of the affected persons in this study reported such symptoms. LFO was first visualized radiographically when the subjects were 20-40 years old, and it may be a physiologic condition. The LFO in these cases existed independent of thoracic posterior longitudinal ligament ossification, diffuse idiopathic skeletal hyperostosis, and degenerative osteoarthritis.
Bovine brain calmodulin (B-CaM) was shown to inhibit the native Tetrahymena calmodulin (T-CaM)-dependent activation of guanylate cyclase in Tetrahymena at the concentrations that failed to affect the basal enzyme activity. The enzyme inhibition was completely reversed by high concentration of T-CaM, but not by Ca2+. The antagonistic interaction between T-CaM and B-CaM was not observed in the calmodulin-dependent cyclic nucleotide phosphodiesterase from bovine brain. Two calmodulins migrated independently on 15% polyacrylamide gel system. These results suggest that B-CaM exerts its inhibitory effect on the guanylate cyclase activation by interacting with the calmodulin-binding site of this enzyme.
Cefroxadine (CXD), an oral cephalosporin antibiotic was studied in the field of obstetrics and gynecology and the following results were obtained. CXD was orally given to 22 cases at daily dose of 1,500 mg 3 times a day. CXD administration was given to 22 cases in all; 4 with cervicitis, 6 with endometritis, 2 with puerperal fever, 4 with bartholinitis, 5 with adnexitis and 1 with vulvitis, respectively. Overall efficacy rate was 77.3% (17/22) (excellent 4, good 13, fair 5). As for side effects, a slight diarrhea was observed. CXD was considered to be a useful antibiotic in the field of obstetrics and gynecology by above the results.
A cell line, designated OKK, has been established from a human maxillary carcinoma in a Japanese man. The cultured cells were inoculated into nude mice, with the subsequent establishment of tumors. Alkaline phosphatases were extracted from these tumors and partially purified by chromatography. The electrophoretically fastest moving isoenzyme, designated tentatively as OKK T isoenzyme, was biochemically and immunologically investigated by comparing it with the Kasahara isoenzyme purified partially from the tumor, which originated from FL cells inoculated into a nude mouse. The properties of the OKK T isoenzyme were identical to those of the Kasahara isoenzyme. Thus, the enzymes showed a similar inhibition by amino acids (L-phenylalanine and L-leucine), the same behavior with respect to other properties, including heat stability, immunological character and molecular weight. The genetic phenotype of the glucose-6-phosphate dehydrogenase of this established cell line was proved not to be identical to that of a HeLa cell line.
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Properties of a heat-labile glucose transport system in Thiobacillus ferrooxidans strain AP-44 were investigated with iron-grown cells. [14C]glucose was incorporated into cell fractions, and the cells metabolized [14C]glucose to 14CO2. Amytal, rotenone, cyanide, azide, 2,4-dinitrophenol, and dicyclohexylcarbodiimide strongly inhibited [14C]glucose uptake activity, suggesting the presence of an energy-dependent glucose transport system in T. ferrooxidans. Heavy metals, such as mercury, silver, uranium, and molybdate, markedly inhibited the transport activity at 1 mM. When grown on mixotrophic medium, the bacteria preferentially utilized ferrous iron as an energy source. When iron was exhausted, the cells used glucose if the concentration of ferrous sulfate in the medium was higher than 3% (wt/vol). However, when ferrous sulfate was lower than 1%, both of the energy sources were consumed simultaneously.
Reportedly, ossification of the posterior longitudinal ligament (OPLL) usually involves the cervical spine and often accompanies other ligamentous ossification such as diffuse idiopathic skeletal hyperostosis (DISH). It is considered serious because it sometimes causes severe radiculomyelopathy; however, the present study, based on a fixed population sample, revealed that OPLL of the thoracic spine is nearly always asymptomatic. The prevalence of thoracic OPLL was 0.6%, with three times as many women as men being affected, compared with cervical OPLL which occurs predominantly among men. No marked radiculomyelopathy was observed, nor definite evidence of neurological involvement due to thoracic OPLL. DISH was rare, especially among women.
Phospholipid composition of Tetrahymena plasma membranes was modified by phospholipase A2-treatment and its effects on the activities of the two membrane-bound cyclases (adenylate and guanylate) were studied. Phospholipase A2 from Crotalus adamanteus was found to hydrolyze preferentially phosphatidylethanolamine of isolated plasma membranes. In the phospholipase A2-treated membranes in which 45% of total phosphatidylethanolamine was converted to its lysolipid, adenylate cyclase activity was to a small extent reduced, whereas guanylate cyclase activity was decreased almost to a half. However, the stimulation rate of the guanylate cyclase activity by calmodulin was unaffected in phospholipase A2-treated plasma membranes. The apparent Km value for substrates was not different between phospholipase A2-untreated and -treated plasma membranes. The ESR analysis demonstrated that the phospholipase A2-treated plasma membranes showed an increased fluidity in the range above 25 degrees C as compared to the untreated control membranes. These results suggest that guanylate cyclase is more dependent on phospholipid environment than adenylate cyclase in Tetrahymena plasma membranes, presumably offering evidence for the different location of two enzymes in the membrane.
Guanylate cyclase [EC 4,6,2,1] was found to be localized principally in the surface membrane (pellicle) of Tetrahymena pyriformis and to some extent in cilia, mitochondria and microsomes. In the pellicle fraction, guanylate cyclase activity with Mn2+ was higher than that with Mg2+. Addition of calmodulin and Ca2+ to the reaction mixture resulted in marked activation of guanylate cyclase with Mg2+ and Mn2+, but the extent of enhancement by calmodulin was greater with Mg2+ than with Mn2+. The activated enzyme could use either Mg2+ or Mn2+ as an equipotent cofactor.
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