Combined atrioventricular block and sinus node dysfunction in Fabry's disease.
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Adult↗
Biomedical subjects
R Kato
Publications and source records attributed to R Kato.
Tracheal reconstruction by esophageal interposition: an experimental study.
The purpose of this study was to assess the possibility of reconstructing a circumferential tracheal defect with autogenous esophagus. In 6 mongrel dogs, a circumferential defect involving seven rings of the cervical trachea was reconstructed by interposing pedicled esophagus. A silicone T tube was used as a stent. The vertical limb of the T tube (usually referred to as the horizontal limb when used in humans) was cut shorter after the cervical wound had healed well, and it eventually was buried subcutaneously. Two dogs died 36 days after operation, and 1 died 28 weeks after operation. In no dog was the cause of death related to the operation or to a respiratory tract complication. Two dogs were put to death 4 weeks and 32 weeks after operation. They were well until then, and all the anastomoses between the trachea and the esophagus had healed fully without formation of granulation tissue. One dog is alive and well 14 months after operation. The vertical limb of the T tube retracted into the subcutaneous space, and there is no open cervical wound. Esophageal interposition might be a feasible technique for tracheal replacement in select groups of patients.
Anastomosis, Surgical↗
Polymorphism in hydroxylation of mephenytoin and hexobarbital stereoisomers in relation to hepatic P-450 human-2.
Stereoselective 4'-hydroxylations of R-(-)-mephenytoin and S-(+)-mephenytoin and 3'-hydroxylation of R-(-)-hexobarbital and S-(+)-hexobarbital were determined in liver microsomes of 14 Japanese subjects who were extensive metabolizers of mephenytoin and in five Japanese subjects who were poor metabolizers of mephenytoin. Content of P-450 human-2 assessed by Western blots was correlated to microsomal S-(+)-mephenytoin 4'-hydroxylation, R-(-)-hexobarbital 3' alpha-hydroxylation, and S-(+)-hexobarbital 3' beta-hydroxylation, and was less correlated to R-(-)mephenytoin 4'-hydroxylation, R-(-)-hexobarbital 3' beta-hydroxylation, and S-(+)-hexobarbital 3' alpha-hydroxylation. Antibodies raised against P-450 human-2 inhibited microsomal S-(+)-mephenytoin 4'-hydroxylation efficiently but was less efficient on R-(-)-mephenytoin 4'-hydroxylation in extensive metabolizers and on 4'-hydroxylation of mephenytoin enantiomers in poor metabolizers. The antibodies also inhibited R-(-)-hexobarbital 3' alpha-hydroxylation and S-(+)-hexobarbital 3' beta-hydroxylation but did not effectively inhibit the hydroxylation of the two other optical isomers of hexobarbital in extensive metabolizers and of four stereoisomers in poor metabolizers. These findings indicate the close relationship between polymorphic mephenytoin 4'-hydroxylation and two stereospecific hexobarbital hydroxylations, and they suggest that P-450 human-2 is a typical S-(+)-mephenytoin 4'-hydroxylase and a major hexobarbital 3'-hydroxylase in the livers of extensive metabolizers. The findings were further supported by the experiments that used P-450 human-2 complementary dexoyribonucleic acid-derived protein in yeast microsomes.
Cytochrome P-450 Enzyme System↗
Disruption of externally supported knitted dacron graft three years after implantation--a case report.
A knitted Dacron velour externally supported prosthesis was broken in two pieces at the supported portion 3 years after femoroposterior tibial bypass grafting. This type of graft problem has never been reported. Details of the clinical course, angiogram, CT scan, and scanning electron micrograph of a portion of the graft are shown. The externally supported Dacron prosthesis broke into two pieces along the broken coil of the middle portion. A possible cause of this failure may have been due to damage of the Dacron fibers in the process of heat fusing the coil. This presentation emphasizes the possibility of this rare externally supported graft complication, and the necessity for careful follow-up not only of the graft patency but also for the mechanical defects of the implanted externally supported Dacron graft itself.
Aged↗
Cytochrome b5 potentiation of cytochrome P-450 catalytic activity demonstrated by a vaccinia virus-mediated in situ reconstitution system.
A cDNA containing the full coding region of human cytochrome b5 was inserted into a vaccinia virus cDNA expression vector. Infection of human thymidine kinase-minus (TK-) 143 cells in culture with this recombinant virus resulted in production of 0.3 nmol of cytochrome b5 per mg of cell lysate protein. The expressed cytochrome had a reduced difference spectrum with a Soret peak at 424 nm, typical of pure cytochrome b5. TK- 143 cells have little detectable endogenous cytochrome b5, cytochrome P-450 (P450), and NADPH-P450 oxidoreductase. To test whether cytochrome b5 potentiated mixed-function monooxygenation in situ, these cells were coinfected with three recombinant vaccinia viruses individually carrying cDNAs encoding cytochrome b5, NADPH-P450 oxidoreductase, and P450 form IIB1. These triple-virus-infected cells were compared to cells infected with the P450IIB1 and NADPH-P450 oxidoreductase recombinant viruses with respect to P450IIB1-catalyzed monooxygenase activities. Cytochrome b5 specifically augmented the deethylation of p-nitrophenetole in microsomal membrane fractions of infected cells or when substrate was incubated directly with cells in situ. No significant increases were seen with P450IIB1-catalyzed testosterone, 7-ethoxycoumarin, or 7-pentoxyresorufin oxidations. These data demonstrate that cytochrome b5 is capable of specifically augmenting monooxygenase activities in intact cells.
Cell Line↗
Monomorphic and polymorphic isozymes of arylamine N-acetyltransferases in hamster liver: purification of the isozymes and genetic basis of N-acetylation polymorphism.
Two forms of cytosolic acetyltransferases, AT-I and AT-II, have been purified from hamster livers, and a comparison made of their chemical and catalytic properties and genetically expressed difference. Homogeneous AT-I and AT-II were 31 and 30 kd respectively on SDS-PAGE and catalyzed efficiently various N- and O-acetylations in their reconstitution systems. AT-I used both acetyl CoA and arylhydroxamic acids as acetyl donors, while AT-II did not utilize arylhydroxamic acids as acetyl donors. In the reconstitution system, purified AT-I, but not AT-II, catalyzed acetyl CoA-dependent O-acetylation of 2-N-hydroxyamino-6-methyldipyrido[1,2-alpha:3', 2'-d]imidazole (N-OH-Glu-P-1) and arylhydroxamic acid-dependent N-acetylation of 4-aminoazobenzene (AAB). On the other hand purified AT-II showed high activities of acetyl CoA-dependent N-acetylation of 2-aminofluorene (AF) and p-aminobenzoic acid (PABA). Polyclonal antibodies raised against AT-I inhibited cytosolic acetylations of N-OH-Glu-P-1 and AAB, and to a lesser extent of AF, while PABA N-acetylation was only marginally inhibited. Using Western blots, both AT-I and AT-II were recognized by the antibodies. AT-I was detectable in all the livers examined, and the content did not differ among the individuals (monomorphic distribution). In contrast, AT-II was distributed polymorphically, and the trimodal distribution of AT-II (high, intermediate and low) was correlated with the phenotype identified by cytosolic N-acetylations of AF and PABA (rapid, intermediate and slow). In addition, cross-mating experiments with intra- and inter-phenotype animals confirmed that hepatic AT-II isozyme is inherited by a Mendelian co-dominant trait. These results indicate that the polymorphic appearance of an acetyltransferase, AT-II, is responsible for the N-acetylation polymorphism in individual hamsters.
4-Aminobenzoic Acid↗
Anti-tumor promoting action of phthalic acid mono-n-butyl ester cupric salt, a biomimetic superoxide dismutase.
Skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by a concurrent and topical application of phthalic acid mono-n-butyl ester cupric salt (PAMBCu) in CD-1 mice initiated with 7,12-dimethylbenz[a]anthracene. PAMBCu inhibited TPA-caused epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. skin inflammation. However, neither PAMBCu nor superoxide dismutase (SOD) inhibited TPA-caused ODC induction in primary cultured mouse epidermal cells. 7-Bromomethylbenz[a]anthracene (BrMBA) is known to be a non-TPA type of tumor promoting agent. Epidermal ODC induction and inflammation caused by BrMBA were not inhibited by a concurrent application of PAMBCu. When mice were topically treated twice with PAMBCu, i.e. concurrently with and 7 h after BrMBA treatment, BrMBA-caused ODC induction was markedly suppressed. The same dose regimen of PAMBCu, however, failed to inhibit tumor promotion and inflammation caused by BrMBA. PAMBCu showed SOD-mimetic activity in superoxide generating systems, i.e. xanthine-xanthine oxidase reaction and TPA-stimulated polymorphonuclear leukocytes (PMN). Mono-n-butyl phthalate, which lacks SOD-mimetic activity, failed to inhibit TPA-caused ODC induction and skin inflammation. Therefore, inhibition by PAMBCu of TPA-caused tumor promotion, epidermal ODC induction and inflammation may be attributable to its SOD-mimetic activity. The results also support the contention that a superoxide anion of non-epidermal cell origin, such as PMN and macrophages, plays a role (probably some enhancing role) in in vivo ODC induction and tumor promotion caused by TPA. Failure of PAMBCu to inhibit BrMBA-caused tumor promotion suggests that superoxide anion generation is not involved in the tumor promoting action of this agent and that the anti-tumor promoting action of PAMBCu is dependent on the nature of the tumor promoting agents.
9,10-Dimethyl-1,2-benzanthracene↗
Purification and characterization of four catalytically active testosterone 6 beta-hydroxylase P-450s from rat liver microsomes: comparison of a novel form with three structurally and functionally related forms.
Four microsomal cytochrome P-450s (P-450), all of which are active testosterone 6 beta-hydroxylases, were purified to electrophoretic homogeneity from livers of phenobarbital-treated (P-4506 beta-1 and P-4506 beta-3) or dexamethasone-treated adult male rats (P-4506 beta-2 and P-4506 beta-4). Purified P-4506 beta-1, P-4506 beta-2, P-4506 beta-3, and P-4506 beta-4 had apparent molecular weights of 52,000, 51,000, 52,000, and 52,500 as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Absolute spectra revealed that all four P-450 forms had characteristic low-spin spectral patterns in their fully oxidized states. P-4506 beta-1 and P-4506 beta-3 displayed spectra of the reduced carbonyl complex with lambda max at 447 nm. P-4506 beta-2 and P-4506 beta-4 showed lambda max at 446 and 448 nm, respectively. Antibodies raised against each P-450 recognized all forms, although differences were observed with respect to the extents of cross-reactivities on Western blots. Form-specific peptide fragments were also detected among the four P-450 proteins after partial protease-digestion. P-4506 beta-1 was identical to P-4506 beta-3 in the first 26 residues of the NH2-terminal amino acid sequence, but differed by 13 residues from P-4506 beta-2. The amino-terminal sequence of P-4506 beta-2 was unique and was not identical with those of any rat P-450 previously reported. This P-450 form was detected in the livers of untreated male rats and was induced by treatment with dexamethasone, but not with phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Modulation of hepatic level of microsomal testosterone 7 alpha-hydroxylase, P-450a (P450IIA), by thyroid hormone and growth hormone in rat liver.
The effects of thyroid hormone and growth hormone on microsomal testosterone 7 alpha-hydroxylase, P-450a, were studied to understand the interaction of these hormone-mediated regulations in rats. In Western blots using anti-P-450a IgG, 1.7-fold higher content of P-450a was observed in livers of female than male adult rats, while no appreciable sex-related difference was detected in prepubertal rats and rats of 24 months of age. Treatment with n-propyl-2-thiouracil or thyroidectomy of male rats increased by 2-fold the hepatic content of P-450a, but neither regimen had a significant effect on the content in female rats. Levels of P-450a in both sexes of thyroidectomized rats were decreased by the supplementation of triiodothyronine (T3, 50 micrograms per kg, i.p. for 7 days) to levels similar to that observed in normal male rats. Hypophysectomy also caused an increase in microsomal P-450a content in male rats. Continuous infusion of human growth hormone, which mimicked the female secretion, further significantly increased the content in hypophysectomized rats to a level similar to that observed in normal female rats. In contrast, hepatic level of P-450a in hypophysectomized male and female rats was reduced by intermittent injection, which mimicked the male secretion. Clear suppression on the level of hepatic P-450a was also observed by the treatment of hypophysectomized rats with 5 or 50 micrograms/kg of T3 and of hGH-infused hypophysectomized rat with 50 micrograms/kg of T3.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Decrease in the metabolic activating capacities of arylamines in livers bearing hyperplastic nodules: association with the selective changes in hepatic P-450 isozymes.
The mechanism of the alteration in carcinogenic arylamine-activating capacities in livers bearing pre-neoplastic (or hyperplastic) nodules induced by the Solt-Farber protocol was investigated in relation to the changes in hepatic cytochrome P-450 isozymes. In the Salmonella mutagenesis test, the numbers of revertants induced with 2-amino-3-methylimidazo[4,5-f]quinoline and 2-aminofluorene were significantly lower in the presence of microsomes of nodule-bearing livers than of control livers. A similar tendency was also observed with another heterocyclic arylamine, 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole. In Western blots using specific antibodies against 5 different forms of cytochrome P-450, hepatic contents of P-450-male (a main constitutive form) and P-450b (a main phenobarbital-inducible form) were decreased in the livers with hyperplastic nodules to 63% and 35% of the corresponding controls, while no significant decrease was observed in the contents of P-448-H (a main 3-methylcholanthrene-inducible form), P-450(6 beta-1) (testosterone 6 beta-hydroxylase) and P-450e (a phenobarbital-inducible form). In accordance with the reduction in P-450-male, capacities for microsomal 16 alpha- and 2 alpha-hydroxylations, but not 6 beta-hydroxylation, of testosterone were decreased in the livers with hyperplastic nodules. Although P-448-H has higher capacities for the activation of arylamines than does P-450-male, the hepatic content of P-450-male is more than ten-fold higher than that of P-448-H in both normal and nodule-bearing livers. These results indicate that the selective decrease in hepatic content of P-450-male is likely to be a main cause of the decrease in arylamine metabolic activating capacities in livers with hyperplastic nodules.
Animals↗
Multi-drug combination therapy with vincristine-melphalan-cyclophosphamide-prednisolone was more effective than cyclophosphamide-prednisolone in stage III myeloma. The Nagoya Myeloma Cooperative Study Group.
A cooperative randomized clinical trial to compare the effectiveness of multi-drug combination chemotherapy (VMCP), vincristine-melphalan-cyclophosphamide-prednisolone) with CP (cyclophosphamide-prednisolone) for the treatment of multiple myeloma was performed. When the whole group of patients was evaluated, the choice of chemotherapy (VMCP or CP) was not a significant prognostic factor associated with response or survival by uni- or multivariate analysis, and the difference between the survival curves of the treatment groups was only marginally significant. However, when the analysis was confined to stage III patients, the choice of chemotherapy became a significant prognostic factor associated with both response rate and survival, and the statistical difference between survival curves was significant. Taking the disease characteristics of multiple myeloma into consideration, the better result obtained with multi-drug combination chemotherapy in the treatment of stage III patients is consistent with other studies supporting the superiority of multi-drug combination chemotherapy for patients with overt systemic disease.
Aged↗
Effects of dietary iodine on chemical induction of thyroid carcinoma.
Effects of dietary iodine on the induction of thyroid carcinoma using N-nitrosobis(2-hydroxypropyl)amine (BHP) were studied. Male Wistar rats were fed with an iodine-adequate diet (IAD group), an iodine-rich diet (IRD group) and an iodine-deficient diet (IDD group), respectively, until the time of sacrifice. From the 2nd experimental month, animals were injected with BHP once a week for 10 weeks. In the IAD and IRD groups, benign nodules and papillary carcinoma were found. The incidence of rats with benign nodules was 100% in both groups and animals with papillary carcinoma in the IAD and IRD groups comprised 33% and 29%, respectively. The area of the thyroid gland occupied by nodular lesions was much narrower in the IRD group than in the IAD group. In the IDD group, the thyroid showed marked enlargement due to multiple nodular proliferation of follicle cells. The incidence of rats with carcinoma was 100%, and not only papillary but also follicular carcinoma and one pulmonary metastasis were found. As the iodine content of the diet decreased, the nodular lesions increased in width and number, and the incidence of carcinoma in rats became higher. These effects of dietary iodine are probably related to the goitrogenic and/or promoting effects of TSH.
Administration, Oral↗
Effects of monensin on subcellular structure, thyroglobulin secretion and peroxidase activity of cultured thyroid cells obtained from patients with hyperthyroidism.
The effects of monensin on subcellular structure, release of thyroglobulin (TG) and peroxidase (PO) activity were investigated using primary cultures of thyroid cells obtained from patients with Basedow's disease (Basedow's cells). TG concentration in the culture medium was measured by a sandwich enzyme immunoassay and the amount of TG in cultured cells was measured with an identical sandwich enzyme immunoassay after lysis of the cells with Triton X-100. PO activity of cultured cells was measured by a biochemical method. Addition of TSH (10 mU/ml/day) to the culture medium increased the synthesis and release of TG. When monensin (1 micron/l) was added to the medium on the last day of a 3-day incubation with TSH, the Golgi complex showed vacuolative change ultrastructurally, and the amount of intracellular TG was increased, whereas the amount of TG in the culture medium and PO activity became lower than those in the control group. These results suggest that in cultured Basedow's cells, TG is secreted through the Golgi complex, and that the activity of PO is elevated after processing in the Golgi complex.
Cells, Cultured↗
High capacity of human skin for N-acetylation of arylamines.
Human skin showed high activity of cytosolic N-acetylation for two typical arylamine substrates, p-aminobenzoic acid (PABA) and 2-aminofluorene (AF). Their specific activities (per milligram protein basis) were comparable with those of hamster skin, which is known to have high acetylating capacities for several arylamines. In hamster skin, two other types of acetylation, N-hydroxy-4-acetylaminobiphenyl-dependent N-acetylation of AF (N,N'-acetyltransfer) and acetyl CoA-dependent O-acetylation of 2-hydroxyamino-6-methyl-pyrido[1,2-a:3',2'-d]imidazole (O-acetylation) also occurred, but no appreciable activity was observed in human skin for these two reactions. These results suggest that arylamines including prohaptens and carcinogens may be modified metabolically through N-acetylation at the first contact site, human skin. In addition, a good correlation was observed for N-acetylations of PABA and AF in human skin, implying that these N-acetylations may be catalyzed by the same or a closely related enzyme in human skin.
4-Aminobenzoic Acid↗
Tension-induced release of endothelium-derived relaxing factor; possible role in establishment of desensitization of norepinephrine-induced contraction in rat aorta.
In order to clarify the mechanisms involved in the endothelium-dependent development of desensitization of norepinephrine-induced contraction in rat aorta, we have tested the effect of repeated generation of tension without receptor stimulation. Even when tension alone, with a magnitude almost equal to that generated by norepinephrine, was applied to the endothelium-intact ring without norepinephrine, the ring became desensitized. In the absence of endothelium, the development of desensitization did not occur. Furthermore, L-NG-monomethyl arginine, which is an inhibitor of endothelium-dependent relaxing factor (EDRF) synthesis, prevented the occurrence of desensitization. It was even able to reestablish contractile force when added after the desensitization had developed, suggesting that an increased release of EDRF is necessary to produce the desensitization. Therefore, these results indicate that endothelium-dependent desensitization does not require adrenergic receptor stimulation, but rather that tension generation alone is sufficient to establish desensitization.
Animals↗
Plasma atrial natriuretic peptide in patients with Graves' disease.
In order to clarify the effect of thyroid hormone on the plasma atrial natriuretic peptide (ANP) concentration, 14 patients with Graves' disease and 6 normal control subjects were studied. They were all under constant sodium intake because dietary sodium is known to affect the amount of plasma ANP. Sodium intake remained constant at 171 mEq daily for five consecutive days at which time the ANP concentration was measured. Graves' disease patients were tested both before and after surgery. The preoperative, hyperthyroid ANP level concentration in Graves' disease patients was 6.7 +/- 2.3 fmol/ml compared to a significantly lower level of 4.2 +/- 1.4 fmol/in normal control subjects. Seven days after surgery when Graves' disease patients became euthyroid their ANP markedly decreased to 4.2 +/- 2.9 fmol/ml. In the present study we were able to confirm that under a constant sodium diet, high plasma ANP in patients with Graves' disease was reduced after surgery when they became euthyroid. Results also suggest that high circulating ANP might play an important role in sodium and water metabolism and hemodynamic changes in hyperthyroidism.
Age Factors↗
Effects of angiotensin II, ACTH, and KCl on the adrenal renin-angiotensin system in the rat.
Angiotensin II, ACTH and potassium chloride were administered to rats for 6 days and the effects on adrenal renin-like activity and adrenal angiotensin II/III immunoreactivity were investigated. Rats infused with angiotensin II (140 pmol/min) either ip or sc showed increases in adrenal angiotensin II/III immunoreactivity (p less than 0.05) and plasma aldosterone concentration (p less than 0.05), but no change in adrenal renin-like activity. Captopril treatment of angiotensin II-infused rats caused a slight decrease in angiotensin II/III immunoreactivity which did not reach statistical significance. In contrast, rats treated with ACTH (Cortrosyn-Z, 3 IU/day, sc) showed an increase in adrenal renin-like activity (p less than 0.01), but no significant change in adrenal angiotensin II/III immunoreactivity. Rats treated with KCl in drinking water showed increases (p less than 0.05) in adrenal renin-like activity, adrenal angiotensin II/III immunoreactivity, and plasma aldosterone. These results suggest that angiotensin II, ACTH and potassium, three major regulators of aldosterone secretion by the adrenal gland, have different effects on the adrenal renin-angiotensin system when administered in vivo.
Adrenal Glands↗
[The influence of face masks and a nasal nozzle on nasal airflow].
In an attempt to detect the influence of various kinds of face masks and a nasal nozzle on nasal airflow, we made measurements of nasal resistance by a head-out body plethysmograph with or without the masks on the face or the nozzle to the nostril of the normal adult subjects. The mean values of nasal resistance with the masks differed from the mean values without the masks significantly. No significant difference between values with and without the nozzle was found. The coefficient variations of 40 consecutive measurements of nasal resistance with the masks or the nozzle had wider ranges than those without the apparatuses. But the variation due to the nozzle was the minimum in the apparatuses.
Adult↗