Early fluctuation in cyclosporine A trough levels affects long-term outcome of kidney transplants.
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Biomedical subjects
Publications and source records attributed to S Inoue.
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We compared intraoperative circulatory and respiratory complications and changes in body temperature during laparoscopic cholecystectomy by intraperitoneal insufflation of carbon dioxide gas (24 cases) with those by abdominal wall lifting (16 cases). The abdominal wall lifting method tended to produce fewer complications than the intraperitoneal insufflation method, but not significantly. In conclusion, the former was thought to be safer than the latter.
A 32-year-old woman was diagnosed with ventricular septal defect (VSD) with severe pulmonary hypertension (PH). Though Pp/Ps was 0.98, an operation was carried out because the index of pulmonary vascular disease (IPVD) was 1.73. Pp/Ps on the operation day was 0.51 and extubation was carried out on the next day. Five days after the operation, she suffered shock, convulsions and loss of consciousness, but these were relieved by endotracheal intubation. On the 7th day, because Pp/Ps was 0.97, we confirmed the diagnosis of PHC. PHC was treated by intravenous continuous infusion of a high dose of PGE1 (220 ng/kg/min) and tolazolin (Tz) (7-18 micrograms/kg/min) in combination with norepinephrine (0.07 microgram/kg/min) via a catheter in the descending aorta. Pp/Ps soon decreased and was 0.60 at 15 hours after administration of PGE1 and Tz. To prevent recurrent PHC, she was administered with PGE1 (20-60 ng/kg/min) intravenously for 3 weeks after improvement of PHC. As side effects of PGE1, she showed swelling and arthralgia of the hands and feet after 2 weeks. Those side effects improved after discontinuing of administration of PGE1.
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The report is a study of the cases in which elderly people (83 years-old male and 81 years-old female) diagnosed has having acute tuberculous pneumonia possibly suffered from subsequent perforation of lymph nodes in the bronchus. Neither of the patients had a prior history of tuberculosis treatment. Both patients were admitted to the hospital after being diagnosed with pneumonia. After the administration of antibiotics, the symptoms of illness improved, but chest roentgenograms were taken failed to show improvement. The patients were then transferred to our hospital, because sputa smear tests for Mycobacteria (Ziehl-Neelsen stain) were performed, and the results were positive. Case I (male) was suspected of having endobronchial tuberculosis, since rhonchi was audible in the left-front upper chest during expiration when performing auscultation. A bronchoscopy was conducted at which time ulcer lesions on the left upper lobe of the bronchus and perforated lymph node of the upper bronchus were detected. Case II (female) was suspected of having lung cancer and a bronchoscopy was performed due to the findings of a chest roentgenogram taken after one month of chemotherapy. A perforated lymph node in right truncus intermedius was detected. In this report, we discussed the early diagnosis of tuberculous pneumonia and the perforation of caseous lymph nodes in the bronchus, which was the main cause of tuberculous pneumonia.
Calcium(2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate dihydrate (KAD-1229) was found to have potent hypoglycemic effects. This study was designed to elucidate its mechanisms by comparing its action with those of the antidiabetic hypoglycemic agents known as sulfonylureas in vivo and in vitro. In fasted beagles, oral administration of 0.1 to 3.0 mg/kg of KAD-1229 induced dose-dependent and significant reductions of plasma glucose levels with 43.4% maximum reduction at 1 hr, and the significant hypoglycemic effects largely disappeared within 2 hr after oral administration; 1.0 to 10 mg/kg of gliclazide also induced dose-dependent and significant reductions of plasma glucose with 44.2% maximum reduction at 3 hr, and the hypoglycemic effects continued for over 7 hr. One and 3.0 mg/kg of KAD-1229 increased plasma insulin levels, with the peak levels at 30 min, whereas 3.0 and 10 mg/kg of gliclazide increased it with the peak levels at 1 to 2 hr after dosing. Similar rapid and short-acting hypoglycemic effects of KAD-1229 were observed in rats. This compound stimulated insulin release from isolated mouse islets at a concentration from 3 x 10(-7) M to 10(-5) M. KAD-1229 stimulated insulin release from hamster's insulin-oma cell line, HIT T15 cells, at a concentration from 10(-8) M to 10(-5) M and inhibited 86Rb+ efflux from these cells with IC50 of 8.4 x 10(-9) M. It also inhibited [3H]glibenclamide binding to microsomes from HIT T15 cells (Ki = 1.3 x 10(-8) M).(ABSTRACT TRUNCATED AT 250 WORDS)
This paper evaluates the influence of the location of chewing on facial and jaw muscles' activity and mandibular movements. Ten subjects with complete dentition performed following chewing sequences; 1) right side chewing (unilateral location-unspecified chewing); 2) chewing on right molars; 3) chewing on right premolars; and 4) chewing on anterior teeth. Bilateral activities of upper lip, cheek, masseter (anterior, middle and posterior parts), and anterior bellies of digastrics were recorded by surface electromyography. Mandibular movements were simultaneously recorded by electrognathography. Chewing on anterior teeth showed smaller masseteric activity in posterior part, smaller envelope of motion, and lower velocity of both opening and closing than unilateral location-unspecified chewing and chewing on right molars. Chewing on premolars showed smaller envelope of motion than chewing on molars. No significant difference was found between unilateral location-unspecified chewing and chewing on premolars or molars.
In a past one decade from January 1981 to August 1991, 231 patients over 18 years old with congenital heart disease (CHD) including 65 patients with cyanotic (C) and 166 with acyanotic (AC) diseases, were surgically treated. There were one operative death (0.6 percent mortality) and three late deaths (1.9%) in 166 patients with AC diseases, whereas there were four operative (6.1%), and four late deaths (6.1%) in 65 patients with C. These patients were followed for 3 to 124 months (the mean of 46.4 +/- 11.9) after the operation. Compared with group AC, group C showed a high rate of early postoperative deaths or late deaths. Group AC comprised patients in their forties (95 patients with ASD and 15 with PDA) and those in their thirties (26 with VSD and 13 with ECD) at the operation. On the contrary, except 5 patients with Ebstein disease, a mean age of patients of group C at the operation lay in their twenties. Surgical outcomes for adult patients of group C still pose much problems compared with AC group in terms of decreased heart function, development of collateral circulatory pathway, and impaired hepatic and renal functions by long lasting hypoxemia. In group C decreased heart function or association of abscess of the brain might be the main cause of postoperative LOS. These findings indicate that early diagnosis, recent advanced operative procedure and appropriate postoperative care can provide symptomatic remission for even adult patients with severe CHD with a low mortality.
Estrogen receptor (ER)-binding fragments were isolated from human genomic DNA by using a recombinant ER protein. Using one of these fragments as a probe, we have identified an estrogen-responsive gene that encodes a putative zinc finger protein. It has a RING finger motif present in a family of apparent DNA-binding proteins and is designated estrogen-responsive finger protein (efp). efp cDNA contains a consensus estrogen-responsive element at the 3' untranslated region that can act as a downstream estrogen-dependent enhancer. Moreover, efp is regulated by estrogen as demonstrated at both the mRNA and the protein level in ER-positive cells derived from mammary gland. These data suggest that efp may represent an estrogen-responsive transcription factor that mediates phenotypic expression of the diverse estrogen action. Thus, the genomic binding-site cloning may be applicable for isolation of the target genes of other transcription factors.
alpha 2-->8-Linked polysialic acid (polySia) chains terminate O-linked oligosaccharide chains on Salmonidae fish egg polysialoglycoproteins (PSGPs). Expression of these surface PSGPs are developmentally regulated and the polySia epitope is functionally implicated in a number of distinct species-specific cell-cell recognition events during fertilization and early embryogenesis. To better understand the functional diversity of these PSGPs, structural studies of the polySia chains isolated from three genera and eight species of Salmonidae fish eggs were carried out by chemical, immunochemical, enzymatic, and 1H NMR methods. A remarkable degree of structural diversity was found, including differences in the N-acyl groups, i.e. N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), and in the presence of either O-acetyl substitution at C4, C7, or C9 or O-lactyl substitution at C9. The presence of heteropolymers containing both Neu5Ac and Neu5Gc residues was also an unexpected finding. Accordingly, the different forms of alpha 2-->8-linked homo- and heteropolymers of these polySia structures include: poly(Neu5Ac), poly(Neu5Gc), poly(Neu5,chi Ac2), poly(Neu5Gc chi Ac), poly(Neu5Ac, Neu5Gc), poly-(Neu5Ac, Neu5,chi Ac2), poly(Neu5Ac, Neu5Gc chi Ac), poly(Neu5Gc,Neu5,chi Ac2), and poly(Neu5Gc, Neu5-Gc chi Ac), where chi represents the site of acetylation at carbon atom 4, 7, or 9. The significance of this new structural information, together with our recent finding of alpha 2-->8-linked polydeaminoneuraminic acid, poly(KDN), in the rainbow trout egg vitelline envelope, is that it demonstrates the natural occurrence of multiple forms of alpha 2-->8-linked polySia chains in Salmonidae fish glycoproteins that have not been previously described. The results also predict that a remarkable array of polysialylated glycoconjugates is yet to be discovered in animals other than teleost fishes.
ER mRNA was detected as 6.0 kb band by Northern blot analysis in vascular smooth muscle cells (VSMC) derived from rat aorta. The presence of ER mRNA in VSMC was confirmed by reverse transcriptase-polymerase chain reaction using specific primers for rat ER cDNA. In addition, the immunocytochemistry of ER was performed in VSMC using a monoclonal anti-ER antibody which recognizes DNA-binding domain of ER. The immunoreactivity was distributed in the cytoplasm as well as in the nuclei. Thus, the expression of ER in VSMC was demonstrated at both the protein and the mRNA level. Furthermore, the expression of c-fos mRNA in VSMC was found up-regulated by 17 beta-estradiol treatment within 30 min. The observation that VSMC possess ER and respond to estrogen supports the idea that estrogen may directly influence vascular cell system through the ER.
Two acidic glycosphingolipids were isolated and purified from rainbow trout ovarian fluid. They were designated as ovarian fluid gangliosides ofg-2a and ofg-2b. Both of these glycolipids were found to contain glucose, galactose, and N-acetylgalactosamine in a molar ratio of 1:2:1, but they differ by the presence of 2 mol of deaminated neuraminic acid (KDN; 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) in ofg-2a and 1 mol each of KDN and 9-O-acetyl-KDN in ofg-2b. On the basis of composition analysis, methylation analysis, mild acid hydrolysis, fast atom bombardment mass spectrometry (FABMS), 400-MHz 1H nuclear magnetic resonance spectroscopy, and immunochemical analysis using a monoclonal antibody (mAb.kdn3G), the complete structures of these gangliosides were determined to be KDN alpha 2-->3Gal beta 1-->3GalNAc beta 1-->4(KDN alpha 2-->3)Gal beta 1-->4Glc beta 1-->Cer for ofg-2a [(KDN)GD1a] and 9-O-AcKDN alpha 2-->3Gal beta 1-->3GalNAc beta 1-->4(KDN alpha 2-->3)Gal beta 1-->4Glc beta 1-->Cer for ofg-2b [(KDN)GD1a(OAc+)]. The ceramide moieties (Cer) in both ofg-2a [(KDN)GD1a] and ofg-2b [(KDN)GD1a(OAc+)] were found by combining of the results from fatty acid analysis and FABMS measurements to be made up of 4-sphingenine and mainly a C24:1 fatty acyl chain (nervonate). The structures of ofg-2a and ofg-2b are novel, and they represent the second example of naturally occurring KDN-gangliosides. Mild acid hydrolysis of both ofg-2a and ofg-2b resulted in formation of (KDN)GM1a.
The recent finding of peptide:N-glycanase (PNGase) in medaka embryos (Seko, A., Kitajima, K., Inoue, Y., & Inoue, S., J.Biol. Chem. 266, 22110 (1991)) raised the question of how widespread is the occurrence of this type of de-N-glycosylating enzyme. In experiments designed to identify PNGase in the mammalian system, we searched for its activity in some cultured cell lines. Incubation of a 14C-labeled N-glycopeptide with extracts prepared from cultured cells resulted in producing the free glycan and the peptide. Detailed characterizations of the products, formed upon incubation of a 14C-labeled N-glycopeptide substrate with the enzyme preparation from C3H mouse loose connective tissue-derived L-929 cells, by HPLC, amino acid and carbohydrate composition analyses, and peptide sequence analysis unequivocally established the reaction products to be the free glycan having di-N-acetylchitobiosyl sequence at its reducing end and free peptide in which the originally glycan-linked Asn residue was converted to the Asp residue. This represents the first demonstration of PNGase in mammalian cells and thus PNGase appears to be a very common enzyme expressed in not only plants and bacteria but also a wide range of animals although its functional significance remains to be clarified.
DNA damage caused by UV radiation in the presence of riboflavin or hematoporphyrin was characterized by the DNA sequencing technique using 32P-labeled DNA fragments and the analysis of 8-hydroxydeoxyguanosine (8-OH-dG) formation in calf thymus DNA. Exposure of double-stranded DNA to 365 or 302 nm radiation in the presence of riboflavin induced the sequence-specific DNA cleavage which is different from that caused by 302 or 254 nm irradiation in the absence of a sensitizer. The specific cleavage sites were the guanine residues located 5' to guanine. On the other hand, when denatured single-stranded DNA was irradiated at 365 nm with riboflavin or hematoporphyrin, cleavages occurred at most guanine residues. With D2O, the sequence-specific damage of double-stranded DNA by riboflavin was not enhanced, whereas the damage to single-stranded DNA by hematoporphyrin was greatly enhanced. Photodynamic action of riboflavin caused the formation of 8-OH-dG in double-stranded DNA. The enhancing effect of D2O on 8-OH-dG formation was not observed with riboflavin. By contrast, hematoporphyrin plus 365-nm light induced the 8-OH-dG formation only in denatured single-stranded DNA and the 8-OH-dG yield was increased about 2-fold in D2O. ESR spin destruction experiments suggested that photoexcited riboflavin reacts with dGMP to produce riboflavin anion radical and guanine cation radical, but not with other mononucleotides. The estimated ratio of 8-OH-dG yield to total guanine loss indicates that the photoexcited riboflavin induces 8-OH-dG formation specifically at the guanine residue located 5' to guanine through electron transfer. The mechanism was discussed in relation to UV carcinogenesis.
Calpain inhibitor I, N-acetyl-leucyl-leucyl-norleucinal (ALLN), a cell-permeable synthetic tripeptide with an aldehyde at its C terminus specifically inhibits the activity of cysteine proteases. Since the regulated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase in Chinese hamster ovary (CHO) cells is blocked by ALLN and ALLN has a cytotoxic effect on cells, we attempted to isolate ALLN-resistant cells that overproduce an ALLN-sensitive protease(s). However, we obtained an ALLN-resistant cell line that overproduced P-glycoprotein (Sharma, R. C., Inoue, S., Roitelman, J., Schimke, R. T., and Simoni, R. D. (1992) J. Biol. Chem. 267, 5731-5734). To circumvent the multidrug resistance (MDR) phenotype during selection, we have stepwise selected an ALLN-resistant cell line of CHO cells in the presence of verapamil, a competitive inhibitor of P-glycoprotein. These non-MDR ALLN-resistant cells overexpress a 35-kDa protein and have increased aldo-keto reductase activity. Partial amino acid sequences of the 35-kDa protein are highly homologous to members of the aldo-keto reductase superfamily. The aldo-keto reductases are NADPH-dependent oxidoreductases and catalyze reduction of a wide range of carbonyl compounds such as aldehydes, sugars, and ketones. Our findings support the concept that a physiological function for aldo-keto reductases may be detoxification.
A novel carbohydrate-rich sialoglycopolyprotein of apparent molecular mass approximately 7000 Da was isolated from the fertilized eggs of the Medaka fish species, Oryzias melastigma. The glycoprotein was identified as a member of the L-hyosophorin family because it exhibited the following several distinctive features of L-hyosophorin molecules: (a) it contains a high proportion of carbohydrate (90% by weight), and (b) the amino acid sequence of the apopeptide was identical with that of the Oryzias latipes L-hyosophorin which has previously been demonstrated to be derived from a high molecular weight form of hyosophorin, i.e. H-hyosophorin, present in the cortical vesicles of unfertilized eggs. The apoprotein of H-hyosophorin is composed of tandem repeats of the L-hyosophorin apopeptide, i.e. it is a polyprotein. The structure of the carbohydrate portion of purified L-hyosophorin of O. melastigma was studied by composition and methylation analysis, selective chemical (periodate-Smith degradation; hydrazinolysis-nitrous acid deamination), and enzymatic (endo-beta-galactosidase; peptide:N-glycanase) degradation, together with instrumental methods (fast atom bombardment-mass spectrometry and 1H NMR). O. melastigma L-hyosophorin was found to contain two types of large, branched tetraantennary glycan units capped with sialic acids. The two glycans differ with respect to the branching pattern of the trimannosyl core (x = 4 or 6 in Eq. A). [formula: see text] The possible physiological significance of the hyosophorin family is discussed in the light of their unique structural features.
The sugar nucleotide, cytidine 5'-(3-deoxy-D-glycero-D-galacto-2-nonulosonic phosphate) (CMP-KDN) is expected to serve as a donor of KDN residues in the synthesis of KDN-containing glycoconjugates. We report here the identification and characterization of CMP-KDN synthetase, a novel enzyme responsible for synthesis of CMP-KDN from KDN and CTP. The enzyme was partially purified from the testis of rainbow trout (Oncorhynchus mykiss), where KDN gangliosides were first discovered (Yu, S., Kitajima, K., Inoue, S., and Inoue, Y. (1991) J. Biol. Chem. 266, 21929-21935), and used to synthesize CMP-[14C]KDN, which was characterized by 1H NMR. Vmax/Km studies showed that KDN was a preferred nonulosonic acid substrate compared to N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc) (4.4 x 10(-3) min-1 for KDN versus 2.3 and 1.8 x 10(-3) min-1 for Neu5Ac and Neu5Gc, respectively). CMP-KDN synthetase activity was maximal at pH 9-10 and at 25 degrees C. The presence of either Mg2+ or Mn2+ was essential for CMP-KDN synthetase activity. 25 mM Mg2+ stimulated formation of CMP-KDN more than 10-fold, yet only stimulated formation of CMP-Neu5Ac and CMP-Neu5Gc 4-fold, relative to 1 mM Mg2+. A kinetic study using mixed substrates showed that both CMP-KDN and CMP-Neu5Ac synthetase activities in the partially purified enzyme were due to the same active site of a single enzyme. In contrast, Neu5Ac and Neu5Gc were the preferred nonulosonic acid substrates for the calf brain CMP-sialic acid synthetase. Thus, mammalian CMP-sialic acid synthetases recognizes similar, yet distinctively different, substrate specificity determinants. Thus, the trout testis enzyme was considered to synthesize activated sugar nucleotides required for synthesis of both (KDN)GM3 and (Neu5Ac)GM3. The expression of CMP-KDN synthetase was shown to be temporally correlated with development and to parallel the developmental expression of (KDN)GM3 in sperm.