Systemic-portal shunt in unilateral iliac vein stenosis.
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Adult↗
Biomedical subjects
M Fujioka
Publications and source records attributed to M Fujioka.
Specific changes in human brain after hypoglycemic injury.
BACKGROUND AND PURPOSE: Very few reports are available on serial changes in the human brain after severe hypoglycemic injury. The aim of this study was to investigate sequential neuroradiological changes in brains of patients after hypoglycemic coma compared with those after cardiac arrest previously studied with the same methods. METHODS: We repeatedly studied CT scans and MR images obtained at 1.5 T in four vegetative patients after profound hypoglycemia associated with diabetes mellitus. RESULTS: In all patients, consecutive CT scans showed symmetrical, persistent low-density lesions with transient enhancement in the caudate and lenticular nuclei and transient enhancement in the cerebral cortex 7 to 14 days after onset. Serial MR images consistently revealed symmetrical lesions of persistent hyperintensity and hypointensity on T1- and T2-weighted images, respectively, in the caudate and lenticular nuclei, cerebral cortex, substantia nigra, and/or hippocampus from 8 days to 12 months after onset. CONCLUSIONS: Repeated MR images revealed specific lesions in the bilateral basal ganglia, cerebral cortex, substantia nigra, and hippocampus, which suggests the particular vulnerability of these areas to hypoglycemia in the human brain. We speculate that the localized lesions represent tissue degeneration, including some combination of selective neuronal death, proliferation of astrocytic glial cells, paramagnetic substance deposition, and/or lipid accumulation. The absence of localized hemorrhages on MR images in hypoglycemic encephalopathy is in marked contrast to the presence of regional minor hemorrhages in postischemic-anoxic encephalopathy.
Aged↗
Maxillary growth following atelocollagen implantation on mucoperiosteal denudation of the palatal process in young rabbits: implications for clinical cleft palate repair.
OBJECTIVE: The implantation of atelocollagen matrix on the denuded surface of palatal bone following cleft palate repair has been used because it enhances wound healing. This study was performed to determine whether the beneficial effect of atelocollagen matrix implantation on the prevention of scar tissue contraction also inhibits the scar's interference with the growth of maxillary bone. METHOD: Fifty New Zealand White rabbits (aged 4 weeks) underwent palatal mucoperiosteal denudation, and etelocollagen matrix was implanted on the left palatal process. The opposite side was left open as a control. RESULTS: Histopathologically, the implantation side exhibited early infiltration of mononuclear cells and fibroblasts, and better growth of connective tissue strands and epithelium. In addition, the formation of rate ridges were seen that were similar to the normal mucosa. The bone of the atelocollagen-implanted side was covered with regenerated periosteum-like layers, but that of the control side was lined by granulation tissue, suggesting the existence of continuous inflammation on the periosteal region. When the animals reached adulthood (aged 24 weeks), the areas of scars and palatal processes, palatal shelf width, molar teeth incline, and bone mineral contents were measured and compared between sides. The atelocollagen-applied scars showed less contraction, the area and width of atelocollagen-implanted palatal processes showed more satisfactory growth, and the dental arch deformity was suppressed in comparison with the control side. CONCLUSIONS: Our results suggest that the use of atelocollagen matrix on the denuded bone surface following cleft palate repair decreases the scar's effect on maxillary growth.
Aging↗
Effects of aortic valve replacement on exercise duration and functional status in adults with valvular aortic stenosis.
OBJECTIVE: To evaluate the effect of aortic valve replacement on left ventricular function, functional status and exercise duration in an adult population with valvular aortic stenosis. DESIGN: Prospective study of initially asymptomatic patients with pre- and postvalve replacement echocardiography, functional status score and exercise data. SETTING: University-affiliated, tertiary care teaching hospital. PATIENTS: Valvular aortic stenosis patients referred from academic and private practice internists and cardiologists (n = 34, 65% men, mean age 68 +/- 11 years, preoperative aortic valve area 0.9 +/- 0.4 cm2). INTERVENTIONS: Annual Doppler echocardiography, functional status questionnaires and, if possible, Bruce protocol maximal exercise tolerance tests. MAIN RESULTS: Aortic valve replacement resulted in a decrease in maximum jet velocity (pre 4.7 +/- 0.7 versus post 2.9 +/- 0.7 m/s, P = 0.0001) and left ventricular mass (pre 167 +/- 37 versus post 134 +/- 32 g, P = 0.0001) and an increase in left ventricular ejection fraction (pre 65 +/- 11 versus post 69 +/- 10%, P = 0.05) at rest. However, there was no change in the ratio of early to atrial diastolic filling velocities (pre 1.2 +/- 0.5 versus post 1.4 +/- 0.8, not significant), exercise tolerance as assessed by estimated functional aerobic impairment (pre 26 +/- 32 versus post 22 +/- 27%, not significant) or functional status score (pre 89 +/- 13 versus post 91 +/- 11, not significant). CONCLUSIONS: When the aortic valve is replaced promptly at symptom onset, despite improvement in resting left ventricular systolic performance, there is no evidence of improvement in exercise capacity or functional status.
Aged↗
[Clinical and echocardiographic evaluation of the Medtronic-Hall 20A valve in the aortic position in patients with small aortic annulus: comparison with the 21 mmSJM valve].
We compared the results of Medtronic-Hall 20A aortic valve (MH20A) replacement with those of 21 mm SJM valve (SJM21A) replacement. The subjects were 17 patients who underwent aortic valve replacement with MH20A. The mean age was 65.4 +/- 8.8 years in the MH20A group. The average body surface area in the MH20A group was 1.37 +/- 0.08 m2, which was significantly smaller than in the SJM21A group (1.55 +/- 0.09 m2). The postoperative follow-up period was 51 months at maximum and 20 months on average. There was one hospital death and two late deaths in the MH20A group. The other patients were categorized NYHA I classification. The trans-valvular peak pressure gradient soon after surgery was 21 +/- 9.3 mmHg in the MH20A group, and 23.9 +/- 8.8 mmHg in the SJM21A group. Preoperative and late postoperative echocardiograms demonstrated significant decrease in mean left ventricular end-diastolic diameter and left ventricular end-systolic diameter in the both groups. Mean left ventricular hypertrophy was decreased to 22.8 +/- 4.6 mm from 25.0 +/- 3.9 mm in the MH20A group, and 24.1 +/- 4.3 mm from 28.5 +/- 5.6 mm in the SJM21A group. These data suggest that aortic valve replacement with MH20A is useful for patients who have smaller body surface area (< 1.50 m2) with a small aortic annulus.
Aged↗
Crystal structure of glycine N-methyltransferase from rat liver.
Glycine N-methyltransferase (GNMT) from rat liver is a tetrameric enzyme with 292 amino acid residues in each identical subunit and catalyzes the S-adenosylmethionine (AdoMet) dependent methylation of glycine to form sarcosine. The crystal structure of GNMT complexed with AdoMet and acetate, a competitive inhibitor of glycine, has been determined at 2.2 A resolution. The subunit of GNMT forms a spherical shape with an extended N-terminal region which corks the entrance of active site of the adjacent subunit. The active site is located in the near center of the spherical subunit. As a result, the AdoMet and acetate in the active site are completely surrounded by amino acid residues. Careful examination of the structure reveals several characteristics of GNMT. (1) Although the structure of the AdoMet binding domain of the GNMT is very similar to those of other methyltransferases recently determined by X-ray diffraction method, an additional domain found only in GNMT encloses the active site to form a molecular basket, and consequently the structure of GNMT looks quite different from those of other methyltransferases. (2) This unique molecular structure can explain why GNMT can capture folate and polycyclic aromatic hydrocarbons. (3) The unique N-terminal conformation and the subunit structure can explain why GNMT exhibits positive cooperativity in binding AdoMet. From the structural features of GNMT, we propose that the enzyme might be able to capture yet unidentified molecules in the cytosol and thus participates in various biological processes including detoxification of polycyclic aromatic hydrocarbons. In the active site, acetate binds near the S-CH3 moiety of AdoMet. Simple modeling indicates that the amino group of the substrate glycine can be placed close to the methyl group of AdoMet within 3.0 A and form a hydrogen bond with the carboxyl group of Glu15 of the adjacent subunit. On the basis of the ternary complex structure, the mechanism of the methyl transfer in GNMT has been proposed.
Amino Acid Sequence↗
Molecular characterization of a novel cancer cell line established from human carcinoma in pleomorphic adenoma (CaPA-4).
A cultured cell line (CaPA-4), derived from an undifferentiated carcinoma in a pleomorphic adenoma of the submandibular gland, was established through xenografted tumors in nude mice. Geneticin treatment eliminated surrounding mouse fibroblasts and yielded enriched tumor cells at an early stage of cell passage. In vitro, the line grew in a cobblestone pattern, revealing its epithelial origin. Chromosomal analysis by Giemsabanding confirmed its human origin, while electron microscopic examination showed its squamous-cell characteristics. CaPA-4 cells stained positive for the c-myc and Ha-ras antibodies. Molecular analysis showed over-expression of both c-myc and Ha-ras mRNA, with point mutation of p53 at codon 248 and of Ha-ras at codon 61. Amplification and rearrangement of the Ha-ras gene were observed; however, no loss of heterozygosity (LOH) of the p53 gene was detected by Southern blotting. This sequence of cancer-related gene activation may represent the malignant transformation from benign pleomorphic adenoma. This report describes the establishment and molecular characterization of this novel cell line from carcinoma in pleomorphic adenoma exhibiting squamous-cell differentiation. This could represent a useful model for investigating the cause of malignant transformation from human salivary-gland mixed tumors.
Adenoma, Pleomorphic↗
Probing the S-adenosylmethionine-binding site of rat guanidinoacetate methyltransferase. Effect of site-directed mutagenesis of residues that are conserved across mammalian non-nucleic acid methyltransferases.
Most mammalian non-nucleic acid methyltransferases share three sequence motifs. To gain insight into the S-adenosyl-methionine (AdoMet)-binding site of guanidinoacetate methyltransferase, we mutated several conserved residues that are found in or near motifs I and II. Conversion of either of two glycine residues of motif I (Gly67 and Gly69) to an alanine resulted in an inactive enzyme. These enzymes, although having UV absorption, fluorescence and far-UV CD spectra virtually identical with those of the wild-type enzyme, seem to be conformationally different from the wild-type enzyme as judged by near-UV CD spectra and the extent of urea denaturation, and are apparently not capable of binding AdoMet. Mutation of Tyr136 of motif II to a valine resulted in a decrease in Kcat/Km values for substrates. Changing this residue to a phenylalanine caused only a minor change in Kcat/Km for AdoMet. This suggests that the aromatic side chain stabilizes the binding of AdoMet. Mutagenic changes of Glu89, which is the residue corresponding to the conserved acidic residue on the C-terminal side of motif I, indicated its contribution to AdoMet binding. These results are consistent with the idea that both motifs I and II are crucial in forming the AdoMet binding site of guanidinoacetate methyltransferase.
Amino Acid Sequence↗
Functional expression of gastric H+,K(+)-ATPase and site-directed mutagenesis of the putative cation binding site and catalytic center.
Gastric H+,K(+)-ATPase was functionally expressed in the human kidney HEK293 cell line. The expressed enzyme catalyzed ouabain-resistant K(+)-dependent ATP hydrolysis. The K(+)-ATPase activity was inhibited by SCH 28090, a specific inhibitor of gastric proton pump, in a dose-dependent manner. By using this functional expression system in combination with site-directed mutagenesis, we investigated effects of mutations in the putative cation binding site and the catalytic center of the gastric H+,K(+)-ATPase. In Na+,K(+)-ATPase, the glutamic acid residue in the 4th transmembrane segment is regarded as one of the residues responsible for the K(+)-induced conformational change (Kuntzweiler, T. A., Wallick, E. T., Johnson, C. L., and Lingrel, J. B. (1995) J. Biol. Chem. 270, 2993-3000). When the corresponding glutamic acid (Glu-345) of H+,K(+)-ATPase was mutated to aspartic acid, lysine, or valine, the SCH 28080-sensitive K(+)-ATPase activity was abolished. However, when this residue was replaced by glutamine, about 50% of the activity was retained. This mutant showed a 10-fold lower affinity for K+ (Km = 2.6 mM) compared with the wild-type enzyme (Km = 0.24 mm). Thus, Glu-345 is important in determining the K+ affinity of H+,K(+)-ATPase. When the aspartic acid residue in the phosphorylation site was mutated to glutamic acid, this mutant showed no SCH 28080-sensitive K(+)-ATPase activity. Thus, amino acid replacement of the phosphorylation site is not tolerated and a stringent structure appears to be required for enzyme activity. When the lysine residue in the fluorescein isothiocyanate binding site (part of ATP binding site) was mutated to arginine, asparagine, or glutamic acid, the SCH 28080-sensitive K(+)-ATPase activity was eliminated. However, the mutant in which this residue was changed to glutamine had about 30% of the activity, suggesting that amino acid replacement of this site is tolerated to a certain extent.
Amino Acid Sequence↗
Rapid natriuresis and preventive hypervolaemia for symptomatic vasospasm after subarachnoid haemorrhage.
To prevent symptomatic cerebral vasospasm, we have used hypervolaemia (HV) or volume expansion in patients with aneurysmal subarachnoid haemorrhage (SAH) in recent years. In these patients we could not perform effective fluid and sodium (Na) replacement because of rapid and overwhelming water and Na loss. Although this phenomenon is characteristic under hypervolaemic states, we regard it important to elucidate the mechanism underlying initiation of vasospasm after aneurysmal SAH. Patients with aneurysmal SAH, operated on within 24 hours of onset, were analysed prospectively. We selected 17 patients in good pre-operative condition. Intravascular volume expansion was accomplished with plasma fractionate or albumin and crystalloid solutions in all patients. We divided the 17 patients into two groups; symptomatic spasm group (S-group) consisting of 4 cases developing transient ischaemic symptoms and non-symptomatic spasm group (NS-group) consisting of 13 cases. In S-group, rapid and marked natriuresis developed characteristically before the onset of ischaemic symptoms. The differences in daily Na balance between the two groups were significant on the 3rd and 5th days (p < 0.05). The mean cumulative Na balance in S-group during the 10 days of the study (-375 +/- 159 mEg) was higher than that of NS-group (-24.4 +/- 225 mEq) (p < 0.05). Rapid natriuresis preceded the development of ischaemic symptoms, and was important as a trigger for symptomatic vasospasm after SAH. We considered that hormonal disorders were implicated in this phenomenon, and atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), renin, and aldosterone were each measured three times during the period, with no significant differences, found between the two groups. It was speculated that another potent natriuretic factor, similar to ANP, induced a rapid selective natriuresis resulting in symptomatic vasospasm.
Aged↗
Metastatic calcification: accumulation of a bone tracer during dynamic data acquisition.
Metastatic calcification is often detected by bone scintigraphy. We recently saw metastatic calcification in the stomach and kidneys of a patient on continuous ambulatory peritoneal dialysis. Tc-99m HMDP accumulation into both organs was noted even in the first frame of dynamic data acquisition of 4 min/frame, suggesting that calcium deposits may create an aggressive process and we may obtain information on the calcium deposit rate to better understand the mechanism of metastatic calcification.
Aged↗
Method development for the determination of cefdinir and its related substances by high-performance liquid chromatography.
The validation of the HPLC method used for the determination of cefdinir and its related substances is described. The developed method was specific and stability-indicating and provided a linear response with concentration. The system and method precision, expressed as relative standard deviations, were not greater than 1%, and the reproducibilities within and between laboratories were acceptable for the assay method. The procedure can quantitate related substances greater than approximately 0.05% of the principal cefdinir peak.
Calibration↗
Transfection of wild-type TP53 induces differentiation in human gingival carcinoma cells.
We investigated the effects of transfection of wild-type TP53 on the growth properties of a human gingival carcinoma cell line, KOSC-3, in which the TP53 gene is mutated at codon 248 and overexpressed. The wild-type TP53 expression plasmid, pCDM8-p53/neo and the control plasmid, pCDM8/neo, were each stably transfected into KOSC-3 cells by using the calcium phosphate method. The number of G418-resistant colonies from wild-type TP53-transfected cells was approximately half that from plasmid controls. Exogenous wild-type TP53 transcripts were identified in four of the 20 G418-resistant clones analysed by reverse transcription PCR. Although the growth rates of the wild-type TP53+ clones did not drastically change during log phase, their saturation density was significantly reduced. The wild-type TP53+ cells were morphologically flat and enlarged when cultured in vitro, and were less able to form colonies in soft agar. In nude mice, the wild-type TP53+ clones formed subcutaneous tumours with conspicuous keratinisation and notable cell death that was not manifested in the parental and plasmid control cells. These findings indicate that the wild-type TP53 gene, even when it coexists with a mutated form, may function as a growth suppressor and differentiation inducer under restricted conditions in gingival squamous cell carcinoma.
Animals↗
Gender differences in left ventricular function at rest and with exercise in asymptomatic aortic stenosis.
In 29 women and 53 men with asymptomatic aortic stenosis, two-dimensional (2-D) and Doppler echocardiography were performed at rest and immediately after treadmill exercise testing to examine gender differences in left ventricular geometry, systolic and diastolic function, functional status, and exercise capacity. Aortic stenosis severity was similar between men and women. Women reported more functional impairment than men (88% +/- 14% vs 95% +/- 7%; p = 0.02). When indexed to body surface area, women had a smaller end-diastolic volume (39 +/- 14 vs 50 +/- 15 ml/m2; p = 0.002), end-systolic volume (13 +/- 6 ml/m2 vs 18 +/- 9 ml/m2; p = 0.01) and left ventricular mass (73 +/- 26 gm/m2 vs 84 +/- 21 gm/m2; p = 0.05), but a higher relative wall thickness in systole (1.5 +/- 0.4 cm vs 1.3 +/- 0.4 cm; p = 0.05), and fractional shortening (43% +/- 7% vs 39% +/- 10%; p = 0.03). Women had higher early and late transmitral velocities than did men (early, 92 +/- 24 cm/sec vs 79 +/- 29 cm/sec; p = 0.05; late, 97 +/- 30 cm/sec vs 68 +/- 23 cm/sec; p < 0.0001), a higher time-velocity integral in early diastole (18.2 +/- 4.8 cm vs 15.1 +/- 4.3 cm; p = 0.006), a significantly shorter exercise duration (4.5 +/- 4.1 minutes vs 8.0 +/- 3.9 minutes; p < 0.0001), a greater degree of functional aerobic impairment (25% +/- 48% vs 2% +/- 33%; p = 0.02), and a smaller increase in cardiac output with exercise (5.4 +/- 3.5 L/min vs 8.0 +/- 4.3 L/min; p = 0.01), in spite of similar peak heart rate and blood pressure responses. In these asymptomatic subjects with aortic stenosis, women had smaller, relatively hypercontractile ventricles, a different diastolic filling profile, more exercise limitation, and poorer functional capacity. These findings demonstrate the importance of gender in the response of the left ventricle to chronic pressure overload.
Adult↗
Characterization of the isoenzymes of cyclic nucleotide phosphodiesterase in human platelets and the effects of E4021.
In extracts of human platelets, three isoenzymes of cyclic nucleotide phosphodiesterase (PDE), namely, PDE2, PDE3, and PDE5, were identified; activities of PDE1 and PDE4 were not detected. In human platelets, the cGMP-hydrolytic activity was about six times higher than the cAMP-hydrolytic activity, and PDE5 and PDE3 are the major phosphodiesterase isoenzymes that hydrolyze cGMP and cAMP, respectively. PDE5 exhibited organ-specific expression in humans, and platelets were among the tissues richest in PDE5. A novel inhibitor of PDE5, sodium 1-[6-chloro-4-(3,4-methylenedioxybenzyl)aminoquinazolin-2-yl ] piperidine-4-carboxylate sesquihydrate (E4021), was a potent and highly selective inhibitor of human platelet PDE5. However, E4021 (up to 10 microM) did not inhibit 9,11-epithio-11,12-methano-thromboxane A2-induced platelet aggregation, in vitro. E4021 plus SIN-1 (3-morpholino-sydnonimine), at concentrations that had little effect individually, inhibited aggregation. These results suggest the unique distribution of phosphodiesterase isoenzymes in human platelets and the PDE5 inhibitors might be useful as a new class of antiplatelet drugs.
3',5'-Cyclic-GMP Phosphodiesterases↗
Degradation kinetics and isomerization of cefdinir, a new oral cephalosporin, in aqueous solution. 1.
Hydrolytic degradation products of cefdinir were studied in acidic (pH 1), neutral (pH 6), and basic (pH 9) solutions. Seven major degradation products were isolated by preparative and/or high-performance liquid chromatography and characterized by UV, IR, 1H-NMR, and mass spectra. To clarify degradation pathways in each pH solution, kinetic and product analyses during hydrolysis of cefdinir were carried out along with the followup reaction of representative degradation products. Cefdinir was shown to degrade via two major degradation routes: beta-lactam ring-opening and pH-dependent isomerizations (lactonization, epimerization at C-6 or C-7, syn-anti isomerization of N-oxime function).
Administration, Oral↗
Degradation kinetics and isomerization of cefdinir, a new oral cephalosporin, in aqueous solution. 2. Hydrolytic degradation pathway and mechanism for beta-lactam ring opened lactones.
Hydrolysis of cefdinir leads to pH-dependent isomerizations and beta-lactam ring-opening. Lactam ring opened gamma-lactones were produced as a mixture of four diastereoisomers based on the lactone methyl, and C-6 isomerizations in acidic to neutral solutions. Cefdinir and its 7-epimer were hydrolyzed to clarify the pathway leading to these lactones and the mechanism of C-6 epimerization with the aid of chiral separation techniques. Chiral separation using a bovine serum albumin column was employed to detect the beta-lactam ring opened products of cefdinir and its 7-epimer; the C-6 and C-7 isomerization was thereby observed; however, it was found to be pH-dependent at pH > or = 9. Optical activity detection applied to the lactones produced from cefdinir and its 7-epimer demonstrated that the corresponding peaks of these lactones were enantiomeric pairs. In addition, the smallest rate constant at pH 4 was observed for C-6 epimerization of the lactones, and it was found to proceed without deprotonation at C-6 by 1H-NMR spectroscopy. From the results of these studies, a plausible mechanism for C-6 epimerization has been proposed. Additionally, it was confirmed that two degradation pathways were involved during hydrolysis of cefdinir to the lactone.
Administration, Oral↗
Runt domain partner proteins enhance DNA binding and transcriptional repression in cultured Drosophila cells.
BACKGROUND: The Drosophila gene runt plays multiple roles during embryogenesis, including one as a pair-rule class segmentation gene. The runt protein (Runt) contains an evolutionarily conserved domain (the Runt domain) that is found in several mammalian proteins including the human protein AML1, which is involved in many chromosome translocations associated with leukaemia. Specific DNA binding activity of a mammalian Runt domain is enhanced by a partner protein called PEBP2beta/CBFbeta. DNA binding activity of Drosophila Runt is also stimulated by this protein, suggesting the existence of a similar Runt partner protein in Drosophila. RESULTS: We report here the cloning of two closely linked Drosophila genes, runt domain partner (rp) beta1 and beta2, that encode homologues of mouse PEBP2beta/CBFbeta. They are highly homologous to each other and to the mammalian counterpart. Either of the rpb proteins is capable of forming a complex with Runt and stimulating its DNA binding activity, but their temporal and spatial distributions are quite dissimilar, suggesting that functional specificity of Runt may be conferred by the interacting partner. Runt represses transcription dominantly when coexpressed with either partner in cultured cells, a function consistent with a direct role for Runt in regulating expression of the even-skipped gene in Drosophila embryos. CONCLUSIONS: Drosophila Runt can interact with either of two Runt domain partners, and the resulting complex functions as an active repressor of transcription.
Amino Acid Sequence↗