Search PubMed⌕ Search

Biomedical subjects

M Tsukamoto

Publications and source records attributed to M Tsukamoto.

At least 19 recordsLinked to original sources
PubMed2000

Infiltrating dendritic/Langerhans cells in primary breast cancer.

It is fully anticipated that dendritic cells (DCs) will become a mainstay for inclusion in biological therapies for patients with cancer including breast cancer. To elucidate the cellular composition of DCs infiltrating human breast cancers, we investigated the correlations between the density of infiltrating DCs and some clinicopathological factors of breast cancer patients, examined cytokine expression on cancer cells and finally, assessed the numbers of CD45RO+ tumor infiltrating lymphocytes (TIL). Tissues adjacent to cancer nests contained significantly more S-100 protein+ and S-100 protein+ CD1a- DCs, but less CD1a+ DCs, than the nests. In invasive ductal carcinomas infiltration by S-100 protein+ DCs within and adjacent to nests, CD1a+ DCs within nests and S-100 protein+ CD1a- DCs adjacent to nests was denser than that in non-invasive carcinomas. With respect to the histological subtypes, there were fewer DCs in scirrhous carcinomas. Patients with stage IV disease had significantly fewer DCs of primary lesions than at other clinical stages. There were good correlations between infiltration by S-100 protein+ DCs and expression of the cytokines GM-CSF, IL-1alpha and TNF-alpha on cancer cells and between GM-CSF expression and S-100 protein+ CD1a- DCs. There was a close correlation between CD45RO+ TIL and S-100 protein+ DC densities both within and adjacent to the cancer nests and the S-100 protein+ CD1a- DC density adjacent to the cancer nests. Despite extensive immunoelectron microscopic observation, CD1a+ DCs within cancer nests contained only few Birbeck's granule-like structure. These data indicate that cancer nests are infiltrated predominantly by CD1a+ DCs, whereas S-100 protein+ CD1a- DCs predominate in surrounding tissues, and a infiltration by DCs may require cytokine expression on cancer cells and simultaneous lymphocyte infiltration. The findings of this clinicopathological study indicate the importance of evaluating simultaneously the types and localizations of infiltrating DCs in cancer tissues.

Adenocarcinoma, Scirrhous↗
PubMed2000

Paraquat-induced membrane dysfunction in pulmonary microvascular endothelial cells.

Membrane dysfunction monitored by lactate dehydrogenase release from cultured pulmonary microvascular endothelial cells of pigs, which were exposed to paraquat at different concentrations (0.1-2 mM), was examined. Paraquat caused a time-dependent increase in lactate dehydrogenase release. Lactate dehydrogenase releases after 72 hr, 32, 58, and 84% by 0.1, 0.5, and 2 mM paraquat, respectively, were well correlated with cell viability measured by cell adherence. In contrast, reductions of two tetrazolium compounds were depleted profoundly by 72 hr after exposure to 0.5 mM paraquat, suggesting depletion of intracellular reductive substances. Extracellular hydrogen peroxide began to significantly increase 56 hr or 32 hr after exposure to 0.5 mM or 1.5 mM paraquat, respectively, preceding the initial increase of lactate dehydrogenase release (64 hr by 0.5 mM or 48 hr by 1.5 mM). Lactate dehydrogenase release 72 hr after exposure to 0.5 mM paraquat was prevented strongly by catalase (1000 units/ml), but weakly by superoxide dismutase (1000 units/ml). These enzymes failed to restore the reduced acid phosphatase activity. Also, 0.1 mM desferal or alpha,alpha'-dipyridyl protected lactate dehydrogenase release. Similarly, 1 mM thiourea or dimethylthiourea, and 0.5 mM alpha-tocopherol or trolox, were effective, but diethylenetriaminepentaacetic acid (0.1 mM) and probucol (5 or 10 microM) were ineffective. Exposure of 0.5 or 1.5 mM paraquat suppressed levels of lipid peroxidation. These results indicate that membrane dysfunction by paraquat is ascribed to an iron-catalyzed reaction of extracellularly increased hydrogen peroxide. A deleterious species for the membrane dysfunction is discussed.

Acid Phosphatase↗
PubMed2000

Preserved extrinsic neural connection between gallbladder and residual stomach is essential to prevent dysmotility of gallbladder after distal gastrectomy.

Many reports have been made on gallbladder dysfunction after gastric surgery. We reported that the gallbladder contractions were abolished after antrectomy. Our hypothesis is that preservation of the neural connection along gastric vessels maintains normal gallbladder function during fasting after antrectomy. Six dogs underwent antrectomy with preservation of the extrinsic nerves and six other dogs underwent conventional antrectomy with dissection of the extrinsic nerves and vessels. Laparotomy alone was performed on another six control dogs. Motor activities of the gallbladder and upper gastrointestinal tract were recorded by strain gauges in conscious dogs. Motilin and CCK-OP were used for pharmacological interventions. In conventional antrectomy, the amplitudes of the cyclic motor activity of the gallbladder and the stomach during fasting were significantly reduced, while this activity was maintained in dogs when extrinsic nerves were preserved. The coordination of the motor activity among the gallbladder, stomach and the duodenum was not impaired in the dogs when extrinsic nerves were preserved. The contractions of the gallbladder induced by exogenous motilin were reduced significantly in conventional antrectomy. Therefore, the preserved neural connection along the gastric vessels maintains normal gallbladder function in the fasting state even after distal gastrectomy.

Animals↗
PubMed2000

Accommodation causes with-the-rule astigmatism in emmetropes.

PURPOSE: To measure the changes in astigmatism when bilateral emmetropes accommodate. METHODS: Bilateral emmetropes accommodative responses were measured with an improved photorefractometer PR-1100, which measured binocular refraction in all meridians simultaneously as a fixation target was shown in natural space. RESULTS: The accommodative responses in the vertical meridian are greater than those in the horizontal meridian. In the horizontal meridian, the accommodative responses are less than the accommodative stimulus. CONCLUSIONS: When accommodating the majority of bilateral emmetropes show with-the-rule astigmatism and lag of accommodation in the horizontal meridian.

Accommodation, Ocular↗
PubMed2000

New cytotoxic agents, BE-54238A and B, produced by a streptomycete.

New cytotoxic substances, designated BE-54238A and B, were isolated from the culture broth of Streptomyces sp. A54238. The active principles were extracted from the mycelium by methanol and purified by Diaion HP-20 and Sephadex LH-20 column chromatographies. BE-54238A and B exhibited cytotoxic activity against murine and human tumor cell lines.

Animals↗
PubMed1999

Evaluation of cationic liposome suitable for gene transfer into pregnant animals.

Cationic liposome-mediated in vivo gene transfer represents a promising approach for somatic gene therapy. To assess the most suitable liposome for gene delivery into a wide range of organs and fetuses in mice, we have explored several types of cationic liposomes conjugated with plasmid DNA carrying the beta-galactosidase gene through intravenous injection into pregnant animals. Transduction efficiency was assessed by Southern blot analysis and expression of the transferred gene was evaluated by enzymatic demonstration of beta-galactosidase activity. Through the analysis of several types of recently synthesized cationic liposome/lipid formulations, DMRIE-C reagent, a liposome formulation of the cationic lipid DMRIE (1, 2-dimyristyloxypropyl-3-dimethyl-hydroxy ethyl ammonium bromide) and cholesterol in membrane-filtered water met our requirements. When the plasmid DNA/DMRIE-C complexes were administered intravenously into pregnant mice at day 11.5 post coitus (p.c.), transferred genes were observed in several organs in dams and were expressed. Furthermore, although the copy numbers transferred into embryos were low, we observed reporter gene expression in the progeny.

Animals↗
PubMed1999

Experimental study on the bilirubin metabolism after major hepatectomy: alterations in the proportions of bile bilirubin subfractions.

Bilirubin metabolism after major hepatectomy was investigated experimentally using rats. After a 70% and an 80% hepatectomy, proportions of bilirubin diglucuronide (BDG) decreased, and reversely, those of bilirubin monoglucuronide (BMG) increased. These changes were even more remarkable after an 80% hepatectomy. Parallel to the decrease in the proportions of BDG, the concentrations of uridine diphosphoglucuronic acid (UDP-GA) in the remnant liver decreased, and there was a significant correlation between the changes in BDG and UDP-GA. Although UDP-glucuronyltransferase (UDP-GT) activity and energy charge of the remnant liver also decreased after surgery, these decreases were mild and returned to the control level earlier than BDG. And there was no significant correlation between the changes in BDG and those in UDP-GT activity and energy charge. In this study, the decrease of the proportions of BDG in the bile juice was long term after partial hepatectomy and the period of the decrease became longer according to the augmentation of the volume of the hepatectomized liver. We clarified that the process of the UDP-GA production was inhibited after hepatectomy and the decrease of the proportions of BDG was derived from a deficiency of substrate of the glucuronidation, UDP-GA.

Animals↗
PubMed1999

Change of liver function in hypertrophying lobe of rabbit liver after portal branch ligation.

Preoperative portal embolization (PE) is useful for the prevention of postoperative liver failure after extended hepatectomy. However, clinical evaluation of liver function in the hypertrophying lobe after PE has not been studied. Here we report functional changes in the hypertrophying lobe using a 80% portal-branch-ligation rabbit model. Liver function was evaluated by the expression of liver-specific genes detected by Northern blot analysis and plasma disappearance rate of indocyanine green (ICG). The weight of the unligated lobe after portal ligation increased about twofold on the 7th postoperative day (POD) and about threefold on the 14th POD. The mRNA levels of the liver-specific genes (albumin, aldolase B, and tyrosine aminotransferase) in the unligated lobe decreased to about 50% on the 1st POD and returned to the preoperative levels on the 7-14th POD. In contrast, the expression of histone H2B mRNA increased on the 3rd-7th POD. The plasma disappearance rate of ICG (K-ICG) in the rabbit that has only the unligated lobe did not significantly change during the first 7 days, but then improved and recovered to 80% of that in the rabbit that has whole liver on the 14th POD. These results indicate that liver function of the hypertrophying lobe after portal branch ligation does not increase during the first 7 days despite an increase in liver weight. This finding suggests that the compensatory hypertrophying liver is enlarging without functional augmentation in the early period after PE.

Animals↗
PubMed1999

Superoxide production from paraquat evoked by exogenous NADPH in pulmonary endothelial cells.

Superoxide production from paraquat in a pulmonary microvascular endothelial cell (PMEC) suspension was demonstrated using 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-alpha]pyraz in-3-one (MCLA), a chemiluminescence probe, to detect superoxide anions. Increased rates of superoxide production from paraquat, which were sensitive to superoxide dismutase (SOD), required the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) in the reaction medium, and occurred instantaneously after the addition of NADPH, which is impermeable to cell membranes. NADH as an electron donor was not as effective, and xanthine or succinate had no influence. Paraquat was anaerobically reduced in the presence of NADPH and PMECs to yield a one-electron reduced radical, and the reduction was inhibited by NADP+. Diphenyleneiodonium, an inhibitor of flavoprotein reductases, also markedly inhibited both paraquat reduction and superoxide production. These results indicate that NADPH-dependent superoxide production from paraquat probably occurs by a flavoprotein with NADPH-dependent reductase activity in cell membranes. NADPH-dependent superoxide production from paraquat was also reproduced using adherent PMECs on wells. Under these conditions, superoxide production was enhanced with agonists, including interleukin-1beta, A23187, and phorbol 12-myristate 13-acetate. The effect of the former two was blocked with staurosporine, while the latter's effect was suppressed with calyculin A.

Animals↗
PubMed1999

Functional analysis of O-linked oligosaccharides in threonine/serine-rich region of Aspergillus glucoamylase by expression in mannosyltransferase-disruptants of yeast.

The glaA gene encoding glucoamylase I (GAI) of Aspergillus awamori var. kawachi was heterologously expressed in mannosyltransferase mutants of Saccharomyces cerevisiae, in which the pmt1 gene and the kre2 gene were disrupted. The GAI enzymes expressed in these yeast mutant cells exhibited a lesser extent of O-glycosylation. Secretion of GAI expressed in the pmt1-disruptant and in the kre2-disruptant, respectively, was almost the same as that of GAI expressed in wild type (wt) strains. The number of O-linked mannose in GAI from wt yeast strain ranged in size from one (Man1) to five (Man5). On the other hand, the O-linked oligosaccharides of GAI from the pmt1-disruptant ranged in size from Man1 to Man4. Man5 was not detected and Man2-Man4 were reduced in proportion to the reduction of Man1. The O-linked oligosaccharides of GAI from the kre2-disruptant ranged from Man1 to Man4, and the molar amount of Man4 was reduced to 27.3%, compared to that of the wt strain. The hydrolyzing abilities for soluble starch and the adsorbing abilities on raw starch were comparable between both disruptants and wt strains. However, the digesting abilities for raw starch of the disruptants were decreased to 70% of those of the wt strains. Stabilities of GAI of the disruptants were reduced toward extreme pH and high temperature, compared to those of the wt strains. These results demonstrate that the O-linked oligosaccharides of GAI are responsible for the enzyme stability and activity toward insoluble substrates but not for secretion.

Aspergillus↗
PubMed1998

The antioxidant action of 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-alpha]pyra z in-3-one (MCLA), a chemiluminescence probe to detect superoxide anions.

The antioxidant effect of 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-alpha]pyraz in-3-one (MCLA), a Cypridina luciferin analog that acts as a chemiluminescence probe to detect O2.-, was investigated. MCLA produced a lag in oxygen consumption induced by cumene hydroperoxide in microsomes or by 2,2'-azobis (2-amidinopropane) dihydrochloride in liposomes and disappeared during the duration of the lag. MCLA profoundly inhibited the propagation reaction in Fe2+-dependent lipid peroxidation in liposomes, and MCLA disappearance accompanied by suppression of oxygen consumption markedly occurred in liposomes susceptible to peroxidation. Thiobarbituric acid-reactive substances in all systems used were also suppressed by MCLA dose dependently. These results indicate that MCLA has an antioxidant property through scavenging free radicals.

Amidines↗
PubMed1998

Results of surgical treatments and prognostic factors for hepatic hilar bile duct cancer.

Results of surgical treatments for 57 patients who underwent resection for hepatic hilar bile duct cancer between 1984 and 1997 were studied. Bile duct resection was performed in eight patients, and combined resection of bile duct and liver was performed in 49 patients, of whom vascular reconstruction was added in 15 patients and pancreatoduodenectomy (PD) in six patients. All the operations of bile duct resection that were not combined with hepatectomy were non-curative. In the patients who underwent combined resection of the bile duct with liver, outcomes of the patients with well-differentiated adenocarcinoma were better than those with other lower-grade tumors. The factors related to the degree of tumor extension, such as serosal invasion, lymph node metastasis, lymphatic vessel invasion, perineural invasion, venous vessel invasion, and vascular involvement, were other factors which significantly influenced the survival. Curative resection yielded significantly better results than non-curative resection. Of all these variables, good tumor differentiation and vascular involvement were recognized as important prognostic factors by multivariate analysis. Most of the postoperative deaths were encountered in patients who underwent additional operations to hepatectomy, such as vascular reconstruction or PD. Improvement of surgical techniques and perioperative care has yielded better outcomes of vascular reconstruction. However, the application of hepatopancreatoduodenectomy should be limited due to poor outcomes of widespread bile duct cancer of which the histological grade is usually low. Whereas prognosis of bile duct cancer involving the hepatic hilus is mainly determined by the biologic characteristics of the tumor, surgeons should consider the fact that most patients die of local recurrence regardless of the biologic character of the tumor when curative resection is not performed.

Adenocarcinoma↗
PubMed1998

Long-term results of porcine bioprostheses in the tricuspid position.

From January 1976 to September 1994, 26 patients underwent a tricuspid valve replacement (TVR) with porcine bioprostheses (Hancock II in 19 patients, Carpentier-Edwards in 3, Hancock standard in 2, Medtronic-Intact in 1, and Liotta in 1). The mean age of these patients was 38.4 years (range, 9 to 70 years). The mean follow-up period was 6.7 years (range, 1.8 to 16.5 years). There was a complete follow-up in 100%. There were two hospital deaths and three late deaths. The actuarial survival rate at 16 years was 78.7%+/-8.6%. Five patients developed structural deterioration. Four of these 5 patients underwent re-TVR. The actuarial freedom rate from structural deterioration at 10 years was 47.1%+/-19.1%. There were no instances of thromboembolism and prosthetic valve endocarditis. Our experience indicated the major problem of the porcine bioprostheses in the tricuspid position thus to be valve durability: however, the long-term actuarial survival rate was satisfactory, including no operative morality with re-TVR due to tricuspid prosthetic structural deterioration. We therefore conclude that the choice of a porcine bioprosthesis in the tricuspid position should be considered not only for patients with isolated tricuspid valve disease, but also for the patients who have not previously received mechanical valves in the mitral or the aortic valve position.

Adolescent↗
PubMed1998

Is atrial fibrillation resulting from rheumatic mitral valve disease a proper indication for the maze procedure?

BACKGROUND: There are a few patients without detectable atrial contraction despite restoration of atrial rhythm after the maze procedure for atrial fibrillation (AF) associated with mitral valve disease. METHODS: From January 1995 to March 1997, 29 consecutive patients with AF associated with mitral valve disease underwent our modified maze procedure combined with mitral or other valve operations. The causes of mitral valve disease were rheumatic mitral stenosis (n = 22) and nonrheumatic mitral regurgitation (n = 7). The 17 patients with postoperative atrial rhythm were divided into group I with rheumatic mitral stenosis (n = 10), and group II with mitral regurgitation of nonrheumatic origins (n = 7). RESULTS: Seventeen patients regained atrial rhythm, 2 patients had junctional rhythm, and another 10 remained in AF. Between the group of patients with restoration of atrial rhythm and that of patients remaining in AF, significant differences were found in the percentage with rheumatic disease, history of AF, and maximum f-wave voltage. The postoperative peak velocity of the atrial filling wave to peak velocity of early filling wave ratio for the left atrium measured using Doppler echocardiography was 0.25 in group I, which was significantly lower than that (0.42) in group II. CONCLUSIONS: Reconsideration of the indications for the maze procedure for AF associated with rheumatic mitral stenosis may thus be reasonable, particularly for cases in which replacement using a prosthetic valve is necessary, but we believe that patients with nonrheumatic mitral valve disease, especially those able to undergo reconstructive operations, are the best candidates for the maze procedure.

Adult↗
PubMed1998

Lucigenin reduction by NADPH-cytochrome P450 reductase and the effect of phospholipids and albumin on chemiluminescence.

To assess lucigenin, a chemilumigenic probe, as a detector of superoxide anion in microsomes, NADPH oxidation, lucigenin disappearance, and chemiluminescence in a system including purified NADPH-cytochrome P450 reductase were examined. NADPH oxidation was increased by adding lucigenin, and concurrently, its disappearance and oxygen consumption were also stimulated. Chemiluminescence, which is negligibly emitted in the presence of the reductase alone, was remarkably amplified with phospholipids and albumin. Menadione inhibited lucigenin disappearance resulting in suppression of chemiluminescence. Lucigenin chemiluminescence measured in microsomes appears not to reflect direct superoxide anion production from microsomal components and from quinones, such as menadione.

Acridines↗
PubMed1998

Altered biliary bilirubin profile in patients with persistent hyperbilirubinaemia after hepatic resection: analysis of bile bilirubin subfractions by high-performance liquid chromatography.

Subfractions of bilirubin in bile, obtained via biliary drainage tubes from 23 patients who had undergone radical surgery for bile duct cancer, were analysed by high-performance liquid chromatography for 14 days after surgery. Five principal conjugated bilirubins were resolved: bilirubin diglucuronide (BDG); bilirubin monoglucuronide monoglucoside (BGG); bilirubin monoglucuronide monoxyloside (BGX); and two isomers of bilirubin monoglucuronide. After surgery, depression in concentration of BDG and elevation of BGG and BGX were found. These alterations were of higher magnitude in patients who had undergone hepatectomy, and especially prolonged in patients with hyperbilirubinaemia. These results suggest that the alteration in proportions of bilirubin conjugates might be a cause of hyperbilirubinaemia after hepatectomy.

Aged↗
PubMed1998

Functional evaluation of the bileaflet mechanical valve in the aortic position using dobutamine-stress echocardiography: is a 23-mm prosthetic valve adequately large enough?

The issue of valve prosthesis-patient mismatch in small annular patients is still controversial. The hemodynamic function of bileaflet mechanical valves in the aortic position was examined using dobutamine-stress echocardiography. Forty-four patients were enrolled in the study and divided into 5 groups, according to prosthesis size, from 21 mm to 29 mm. The aortic peak pressure gradient (APG) increased significantly in all groups with dobutamine-stress and exceeded 50 mmHg in 83% of the 21-mm group, in 64% of the 23-mm group, and in 33% of the 25-mm group. The APG even exceeded 80 mmHg in 22% and 18% of the 21-mm and 23-mm groups, respectively. In these cases, the potential of 'valve prosthesis-patient mismatch' was considered. From the relationship between the APG and the prosthesis valve area index (VAI), 'critical VAIs' were found where patients were likely to enter the 'mismatch' status; that is, 1.22 and 1.77 cm2/m2, respectively, for the 5 and 10 microg/kg per min stages of dobutamine stress. This critical VAI range is useful in predicting the 'mismatch' patients preoperatively. Alternative procedures or prostheses should then be selected for them.

Adult↗