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Biomedical subjects

M Hosono

Publications and source records attributed to M Hosono.

At least 55 records · Page 3Linked to original sources

F344/Shi rats bearing type b catalase-1 locus are sensitive to sodium L-ascorbate promotion of two-stage urinary bladder carcinogenesis.

Our previous data showed that F344/DuCrj and LEW/Crj rat strains bearing the type a catalase-1 locus (CS1a) are sensitive to the promoting activity of sodium L-ascorbate (Na-AsA) in 2-stage urinary bladder carcinogenesis, whereas ODS/Shi and WS/ Shi rat strains bearing the type b catalase-1 locus (CS1b) are resistant. In present study, we investigated the susceptibility of F344/Shi rats also bearing the CS1 to the Na-AsA-promoting effects on bladder tumor development. Male rats, 6 weeks old, were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 4 weeks, then fed either basal diet supplemented with 5% Na-AsA or no chemicals for 32 weeks. The rats given BBN alone had a few small carcinomas in the urinary bladder. In contrast, animals administered BBN-Na-AsA had many large carcinomas. Administration of Na-AsA was associated with significant elevation of urinary pH and L-ascorbic acid. The results indicate that F344/Shi rats are sensitive to the promoting effects of Na-AsA on 2-stage urinary bladder carcinogenesis, and thus that the CS1 locus may not influence susceptibility to promotion.

Alleles↗

Localization of colorectal carcinoma by rhenium-188-labeled B72.3 antibody in xenografted mice.

In order to evaluate the feasibility of 188Re-labeled antibodies for radioimmunotargeting, monoclonal antibody B72.3, recognizing TAG-72, expressed on the surface membranes of colorectal cancer cells, was directly labeled with 188Re, obtained from a 188W/188Re generator, using stannous tartrate and compared with 125I-labeled B72.3. As a control, a human IgG was also radiolabeled with 188Re and 125I. Prepared antibodies for 188Re labeling could be stored as kits. Biodistribution was determined in nude mice inoculated with human colorectal carcinoma LoVo. Labeling efficiency and immunoreactivity of 188Re-B72.3 were 80.3% and 64.7%, respectively. 188Re-B72.3 localized specifically in the LoVo tumors. Although the absolute tumor accumulation level of 188Re-B72.3 was lower than 125I-B72.3, 188Re-B72.3 demonstrated higher tumor-to-blood contrast than the 125I-labeled counterpart, 2.04 +/- 0.44 vs. 1.05 +/- 0.28 at 96 hours, because of fast clearance from the blood. 188Re-B72.3 seemed efficient for the imaging and therapy of colorectal carcinoma.

Animals↗

[Blunt traumatic rupture of right ventricle and pericardium].

A 60-year-old man was transferred to our hospital for blunt trauma of the chest suffered in a traffic accident. He had a weak pulse, and cardiopulmonary resuscitation was continued in the ambulance. Chest roentgenography revealed left hemothorax, and echocardiography revealed pericardial bleeding. He was immediately transported to the operating room, because of severe hypotension due to massive bleeding from the chest drainage tube. Median sternotomy was performed under stand-by cardiopulmonary bypass. There was projectile bleeding from the anterior wall of the right ventricle. The site of rupture was sutured with felt strip. A tear in the pericardium was also present at the apex. Postoperative recovery was uneventful. Fulda et al. reported that the incidence of combined pericadial and cardiac chamber rupture was 8% for those patients suffering blunt chest trauma, and that the rate of survival was less than 15% for blunt heart rupture. We have reported here successful repair of combined rupture of the right ventricle and pericardium.

Accidents, Traffic↗

Apoptotic cell death induced by physarumin (hemagglutinin from myxomycete, Physarum polycephalum).

Physarumin, a carbohydrate-binding protein (hemagglutinin or lectin), was isolated from the plasmodium of Physarum polycephalum. Physarumin agglutinated not only several species of erythrocytes but also tumor cells such as AH109A ascites hepatoma cells, sarcoma 180 ascites cells and mouse leukemia P388 cell lines. Physarumin had tumor cell growth-inhibitory activity, and induced the apoptosis of P388 cell lines. Physarumin-induced apoptosis required binding to a 68 kDa counter-receptor on the P388 cell surface. Since the agglutinating and antiproliferative activities of physarumin were inhibited by asialofetuin and thyroglobulin, respectively, it is suggested that physarumin reacts with the galactose moiety of carbohydrate chains of physarumin receptor.

Animals↗

Biodistribution and dosimetric study in medullary thyroid cancer xenograft using bispecific antibody and iodine-125-labeled bivalent hapten.

UNLABELLED: The purpose of this study was to evaluate biodistributions and absorbed doses of anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA)-indium (anti-DTPA-In) bispecific monoclonal antibody (BsMAb) F6-734 and 125I-labeled DTPA-indium dimer hapten (125I-di-DTPA-In hapten) in athymic mice xenografted with human medullary thyroid cancer. METHODS: Bispecific monoclonal antibodies F6-679 (anti-CEA/antihistamine) and G7A5-734 (antimelanoma/anti-di-DTPA-In) were used as irrelevant BsMAbs. Athymic mice inoculated with TT medullary thyroid cancer cells expressing CEA were administered BsMAbs F6-734, F6-679 or G7A5-734 and then, 48 hr later, 125I-di-DTPA-In hapten. Iodine-125-labeled F6 F(ab')2 fragment was injected into other groups of mice. Biodistributions were examined at 30 min and 5, 24, 48 and 96 hr after injection of 125I-di-DTPA-In hapten or 125I-labeled F6 F(ab')2. RESULTS: In mice injected with BsMAb F6-734 and 125I-di-DTPA-In hapten, tumor uptake was 9.1%+/-2.1%, 8.7%+/-3.5%, 8.0%+/-2.3%, 5.1%+/-0.9% and 3.5%+/-1.5% of the injected dose/g at 30 min and 5, 24, 48 and 96 hr, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 37.0+/-12.5, 32.3+/-10.9 and 10.4+/-2.7 at 24 hr. Iodine-125-F6 F(ab')2 fragment showed a tumor uptake of 7.39% injected dose/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 1.8+/-0.6, 7.3+/-2.9 and 3.6+/-1.6 at 24 hr. In mice injected with F6-679 or G7A5-734, tumor uptake and tumor-to-normal tissue ratios were much lower than in the mice injected with F6-734. These results were confirmed by autoradiographic studies that demonstrated clear tumor-to-normal tissue contrast. CONCLUSION: This two-step targeting method seems very potent for the diagnosis and therapy of human medullary thyroid cancer and other CEA-producing tumors because it combines high tumor uptake and low normal tissue background.

Animals↗

[Operative results of composite aortic root replacement by a Svensson's method].

The results of reconstruction of the aortic root performed on 9 patients by Svensson's method were examined. Nine subjects comprised 6 men and 3 women aged 23-69 years. In the preoperative diagnosis, annulo-aortic ectasia (AAE) was found in 7 cases, acute Type A aortic dissection in 1 case and AAE accompanied by chronic dissection after AVR in 1 case. Every patient underwent reconstruction by direct implantation of the right coronary artery button and interposition grafting for the left coronary artery, using a composite valve graft made of SJM valve and collagen coating artificial graft. Although one patient was lost due to multiple cerebral infarction, no marked changes were observed in other 8 patients. Angiography at short-term after operation showed no problems in the composite valve graft, and revealed good coronary arterial flow. Now, 2-62 months after operation (41 months on average), no late death occurred. On angiography of 2 cases performed after a long-term period, patency of the interposition graft was excellent. The early and late results of aortic root reconstruction by Svensson's method appeared favorable.

Adult↗

[Successful repair of tricuspid regurgitation due to blunt trauma].

A 19-year-old man developed paralysis of the left arm as a result of left brachial plexus injury by a traffic accident. He underwent operation for the brachial plexus paralysis, and then severe heart failure developed postoperatively. Echocardiography revealed severe tricuspid valve regurgitation. Tricuspid valve plasty was performed 14 months after the traffic accident. The anterior leaflet of the tricuspid valve was torn and the chordae attached there were torn as well. The torn anterior leaflet was sutured directly, and the prolapsed portion of this leaflet was collected by transfer of the elongated chordae. Annuloplasty (DeVega technique) was then added. Postoperative echocardiography revealed trivial regurgitation of the tricuspid valve. Only 9 cases of successful repair of traumatic tricuspid regurgitation have been reported in Japan.

Accidents, Traffic↗

[Nuclear oncology with monoclonal antibodies and peptides].

Imaging and therapy using radiolabeled monoclonal antibodies have proved useful in many clinical studies. However, immunogenicity of mouse antibodies to human and insufficient tumor-to-normal tissue ratios remained to be solved. Chimerization and humanization by genetic engineering, and multistep targeting techniques have enabled lower immunogenicity and higher tumor-to-normal tissue contrast. Peptides like somatostatin-analogs have been reportedly useful in imaging tumors, which are either somatostatin receptor positive or negative. Elevated normal tissue accumulation of radiolabeled peptides is a drawback in aiming internal radiation therapy.

Animals↗

[Influence of left ventricular wall thickening on myocardial injury in aortic valve replacement].

We retrospectively examined the influence of left ventricular wall thickening on myocardial injury in aortic valve replacement. Thirty-five patients who underwent aortic valve replacement in our hospital between January 1995 and July 1997 were studied. We divided these patients into 3 groups: group N (left ventricular thickness (LVT) < or = 10 mm), group H (10 < LVT < or = 15 mm), and group S (LVT > 15 mm). All patients of group S had aortic stenosis. CK and CK-MB were significantly higher and the cardiac index was significantly lower in group S than in the other groups. Intra-aortic balloon pumping was required for 50% of patients in group S, and a total dose of catecholamine above 10 micrograms/kg/min was also required for 50% of patients in this group. In the other groups, these percentages were significantly lower. Myocardial protection and postoperative care were difficult for patients with severe left ventricular hypertrophy with LVT over 15 mm in this study. Left ventricular wall thickness was a more important factor in determining difficulty with intraoperative myocardial protection than was left ventricular mass.

Adolescent↗

Age-related decline in humoral immunity caused by the selective loss of TH cells and decline in cellular immunity caused by the impaired migration of inflammatory cells without a loss of TDTH cells in SAMP1 mice.

We investigated the cellular basis of the age-related decline in antibody (Ab) and delayed-type hypersensitivity (DTH) responses to sheep red blood cells (SRBC) in vivo in short-lived senescence-accelerated mouse (SAM) P1. In SAMP1 mice, age-related decreases in CD4+ T cells in the peripheral blood occurred earlier than in control mice and occurred in parallel with the age-related decline in Ab and DTH responses. In addition, the involution of the thymus was faster. The injection of thymic T cells from young mice before sensitization completely restored the Ab responses in aged SAMP1 mice. These data suggest that the age-related decline in Ab response is due to the age-related early loss of helper-T (TH) cells. On the other hand, the local transfer of spleen cells from sensitized aged donors into the footpads of naive syngeneic recipients evoked strong DTH responses, demonstrating the existence of DTH-mediating T (TDTH) cells in the spleens of aged SAMP1 mice. Moreover, the local injection of naive spleen cells from young donors, together with the antigen, into the footpads caused DTH responses in sensitized aged recipients. These findings indicate that TDTH cells were induced and were able to migrate and function as effector cells in aged mice. When naive spleen cells from aged donors were injected locally into the footpad, they restored the DTH response in aged mice, but this effect did not work if the cells were injected intravenously. This demonstrates that the inflammatory cells of the aged mice were able to work at the local site, but could not migrate there. The intravenous injection of naive spleen cells from young donors restored the DTH response in aged mice, suggesting that the endothelial cells of aged mice were not impaired and permitted the inflammatory cells to migrate into the extravascular tissues. Thus, although the age-related decline of the Ab and DTH responses occur in parallel, we found different effects of aging on TH and TDTH cells in SAMP1 mice. Furthermore, our data suggest that the reason for the low DTH response in aged SAMP1 mice is not the loss of TDTH cells, but rather the impaired migration of inflammatory cells into the local site.

Aging↗

The structure of Silurus asotus (catfish) roe lectin (SAL): identification of a noncovalent trimer by mass spectrometry and analytical ultracentrifugation.

We identified a noncovalent trimer of Sirurus asotus roe lectin (SAL) at Mr 95,362 along with its monomer at M(r) 31,750 by electrospray ionization mass spectrometry when SAL was dissolved in 0.5% acetic acid, sprayed into the ion source with methanol as a sheath liquid, and desolvated at 75 degrees C in a heated capillary column. The molecular weight of SAL, determined by the sedimentation equilibrium method, was 95,200 and the sedimentation coefficient (S20,w) of SAL in water was 5.58. SAL existed as a noncovalent trimer in solution and showed the ability to agglutinate rabbit erythrocytes. SAL showed three peaks (sal 1, sal 2, and sal 3) by C8 reverse-phase HPLC, and these appeared to be a monomer, a dimer, and a trimer, respectively, by matrix-assisted laser desorption ionization-time of flight mass spectrometry, sal 1 and sal 2 were shown to have a structure interchangeable with that of sal 3 in water.

Amino Acids↗

Functional roles of protein domains on rice alpha-amylase activity.

Characteristics of two rice alpha-amylases Amy1A and Amy3D, and those of two chimeric enzymes Amy1A/3D and Amy3D/1A, engineered from the two isozymes, were compared in the light of the functional roles of protein domains in alpha-amylase. The enzymes that have an Amy1A-type N-terminal domain, Amy1A and Amy1A/3D, showed high activity against soluble starch, while the enzymes that have an Amy3D-type barrel structure, Amy3D and Amy1A/3D, showed high activity in oligosaccharide hydrolysis. Rigidity of protein folding also significantly affected the enzyme activity in both soluble starch and oligosaccharide hydrolysis. Thus, the present work suggests that the structure of the N-terminal domain is important for stability and soluble starch hydrolysis, while the barrel structure that forms the active site significantly affects enzyme activities in oligosaccharide degradation. We have already characterized two rice alpha-amylase isozymes, Amy1A and Amy3D, and a chimeric enzyme engineered from these two isozymes, Amy1A/3D (Terashima et al. 1995, 1996a,b). In spite of the high homology (70%) of their amino acid sequences, Amy1A and Amy3D showed distinct differences in their enzymatic characteristics. The chimeric enzyme Amy1A/3D, which consists of an Amy1A-type N-terminal domain and an Amy3D-type barrel structure, inherited enzymatic characteristics from the both isozymes. In this work, one other chimeric enzyme, Amy3D/1A, which is the counterpart of Amy1A/3D, has been characterized. The characteristics of these four enzymes are discussed in the light of the functional roles of protein domains.

Amylases↗

Septum-like structures in lipoma and liposarcoma: MR imaging and pathologic correlation.

OBJECTIVE: To investigate the septum-like structures in predominantly lipomatous tumors, by correlating fat-suppressed MR images with histopathologic findings. DESIGN AND PATIENTS: The MR findings of three cases of well-differentiated liposarcoma (atypical lipoma), one case of lipoma-like component of dedifferentiated liposarcoma, and nine cases of lipoma were analyzed. T1-, T2-, and fat-suppressed T1-weighted images after Gd-DTPA administration were obtained. Surgical specimens from five patients (four with liposarcoma and one with lipoma) were also scanned with a MR unit, and compared with the pathologic findings. RESULTS AND CONCLUSIONS: Enhancement features of lipoma and liposarcoma were well visualized on fat-suppressed T1-weighted images after Gd-DTPA administration. The septum-like structures of liposarcoma are thick and enhanced considerably, while septa of lipoma are thin and enhanced only slightly. Pathologically, the septum-like structures of liposarcoma contained muscle fibers and the septa of lipoma represented fibrous capsule. Identification of well-enhanced septa in a predominantly lipomatous tumor helps to differentiate malignant tumors from lipomas. As the septum-like structures of liposarcoma contain a skeletal muscle component the tumor might need more extensive surgical procedures including resection of adjacent muscles.

Aged↗

MR appearance of parasymphseal insufficiency fractures of the os pubis.

OBJECTIVE: To clarify the MRI features of parasymphyseal insufficiency fractures of the os pubis. DESIGN AND PATIENTS: MRI was performed in four postmenopausal women with parasymphyseal insufficiency fractures. The diagnosis was confirmed with plain films in every patient. T1-weighted and T2-weighted images were obtained in four patients using a 1.5-T unit. Postcontrast T1-weighted imaging was also done in three patients. RESULTS AND CONCLUSIONS: MRI of pubic parasymphyseal insufficiency fracture characteristically demonstrates a hyperintense mass lesion with a hypointense rim on T2-weighted imaging, showing peripheral and septal enhancement after contrast administration. It is important to have this entity in mind in patients with osteoporosis, especially in patients with a history of pelvic irradiation for malignant disease, so as not to misinterpret it as a chondroid tumor or bone metastasis.

Aged↗

Lack of promotion of urinary bladder carcinogenesis by sodium bicarbonate and/or L-ascorbic acid in male ODS/Shi-od/od rats synthesizing alpha 2 mu-globulin but not L-ascorbic acid.

The study was designed to investigate whether sodium bicarbonate (NaHCO3) and/or L-ascorbic acid (AsA) promote urinary bladder carcinogenesis in male ODS/Shi-od/od (ODS) rats, which, unlike male F344 rats, are resistant to sodium L-ascorbate (Na-AsA)-promoting effects. Whereas F344 rats can synthesize AsA and alpha 2 mu-globulin (A2 mu-G), only A2 mu-G in produced in ODS rats. The two strains were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 2 wk and then were fed basal CA-1 diet supplemented with 3% NaHCO3 plus 5% AsA (NaHCO3 + AsA), 3% NaHCO3, 5% AsA, or no chemicals for 32 wk. ODS rats given BBN-NaHCO3 or BBN-(NaHCO3 + AsA) had only a few small carcinomas in the urinary bladder, like those receiving BBN alone or BBN-AsA. In contrast, F344 rats administered BBN-NaHCO3 or BBN-(NaHCO3 + AsA) had many more, larger, carcinoma than animals of the same strain given BBN alone or BBN-AsA. AsA alone did not have any effect in either strain. Administration of NaHCO3 alone or NaHCO3 + AsA was associated with significant elevation of urinary pH and Na+ concentration to the same extent in both strains but, again, AsA alone was without effect. NaHCO3 + AsA and AsA alone increased the urinary concentration of total ascorbic acid in both strains but the observed levels wer lower in ODS rats. The results indicate that ODS rats are resistant to the modifying effects of NaHCO3 and/or AsA on two-stage urinary bladder carcinogenesis, and thus that the susceptibility to the promotional activity of sodium-salt-type compounds may be regulated by factors other than A2 mu-G-synthesizing ability and urinary levels of pH, Na+ and total ascorbic acid.

Animals↗

Strain differences in sensitivity to the promoting effect of sodium L-ascorbate in a two-stage rat urinary bladder carcinogenesis model.

Rat strain differences in sensitivity to the promoting effect of sodium L-ascorbate (SA) on the development of urinary bladder tumors were investigated. In experiment 1, WS/Shi (WS), ODS/Shiod/od (ODS), and LEW/Crj (LEW) rats were initiated with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in their drinking water and subsequently given basal Oriental MF diet (M) with or without a 5% SA supplement. In LEW rats the SA treatment increased the induction of neoplastic lesions in the urinary bladder, whereas WS and ODS animals proved unresponsive to its promoting effects. In experiment 2, WS and F344 rats were maintained on two kinds of commercial basal diets, M and CLEA CA-1 (C), during administration of SA, since dietary factors can influence promoting effects. Feeding M during the promotion period in F344 rats yielded significantly more neoplastic lesions than feeding C, but in WS rats no such dietary influence was apparent. In experiment 3, strain differences in biosynthesis of alpha-2u-globulin (alpha 1a-g) were assessed because both alpha 2a-g in the urine and administration of sodium salts of organic acids such as SA have been reported to be involved in tumor promotion. Immunohistochemical analysis of renal tubules and Western blotting analysis of urine revealed the presence of alpha 2a-g in all three strains examined. These data suggest that differences in susceptibility to promotion are due to genetic factors rather than dietary factors and the ability to synthesize alpha 2a-g.

Animals↗

Three phase 99Tcm (V)DMSA scintigraphy in Paget's disease: an indicator of pamidronate effect.

The use of three phase 99Tcm (V)DMSA scintigraphy is reported in a patient with Paget's disease of bone before and after intravenous pamidronate therapy. It was a useful modality for estimating the activity of Pagetoid lesions and the therapeutic effect of pamidronate, from a different aspect to bone scintigraphy. Three phase 99Tcm (V)DMSA scintigraphy evaluates both the blood flow and the metabolic activity of Pagetoid bone.

Aged↗

Effect of cilnidipine, a novel dihydropyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons.

We investigated the effects of cilnidipine, a dihydropyridine derivative, on neuronal Ca++ channels in rat dorsal root ganglion neurons. Voltage-dependent Ca++-channel currents were recorded, using 5 mM Ba++ as the charge carrier, by means of the whole-cell patch-clamp technique. The Ba++ current was subdivided pharmacologically into calciseptine-sensitive (L-type), omega-conotoxin GVIA- (omegaCgTx) sensitive (N-type), omega-agatoxin IVA- (omegaAgTx) sensitive (P/Q-type) and toxin-resistant currents. Cilnidipine inhibited the L-type current with an IC50 of 100 nM in neurons pretreated with omegaCgTx plus omegaAgTx. In neurons pretreated with Cal plus omegaAgTx, cilnidipine induced a potent inhibition of the N-type current, but was unable to block the residual Ba++ current. The IC50 for cilnidipine in respect of the N-type current was 200 nM. Cilnidipine (300-500 nM) modified neither the voltage-dependent inactivation curve nor the decay of the N-type current. Furthermore, elevation of the holding potential did not enhance the inhibitory action of cilnidipine (300 nM) on the N-type current. No effect was induced by 100 nM cilnidipine on the P/Q-type current. However, nicardipine (1 microM) barely inhibited the N-type current at a concentration that almost completely blocked the L-type current. In conclusion, cilnidipine has potent inhibitory actions on N-type as well as L-type voltage-dependent Ca++-channel in rat dorsal root ganglion neurons. The former action may bestow an additional clinical advantage for the treatment of hypertension, such as suppression of reflex tachycardia.

Animals↗