Biomedical subjects
Publications and source records attributed to H Nakano.
Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (5-ALA) is a promising new treatment for superficial malignant nonmelanoma tumours, including cutaneous malignant lymphoma. Here, we report a case of cutaneous anaplastic large cell lymphoma effectively treated by PDT with topical 5-ALA in combination with radiotherapy.
Little is known about the mechanisms of mandibular condylar growth. In this study, gene expression in the mandibular condylar cartilage of young post-natal mice was monitored by means of a cDNA microarray, real-time PCR, and laser microdissection before and after the initiation of mastication (newborn, 7 days, 21 days, initiation of mastication, and 35 days). Insulin-like growth factor-1 (IGF-I), transforming-growth-factor-beta-2 (TGFbeta2), and aggrecan mRNAs were clearly expressed at 21 days, while the expression of osteopontin mRNAs was most clear at 35 days. Parathyroid-hormone-related protein (PTHrP), Indian-hedgehog (Ihh), and insulin-like growth factor-2 (IGF-2) mRNAs were clearly expressed during lactation (newborn and 7 days). Heat-shock-protein 84 (HSP-84) and heat-shock-protein 86 (HSP-86) were clearly expressed at 35 days. These results revealed that gene expression changed during mandibular condylar cartilage growth, and that, interestingly, these changes coincided with the initiation of mastication.
We reported a successful surgery for the huge ruptured coronary aneurysm resulting in cardiac shock. The rupture of atherosclerotic coronary aneurysm is extremely rare except congenital cardiac disease and as a coronary artery-pulmonary artery fistula or a coronary arterio-venous fistula. Excision of the aneurysm, closure of the coronary ostium and coronary artery bypass using saphenous vein graft was performed. The post operative course was uneventful. The histological findings revealed atherosclerotic coronary aneurysm.
RCAS1, which acts as a ligand for a putative receptor on immune cells such as peripheral lymphocytes and natural killer cells, is strongly expressed in human cancers. RCAS1 can induce these cells to undergo apoptotic cell death, which suggests that RCAS1 expression may prohibit the stromal reaction occurring in a tumour. To clarify the clinical significance of RCAS1 expression in uterine endometrial cancer, we analysed the association between RCAS1 expression and clinicopathologic variables by statistical methods. With the use of immunohistochemical techniques, we performed a retrospective study of RCAS1 expression in resected tumour tissue from 147 patients with uterine endometrial cancer. We evaluated the statistical correlation between RCAS1 expression and clinicopathologic variables. RCAS1 was expressed in 106 of 147 patients with uterine endometrial cancer; 30 of these 147 patients showed RCAS1 overexpression. Overexpression of RCAS1 was significantly correlated with age at surgery, stage, extent of myometrial invasion, and positive peritoneal cytologic results. Multivariate analysis revealed that RCAS1 expression and metastasis were clinically significant prognostic factors for the overall survival. These findings indicated that analysis for RCAS1 expression can provide crucial information about the clinical behaviour of uterine endometrial cancer, which may be valuable for the management of patients with this disease.
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Laser ultrasonic technique has been employed to carry out the sound velocities and attenuation measurements as a function of temperature in alumina, two kinds of silicon nitride and partially stabilized zirconia (PSZ) samples. Accuracy of the laser technique used has been checked in terms of the diffraction effect and reproducibility of the results. Results of attenuation at room temperature have been compared with quartz transducer technique. In PSZ, velocity behavior has become non-linear and also, a peak in attenuation has been observed around 500 degrees C. In one of the silicon nitride sample, which uses glassy sintering agent, attenuation has shown a sharp peak around 950 degrees C. Interestingly, when the experiment was repeated from 800 to 1000 degrees C, this anomalous attenuation peak has disappeared, leaving a background increasing towards higher temperatures.
The placental trophoblast is considered to act as a barrier between mother and fetus, mediating the exchange of various materials across the placenta. ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp) and multidrug-resistance protein (MRP) are expressed in the placenta and function as efflux transport systems for xenobiotics. In the present study, we aimed to determine the localization of MRP1 in the human placenta in comparison with that of P-gp. Western blotting analysis with human placental membrane vesicles indicated that P-gp and MRP1 are localized on the brush-border membranes and basal membranes, respectively. Immunohistochemical analysis with human normal full-term placenta showed that anti-P-gp monoclonal antibody F4 stained the brush-border side of the trophoblast cells, whereas anti-MRP1 monoclonal antibody MRPr1 stained the basal side. These results confirm that P-gp and MRP1 are located on the brush-border membranes and basal membranes, respectively, of human full-term placental trophoblast. MRP1 was also detected on the abluminal side of blood vessels in the villi. Accordingly, MRP1 may play a role distinct from that of P-gp, which is considered to restrict the influx of xenobiotics into the fetus.
BACKGROUND AND AIM: We studied the effects of long-term methionine administration on the vascular endothelium of Japanese white rabbits. METHODS AND RESULTS: Eleven rabbits were divided into a control group (n = 6) and a methionine-fed group (n = 5), and reared for 22 weeks. Blood samples were collected at baseline and after 22 weeks for the measurement of serum homocysteine and cysteine, serum lipids and serum superoxide dismutase activity. At the end of experiments, the animals were sacrificed, and the thoracic aorta was removed for the measurement of isometric tension and histopathological examination. The blood samples taken from the methionine group in the 22nd week showed slight but significant increases in serum homocysteine and cysteine levels (Hcy: 13.7 +/- 1.4 vs 21.0 +/- 4.9, p < 0.01; Cys: 241.6 +/- 37.8 vs 342.6 +/- 35.0, p < 0.01). In the isometric tension experiments, the methionine group had a significantly decreased (p < 0.01) vasodilatation reaction induced by acetylcholine, an endothelium-dependent vasodilator. The histopathological examination (immunostaining in response to eNOS and tissue factor) showed significant increases in endothelium expression in the methionine group before atherosclerotic changes appeared. CONCLUSIONS: The above results suggest that vascular endothelial dysfunction played an important role in the atherosclerosis occurring after excess methionine feeding.
OBJECTIVES: To investigate the influence of forced lateral bite on mandibular growth, micro X-ray computed tomography (CT) was used for the purpose evaluating condylar cartilage and cancellous bone formation in 10 male Wister rats (3 weeks of age). SETTINGS AND SAMPLE POPULATION: The rats were divided into two groups--experimental and control. In experimental group, an inclined crown was cemented onto the maxillary incisors to produce 2.5 mm shift toward the left side during mastication. Right-left differences in whole mandibular length, mandibular height, condylar size, trabecular structure of the condylar head and three-dimensional (3-D) finite element analysis were assessed using 3-D images reconstructed from micro X-ray CT scans when the mice had reached 21 weeks. MEASUREMENTS AND RESULTS: Asymmetrical growth was found in the experimental group, in which the left condylar head became thicker and shorter than the right condylar head during development. When comparing the left and right condyles of the experimental animals, histomorphometric analysis from micro X-ray CT showed that the bone volume (BV) of the cancellous bone, the surface area of the cancellous bone (BS), the BS/BV ratio, the BV fraction (BV/TV), and the trabecular thickness and trabecular number were less for the right condyle than for the left condyle. CONCLUSIONS: These findings suggested that artificial changes in the mastication do influence the growth of condylar head, condylar bone trabecular structure, and mineralization.
Heparanase (HPA) degrades heparan sulfate proteoglycan in the extracellular matrix. To understand its role during implantation and placental development in bovine placentae, we cloned and characterized a full-length cDNA encoding bovine HPA and identified HPA localization in placentae. A full-length bovine HPA cDNA was cloned with a 1635 nucleotide open-reading-frame corresponding to a protein of 545 amino acids. The predicted amino acid sequence shares 80.0% and 76.5% identity with human and rat HPA, respectively. In placentomes of 60 and 210 days' gestation, in situ hybridization demonstrated HPA mRNA expression in binucleate cells. Binucleate cells may be a source of HPA throughout gestation in bovine placentae; they may assume specific role(s) in foetal and maternal dialogue. Western blot analysis of bovine placental extracts (day 60) was performed using anti-bovine HPA antibody prepared by immunization of rabbits with synthetic peptide conjugate corresponding to amino acid residues 474-489 of bovine HPA; it showed two immunoreactive proteins with approximate molecular weights of 55kDa and 65kDa. Further, immunofluoresence double staining of HPA and placental lactogen (PL) revealed that binucleate cells expressing HPA had immunoreactivity of PL. These results suggest that HPA is specifically expressed in bovine placental binucleate cells and that it may take migratory roles in placentogenesis for degrading the extracellular matrix.
It is difficult to accurately diagnose the nature of polypoid lesions in the gallbladder. To increase diagnostic accuracy, we have developed an endoscopic technique for obtaining gallbladder bile, termed endoscopic transpapillary catheterization into the gallbladder (ETCG). We describe here a case of gallbladder carcinoma diagnosed preoperatively by the detection of human telomerase reverse transcriptase (hTERT) mRNA, a catalytic subunit of telomerase, in gallbladder bile obtained using the ETCG technique. A patient with a polypoid lesion 15 mm in diameter in the gallbladder was admitted to our hospital for further examinations. Gallbladder bile collected by the ETCG technique was evaluated cytologically and also analyzed for telomerase activity and hTERT mRNA. Although the results for cytology and telomerase activity were negative, that for hTERT mRNA was positive. Open surgery was carried out and it was confirmed that the lesion was an adenocarcinoma invading the subserosa. The molecular biological analysis of gallbladder bile collected using the ETCG technique was shown to be effective for diagnosing the nature of the polypoid lesion in the gallbladder.
The aim of this study was to determine whether Salmonella enteritidis (SE) inoculated into the peritoneal cavity would colonize tissues of reproductive organs in Japanese quail hens. Quail hens regularly laying were intraperitoneally inoculated with 5 x 10(7) or 5 x 10(8) SE cells, and the ovary, oviduct, kidney, spleen, liver, and large intestine were excised 24 or 48 h after the treatment. Paraffin sections of these organs were immunostained for SE. Invasion of SE was found in the tissues of the ovarian stroma, the follicular wall including superficial and theca layers, and occasionally in the granulosa layer and yolk. The SE immunoreaction product frequently was found in the fibroblast-like and macrophage-like cells in the stroma and surface layer of follicles. The SE immunoreaction products were identified on the mucosal surface, in the mucosal epithelium, and in the stromal tissues in all segments of the oviduct. Many of the bacteria were contained in the cytoplasm of mucosal epithelial cells and stromal cells in those tissues. The SE immunoreactions were also found in the tissues of kidney, spleen, and liver and in the large intestine. These results suggest that SE organisms introduced into the peritoneal cavity can invade and colonize the tissues of ovary and oviduct and may be responsible in the production of contaminated eggs.
BACKGROUND AND OBJECTIVES: Therapy with recombinant Factor VIIa (rFVIIa) for haemophiliacs with inhibitors still has some unresolved problems, such as the requirement for frequent infusions of rFVIIa every 2-3 h to sustain haemostatic activity for an extended time-period and that the therapeutic dose of rFVIIa is not always predictable. In the present study, we searched for an effective combination of plasma-derived FVIIa with other blood coagulation factors, and demonstrated that a therapeutic approach combining plasma-derived FVIIa and Factor X (FX) was more useful for treating haemophiliacs with inhibitors than FVIIa alone. MATERIALS AND METHODS: The haemostatic effects of FVIIa and FX were evaluated in vitro and in vivo. In in vitro experiments we assessed the following: the ability to enhance the thrombin generation rate in a reconstituted blood coagulation model without Factor VIII (FVIII) or Factor IX (FIX); the ability to correct the activated partial prothrombin time (APTT) of FVIII-depleted plasma or FIX-depleted plasma; and the ability to correct the clotting time of haemophilia-like whole blood using thromboelastography (TEG). In in vivo experiments, the haemostatic activity of the combination treatment of FVIIa and FX was determined by measuring the bleeding time and TEG using a monkey haemophilia B model produced by the injection of anti-human FIX polyclonal antibodies. The degree of thrombogenicity of the combination was evaluated using the rabbit stasis model. RESULTS: The addition of FX to FVIIa dramatically enhanced the thrombin generation rate in the reconstituted blood coagulation model and corrected the prolonged APTTs of FVIII- and FIX-depleted plasmas to levels achieved by the replacement therapies. In contrast, the addition of prothrombin to FVIIa did not show such enhancing activity. Furthermore, FVIIa-induced whole blood clotting times in the FVIII- and FIX-inhibited states were also shortened by the addition of FX in a concentration-dependent manner. Finally, the co-administration of FVIIa (80 microg/kg) and FX (800 microg/kg) in a monkey haemophilia B model resulted in a more robust and persistent haemostatic effect on the secondary bleeding time and whole-blood clotting time of TEG than that of FVIIa alone. The results of rabbit stasis tests for evaluating the risk of thrombogenicity showed that the combination of FVIIa and FX was less thrombogenic than FEIBA. CONCLUSIONS: The present study demonstrated that the combination of FVIIa and FX appeared to have a higher and more sustainable haemostatic potential than FVIIa alone, and less thrombogenicity than FEIBA. A therapeutic approach combining FVIIa and FX could be a promising and novel approach to compensate for the disadvantages of rFVIIa and FEIBA for haemophiliacs with inhibitors.
Benign mammary mixed tumors in dogs resemble human salivary pleomorphic adenomas with regard to their histogenesis, including the occurrence of cartilaginous or bony metaplasia as well as the expression pattern of cytoskeletal proteins in proliferative myoepithelial cells. Recently, a monoclonal antibody specific for class II beta-tubulin has been developed. The epitope it recognizes was determined to be the heptapeptide Glu-Glu-Glu-Glu-Gly-Glu-Asp, which is the common sequence found among the canine, rat, mouse, and human class II beta-tubulin-specific regions. We carried out immunohistochemical studies on mammary mixed tumors obtained from three female dogs using this the monoclonal antibody. The antibody to class II beta-tubulin reacted intensely with proliferative myoepithelial cells in canine mammary mixed tumors, whereas staining was barely detectable in normal myoepithelial cells surrounding alveoli and alveolar ducts within the tumor and adjacent normal tissue. Proliferative myoepithelial cells also expressed vimentin, but alpha-smooth muscle actin (alphaSMA) staining was barely detectable. Immunoblot analysis showed that class II beta-tubulin and vimentin were expressed in myoepithelial cell lines prepared from the three mammary mixed tumors. On the other hand, only one cell line, which was negative for alphaSMA, produced cartilage-specific type II collagen. These results suggest that class II beta-tubulin could be a new molecular marker of proliferating myoepithelial cells in canine mammary mixed tumors and that differential expression of cytoskeletal components is associated with cartilaginous metaplasia of proliferative myoepithelial cells in mixed mammary tumors.
PURPOSE: The aim of the present study was to establish the accurate cutoff points of post-treatment serum beta-hCG values in identifying chemotherapeutic refractory cases among patients with low-risk persistent trophoblastic disease (PTD) treated with 8-day methotrexate-folinic acid as the primary therapy. MATERIALS AND METHODS: The values of serum beta-hCG measured before initiating treatment and weekly thereafter in 26 patients with low-risk PTD undergoing 8-day methotrexate-folinic acid treatment were analyzed. Thereafter, we determined the weekly cutoff points to identify the patient refractory for treatment by means of receiver-operating characteristic (ROC) plots analysis. RESULTS: The values of cutoff points in the pretreatment, the post-treatment 1st, 2nd, 3rd, and 4th week were 18.6, 15.0, 5.4, 3.4, and 2.0 ng/ml, respectively, and the value of accuracy during these weeks was appropriate (> 80%). When using the cutoff points of one and two weeks after initiating treatment, the accuracy in identifying chemotherapeutic refractory patients was 87.5% and 88.0%, respectively, with the highest values exceeding 85%. The sensitivity and specificity at one week were 92.9 and 80.0%, respectively. Similarly, the sensitivity and specificity at two weeks were 93.3 and 80.0%, respectively. CONCLUSION: These results suggest that the cutoff points of one and two weeks after initiating treatment are useful in identifying chemotherapeutic refractory patients among low-risk PTD patients, receiving 8-day methotrexate-folinic acid treatment.
Recently, off-pump coronary artery bypass grafting (off-pump CABG: OPCAB) has been considered a safe alternative to conventional CABG (CCAB) for myocardial revascularization, because OPCAB improves operative mortality and morbidity from the view of reduction of multi-organ complications, duration of hospital stay, risks of blood transfusion and operative costs. This study was performed to estimate the benefit of OPCAB by examining the change of myocardial oxygen metabolism during OPCAB. Twenty five patients who had undergone OPCAB including the internal thoracic artery (LITA) on the segment 8 of the left anterior descending coronary artery (LAD) were studied in this series, and divided in 2 groups [17 angina pectoris (AP) cases, 8 old myocardial infarction (OMI) cases]. With 3-wave length near infrared spectroscopy (TOS-96: TOSTEC, Tokyo, Japan), the tissue hemoglobin (Hb) volume in the myocardium [Hb index (HbI) = 10 x calibrated absorption at 801 nm/clinical absorption intensity at 801 nm] and the myocardial tissue oxygen saturation (rSo2) on the surface of the left ventricle surrounded by LAD and the 2nd diagonal branch were measured at 5 minutes before and after OPCAB to LAD, and myocardial oxygen metabolism (OM) was calculated [OM = (20-1.34 x systemic Hb x rSo2/100) x HbI]. During OPCAB, several hemodynamic data, systemic Hb and arterial gas findings were not changed. In both groups, the HbI and the OM were significantly increased [HbI: AP group; 1.04 +/- 0.23 to 1.57 +/- 0.41 (p < 0.0001), OMI group; 0.99 +/- 0.28 to 1.55 +/- 0.39 (p = 0.0051), OM: AP group; 11.6 +/- 3.1 to 17.5 +/- 6.0 (p = 0.0010), OMI group; 10.6 +/- 2.3 to 16.1 +/- 2.8 (p = 0.0007)]. The rSo2 was not changed and remained within normal limit during OPCAB. These findings suggested that the regional myocardial oxygen metabolism would be improved immediately just after OPCAB and this finding might be one of the reasons why OPCAB shows the good mortality and morbidity compared with CCAB.
Femtosecond laser-produced plasmas are bright ultrafast line x-ray sources potentially suitable for different applications including material science and biology. The conversion efficiency of the laser energy incident onto a solid target into the x-ray emission is significantly enhanced when a laser prepulse precedes the main pulse. The details of x-ray line emission from solid targets irradiated by a pair of ultrashort laser pulses are investigated both theoretically and experimentally. Insight into spatial and temporal characteristics of the line x-ray source is provided by numerical simulations and a simplified analytical model. Optimal time separation of the laser pulses is searched for in order to reach the maximum conversion of laser energy into the emission of selected x-ray lines. We deduced how the optimal pulse separation scales with laser and target parameters.