Biomedical subjects
Publications and source records attributed to S Nakajima.
Panel-touch behavior of 3 geldings was successfully established by a response-termination type of autoshaping procedure. An omission or negative contingency introduced after the training of an animal, however, decreased the response rate to a near-zero level.
The Intelligent Prosthesis may enable lower limb amputees to walk faster than with conventionally damped prostheses and as a result the physical burden involved in walking could be expected to be considerably higher. The aim of this study was to investigate whether or not physiological cost index (PCI) is applicable as an indicator for monitoring the amount of exercise load involved in walking with an Intelligent Prosthesis. The method used a treadmill and monitored gas exchange, ventilation and heart rate (HR) in 6 unilateral trans-femoral amputees, ages were between 17 and 34 with an average age of 23.1. The exercise protocol was as follows: for each person speeds at 0.8 times the subject's free level walking speed, 1.0 times, 1.2 times, 1.4 times and for some 1.6 times were applied. In each case the index of correlation between PCI and oxygen uptake in response to walking speed was calculated. A significant correlation was observed between PCI and oxygen uptake in each case, which indicated a close relationship between cardiopulmonary factor and energy consumption while walking. These results suggest that PCI is of use as an indicator for ascertaining the amount of exercise load in walking with an Intelligent Prosthesis.
For the purpose of improving the efficiency of a body-powered prosthesis, a control cable system was developed which uses a pulley and a cable housing which includes a highly slippery plastic liner. Improvements were also made to the harness. In this paper, the mechanism of these systems is firstly described and then, the results of a clinical evaluation test of a practical model is presented along with an efficiency evaluation by a testing instrument. For the design of each system, the material and size suitable for the conditions of cosmetic and general versatility were considered. The clinical test was performed on 12 subjects to prove the effectiveness of the system. This test procedure was repeated. These tests proved the effectiveness of the systems.
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Selection of treatment for ulcerative colitis is based on the definition of clinical severity. In those medication is a main course. Mild and moderate cases are treated mainly with salicylazosulfapyridine or mesalazine. Patients with proctitis-type are added betamethazone suppositories and those with left-sided and total colitis-type predonisolone enema therapy simultaneously. If there is no response, they are given additional oral predonisolone. Even after remission, patients should be carefully observed. A good patient-physician relationship, continuation of maintenance therapy, and periodic follow-up examinations using colonoscopy or barium enema are essential to successful long-term management of this disease. Patients who have repeated relapsing should receive the stronger treatment, according to the endoscopic findings and clinical course in addition to the clinical severity.
The study was carried out to evaluate the therapeutic effects of zanamivir, a highly selective, potent and specific inhibitor of influenza A and B virus neuraminidases, in adult patients with acute influenza-like illness. Patients who presented within 36 h of the onset of influenza-like symptoms were randomly assigned to receive one of three treatments, twice daily, for 5 days: 10 mg zanamivir powder for inhalation (zanamivir inhalation group), 10 mg zanamivir powder for inhalation plus 6.4 mg zanamivir nasal spray (zanamivir inhalation plus intranasal group) or placebo (placebo group). The primary end point was the time to alleviation of the three major symptoms (fever, headache and myalgia). The secondary end point was the time to alleviation of five influenza symptoms (fever, headache, myalgia, cough and sore throat). One hundred and sixteen patients with influenza-like illness were recruited to the study. No differences were observed between the two groups of patients who received zanamivir (inhalation group or inhalation plus intranasal group). Patients who received zanamivir recovered significantly faster (median 3 days to recovery) than the patients in the placebo group (median 4 days to recovery; P < 0.01). Topically administered zanamivir was well tolerated. This study confirms that in adults, topically administered zanamivir is well tolerated and is effective in reducing the time to alleviation of influenza symptoms.
OBJECTIVE: To induce the model of Mongolian gerbil infected by Helicobacter pylori (HP) and to observe the changes of the infiltration and the proliferation of inflammatory cells before and after the bactericidal treatment. METHODS: The animal model of HP infection was induced by inoculating the HP strain (American Type Culture Collection) to male Mongolian gerbil MGS/Sea (SPF). Half a month, 1 month and 3 months after inoculation, kill the animals and make HE staining and immunohistochemistry staining of the stomach to observe the pathological changes. RESULTS: The infiltration of a great number of inflammatory cells was observed with the center of the mucosa of pylorus at the second week of HP infection. At the 3rd month of infection, ulcer appeared near the lesser curvature side of the pylorus. On the early stage of infection, the lesion was acute inflammation characterized by the neutrophilic infiltration, and then transformed into the chronic inflammation characterized by the lymphatic infiltration and the wide formation of lymphatic follicles. CONCLUSION: Mongolian gerbil is an ideal and standard animal model of HP infection.
6-N-formylamino-12,13-dihydro-1, 11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo [2,3-a]pyrrolo [3, 4-c]carbazole-5,7(6H)-dione (NB-506), a potent inhibitor of DNA topoisomerase I, is currently under development for the treatment of cancer. We investigated the pharmacokinetics of NB-506 after i.v. administration in rats and dogs. The plasma concentration of NB-506 decreased biexponentially in rats and dogs with terminal half-lives of approximately 2 h. The area under the curve increased nonlinearly with increasing dose in rats. In contrast, there was a linear relationship between the area under the curve and the dose in dogs. In rats, the plasma clearance decreased with increasing dose up to 187.5 mg/m2 but remained virtually unchanged at the highest dose. The Vdss of NB-506 in rats and dogs was much greater than the plasma volume, indicating that NB-506 is highly distributed to tissue from plasma in these animals. There were marked species differences in the plasma concentrations of ED-501 after i.v. administration of NB-506 to rats and dogs. To better understand the mechanisms of nonlinear pharmacokinetics in rats, in vivo metabolites were determined. After i.v. administration of [14C]NB-506 to rats, two unknown metabolites (RBM-1 and RBM-2), deformyl metabolite (ED-501), and unchanged drug (NB-506) were identified. Mass and NMR spectra analysis revealed that RBM-1 is an 11-O-glucuronide of NB-506 (ED-594) and that RBM-2 is an 11-O-glucuronide of ED-501 (ED-595). In this study, the pharmacokinetics of NB-506 was demonstrated to be nonlinear in rats, probably because of saturation of the enzyme systems catalyzing the deformylation and glucuronidation of NB-506 in rats.
We used a two-color analysis system to assess the porphyrin uptake and DNA content in four established cell lines of glioma employing flow cytometry (FCM). The FCM study revealed porphyrin uptake in all cells, regardless of the phase of the cell cycle they were in. However, those in the G0/G1 phase showed moderate uptake of porphyrin and those in the G2/M phase showed a higher uptake. These results indicated the advantage of using porphyrin as the carrier of tumor targeting agents as a therapeutic strategy for malignant tumors.
Immune cell migration into and through mucosal barrier sites in general and airway sites in particular is a critical feature of immune and inflammatory responses, but the determinants of transepithelial (unlike transendothelial) immune cell traffic are poorly defined. Accordingly, we used primary culture airway epithelial cells and peripheral blood mononuclear cells to develop a cell monolayer system that allows for apical-to-basal and basal-to-apical T cell transmigration that can be monitored with quantitative immunofluorescence flow cytometry. In this system, T cell adhesion and subsequent transmigration were blocked in both directions by monoclonal antibodies (mAbs) against lymphocyte function-associated antigen 1 (LFA-1) or intercellular adhesion molecule 1 (ICAM-1) (induced by interferon gamma [IFN-gamma] treatment of epithelial cells). The total number of adherent plus transmigrated T cells was also similar in both directions, and this pattern fit with uniform presentation of ICAM-1 along the apical and basolateral cell surfaces. However, the relative number of transmigrated to adherent T cells (i.e., the efficiency of transmigration) was increased in the basal-to-apical relative to the apical-to-basal direction, so an additional mechanism was needed to mediate directional movement towards the apical surface. Screening for epithelial-derived beta-chemokines indicated that IFN-gamma treatment caused selective expression of RANTES (regulated upon activation, normal T cell expressed and secreted), and the functional significance of this finding was demonstrated by inhibition of epithelial-T cell adhesion and transepithelial migration by anti-RANTES mAbs. In addition, we found that epithelial (but not endothelial) cells preferentially secreted RANTES through the apical cell surface thereby establishing a chemical gradient for chemotaxis across the epithelium to a site where they may be retained by high levels of RANTES and apical ICAM-1. These patterns for epithelial presentation of ICAM-1 and secretion of RANTES appear preserved in airway epithelial tissue studied either ex vivo with expression induced by IFN-gamma treatment or in vivo with endogenous expression induced by inflammatory disease (i.e., asthma). Taken together, the results define how the patterns for uniform presentation of ICAM-1 along the cell surface and specific apical sorting of RANTES may serve to mediate the level and directionality of T cell traffic through epithelium (distinct from endothelium) and provide a basis for how this process is precisely coordinated to route immune cells to the mucosal surface and maintain them there under normal and stimulated conditions.
In this study, we determined the ligand-dependent activation function domain 2 (AF-2) of the human vitamin D receptor (hVDR) and characterized it using site-directed mutagenesis. A single mutation at glutamic acid-420 (E420Q) and an additional mutation at leucine-417 (L417A-E420Q) eliminated ligand-dependent transcriptional activation. In addition, lysine-264 was also demonstrated to be vital for ligand-induced transactivation. However, bacterial-overexpressed transcriptional factor IIB (TFIIB) was able to bind to both AF-2 and lysine-264 mutant hVDRs in vitro. The ligand-dependent transactivation via wild type hVDR was interfered with weakly only when a 10-fold molar excess of L417A-E420Q plasmid was co-transfected. This suppressive effect was diminished by introducing an additional mutation at a cysteine residue in the DNA binding domain. Thus, we conclude that the AF-2 domain of the hVDR located between amino acids 417 and 420, as well as lysine-264, are essential for ligand-dependent transactivation, and that TFIIB was not necessary for the function of these two regions of the hVDR. Our finding that AF-2 mutant hVDRs exhibit only very weak suppressive effect may indicate a difference in the molecular mechanism of the VDR-mediated transactivation from other nuclear receptors.
Three-dimensional image reconstruction for preoperative surgical planning and intraoperative navigation for the resection of low-grade gliomas was performed in 20 patients. Thirteen of these surgeries were performed while the patient received a local anesthetic to allow for cortical mapping. Ninety percent of the patients were functionally intact postoperatively. The authors propose that the combination of the three-dimensional image reconstruction and surgical navigation, in conjunction with intraoperative cortical mapping, provides an additional means for surgeons to improve the safety and precision of the procedures.
UV radiation induces two major classes of pyrimidine dimers: the pyrimidine [6-4] pyrimidone photoproduct (6-4 product) and the cyclobutane pyrimidine dimer (CPD). Many organisms produce enzymes, termed photolyases, that specifically bind to these damage products and split them via a UV-A/blue light-dependent mechanism, thereby reversing the damage. These photolyases are specific for either CPDs or 6-4 products. A gene that expresses a protein with 6-4 photolyase activity in vitro was recently cloned from Drosophila melanogaster and Xenopus laevis. We report here the isolation of a homolog of this gene, cloned on the basis of sequence similarity, from the higher plant Arabidopsis thaliana. This cloned gene produces a protein with 6-4 photolyase activity when expressed in Escherichia coli. We also find that a previously described mutant of Arabidopsis (uvr3) that is defective in photoreactivation of 6-4 products carries a nonsense mutation in this 6-4 photolyase homolog. We have therefore termed this gene UVR3. Although homologs of this gene have previously been shown to produce a functional 6-4 photolyase when expressed in heterologous systems, this is the first demonstration of a requirement for this gene for photoreactivation of 6-4 products in vivo.
Recently aortic root replacement and free-hand aortic valve replacement with cryopreserved allograft are accepted and established as useful procedures in USA and Europe. Otherwise allograft aortic valve failure due to structural valve degeneration, progressive loss of leaflet extensibility or progressive aortic root dilatation are reported. Aortic root replacement and free-hand aortic valve replacement with cryopreserved allograft were performed on three patients in the Department of Cardiovascular Surgery, NCVC between March of 1992 and March of 1994. We evaluated the mid-term function of implanted allograft. Case 1, 2, 58-year-old male and 42-year-old male with aortic regurgitation due to Aortitis had modified Bentall procedures with composite graft and had redo surgery for aortic regurgitation due to graft detachment with cryopreserved allograft using "aortic root replacement". Case 3: 54-year-old male received a cryopreserved allograft for aortic stenosis/regurgitation using "free-hand technique". Postoperative echocardiogram showed excellent valve function without regurgitation any calcification in all cases. However chest computed tomography suggested the new calcification of allograft wall at 15 months after operation in Case 1 who was administered steroid agents, despite no calcification in Case 2 during 17 months follow-up.
We report four patients with a new type of familial parkinsonism and dementia consisting of an autosomal dominant inheritance, dopa-responsive parkinsonism, severe dementia, variable myoclonus and autonomic disturbances. Autopsy of two patients revealed symmetrical cerebral atrophy with fronto-temporal dominant distribution, and marked depigmentation in the substantia nigra and locus ceruleus. Neuronal loss and gliosis were observed in the deep cerebral cortex and amygdala as well as in the areas vulnerable to Parkinson's disease. In the cerebral cortex, swollen neurons with frequent granulovacuolar changes were observed, consisting of ballooned neurons and those with argyrophilic intracytoplasmic inclusions, in addition to neuropil threads. Atypical neurofibrillary tangles, which barely stained with tau antibodies, were numerous in the upper cortical layers, consisting of 15-nm straight tubules. In addition, tau-negative astrocytic fibrillary tangles were also frequent. Electron microscopically, the ballooned neurons and argyrophilic neuronal inclusions contained filamentous structures coated with fuzzy electron-dense deposits. The inclusions showed immunohistochemical features different from those of cortical Lewy bodies and Pick bodies. Occasional Lewy bodies were present in the brain stem lesions of both patients. In two of our patients, the pathology in the brain stem was similar to that of Parkinson's disease, whereas their cerebral pathology was unusual and has not been reported previously.
Norwalk-like virus genes were detected by RT-PCR in the caecum contents of pigs. Positive PCR products were produced from four out of 1,117 samples by nested PCR using human SRSV primers. Nucleotide sequences between 4,561 and 4,852 numbered according to the Norwalk virus genomic RNA in the RNA polymerase region were determined. Between the Norwalk virus sequence and the sequences detected in pigs, there was 58.2% to 59.9% sequence homology. The swine sequences were located on genogroup II of human SRSVs, but formed a subgroup in the phylogenetic tree of caliciviruses.
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Helicobacter pylori seem to avoid areas of intestinal metaplasia in the gastric mucosa, but attachment of these bacteria to epithelium with the appearance of incomplete intestinal metaplasia has been documented. To characterize the nature of the epithelium to which H pylori was attached, we carried out an immunohistochemical study using monoclonal antibodies against gastric surface mucous cell mucins (M1), blood group-related carbohydrates antigens (Le(a), sialyl Le(a), Le(b), type 1H, and type 2H) and sialyl Tn antigen. The results of this study suggest that these areas of H pylori attachment represent a hybrid epithelium whose cells share characteristics of both gastric surface mucous cells and intestinal metaplastic cells. Whether all areas of incomplete intestinal metaplasia represent an intermediate stage between the normal gastric epithelium and the fully developed complete type of metaplasia remains to be determined.