Biomedical subjects
Publications and source records attributed to H Sugiyama.
A new type of hairpin polyamide-CPI conjugate possessing a vinyl linker has been synthesized. Sequence-selective alkylation of double-stranded DNA by conjugates was investigated by high resolution denaturing gel electrophoresis using 450 bp DNA fragments. Highly-efficient DNA alkylation predominantly occurs at the purines of 5'-(A/T)G(T/A)CPu-3' site at nanomolar concentration.
Thirty-one patients undergoing internal fixation for femoral neck fractures who were examined by magnetic resonance imaging at 2, 6, and 12 months after surgery and who could be followed up more than 2 years were enrolled in the current study. The items investigated were timing of the appearance of the band image on T1 weighted images, magnetic resonance imaging classification, and plain radiographs. Band images were observed 2 months after surgery in eight patients and 6 months in 12 patients (39% of all patients). According to the location and extent of the band image on magnetic resonance imaging, one patient was classified in the B1 Group (lateral type), four patients in the B2 Group (surface type), three patients in the B3 Group (intermediate type), and four patients in the B4 Group (extended type). Band images appeared in all patients in the B4 Group 6 months after surgery. Femoral heads of the patients in the B3 and B4 Groups by magnetic resonance imaging classification all were collapsed. On plain radiographs, osteonecrosis of the femoral head could be diagnosed in eight patients between 11 and 24 months after injury. The interval giving the greatest sensitivity, specificity, and accuracy of the diagnosis of osteonecrosis of the femoral head by magnetic resonance imaging was 6 months after surgery.
Attempts have been made to use manganese peroxidase (MnP) for chlorine-free pulp biobleaching, but they have not been commercially viable because of the enzyme's low stability. We developed a new pulp biobleaching method involving mesoporous material-immobilized manganese peroxidase from Phanerochaete chrysosporium. MnP immobilized in FSM-16, a folded-sheet mesoporous material whose pore size is nearly the same as the diameter of the enzyme, had the highest thermal stability and tolerance to H(2)O(2). MnP immobilized in FSM-16 retained more than 80% of its initial activity even after 10 days of continuous reaction. We constructed a thermally discontinuous two-stage reactor system, in which the enzyme (39 degrees C) and pulp-bleaching (70 degrees C) reactions were performed separately. When the treatment of pulp with MnP by means of the two-stage reactor system and alkaline extraction was repeated seven times, the brightness of the pulp increased to about 88% within 7 h after completion of the last treatment.
Dermoid cysts are benign cystic teratomas lined by skin and epidermal appendages. We report a dermoid cyst occurring in a 26-year-old female whose chief complaint was irregular vaginal bleeding. Abdominal magnetic resonance image demonstrated a space-occupying lesion in the right lower abdomen. The mass showed hyperintensity on the T2 image and the signal was homogeneous for the interior. During abdominal surgery we made the diagnosis of subserous tumor of the colon and resected the ileocecal portion of the colon. The tumor measured 5.4 x 4.8 x 3.5 cm and was soft and elastic. On cross section, a unilocular cyst filled with atheromatous material was found. Pathological examination revealed a dermoid cyst. In the view of this diagnosis, a simple excision would have been an adequate treatment.
Glucocorticoid has long been used to treat patients with glomerulonephritis because it ameliorates mesangial cell proliferation and proteinuria, in part by suppressing nuclear factor-kappa B (NF-kappaB) activation, which regulates the transcription of various pro-inflammatory genes. Recent evidence shows that NF-kappaB activation increases the resistance to TNF-alpha-induced apoptosis in mesangial cells. We examined glomerular cell proliferation and apoptosis along with NF-kappaB activation in the Thy-1.1 nephritis model. We also evaluated TNF-alpha-induced apoptosis in cultured mesangial cells. Methylprednisolone treatment ameliorated mesangial hypercellularity in Thy-1.1 nephritis by decreasing proliferating cells and increasing apoptosis in the glomeruli. These effects were associated with suppressed NF-kappaB activation. This in vitro study revealed that treatment with methylprednisolone and TNF-alpha induced cultured mesangial cell apoptosis. These results suggest that methylprednisolone may accelerate the resolution phase of Thy-1.1 nephritis in part by sensitizing mesangial cells to apoptosis.
The reaction mechanism of biodesulfurization was investigated using whole cells of Rhodococcus erythropolis KA2-5-1, which have the ability to convert dibenzothiophene (DBT) into 2-hydroxybiphenyl. The desulfurization patterns of alkyl DBTs were represented by the Michaeis-Menten equation. The values of rate constants, the limiting maximal velocity (Vmax) and Michaelis constant (Km), for desulfurization of alkyl DBTs were calculated. The relative desulfurization activities of various alkyl DBTs were reduced in proportion to the total carbon numbers of alkyl substituent groups. Alkyl DBTs that had a total of six carbons of alkyl substituent groups were not desulfurized. The type or position of alkyl substituent groups had little effect on desulfurization activity. The desulfurization activity of each alkyl DBT, when mixed together, was reduced. This phenomenon was caused by apparent competitive inhibition of substrates. Using the apparent competitive inhibition model, the desulfurization pattern of a multiple components system containing alkyl DBTs was elucidated. This model was also applicable for biodesulfurization of light gas oil.
The fibers of the anterior belly digastric muscle of mice, fed a granulated diet for various periods, have been studied histochemically and morphometrically. The diameters of the anterior belly digastric fibers in normal mice fed only a granulated diet were smaller than those in mice fed a solid diet. Differences in the succinate dehydrogenase (SDH) activity of muscle fibers between op/op and normal mice gradually appeared in the anterior belly digastric muscle and, by the age of 90 days, under-development of muscle fibers was observed in the mild-belly region of the anterior belly digastric muscle of op/op mice fed a granulated diet. These results indicate mechanical stress in mastication plays an important role in the development of the anterior belly digastric muscle structures.
To elucidate whether a relationship exists between the site of trauma and severity of acute hyperextension spinal cord injury without bone damage, we examined the clinical features of 25 male and 10 female patients aged 13 to 88 years. None of the patients had vertebral damage such as fracture and dislocation. The site of impact was classified as the buccal, forehead, or mandibular region. The neurological findings were assessed according to Frankel's classification at admission and at follow up after 3 months or more to assess outcome. Eleven patients suffered trauma in the buccal region, one patient in Frankel's grade B, three in grade C, and seven in grade D at admission. All 11 of these patients showed an improvement of one grade or more to an outcome of C in one patient, D in one, and E in nine. Trauma occurred at the forehead region in 18 patients, four in grade B, 10 in grade C, and four in grade D. Improvement was seen at follow up by one grade or more to C in one patient, D in 10, and E in seven. Trauma occurred at the mandibular region in six patients, four in grade B and two in grade C. Four of these patients showed improvement of one grade or more to grade B in one, grade C in four, and grade E in one. Overall, seven patients had poor outcomes, five of whom suffered trauma to the mandibular region, indicating that impact to the mandibular region tends to have an unfavorable clinical outcome. Our findings indicate that the site of trauma greatly influences the severity of hyperextension spinal cord injury.
Fecal samples from 232 weaned piglets (1 and 3 months old) and 252 fattening porkers (6 months old) in 8 stock-raising farms located in Kanagawa Prefecture, Japan, from June 1998 to June 2000 were examined to determine the prevalence of Cryptosporidium infection. Detection of oocysts was performed using the ethyl acetate fecal concentration method and immunofluorescent staining. C. parvum oocysts were identified in 77 (33.2%) 1-3 months old weaned piglets from four farms. The odds of excreting among 1-3 months old piglets were more than 100 times greater than among 6 months old porkers (95% confidence interval: 17-902). This strongly suggests that weaned piglets are important reservoirs of pathogenic microbes whose potential contamination of drinking water has epidemiological implications for human health.
It is characterized by mainly depressive mood and psychomotor retardation. Another symptoms are retardation of thought, diurnal change, anxiety, irritability, delusion of belittlement, etc. There are often somatic symptoms as loss of appetite, sleep disturbance, loss of body weight, constipation, etc. Depressive symptoms are often seen in schizophrenia, brain injury, endocrinosis illness and other somatic illness. Diagnosis of depression is carefully carried out by detailed interviews and symptoms. Recently diagnosis of depression is determined mechanically by DSM-IV or ICD-10. Neuro-endocrine tests as DST or Dex-CRH test, are useful strategies in examination of depression.
A 56-year-old woman was admitted to our hospital, on October 10, 1999 because of tingling numbness of the Th3 area and paraparesis. Her medical history included the diagnosis of pulmonary sarcoidosis which had responded to steroid therapy. On radiographic examination, a Th2 compression fracture and gadolinium enhanced areas were shown in MRI. We diagnosed vertebral sarcoidosis and restarted steroid therapy. Next day, she had no paresis and she was discharged after 20 days. However, the patient returned to our hospital with recurrence of the same pain and paraparesis on January 1, 2000, and spinal fusion of the Th2-3 was performed by a transpleural anterolateral approach using a block of iliac bone as a graft. Histology and cultural studies of tissue revealed tuberculosis. There is a diagnostic dilemma, "sarcoidosis or tuberculosis?", but it is necessary to be aware of this at the time of the initial diagnosis.
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5-Formyluracil (5-foU) is a potentially mutagenic lesion of thymine produced in DNA by ionizing radiation and various chemical oxidants. Although 5-foU has been reported to be removed from DNA by Escherichia coli AlkA protein in vitro, its repair mechanisms are not fully understood. In this study, we used the borohydride trapping assay to detect and characterize repair activities for 5-foU in E. coli extracts with site-specifically designed oligonucleotides containing a 5-foU at defined sites. The trapping assay revealed that there are three kinds of proteins that form covalent complexes with the 5-foU-containing oligonucleotides. Extracts from strains defective in the nth, nei, or mutM gene lacked one of the proteins. All of the trapped complexes were completely lost in extracts from the nth nei mutM triple mutant. The introduction of a plasmid carrying the nth, nei, or mutM gene into the E. coli triple mutant restored the formation of the corresponding protein-DNA complex. Purified Nth, Nei, and MutM proteins were trapped by the 5-foU-containing oligonucleotide to form the complex in the presence of NaBH(4). Furthermore, the purified Nth, Nei, and MutM proteins efficiently cleaved the oligonucleotide at the 5-foU site. In addition, 5-foU was site-specifically incorporated into plasmid pSVK3, and the resulting plasmid was replicated in E. coli. The mutation frequency of the plasmid was significantly increased in the E. coli nth nei mutM alkA mutant, compared with the wild-type and alkA strains. From these results it is concluded that the Nth, Nei, and MutM proteins are involved in the repair pathways for 5-foU that serve to avoid mutations in E. coli.
An important approach to improve chemotherapy of members of the bleomycin (BLM) family of antibiotics is to find compounds (amplifiers) that enhance the activity of BLM-mediated DNA cleavage and apoptosis. Using a DNA-sequencing technique and pulsed field gel electrophoresis, we have investigated whether BLM-mediated cleavage of isolated and cellular DNA is amplifed by three compounds (RW-12, LS-20, 1S-5Me) which have a conformationally flexible, unfused polyaromatic system and cationic side chain in the molecules. RW-12 enhanced most effectively both pepleomycin (PEM)-induced cytotoxicity and apoptosis. The order of the maximum enhancing effect of amplifiers on PEM-mediated DNA damage is RW-12 > LS-20 > 1S-5Me. RW-12 amplified PEM-mediated DNA cleavage most effectively not only in vitro but also in cultured cells. We have reported that the order of the DNA binding constants of these compounds is RW-12 > LS-20 > 1S-5Me. In this study, we found a good correlation between PEM-mediated cleavage of isolated DNA and cellular DNA. These results suggest that BLM amplifiers bind to DNA and by doing so enhance drug-mediated DNA degradation, ultimately leading to apoptosis. The present study on amplifiers of anticancer agents shows a novel approach to the potentially effective anticancer therapy.
The alpha-C-H bonds of 3-methyl-2-butanone, 3-pentanone, and 2-methyl-3-pentanone were activated on the sulfur center of the disulfide-bridged ruthenium dinuclear complex [(RuCl(P(OCH3)3)2)2(mu-S2)(mu-Cl)2] (1) in the presence of AgX (X = PF6, SbF6) with concomitant formation of C-S bonds to give the corresponding ketonated complexes [(Ru(CH3CN)2(P(OCH3)3)2)(mu-SSCHR1COR2)(Ru(CH3CN)3(P(OCH3)3)2)]X3 ([5](PF6)3, R1 = H, R2 = CH(CH3)2, X = PF6; [6](PF6)3, R1 = CH3, R2 = CH2CH3, X = PF6; [7](SbF6)3, R1 = CH3, R2 = CH(CH3)2, X = SbF6). For unsymmetric ketones, the primary or the secondary carbon of the alpha-C-H bond, rather than the tertiary carbon, is preferentially bound to one of the two bridging sulfur atoms. The alpha-C-H bond of the cyclic ketone cyclohexanone was cleaved to give the complex [(Ru(CH3CN)2(P(OCH3)3)2)(mu-SS-1- cyclohexanon-2-yl)(Ru(CH3CN)3(P(OCH3)3)2)](SbF6)3 ([8](SbF6)3). And the reactions of acetophenone and p-methoxyacetophenone, respectively, with the chloride-free complex [(Ru(CH3CN)3(P(OCH3)3)2)2(mu-S2)]4+ (3) gave [(Ru(CH3CN)2(P(OCH3)3)2)(mu-SSCH2COAr)(Ru(CH3CN)3(P(OCH3)3)2)](CF3SO3)3 ([9](CF3SO3)3, Ar = Ph; [10](CF3SO3)3, Ar = p-CH3OC6H4). The relative reactivities of a primary and a secondary C-H bond were clearly observed in the reaction of butanone with complex 3, which gave a mixture of two complexes, i.e., [(Ru(CH3CN)2(P(OCH3)3)20(mu-SSCH2COCH2CH3)(Ru(CH3CN)3(P(OCH3)3)2)](CF3SO3)3 ([11](CF3SO3)3) and [(Ru(CH3CN)2(P(OCH3)3)2)(mu-SSCHCH3COCH3)(Ru(CH3CN)3(P(OCH3)2)](CF3SO3)3 ([12](CF3SO3)3), in a molar ratio of 1:1.8. Complex 12 was converted to 11 at room temperature if the reaction time was prolonged. The relative reactivities of the alpha-C-H bonds of the ketones were deduced to be in the order 2 degrees > 1 degree > 3 degrees, on the basis of the consideration of contributions from both electronic and steric effects. Additionally, the C-S bonds in the ketonated complexes were found to be cleaved easily by protonation at room temperature. The mechanism for the formation of the ketonated disulfide-bridged ruthenium dinuclear complexes is as follows: initial coordination of the oxygen atom of the carbonyl group to the ruthenium center, followed by addition of an alpha-C-H bond to the disulfide bridging ligand, having S=S double-bond character, to form a C-S-S-H moiety, and finally completion of the reaction by deprotonation of the S-H bond.
As TEI-9874, 2-(4-(6-cyclohexyloxy-2-naphtyloxy)phenylacetamide)ben zoic acid reduces allergen-specific immunoglobulin E (IgE) production by human peripheral blood mononuclear cells in vitro, we evaluated its potency on an allergen-induced asthmatic model in Brown-Norway rats. Inhaled ovalbumin induced the immediate-phase asthmatic response, the late-phase asthmatic response, the infiltration of leukocytes into bronchoalveolar lavage fluid, and an increase of serum anti-ovalbumin IgE. These parameters were suppressed by the treatment with TEI-9874 (3, 10, and 30 mg/kg p.o.). The ovalbumin-induced airway hyperresponsiveness was prevented by TEI-9874 (30 mg/kg p.o.). Furthermore, the suppression of the immediate-phase asthmatic response and the late-phase asthmatic response by TEI-9874 was almost completely extinguished by the exogenous administration of rat anti-ovalbumin antiserum. These results indicate that the efficacy of TEI-9874 on the asthmatic response is mainly mediated by the suppression of allergen-specific IgE production and TEI-9874 appears to be a good candidate as therapy for IgE-mediated allergic asthma.
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