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Biomedical subjects

T Nakashima

Publications and source records attributed to T Nakashima.

At least 55 records · Page 3Linked to original sources

Degradation of bisphenol A in water by TiO2 photocatalyst.

The photocatalytic degradation of bisphenol A (BPA), a representative endocrine disruptor, was carried out in TiO2 aqueous suspension. The main purposes were to confirm the total mineralization of BPA and to evaluate the estrogenic activity in the treated water during the photocatalytic reaction. An initial BPA concentration of 175 microM in water was totally degraded to carbon dioxide by TiO2-photocatalyzed reactions under UV irradiation of 10 mW cm-2 for 20 h. Four HPLC peaks indicating intermediate products appeared in chromatograms monitored at 275 nm, but the heights relative to that of the initial BPA were very low, at most 0.04 in the time period 5-10 h after the start of UV irradiation. All of the peaks finally disappeared after 20 h. For the treated water, the transcriptional estrogenic activity in response to human estrogen receptor in a yeast hybrid assay decreased drastically to less than 1% of the initial BPA's activity within 4 h. On the basis of these results, we conclude that TiO2 photocatalysis could be a useful technology for the purification of water containing BPA without generating any serious secondary pollution.

Benzhydryl Compounds↗

Clonal expansion of freshly isolated CD4T cells by randomized peptides and identification of peptide ligands using combinatorial peptide libraries.

We synthesized Xn (n = 9 -- 19) peptides that consist of 9 to 19 residues with random sequences. X19 is considered to deliver antigenic stimuli to CD4 T cells, because: (a) X19 induces proliferation of peripheral blood mononuclear cells (PBMC), in the presence of IL-2, which is abrogated by monoclonal antibodies to class II HLA; (b) X19 + IL-2 induces proliferation of CD4 T cell clones of distinct specificities; and (c) T cell clones recognizing the same TCR ligands with distinct V beta usage are equally stimulated by X19 + IL-2. We next co-cultured single peripheral CD4 T cells with X19 and mitomycin-treated autologous PBMC. Indeed, single T cells of CD45RA(-) memory phenotype exhibited clonal expansion, with variable rates of proliferation, when IL-4, IL-7, IL-9, IL-15 and agonistic antibody to CD29 were included in the culture. These T cell clones showed heterogeneous proliferation patterns against KGXXXXXXXXXGK-based and KGXXXXXXXXXGKGKK-based combinatorial peptides libraries, in the presence of IL-2. Pattern-match search on a T cell clone resulted in peptide ligand candidates, one of which induced proliferation, as did protein molecules carrying the corresponding sequence. These results indicate that X19 can induce proliferation of peripheral memory T cells, the peptide ligands of which can be determined using combinatorial peptide libraries.

Amino Acid Sequence↗

A novel role for interleukin-18 in human natural killer cell death: high serum levels and low natural killer cell numbers in patients with systemic autoimmune diseases.

OBJECTIVE: Patients with systemic autoimmune diseases have been reported to have reduced numbers of peripheral blood natural killer (NK) cells compared with healthy subjects. The ability of selected cytokines to trigger NK cell death prompted us to compare the levels of peripheral blood cytokines with the numbers of NK cells in patients with various systemic autoimmune diseases. METHODS: We used enzyme-linked immunosorbent assays to measure the concentration of selected cytokines (interleukin-18 [IL-18], IL-15, IL-12, IL-2, interferon-gamma [IFNgamma], and tumor necrosis factor alpha [TNFalpha]) in sera from 58 patients with systemic autoimmune diseases and 33 healthy controls. The absolute number of T cells and NK cells in the peripheral blood was measured in parallel using flow cytometry. The ability of selected cytokines to induce NK cell death was then measured using 3,3'-dihexyloxacarbocyanine iodide dye, propidium iodide staining, and caspase 3 activity. RESULTS: Levels of IL-18, IL-15, IFNgamma, and TNFalpha were elevated in sera from patients with systemic autoimmune diseases compared with normal controls. The percentage of NK cells and natural killer T cells were significantly decreased in the peripheral blood of patients with systemic autoimmune diseases compared with normal controls. Serum concentrations of IL-18, IL-15, and TNFalpha were inversely related to the number of NK cells in both patients and healthy controls. The combination of IL-18 and IL-15 or IL-18 and IL-12 induced NK cell death in vitro. The combination of IL-18 and IL-15 or IL-18 and IL-12 enhanced IFNgamma and TNFalpha production by NK cells in vitro. Cytokine-induced NK cell death is caspase-dependent and is partially blocked by neutralizing antibodies against TNFalpha. CONCLUSION: High levels of IL-18 and IL-15 are associated with the decreased number of NK cells that is observed in patients with systemic autoimmune diseases.

Adolescent↗

Maspin expression in stage I and II oral tongue squamous cell carcinoma.

BACKGROUND: A relatively high failure rate in the therapy of patients with early oral tongue squamous cell carcinomas (SCCs) is evidenced by untreated clinically negative neck lymph node metastasis. It is important to predict the malignant potential of oral tongue SCC in stage I and II patients, because the development of lymph node metastasis directly affects the prognosis of the patients. METHODS: We evaluated maspin expression immunohistochemically in patients with stage I and II oral tongue SCCs and determined whether the expression level may be a useful factor in predicting metastatic potential and prognosis of these SCCs. RESULTS: Clinical follow-up data showed a longer disease-free interval and overall survival periods for tumors immunohistochemically positive for maspin than for tumors negative for maspin, with the difference in disease-free interval being statistically significant (p =.01). The absence of maspin expression was found more frequently in cases of subsequent cervical lymph node metastasis than in cases without metastasis (p =.03). CONCLUSIONS: Decreased maspin expression may be a significant factor associated with the metastatic potential of stage I and II oral tongue SCCs.

Adult↗

Endobronchial metastasis from prostate cancer.

We describe a case of endobronchial metastasis from prostate cancer originally diagnosed as primary bronchogenic carcinoma. We conducted a sleeve lobectomy and determined a final diagnosis using a serumprostate-specific antigen and immunohistochemical studies.

Aged↗

Random amplified polymorphic DNA analysis applied to acute otitis media caused by penicillin non-susceptible Streptococcus pneumoniae.

The spread of penicillin non-susceptible Streptococcus pneumoniae (PNSSP) is an emerging problem for the treatment of acute otitis media (AOM). Attendance of children at day care centers, as well as the spread of PNSSP, is a risk factor for AOM. The status of the spread of PNSSP during the acute infection phase of AOM has not been evaluated. We examined the clonality of samples from seven children in a day care center who simultaneously developed AOM caused by PNSSP. The seven isolates from the children, and six control samples were grouped by serotyping, by determining resistance to antimicrobial agents, and by genotyping, carried out by sequencer-based random amplified polymorphic DNA (RAPD), and validated by bootstrap analysis. There was no evidence to indicate the direct dissemination of PNSSP among these patients in the day care center, although the simultaneous occurrence of PNSSP AOM had initially suggested a clonal outbreak. The possible presence of a common ancestral strain suggested the importance of surveillance during the carrier state. The result of RAPD genotyping was highly reproducible, as validated by the high bootstrap score. The use of an automated sequencer, in combination with a careful choice of primers, and commercially established kits, played a significant role in the reproducibility of the studies.

Child↗

Phytoalexins from Pinus strobus bark infected with pinewood nematode, bursaphelenchus xylophilus.

From the bark of Pinus strobus infected with pinewood nematode, Bursaphelenchus xylophilus, a stilbenoid 3-O-methyldihydropinosylvin and a flavanone (2S)-pinocembrin were isolated as active principles of inducibly produced antifungal compounds. The structures of the compounds were determined on the basis of spectroscopic analyses. Close investigations of spectroscopic analyses led to the complete assignment of 13C NMR and 1H NMR chemical shifts for the former compound and to the determination of the stereochemistry of the latter compound from P. strobus to be 2S. Furthermore, the distribution and time course accumulation of the identified compounds were investigated. The former compound was demonstrated to be nematocidal and the concentrations of the compound in the inoculated branches were sufficient enough to inactivate the pinewood nematode within one week after inoculation.

Animals↗

Effects of alpha-tocopherol on cisplatin-induced ototoxicity in guinea pigs.

Cisplatin (CDDP), an antitumor agent widely used in the treatment of head and neck cancers, has dose-limiting side effects such as ototoxicity and nephrotoxicity. Recently, evidence has been accumulated to demonstrate that these side effects are closely related to oxidative stress. In the present study, we attempted to suppress CDDP-induced ototoxicity and nephrotoxicity in guinea pigs by administering alpha-tocopherol, a naturally occurring antioxidant. Hartley albino guinea pigs (250 approximately 300 g) were treated with CDDP (4 mg/kg intraperitoneally (I.P.)) for 3 days in the presence and absence of alpha-tocopherol (50 mg/kg I.P.) injection for 6 days. The combined treatment of animals with alpha-tocopherol distinctly improved the CDDP-induced side effects. These were: loss of Preyer's reflex at high frequencies; distinct elevation of auditory brain stem response threshold at 16 kHz; increased lipid peroxidation in the cochlea determined by the malondialdehyde-thiobarbituric acid method; substantial losses of outer hair cells in the basal and second turns of the cochlea; fragmentation of nuclear DNA detected by the TUNEL method in cochlear hair cells and cells in the stria vascularis; and increases in serum BUN and Cr. These results strongly suggest that alpha-tocopherol suppresses CDDP-induced ototoxicity and nephrotoxicity via the suppression of the increased production of reactive oxygen species.

Animals↗

Chemotaxonomy on the leaf constituents of Thujopsis dolabrata Sieb. et Zucc.-Analysis of neutral extracts (diterpene hydrocarbon).

The leaf terpenes in Thujopsis dolabrata from all regions in Japan were analyzed using GC and GC-MS. The results show that the major constituents of the diterpene hydrocarbon fraction in this conifer are dolabradiene, hibaene, rimuene, 13-epi-dolabradiene and abietatriene. There were wide variations in the contents of the constituents among individuals and habitats. The results also show that T. dolabrata trees from 34 habitats can be classified into three groups based on the composition of the leaf diterpene hydrocarbon.

Journal Article↗

Expression of midkine in the cochlea.

Midkine (MK) is one of a new family of heparin-binding growth factors involved in the regulation of growth and differentiation. We have analyzed expression of MK in the cochlea using ICR mice within 1 day from birth. The expression of MK in the cochlea was confirmed by Western blotting and immunohistochemistry. Anti-MK immunoreactivity was observed in the stria vascularis, spiral prominence, spiral ganglion, and ganglion nerve fibers. These findings suggest that MK plays a role in the development of the cochlea.

Animals↗

Effects of anterior inferior cerebellar artery occlusion on cochlear blood flow--a comparison between laser-Doppler and microsphere methods.

The effects of anterior inferior cerebellar artery (AICA) occlusion on blood flow were investigated in rats using the laser-Doppler and microsphere methods. A specially designed microclamp was held in a micromanipulator and positioned to occlude the left AICA. After the middle ear mucosa had been removed, a 1.0-mm laser-Doppler probe was placed on the basal turn of the left cochlea. Non-radioactive microspheres were injected intracardially during the AICA occlusion and the numbers of microspheres in various parts of the cochlea were counted, including in the bone surrounding the cochlea. Upon AICA clamping, the blood flow measured by laser-Doppler flowmetry decreased to 46.9+/-11.9% of the baseline value, and the number of microspheres trapped in the cochlea was 17.2+/-13.3% compared with the contralateral side in 15 animals. The number of microspheres in the bone surrounding the cochlea in the AICA-clamped side was 81+/-15% of that of the contralateral side. In animals in which there were few if any microspheres in the cochlea, laser-Doppler output was 30-40% of the baseline value. From these findings, we infer that during complete interruption of cochlear blood flow in rats, residual laser-Doppler output was essentially attributable to blood flow in the bone surrounding the cochlea.

Animals↗

Surgical strategy for cholesteatoma in children.

OBJECTIVE: We reviewed our experience with childhood cholesteatoma in children under 15 years old. Based on cumulative postoperative data, we propose a modified canal-wall-up technique in conjunction with a planned, staged operation. METHODS: From 1982 to 1997, 56 children with cholesteatoma (58 ears, total) underwent surgery in our department. In the early period (1982-1990), canal wall-down mastoidectomy was performed in 52% (21 of 40 ears), and canal wall-up mastoidectomy in 48% (the remaining 19 ears). In the late period (1991-1997), 18 ears with cholesteatoma underwent surgery. The canal-wall up mastoidectomy was performed in 89% (16 ears), and canal-wall-down mastoidectomy in the remaining 11% (two ears). RESULTS: In the early period (1982-1990), cholesteatoma recurred more frequently in the canal-wall-up mastoidectomy group than in the canal-wall down mastoidectomy group (53 vs. 14%). Other postoperative complications, such as erosion of the mastoid cavity, otorrhea, and perforation of the eardrum, occurred more frequently in the canal-wall-down mastoidectomy group than in the canal-wall-up mastoidectomy group. In the late period (1991-1997), in the canal-wall-up mastoidectomy group, ten ears underwent one-stage surgery. Planned staged tympanoplasty was completed in six ears. After one-stage surgery, four of ten ears experienced residual cholesteatoma. Two of the recurrent ears had undergone planned staged tympanoplasty. As revealed by postoperative computed tomography (CT) images, 12 of 15 ears had aeration in the attic and antrum as well as in the tympanic cavity. In these cases, no attic retraction pocket formation was observed. CONCLUSION: Our strategy for pediatric cholesteatoma in the future is to use canal-wall-up mastoidectomy when possible. If aeration in the attic and antrum is observed by preoperative CT-scan image and no erosion in the malleus and incus exists, the one-stage surgery will be chosen. If no aeration is observed by CT-scan and/or erosion exists in the surgical findings, planned staged tympanoplasty will be necessary. This strategy allows a high incidence of aeration of the attic and antrum, and prevents the formation of the attic retraction pocket while enabling the early detection of residual cholesteatoma by means of CT.

Adolescent↗

Laboratory data and treatment outcomes of head and neck tumor patients in the elderly.

OBJECTIVE: To elicit the factors influencing the choice of treatment and the prognosis of elderly patients, we studied the clinical and laboratory data of head and neck tumor patients. The patients were divided into two groups (group A: younger than 75, group B: 75 years of age or older) and the treatment outcomes as well as the features of the laboratory data were analyzed. METHODS: The clinical records of 1350 patients (888 males, 462 females) with head and neck tumors who received their initial treatment at our hospital were reviewed. The collected data including age, the site of the primary lesion, pre-treatment health states, pre-operative laboratory results were examined. According to the treatment policy, we grouped the patients according to whether or not they had received the standard therapy for the disease and then analyzed their treatment outcomes. RESULTS: Standard therapy was not performed in 62 (5.6%) of the 1114 patients in group A and in 43 (18.2%) of the 236 patients in group B. A further analysis performed in group B (elderly patients) revealed that standard therapy was performed in 193 patients, while 43 received non-standard therapy. The prognosis for the non-standard therapy cases was poor. The averages of the laboratory test findings between groups A and B were compared, but no marked differences were observed. However, differences were observed in the ratio of patients whose data were in the normal range between group A and group B. When the laboratory data were compared between the standard and non-standard groups of the elderly, serum albumin and CBC (especially hemoglobin) showed a close relationship to the treatment modality. CONCLUSION: The ratio of patients who did not receive standard therapy was high in the age group of 75 years or older. The prognosis of patients with head and neck tumors is therefore considered to depend on whether or not a patient receives the standard therapy against the disease. The pre-treatment clinical data and the laboratory findings vary markedly among elderly patients 75 years of age or older. Regarding the treatment of head and neck tumors in the elderly, the laboratory data and clinical conditions of each individual patient should be checked carefully and every possible means should be employed in order to allow such patients to receive the standard therapy whenever possible.

Adult↗

Hypophysis surgery with or without endoscopy.

OBJECTIVE: Hardy's operation with microscope has long been the standard method for pituitary adenoma. But a new approach via the nasal cavity using an endoscope has been adopted recently. In this study, the postoperative outcome as well as the preoperative evaluation of endoscopic hypophysectomy and non-endoscopic one were compared at our faculty. METHOD: We performed the non-endoscopic transnasal hypophysectomy on 18 patients and the endoscopic transnasal hypophysectomy on thirteen patients who had a pituitary lesions from February 1996 to October 1999. As to these patients the situations from preoperation through postoperation such as chief complaints, serum hormone level, final diagnosis, tumor size, as well as operating time or blood loss during the operation were discussed precisely. Then the merits and demerits of endoscopic hypophysectomy were discussed. RESULT: Five PRL-producing adenoma, three GH-producing adenoma, nine non-functioning adenoma, and two ACTH or TSH-producing adenoma were included in this discussion as endoscopic group. The age of non-endoscopic group are from 23 to 73 (49.4 in average), and they include ten males and eight females. On the other hand three PRL-producing adenoma, two GH-producing adenoma, two non-functioning adenoma, and one Rathke's cyst were included in this discussion as endoscopic group. The age of endoscopic group are from 19 to 73 (49.1 in average), and they include seven males and six females. As to non-endopscopic group the blood loss during each operation is 568 ml and operating time is 256 min in average. For endoscopic group the blood loss is 296 ml and operating time is 234 min in average. CONCLUSION: By microsurgery in the pituitary operation with endoscopy, the minimal invasive surgery becomes possible by reducing blood loss and shortening operating time. During the operation cooperation between neurosurgeon and ENT surgeon is indispensable in order to perform hypophysectomy smoothly. The development of optical better aids and operation instruments for endonasal hypophysectomy is desired in the future. The navigation system was more useful than X-ray fluoroscopy to obtain the detailed information.

Adenoma↗

Ribosomal protein L5 has a highly twisted concave surface and flexible arms responsible for rRNA binding.

Ribosomal protein L5 is a 5S rRNA binding protein in the large subunit and plays an essential role in the promotion of a particular conformation of 5S rRNA. The crystal structure of the ribosomal protein L5 from Bacillus stearothermophilus has been determined at 1.8 A resolution. The molecule consists of a five-stranded antiparallel beta-sheet and four alpha-helices, which fold in a way that is topologically similar to the ribonucleoprotein (RNP) domain. The molecular shape and electrostatic representation suggest that the concave surface and loop regions are involved in 5S rRNA binding. To identify amino acid residues responsible for 5S rRNA binding, we made use of Ala-scanning mutagenesis of evolutionarily conserved amino acids occurring in the beta-strands and loop regions. The mutations of Asn37 at the beta1-strand and Gln63 at the loop between helix 2 and beta3-strand as well as that of Phe77 at the tip of the loop structure between the beta2- and beta3-strands caused a significant reduction in 5S rRNA binding. In addition, the mutations of Thr90 on the beta3-strand and Ile141 and Asp144 at the loop between beta4- and beta5-strands moderately reduced the 5S rRNA-binding affinity. Comparison of these results with the more recently analyzed structure of the 50S subunit from Haloarcula marismortui suggests that there are significant differences in the structure at N- and C-terminal regions and probably in the 5S rRNA binding.

Amino Acid Sequence↗

Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseases.

BACKGROUND/AIMS: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. METHODS: Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. RESULTS: Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. CONCLUSION: Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses.

Adult↗

Growth factors, extracellular matrix components and cell adhesion molecules Warthin's tumor.

We studied expressions of various growth factors, their receptors, cell adhesion molecules and extracellular matrix components in Warthin's tumor of the salivary gland with immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Various growth factors and their receptors, such as transforming growth factor-alpha (TGF-alpha), heparin-binding epidermal growth factor-like growth factor (HB-EGF), TGF-beta2, TG-beta3, insulin-like growth factor (IGF)-I and -II, vascular endothelial growth factor (VEGF), EGF receptor (EGFR), erb-B4, TGF-betaRI and II, Flt and Flk-1 and IGF receptor Ibeta, were found in epithelial cells and/or in some lymphoid cells. Fibronectin, laminin, collagen type IV and tenascin were found in stroma of the lymphoid tissue. Integrins such as alpha3beta1 and beta3, Thy-1, CD44 and VCAM-1 were also expressed in epithelial and/or lymphoid cells. These various proteins may interact and regulate the proliferation and cell attachment of both epithelial and lymphoid components in this unique tumor.

Adenolymphoma↗