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Biomedical subjects

T Oyama

Publications and source records attributed to T Oyama.

At least 73 records · Page 4Linked to original sources
PubMed2000

BRCA1 expression status in relation to DNA methylation of the BRCA1 promoter region in sporadic breast cancers.

To understand the biological role of BRCA1 in sporadic breast cancers, the relationship between DNA methylation of the BRCA1 promoter region and BRCA1 expression was studied using molecular biological and immunohistochemical methods. Furthermore, BRCA1 expression was compared with the expression of various cell cycle regulatory proteins and the morphological nuclear grade of cancer cells. Of 32 sporadic breast cancers investigated in this study, 10 (31%) revealed DNA methylation of the BRCA1 promoter region. The expression of BRCA1 was observed in the nuclei of cancer cells and 18 (56%) of 32 cancers were positive for BRCA1 immunoreactivity. Breast cancers with BRCA1 methylation lacked BRCA1 expression, except for only three cancers, and there was a significant inverse relationship between BRCA1 methylation and its expression in sporadic breast cancers (P = 0.043). Compared with the expression of various cell cycle regulatory proteins, breast cancers with BRCA1 methylation showed decreased expression of estrogen receptor (P = 0. 016) and p27 (P = 0.018) and increased expression of p21 (P = 0.011). Furthermore, breast cancers without BRCA1 expression or with BRCA1 methylation had a tendency to contain nuclei with higher grade. These findings indicate that BRCA1 methylation might greatly influence its expression and BRCA1 expression might play an important role in cell cycle regulation and influence the grade of malignancy of sporadic breast cancers.

BRCA1 Protein↗
PubMed2000

Maximal flow pulsation in the pial arterioles of rats at increased intracranial pressure.

Red cell velocity in the brain pial arterioles ( 12-58 microm in diameter) of rats was measured by a fiber-optic laser-Doppler anemometer microscope to study the effects of intracranial pressure (ICP) on flow pulsation. The amplitude of velocity pulsation in the pial arterioles was 24+/-9% (mean +/- SD) of the temporal mean velocity under normal physiological conditions (ICP = 5 mmHg). It increased gradually up to 40+/-11% with increasing ICP up to 50 mmHg on average. It also increased with the vessel diameter at fixed values of ICP. In each arteriole, the velocity amplitude increased steeply at a critical value of ICP as ICP increased. The critical value of ICP ranged between 20 and 40 mmHg,. increased with the vessel diameter, and decreased downstream along arterial trees. These results suggest a correlation between the critical ICP and the internal pressure of the pial arteriole.

Animals↗
PubMed2000

Prostaglandin E2 predominantly induces production of hepatocyte growth factor/scatter factor in human dental pulp in acute inflammation.

Hepatocyte growth factor (HGF), which is also known as the scatter factor, is a broad-spectrum and multifunctional cytokine, mediates epithelial-mesenchyme interaction, and is shown to be involved in the development and regeneration of various tissues, including tooth. Here, we report that HGF was present in adult human dental pulps, and its levels increased during acute inflammation of the tissue. Levels of HGF mRNA in dental pulps also increased with inflammation, as determined by reverse-transcription/polymerase chain-reaction. The production of HGF in fibroblasts from dental pulps in culture was dose-dependently stimulated by inflammatory cytokines such as interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha, and by prostaglandin (PG) E2, as determined by an enzyme-linked immunosorbent assay. We also showed that indomethacin did not affect the increase in HGF production by the cells with IL-1alpha, TNF-alpha, and PGE2. The levels of HGF mRNA in the cells were simultaneously increased by these stimulants, as determined by Northern blotting. Since the production of PGs is known to increase at the beginning of inflammation, PGE2 may be involved in the regeneration of dental pulps by the induction of HGF expression after inflammation.

Adolescent↗
PubMed2000

Effects of roxithromycin on tumor necrosis factor-alpha-induced vascular endothelial growth factor expression in human periodontal ligament cells in culture.

BACKGROUND: Aberrant angiogenesis is associated with lesion formation in chronic periodontitis. However, little is known about the mediators that contribute to angiogenesis or about therapeutic agents that control the production of the mediators. Roxithromycin (RXM), which is a new 14-member macrolide antibiotic, has a wide antibacterial spectrum against oral pathogens and an immunomodulatory effect. In the present study, we examined the effects of RXM on tumor necrosis factor (TNF)-alpha-induced vascular endothelial growth factor (VEGF) in human periodontal ligament (HPDL) cells. In addition, the effect of RXM on VEGF expression in HPDL cells was examined. METHODS: HPDL cells were plated at 5 x 10(5) cells/ml in 150 cm2 cell culture dishes. The confluent-stage cells were pretreated with or without 10 microg/ml of RXM or other antibiotics in 1% FBS-containing alpha-MEM for 24 hours, followed by simultaneous treatment with 10 ng/ml of TNF-alpha and 10 microg/ml of these antibiotics. After incubation for various periods, the culture supernatants and sediments were collected and analyzed by ELISA, Northern blot, and gel shift assays. RESULTS: VEGF mRNA and its protein were constitutively expressed in HPDL cells, and the level of expression was markedly enhanced by stimulation with TNF-alpha. RXM strongly inhibited the expression of VEGF mRNA and the production of VEGF. Furthermore, RXM suppressed activation of transcription factors AP-1 and SP-1, which were critical factors in VEGF transcription, in TNF-alpha-stimulated HPDL cells. CONCLUSION: These results indicate that TNF-alpha, one of the proinflammatory cytokines implicated in the pathogenesis of periodontitis, induces excess induction of VEGF in HPDL, which may account for increased angiogenesis in periodontitis lesions. Interestingly, the antibiotic roxithromycin inhibits TNF-mediated VEGF induction, suggesting its possible therapeutic utility in periodontitis and other chronic inflammatory conditions involving VEGF induction.

Adult↗
PubMed1999

Granular Cell Tumor of the Breast Diagnosed by Core Needle Biopsy: A Case Report.

Granular cell tumor rarely occurs in the breast. We report a 69-year-old woman with a right breast mass that simulated carcinoma on palpation, mammography, and ultrasonography. Aspiration biopsy cytology showed no malignant atypical cells. Core needle biopsy was performed to obtain an accurate diagnosis. The lesion was histologically confirmed to be a granular cell tumor. Immunostaining was positive for S-100 protein and vimentin, and negative for keratin, carcinoembryonicantigen, estrogen receptor and gross cystic disease fluid protein-15. The tumorwas treated by wide local excision. Surgeons should be aware that granular cell tumor can resemble breast cancer in order to avoid performing a needless radical mastectomy.

Journal Article↗
PubMed1999

The efficacy of technetium-99m-MIBI scan and intraoperative methylene blue staining for the localization of abnormal parathyroid glands.

The efficacy of the technetium-99m-2-methoxyisobutylisonitrile (Tc-MIBI) scan and intraoperative methylene blue staining was analyzed in a consecutive series of 15 patients with primary hyperparathyroidism who underwent neck surgical exploration. A total of 17 abnormal parathyroid glands were removed, 7 of which were confirmed histologically as adenomas and 10 as hyperplasias. The Tc-MIBI scan and the thallium-201-technetium-99m subtraction (Tl/Tc) scan preoperatively localized 11 (69%) of 16, and 6 (40%) of 15 abnormal parathyroid glands, respectively. The Tc-MIBI scan correctly localized two ectopic abnormal parathyroid glands which were not localized by the Tl/Tc scan or ultrasonography (US). However, it also demonstrated false-positive accumulations caused by thyroid diseases in two patients. There were 4 abnormal parathyroid glands not detected by the preoperative imaging techniques, whereas all 17 abnormal parathyroid glands were stained with methylene blue, the infusion of which caused no adverse effects or toxicity. In conclusion, Tc-MIBI scanning and intraoperative methylene blue staining are effective techniques for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism.

Adenoma↗
PubMed1999

Atypical cystic lobules: an early stage in the formation of low-grade ductal carcinoma in situ.

Evidence from many studies has established the neoplastic potential of ductal carcinoma in situ, but the origin and the morphological characteristics of the early stages of this proliferation remain unidentified. Workers writing in the early twentieth century observed a cystic transformation of lobules and proposed that it represented one such early stage, and contemporary European and Japanese pathologists have reached the same conclusion. We describe the characteristics of this cystic transformation, which we call us "atypical cystic lobules," and present evidence to support the proposal that the alteration is a step in the formation of low-grade ductal carcinoma in situ. Atypical cystic lobules are a proliferation of luminal cells showing low-grade cytological atypia without architectural atypia. The study group comprised 21 cases of atypical cystic lobules from specimens also showing conventional low-grade ductal carcinoma in situ or lobular neoplasia. Immunohistochemical staining for hormone receptors, keratin 19, and cyclin D1 revealed that atypical cystic lobules demonstrated a consistent immunophenotype, which differs from the pattern shown by normal lobules and benign lesions and matches that of low-grade ductal carcinoma in situ. In about 40% of the cases, atypical cystic lobules merged with fully established micropapillary/cribriform ductal carcinoma in situ. The similarities in the cytological and immunohistochemical features and the proximity of the two types of proliferation suggest that atypical cystic lobules represent an early stage in the formation of certain types of low-grade ductal carcinoma in situ.

Bile Duct Neoplasms↗
PubMed1999

Expression of vascular endothelial growth factor (VEGF) in human thyroid neoplasms.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is an angiogenic factor that plays important roles in tumor growth. Angiogenesis studies on VEGF deal with various types of malignant tumors, but very little is known about the role or significance of VEGF in human thyroid neoplasms. Therefore, in the current study, we determined whether VEGF is found in normal and neoplastic thyroids and whether its expression is altered in different histological types of thyroid neoplasms. Reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that all specimens of thyroid tumors expressed bands corresponding to 121-, 165-, and 189-amino acid forms of VEGF. Northern blot analysis showed an increase in VEGF mRNA levels in neoplastic tissues in comparison with normal thyroid samples. By nonisotopic in situ hybridization, most of the tumor cells in follicular adenomas expressed VEGF mRNA, whereas VEGF mRNA expression was identified only in epithelium of isolated follicles in normal thyroid tissues. In papillary thyroid carcinomas, an intense labeling with VEGF probe was often found in overlying tumor cells of neoplastic papillae. VEGF expression was distinctly intensified in undifferentiated carcinoma cells that were immediately adjacent to necrotic foci. The immunohistochemical localizations of VEGF protein were comparable to the localization of VEGF mRNA. In conclusion, our results suggest that the histological types of thyroid tumor may determine the vascular pattern through a paracrine mechanism involving VEGF.

Blotting, Northern↗
PubMed1999

Effects of similarity on apparent motion and perceptual grouping.

Effects of similarity in colour, luminance, size, and shape on apparent motion and perceptual grouping were examined in part 1 in two parallel experiments on the same seven subjects. In both experiments, the effect of similarity was compared with that of proximity in competitive, bistable stimulus situations. A combination of a larger horizontal separation between the homogeneous stimulus elements and a smaller constant vertical separation between heterogeneous stimulus elements produced two kinds of apparent motion (or perceptual grouping) with equal probabilities. Such matched separations between homogeneous stimulus elements were obtained by the double staircase method in various stimulus conditions. In both experiments on apparent motion and perceptual grouping matched separation was found to increase as the difference between the heterogeneous stimulus elements increased. High correlations (0.71 to 0.94) of matched separations were found between apparent motion and perceptual grouping in four stimulus series: colour, luminance, size, and shape. Six of the seven subjects were also tested in part 2. Here, the effects of differences were found to work additively across different perceptual attributes in both phenomena, when multiple differences were combined in heterogeneous elements. The experimental results are discussed from the point of view that apparent motion is an example of perceptual constancy.

Humans↗
PubMed1999

Natural history of fibroadenomas based on the correlation between size and patient age.

BACKGROUND: Several recent studies have reported that most fibroadenomas remain static or regress when they are managed conservatively; however, no such studies have evaluated the breast disorder in Japanese women. To understand the natural history of fibroadenomas in Japanese women, we examined the correlation between the sizes of the fibroadenomas and the women's age. METHODS: Fifty-eight consecutive patients (age range, 17-51 years; mean, 33.9 years) with histologically confirmed fibroadenoma were enrolled in this study. The sizes of the excised fibroadenomas were analyzed in relation to the women's ages. RESULTS: The fibroadenomas decreased significantly in size (Y, mm) with patient age (X, years) (P = 0.0012) according the equation Y = -0.340X + 27.0 (95% confidence limits for the slope, -0.139 to -0.540). From this equation, the mean sizes of the fibroadenoma in women aged 20, 30 and 40 years were expected to be 20.2 mm (95% confidence interval, 16.2-24.2 mm), 16.8 mm (95% confidence interval, 10.8-22.8 mm) and 13.4 mm (95% confidence interval, 5.4-21.4 mm), respectively. The mean annual decrease in the size of the fibroadenomas was 0.340 mm. CONCLUSIONS: Our results indicate that in Japanese women fibroadenomas increase in size more frequently in younger than in older women. Moreover, it is speculated that most fibroadenomas might stop growing when they reach an approximate maximum diameter of 20 mm, after which time they might remain static or regress.

Adolescent↗
PubMed1999

Crystal structure of beta-amylase from Bacillus cereus var. mycoides at 2.2 A resolution.

The crystal structure of beta-amylase from Bacillus cereus var. mycoides was determined by the multiple isomorphous replacement method. The structure was refined to a final R-factor of 0.186 for 102,807 independent reflections with F/sigma(F) > or = 2.0 at 2.2 A resolution with root-mean-square deviations from ideality in bond lengths, and bond angles of 0.014 A and 3.00 degrees, respectively. The asymmetric unit comprises four molecules exhibiting a dimer-of-dimers structure. The enzyme, however, acts as a monomer in solution. The beta-amylase molecule folds into three domains; the first one is the N-terminal catalytic domain with a (beta/alpha)8 barrel, the second one is the excursion part from the first one, and the third one is the C-terminal domain with two almost anti-parallel beta-sheets. The active site cleft, including two putative catalytic residues (Glu172 and Glu367), is located on the carboxyl side of the central beta-sheet in the (beta/alpha)8 barrel, as in most amylases. The active site structure of the enzyme resembles that of soybean beta-amylase with slight differences. One calcium ion is bound per molecule far from the active site. The C-terminal domain has a fold similar to the raw starch binding domains of cyclodextrin glycosyltransferase and glucoamylase.

Amino Acid Sequence↗
PubMed1999

Effects of intracranial pressure on the pial microcirculation in rats studied by a fiber-optic laser-Doppler anemometer microscope.

The fiber-optic laser-Doppler anemometer microscope (FLDAM) developed in our laboratory was applied to measure red cell velocity in individual pial microvessels in rats to determine the effect of intracranial pressure (ICP) on the pial microcirculation. The red cell velocity and the vessel diameter of pial microvessels were measured through a closed cranial window at controlled values of ICP between 0 and 50 mmHg. As ICP increased from 0 to 50 mmHg, the average relative diameter of venules with respect to the diameter at an ICP of 5 mmHg decreased from 1.18 +/- 0.12 (mean +/- SD) to 0.74 +/- 0.08 and the average relative velocity increased from 0.80 +/- 0.20 to 1.83 +/- 0.42 monotonically. The changes in diameter and velocity of arterioles with ICP were small, and they were not significantly different from those values at an ICP of 5 mmHg except for the diameter at an ICP of 20 mmHg. The mean volume flow rates calculated assuming a circular vessel cross-section did not show any statistically significant change with ICP between 0 and 50 mmHg in both arterioles and venules, which supports the concept of autoregulation.

Animals↗
PubMed1998

Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo.

Defective function of dendritic cells (DC) in cancer has been recently described and may represent one of the mechanisms of tumor evasion from immune system control. We have previously shown in vitro that vascular endothelial growth factor (VEGF), produced by almost all tumors, is one of the tumor-derived factors responsible for the defective function of these cells. In this study, we investigated whether in vivo infusion of recombinant VEGF could reproduce the observed DC dysfunction. Continuous VEGF infusion, at rates as low as 50 ng/h (resulting in serum VEGF concentrations of 120 to 160 pg/mL), resulted in a dramatic inhibition of dendritic cell development, associated with an increase in the production of B cells and immature Gr-1(+) myeloid cells. Infusion of VEGF was associated with inhibition of the activity of the transcription factor NF-kappaB in bone marrow progenitor cells. Experiments in vitro showed that VEGF itself, and not factors released by VEGF-activated endothelial cells, affected polypotent stem cells resulting in the observed abnormal hematopoiesis. These data suggest that VEGF, at pathologically relevant concentrations in vivo, may exert effects on pluripotent stem cells that result in blocked DC development as well as affect many other hematopoietic lineages.

Animals↗
PubMed1998

Defective function of Langerhans cells in tumor-bearing animals is the result of defective maturation from hemopoietic progenitors.

Langerhans cells (LC), the APCs in the skin, serve as a model for investigation of dendritic cell (DC) function in tissues. DC play a crucial role in the generation of antitumor immune responses. In this study, we investigated the effect of the presence of tumor in vivo on the ability of LC to take up Ag, migrate to draining lymph nodes, and stimulate primary T cell responses. In two animal models, these functions were substantially inhibited. This effect was not restricted to LC located in the skin near a tumor but was also seen at sites distant from the tumor. The duration of tumor exposure, and not its ultimate size, were found to be important, suggesting that tumors could be inhibiting the maturation of LC rather than directly inhibiting their function. Model experiments with radiation chimeras supported this hypothesis. To investigate the potential role of vascular endothelial growth factor (VEGF) in these effects we used anti-VEGF-neutralizing Ab to treat animals bearing tumors. Treatment with the Ab at a dose of 10 microg i.p. per mouse, twice a week for 4 wk, significantly improved the number and function of LC as measured by their ability to migrate to lymph nodes and stimulate primary T cell responses, even at doses that do not affect the growth of these established poorly immunogenic tumors. Thus, inhibition of VEGF signaling may improve DC function in tumor-bearing hosts and possibly serve to improve the efficacy of cancer immunotherapy.

Animals↗
PubMed1998

Prognostic and Therapeutic Implications of the MIB-1 Labeling Index in Breast Cancer.

BACKGROUND: Assessment of tumor proliferative activity is considered to be the most powerful prognostic factor aside from axillary lymph node status. The purpose of this study is to assess the clinical value of measurement of proliferative activity using the MIB-1 labeling index in patients with breast cancer. METHODS: Surgical specimens from 36 patients with benign breast disorders and146 patients with breast cancer were investigated. The MIB-1 labeling index wasdetermined on the specimens stained by immunohistochemical methods as much as possible. Clinical factors associated with the MIB-1 labeling index were reviewed. RESULTS: The MIB-1 labeling index for non-proliferative disorders, proliferative disorders, and breast cancer was 3.4 +/-1.9%, 8.9 +/-6.2% and 20+/-12%, respectively. The MIB-1 labeling index and tumor size, lymph node metastasis status, and clinical stage according to the TNM classification correlated significantly. Survival rate was inversely correlated with the MIB-1 labeling index. No patientwith an MIB-1 labeling index of less than 10% had lymph node metastases, and all are alive without recurrence. Patients with an MIB-1 labeling index of over 30% had an extremely poor prognosis. CONCLUSION: The MIB-1 labeling index is very useful for predicting both either extremely good or extremely poor prognosis, and axillary lymph node metastasis

Journal Article↗