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T Oyama

Publications and source records attributed to T Oyama.

At least 19 recordsLinked to original sources
PubMed2000

Highest microvessel count as a long-term prognostic factor in Japanese breast cancer patients.

The aim of this study was to determine whether microvessel density (MVD) could add useful information in predicting the prognosis of breast cancer patients. In our study, MVD was calculated by counting microvessels per x200 field in the highest neovascularized area of the tumor (highest microvessel count, HMC). HMC significantly increased according to the increased number of positive nodes. Higher HMC significantly correlated with worse relapse-free survival (RFS) of patients with negative node, one to three positive nodes in the axilla or with stage I and II tumors. HMC, however, was not predictive for RFS of patients with four or more positive nodes or with stage III tumors. Multivariate analysis revealed that HMC was second only to nodal status and tumor size as being predictive for RFS. These results suggest that HMC could be used in selection of patients with early-stage breast cancer who are at high risk for having occult metastasis.

Adult↗
PubMed2000

Palladium-catalyzed borylation of aryl halides or triflates with dialkoxyborane: A novel and facile synthetic route to arylboronates

A direct borylation of aryl halides or triflates with dialkoxyborane was investigated. The coupling reaction of pinacolborane with aryl halides or triflates in the presence of a catalytic amount of PdCl(2)(dppf) together with a base provided arylboronates in high yields. The product distributions were strongly dependent on the base employed, and the tertiary amine, especially Et(3)N, was effective for the selective formation of the boron-carbon bond. The reaction conditions were so mild that arylboronates having a variety of functional groups such as carbonyl, cyano, and nitro groups were readily prepared.

Journal Article↗
PubMed2000

Reactive follicular hyperplasia in the lymph node lesions from systemic lupus erythematosus patients: a clinicopathological and immunohistological study of 21 cases.

To clarify the clinicopathological and immunohistological findings of reactive follicular hyperplasia in systemic lupus erythematosus (SLE) lymphadenopathy, we examined 21 such cases, including four males and 17 females. Three main patterns could be delineated: pattern A, histological features of Castleman's disease (n = 6); pattern B, follicular hyperplasia with pronounced arborizing vasculature in the paracortex resembling T-zone dysplasia with hyperplastic follicles (n = 6); and pattern C, follicular hyperplasia without any other specific findings (n = 9). The patients who showed patterns A and B on histology were all female with a median age of 36 years, and presented with the lymphadenopathy within 4 months, some before a definitive diagnosis could be made. The group with pattern C included four males and five females with an age ranging from 20 to 58 years (mean, 37 years). In seven of them, the lymphadenopathy was noted 6 months or more after the therapy had been initiated. In a virological study, a small to moderate number of the lymphoid cells were positive for the Epstein-Barr virus-encoded small RNA in five of 10 cases examined. Human herpesvius 8 was not detected in the four cases examined by polymerase chain reaction and immunohistochemistry. The present study demonstrated that SLE lymphadenopathy showed histological variety and occasionally represented histopathological findings of multicentric Castleman's disease or findings similar to T-zone dysplasia with hyperplastic follicles in the biopsied specimens. We emphasize that careful attention to these morphological features, together with clinical and laboratory examinations, should allow a firm diagnosis of SLE to be made, providing information that is pertinent to the treatment of the disease. Moreover, disarray of the follicular dendritic cell (FDC) network, which could be easily detected by immunohistochemistry, was found in approximately 60% of our series. SLE lymphadenopathy should be listed as one of the diseases occasionally associated with disarray of the FDC network, although its clinicopathological significance remains unclear.

Adult↗
PubMed2000

Evaluation of the interobserver agreement in the number of mitotic figures of breast carcinoma as simulation of quality monitoring in the Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) protocol.

In the National Surgical Adjuvant Study for Breast Cancer (NSAS-BC), node-negative breast cancers were divided into higher- and lower-risk groups according to the histopathological nuclear grade given at individual collaborating hospitals, and the higher-risk group was entered into a randomized protocol of adjuvant therapy. Because the nuclear grade was the composite of nuclear atypia and mitotic counts, maintenance of interobserver agreement in mitotic counts was indispensable for the success of the protocol study. Fourteen pathologists participating in the protocol judged whether or not 20 photomicrographs suspected of showing mitotic cancer-cell figures truly showed mitoses. After standardizing the counting method, these pathologists counted the number of mitotic figures per 10 high-power fields of hematoxylin-eosin-stained main-tissue sections of 20 tumors. Areas where mitotic counts were considered to be the most frequent by each pathologist were compared for these tumors. For the judgment of whether the photomicrograph indicated mitosis, the level of interobserver agreement was moderate (kappa = 0.569). In the observations of 20 tumors, interobserver agreement level of mitotic counts was moderate (kappa = 0.506), that of nuclear atypia scoring was fair (kappa = 0.265), and that of nuclear grading was substantial (kappa = 0.633). The counted area was almost the same among the observers in 9 tumors, split into two areas in 6, and dispersed in 5. Concordance in judgment was achieved in 7 of the first 9 and in all of the third 5, but only in one of the second 6. The cause of discordance was mostly derived from tumor heterogeneity and the difference in the site where mitoses were counted. Interobserver agreement level was considered to be satisfactory, and it was expected that the case entry would be performed appropriately in the protocol study. The selection of the counting area was confirmed to be important for the acquisition of high-level agreement level in mitotic counts.

Breast Neoplasms↗
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

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↗
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

Frequent overexpression of the cyclin D1 oncogene in invasive lobular carcinoma of the breast.

Invasive lobular carcinoma comprises approximately 10% of human mammary cancers, yet little is known about the molecular basis of this carcinoma. Because cyclin D1 plays a role in the pathogenesis of breast carcinomas of the ductal type, we hypothesized that this confirmed oncogene might also participate in the development of lobular carcinomas. We sought to determine the frequency of cyclin D1 protein overexpression in invasive lobular carcinoma, to investigate the cause of the protein accumulation, and to identify the effects of high levels of the protein on the regulation of the cell cycle. The study group comprises 27 indisputable cases of invasive lobular carcinoma showing varying degrees of cytological atypia. Immunohistochemical staining using well-characterized monoclonal and polyclonal antibodies disclosed cyclin D1 protein in the majority of the invasive lobular carcinoma cells in 80% of the tumors. In marked contrast, only rare cells of the noninvasive component (lobular carcinoma in situ) in the same tissue sections showed positive staining. Southern blotting of nine cases did not reveal evidence of cyclin D1 gene amplification. Immunohistochemical staining for Ki-67, a protein present in all dividing cells, showed that most cells positive for cyclin D1 did not stain for Ki-67. We conclude that the vast majority of invasive lobular carcinomas show overexpression of cyclin D1 protein. The absence of cyclin D1 protein expression in the noninvasive cells suggests that the molecule plays a role in the progression to the invasive form of lobular carcinoma. In contrast to the ductal types of breast cancer, cyclin D1 gene amplification does not seem to cause the cyclin D1 protein overexpression in lobular cancers. The lack of correlation between cyclin D1 and Ki-67 expression suggests that the cyclin D1 oncogene acts through mechanisms other than simple acceleration of the cell cycle clock in this subtype of human breast carcinoma.

Breast Neoplasms↗