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Biomedical subjects

T Hojo

Publications and source records attributed to T Hojo.

At least 37 records · Page 2Linked to original sources
PubMed2002

Enzyme and plasma protein induction by multiple oral administrations of phenobarbital at a therapeutic dosage regimen in dogs.

In dogs effects of phenobarbital (PB) on hepatic cytochrome P450 (CYP) activities and on concentrations of plasma alpha 1-acid glycoprotein (AGP) were examined. Total body clearance (Cl(B)) of antipyrine and plasma AGP concentrations were monitored during oral PB treatment at a therapeutic dose for 35 days. Cl(B) of antipyrine, which reflects hepatic CYP activities, gradually increased and was maintained at about threefold concentrations compared with that before treatment, suggesting that PB induced CYP activities at a large extent even in a therapeutic dose, necessary for an antiepileptic effect. Plasma AGP concentrations also increased significantly (about fourfold). Dogs were killed at the 35th day of the PB treatment, and hepatic CYP content and enzyme kinetics of several CYPs were determined using liver microsomes. CYP content was about twofold higher than that from untreated dogs. The V(max) values for CYP1A-like activity (ethoxyresorufin O-deethylation), 2B-like activity (ethoxycoumarin O-deethylation), 2C-like activity (tolbutamide hydroxylation) and 3A-like activity (midazolam 4-hydroxylation) were higher (2-4-fold) than that in untreated dogs. In summary, a therapeutic dose of PB for antiepileptic therapy significantly induced hepatic CYPs and plasma AGP in dogs. Therefore, during antiepileptic therapy with PB, special attention must be paid to the pharmacokinetics of drugs simultaneously administered.

Administration, Oral↗
PubMed2001

Observation of the decay B --> Kl+l-.

We report a search for the flavor-changing neutral current decay B-->K(*)l+l- using a 29.1 fb(-1) data sample accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB e+e- storage ring. We observe the decay process B-->Kl+l-(l = e, mu), for the first time, with a branching fraction of B(B-->Kl+l-) = (0.75(+0.25)(-0.21)+/-0.09)x10(-6).

Journal Article↗
PubMed2001

Association of maspin expression with the malignancy grade and tumor vascularization in breast cancer tissues.

Maspin belongs to a tumor suppressing protein which is usually expressed highly in myoepithelial cells, and is significantly downregulated in breast cancer cells. We focused on identifying the correlation between maspin expression and the clinicopathological features of human breast cancer tissues using immunohistochemistry. There was a significant correlation in that maspin-positive tumor specimens showed a low pathological grade of malignancy, such as a lower infiltration of the tumor into the surrounding tissue and a downregulation of c-erbB2 expression. Moreover, maspin-positive cases showed a significant decrease in tumor vessels positively stained with anti-factor VIII-related antigen antibody. These results suggest that maspin production in myoepithelial cells could downregulate the malignant phenotype of breast cancer.

Biomarkers, Tumor↗
PubMed2001

Observation of B --> J/psi K(1)(1270).

We report the first observation of the exclusive decay process B-->J/psi K(1)(1270) using a sample of 11.2M BB macro meson pairs collected in the Belle detector at the KEKB asymmetric energy e(+)e(-) collider. We measure branching fractions of B[B(0)-->J/psi K(0)(1)(1270)] = (1.30+/-0.34+/-0.32) x 10(-3) and B[B(+)-->J/psi K(+)(1)(1270)] = (1.80+/-0.34+/-0.39) x 10(-3), where the first error is statistical and the second is systematic. These modes constitute approximately 15% of the total number of B-->J/psi X decays. No evidence is seen for B-->J/psi K(1)(1400) and we set an upper limit for this branching fraction.

Journal Article↗
PubMed2001

Observation of Cabibbo suppressed B --> D(*)K- decays at Belle.

We report observations of the Cabibbo suppressed decays B-->D((*))K- using a 10.4 fb(-1) data sample accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB e(+)e(-) storage ring. We find that the ratios of Cabibbo suppressed to Cabibbo favored branching fractions are B(B--->D0K-)/B(B--->D0pi(-)) = 0.079+/-0.009+/-0.006, B(B(0)-->D+K-)/B(B(0)-->D+pi(-)) = 0.068+/-0.015+/-0.007, B(B--->D(*0)K-)/B(B--->D(*0)pi(-)) = 0.078+/-0.019+/-0.009, and B(B(0)-->D(*+)K-)/B(B(0)-->D(*+)pi(-)) = 0.074+/-0.015+/-0.006. These are the first observations of the B-->D+K-, D(*0)K-, and D(*+)K- decay processes.

Journal Article↗
PubMed2001

Observation of large CP violation in the neutral B meson system.

We present a measurement of the standard model CP violation parameter sin2 phi(1) based on a 29.1 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B meson is fully reconstructed as a J/psi K(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psi K(L), or J/psi K(*0) decay and the flavor of the accompanying B meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we determine sin2 phi(1) = 0.99+/-0.14(stat)+/-0.06(syst). We conclude that we have observed CP violation in the neutral B meson system.

Journal Article↗
PubMed2001

Development of a new drug delivery system for protein drugs using silicone (II).

In order to achieve a zero-order release of protein drugs, we have developed a new drug delivery system using silicone, which is named the covered-rod-type formulation. Preparation of the covered-rod-type formulation was conducted under mild conditions without heat treatment or the use of organic solvents. The covered-rod-type formulation released human serum albumin (HSA) or interferon (IFN) at a constant rate for 30-100 days in vitro without significant initial burst. When the IFN covered-rod-type formulation was implanted in nude mice, the serum IFN concentration was maintained at a constant level during the period of observation, i.e., 28 days. The covered-rod-type formulation enabled precise control of the release of the protein drugs and would be expected to increase the duration of the drug effect and to reduce the frequency of administration and side effects.

Animals↗
PubMed2001

Measurement of B(0)(d)-B_(0)(d) mixing rate from the time evolution of dilepton events at the upsilon(4S).

We report a determination of the B(0)(d)-&B_(0)(d) mixing parameter Deltam(d) based on the time evolution of dilepton yields in Upsilon(4S) decays. The measurement is based on a 5.9 fb(-1) data sample collected by the Belle detector at KEKB. The proper-time difference distributions for same-sign and opposite-sign dilepton events are simultaneously fitted to an expression containing Deltam(d) as a free parameter. Using both muons and electrons, we obtain Deltam(d) = 0.463+/-0.008 (stat)+/-0.016 (syst) ps(-1). This is the first determination of Deltam(d) from time evolution measurements at the Upsilon(4S). We also place limits on possible CPT violations.

Journal Article↗
PubMed2001

Measurement of the CP violation parameter sin2 phi(1) in B(0)(d) meson decays.

We present a measurement of the standard model CP violation parameter sin2 phi(1) (also known as sin2beta) based on a 10.5 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-) collider. One neutral B meson is reconstructed in the J/psiK(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psiK(L), or J/psipi(0) CP-eigenstate decay channel and the flavor of the accompanying B meson is identified from its charged particle decay products. From the asymmetry in the distribution of the time interval between the two B-meson decay points, we determine sin2 phi(1) = 0.58(+0.32)(-0.34)(stat)+0.09-0.10(syst).

Journal Article↗
PubMed2001

Time-sequential changes in biomechanical and morphological properties of articular cartilage in cryopreserved osteochondral allografting.

This study examined time-sequential changes in the biomechanical and morphological properties of articular cartilage that had received cryopreserved osteochondral allografting. Osteochondral blocks obtained from the femurs of 18 rabbits were cryopreserved with dimethylsulfoxide (DMSO), using a two-step freezing method, and allografted to the femurs of another 18 rabbits. Specimens for biomechanical and morphological examinations were prepared at the second, fourth, and twelfth weeks after allografting (n = 18). In 12 allografted rabbits, biomechanical features were examined with an indentation test apparatus, and histological changes were studied with a light microscope (second week, n = 4; fourth week, n = 4; twelfth week, n = 4). In the other 6 allografted rabbits, cartilage surfaces were studied with a scanning electron microscope (second week, n = 2; fourth week, n = 2; twelfth week, n = 2). For controls, fresh, DMSO-treated, or DMSO-treated + cryopreserved specimens were examined biomechanically and morphologically. In the time-sequential examination of biomechanical features, both the parameter for elasticity (i.e., ratio of instant elastic strain to maximum strain) and the parameter for viscosity (i.e., average retardation time) significantly changed. Light microscopy showed chronological decreases in safranin-O staining intensity in the matrix, and progression of degeneration. On scanning electron microscopy, disruption of the cartilage surface was also recognized. Therefore, changes in biomechanical properties due to cryopreservation could cause irreversible changes in the cartilage in cryopreserved osteochondral allografting.

Animals↗
PubMed2001

Down regulation of the tumor suppressor gene maspin in breast carcinoma is associated with a higher risk of distant metastasis.

BACKGROUND: Maspin (mammary serpin) is a relatively novel serine protease inhibitor with tumor suppressing function in breast cancer. Maspin expression was found in normal breast epithelial cells, but was decreased during tumor progression. Only a few systematic analyses of this phenomenon have been undertaken so far. In this study we developed specific nested reverse transcription polymerase chain reaction (RT-PCR) conditions for the detection of maspin expression in human breast carcinoma and assessed maspin's association with the clinical behavior of primary breast cancers. METHODS: Tumor specimens obtained from 45 primary breast cancer patients were analyzed for maspin expression by a nested RT-PCR assay. Recurrence free survival was evaluated and correlated to maspin expression. RESULTS: The maspin transcript was detected in 29 (64%) breast cancer specimens whereas no expression was found in 16 (36%) cancer specimens. This expression was unrelated to any of the established prognostic factors. However, 6 out of 8 patients who developed distant metastasis (lymph nodes, lung, liver, bone, pleura) within 3 yr after their initial diagnosis showed no maspin expression of the primary breast cancer (p < 0.05). CONCLUSIONS: The lack of maspin expression in breast cancer seems to be associated with a short disease free survival and supports maspin's function as an indicator of tumor aggressiveness and metastatic potential. Nested RT-PCR is a sensitive method to determine maspin expression in human breast cancer tissue.

Adult↗
PubMed2001

Expression of the tumor suppressor gene Maspin in human pancreatic cancers.

The tumor suppressor gene maspin, a unique member of the serpin superfamily, inhibits cell motility, invasion, and metastasis in breast and prostate cancers. Maspin is expressed in normal human mammary and prostate epithelial cells but down-regulated during cancer progression. In this study, we analyzed the expression of maspin in various human cancer cells by means of Northern blot and immunohistochemistry. Maspin gene expression proved to be up-regulated in pancreatic cancer. Maspin expression was not detected in any of 6 gastric cancers, 4 melanomas, or 6 of 7 breast cancer cell lines examined. In contrast, 5 of 9 pancreatic cancer cell lines showed maspin expression, although maspin expression was not detected in normal pancreatic tissue. Furthermore, maspin was expressed in 23 of 24 tumor specimens obtained from pancreatic cancer patients as well as all high-grade precancerous lesions (PanIN3 and intraductal carcinoma extension). In contrast, no expression was observed in normal and low-grade precancerous lesions. Our results show that maspin is a new factor associated with pancreatic cancer. In addition, the detection of maspin in pancreatic tumor tissues and its lack of expression in all normal pancreatic tissues suggests that maspin may be a useful marker of primary human pancreatic cancer.

Disease Progression↗
PubMed2001

[Clinical experience of intra-arterial chemotherapy for liver metastases of breast cancer patients].

The aim of this study was to evaluate retrospectively the effect of intra-arterial chemotherapy for liver metastases of breast cancer patients. Eleven patients treated between August 1991 and July 1997 at Keio University Hospital, Tokyo, Japan, were the subjects for this study. The duration of disease-free periods after the operation ranged from 9 to 78 months (median 27 months). The site of the recurrence was the liver alone in 6 cases, and the liver and lung in 1 case, bone in 1 case, lymph nodes in 2 cases, and a local region, in 1 case. The main drugs were adriamycin (ADM) and 5-fluorouracil (5-FU), administered in a single injection or continuously via an indwelling catheter in the hepatic artery. This method had a 36% response rate, including PR in 4 cases, NC in 3 cases and PD in 4 cases. The survival duration was 1 to 19 months (median 14 months) following this treatment, and 3 to 49 months (median 17 months) after the recognition of the recurrence. The only side effects of Grade 3 or 4 were leucocytopenia or granulocytopenia and nausea. These results suggest that intra-arterial chemotherapy for liver metastases of breast cancer patients may be an effective method for the control of liver metastases with minor side effects. However, further study may be necessary to establish methods to manage the indwelling catheter and to control patients with multiple metastases of the other organs, to improve the prognosis for recurrent breast cancer patients.

Adult↗
PubMed2000

Lymph node metastasis from breast cancer diagnosed by F-18 FDG whole-body PET (case report).

We report a 48-year-old woman with lymph node (LN) metastases from breast cancer in whom diagnosis was difficult by conventional imaging methods but easy by F-18 fluorodeoxyglucose (FDG) PET. She was given a diagnosis of right breast cancer and then underwent modified radical mastectomy in December 1997. During routine CT and US studies in September 1998, a questionable LN measuring 1 cm in diameter was detected in the right supraclavicular region, but a definitive diagnosis of this LN was difficult by these tests. The patient underwent FDG PET test, which showed strong nodular activity (SUV= 7.1) in the right supraclavicular region, indicating a metastatic lesion. Moreover, an unexpected second metastatic LN lesion (SUV= 5.5) in the medial aspect of the right axillary was diagnosed by PET. The PET results were confirmed by pathological examination of the surgical specimens. FDG PET is a useful tool to detect small malignant lesions that are not easily diagnosed by conventional imaging techniques such as CT and US. It is expected that PET test will be feasible at many institutions.

Adenocarcinoma↗
PubMed2000

Identification of high-risk breast cancer patients from genetic changes of their tumors.

To identify the genetic prognostic markers for breast cancer, we analyzed loss of heterozygosity (LOH) at 11p, 16q, 17p, 17q, and 18q, as well as amplification of the ERBB2, INT2, and MYC genes, in 131 patients with breast carcinoma, 49 of whom had lymph node involvement, but none of whom had distant metastases. Among the several chromosome arms tested, LOH at 17q was correlated with lymph node metastasis. Amplification of the ERBB2, MYC, and INT2 genes was found more frequently in tumors from patients with lymph node metastases than in tumors from those without lymph node metastases. Univariate analysis demonstrated that LOH at 17q and INT2 amplification were factors influencing disease-free survival (DFS). A multivariate analysis was performed on 89 tumors that were able to be evaluated for both LOH at 17q and INT2 amplification, and the results showed that patients who had tumors with these genetic changes were more likely to have a poor prognosis. The findings of this study suggest that investigating genetic changes, in addition to conventional clinicopathologic factors, may contribute to defining groups of breast cancer patients with differences in prognosis.

Blotting, Southern↗
PubMed2000

Maspin--a novel protease inhibitor with tumor-suppressing activity in breast cancer.

Maspin (mammary serpin) is a novel serine protease inhibitor related to the serpin family with a tumor-suppressing function in breast cancer. Maspin was originally identified from normal mammary epithelium by subtractive hybridization and might function as a class II tumor-suppressor gene. Maspin's decreased expression with increased level of malignancy and its loss in metastatic cells is regulated at the transcriptional level. Cytosin methylation and heterochromatinization in the promoter region might account for this down-regulation of maspin. Transfection of tumor cells with maspin cDNA inhibits invasion and motility and decreases tumor growth and metastatic ability in nude mice. Maspin interacts with the p53 tumor-suppressor pathway and function as an inhibitor of angiogenesis in vitro and in vivo. The progressive loss of expression of maspin during tumor progression makes this new protein an interesting diagnostic and prognostic marker. The re-expression of maspin by pharmacological intervention potentially offers a promising approach as a therapeutic option in breast cancer therapy.

Animals↗
PubMed1998

Protein release from collagen matrices.

The effective delivery of protein drugs is an important research subject in the field of pharmacology, and to prolong the effect of protein drugs, many studies are being conducted to control the release of proteins from various carrier materials. Collagen is one of the most useful candidates for this purpose, and many studies have been reported; pharmaceutical formulations containing collagen in gel, film and sponge form are used to incorporate low-molecular-weight compounds such as antibiotics and carcinostatics, and the release of these compounds is controlled by the concentration of the gel as well as the shape and degree of crosslinking of the matrix. However, it is still difficult to retain protein drugs in the collagen. In this article, we report on the controlled release of protein drugs using collagen which exhibits good biocompatibility as a carrier, focusing on a new drug delivery system, the Minipellet, which we have developed.

Journal Article↗