Search PubMed⌕ Search

Biomedical subjects

T Tominaga

Publications and source records attributed to T Tominaga.

At least 37 records · Page 2Linked to original sources
PubMed2004

GAFChromic film dosimetry with a flatbed color scanner for Leksell Gamma Knife therapy.

GAFChromic films MD-55-2 have recently been established widely in industrial, scientific, and medical applications as radiation dosimeters. We applied these films to the dosimetry for Leksell Gamma Knife therapy. We used a flatbed image scanner to take digital images of irradiated MD-55-2, and the data were converted to Red, Green and Blue pixel values. The absorbed dose, as derived from the response curve of the Red pixel value, was consistent with the Leksell Gamma Plan dose planning system, for exposures using collimator sizes, 4 mm, 8 mm, and 14 mm. However, the maximum dose in the exposure of the 18 mm collimator was measured to be about 5% smaller than Gamma Plan due to the density effect of the compound material in the head phantom.

Algorithms↗
PubMed2004

Familial leptomeningeal amyloidosis with a transthyretin variant Asp18Gly representing repeated subarachnoid haemorrhages with superficial siderosis.

OBJECTIVES: To report the clinical features of two Japanese brothers with familial leptomeningeal amyloidosis, showing a causative gene abnormality of a transthyretin (TTR) variant Asp18Gly, previously reported only in a Hungarian family. METHODS: The authors reported on a 42 year old man (patient 1) and his 45 year old brother (patient 2), both suffering from subarachnoid haemorrhage (SAH) without and with hydrocephalus, respectively. DNA sequences of the TTR gene were determined in both patients and the patients' clinical features described. A surgical biopsy of the leptomeninges was performed on patient 1. RESULTS: DNA sequence analyses demonstrated the glycine-for-aspartate substitution at position 18 of the TTR variant. Both patients revealed pyramidal tract signs and cerebellar ataxia. Audiometric studies showed bilateral, mild sensorineural hearing loss in the patients whose cerebrospinal fluid (CSF) protein levels increased. T1 weighted MRI after contrast administration showed diffuse leptomeningeal enhancement along the Sylvian fissures and over the surface of the brainstem, cerebellum, and spinal cord. Gradient echo T2* weighted MRI showed superficial siderosis mainly in the cerebellum. A biopsy of the leptomeninges was obtained from the spinal cord of patient 1. While performing the biopsy, the authors observed the varicose, elongating, and fragile veins on the dorsal surface of the spinal cord. Immunohistochemical study revealed marked deposits of TTR derived amyloid on his leptomeninges. CONCLUSIONS: This is the second report of familial leptomeningeal amyloidosis with an Asp18Gly TTR gene mutation, clinically causing only CNS symptoms. Repeated SAH from fragile veins on the dorsal surface of the spinal cord seemed to induce superficial siderosis of the CNS. So far, there have been two reliable hallmarks leading to the diagnosis of leptomeningeal amyloidosis: diffuse leptomeningeal enhancement on contrast MRI and greatly increased CSF protein content. This study has contributed a third hallmark: the presence of superficial siderosis is useful in diagnosing leptomeningeal amyloidosis.

Adult↗
PubMed2003

Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer.

BACKGROUND: To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and randomly assigned to receive letrozole or fadrozole in a multicentre, randomised double-blind trial in Japan. One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily (n = 77) or fadrozole 1.0 mg twice daily (n = 77), for a minimum of 8 weeks. RESULTS: Letrozole showed a significantly higher overall objective response rate [complete response (CR) + partial response (PR)] than fadrozole (31.2% and 13.0%, respectively; P = 0.011, Fisher's exact test). Clinical benefits defined as CR, PR and stable disease (no change in status for more than 24 weeks) were also higher in patients treated with letrozole (50.6%) than fadrozole (35.1%). Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue, bone and viscera (P = 0.011, stratified Mantel-Haenszel test). Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference (P = 0.175, log-rank test). Letrozole markedly reduced the estradiol, estrone and estrone sulfate levels in peripheral blood within 4 weeks. The suppressive effect of fadrozole on these hormone levels was insufficient. Adverse drug reactions were observed in 35.9% of the patients treated with letrozole and in 39.5% of those treated with fadrozole with no significant difference between the two groups (P = 0.74, Fisher's exact test). Most of the adverse drug reactions were rated as grade 1 or 2. CONCLUSIONS: The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily, with similar safety and tolerability profiles.

Administration, Oral↗
PubMed2002

The effects of body mass index on age at menopause.

OBJECTIVE: We examined which of body mass index (BMI, kg/m(2)), serum cholesterol (mg/dl), or systolic blood pressure (SBP, mm Hg) affected age at natural menopause. DESIGN: A population-based follow-up program. METHODS: We determined the age at natural menopause in 1136 women followed biennially since their first examination in 1958-1959 through the 16th examination in 1988-1989. Four-hundred and ninety-three naturally menopausal women were classified into three groups by BMI, serum cholesterol and SBP measurement levels at age 40 or 41 y: the upper 25%, middle 50%, and lower 25%. We then studied whether there was a difference in age at menopause among the three groups thus classified. The 1136 natural menopausal women were also classified as early (n=454; 45-49 y at menopause (48.3+/-1.2 y)) or late (n=682; >or=50 y at menopause (52.3+/-1.6 y)) menopausal and compared for premenopausal trends in BMI, serum cholesterol and SBP in the early and late menopausal women by means of a longitudinal data analysis model. RESULTS: When women were classified into the three groups based on a BMI that was measured at 40 or 41 y, age at menopause in the upper 25% (50.4+/-2.8 y) was significantly higher (P<0.05) than that in the lower 25% (49.7+/-2.8 y). The entire premenopausal trend in BMI in late menopausal women shifted upward compared to that in early menopausal women. On the other hand, the premenopausal trend more than 4 y before menopause in serum cholesterol and the entire premenopausal trend in SBP in late menopausal women were identical to those in early menopausal women. CONCLUSION: Among the variables studied, only BMI is related to age at menopause, and the greater the BMI, the later the age at menopause.

Adult↗
PubMed2002

NOR-1: a nitric oxide releasing agent for calibrating low levels of nitric oxide by the chemiluminescence method.

Nitric oxide (NO) is formed in small amounts in vivo and is rapidly oxidized by interacting with oxygen, making measurement of its level difficult. The chemiluminescence assay is the most widely used method for detecting NO and is extremely sensitive to very small amounts of NO. However, it is difficult to prepare small amounts of NO to be used as a standard for NO analysis. NOR-1, a derivative of NOR-3, is a newly discovered NO donor with rapid NO-releasing activity. We assessed the dynamics of NO release and decomposition using NOR-1. Our results demonstrate that NOR-1 is stable in dimethylsulfoxide (DMSO) and is able to dilute at lower concentration (to picomolar levels) by DMSO without decomposition. NOR-1 released persistently 1.4 more excess of NO with 15 min of incubation. There was a linear relationship between the concentration of NOR-1 and that of NO released from NOR-1 (r=0.997) These findings suggest that NOR-1 is a useful reagent for the calibration of lower NO detection.

Benzoates↗
PubMed2001

mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation.

The formin homology protein mDia is a Rho GTPase effector protein that participates in stress fiber formation, cytokinesis, and transcriptional activation of the serum response factor. Although the function of another effector of Rho, Rho-associated kinase, is well established, relatively little is known about the functional mechanism and the downstream targets of mDia. Our recent report of a Rho-mDia-Src-tyrosine kinase pathway suggested an important role for mDia in cell adhesion turnover. We identified a new mDia-interacting protein which is expressed ubiquitously. The new protein mainly binds to the proline-rich region of mDia through its Src homology 3 domain and also binds to Grb2 through its proline-rich domain. The protein is localized at the cell periphery and membrane ruffles and co-localizes with mDia. Co-expression of vSrc and the mDia-interacting protein induces significant morphological changes at focal contacts and activation of vSrc. Furthermore, we found that the mDia-interacting protein plays an important role in stress fiber formation induced by active mDia1. Our results suggest that this new protein regulates actin polymerization and cell adhesion turnover in the downstream portion of the Rho-mDia pathway by interacting with Grb2 and Src.

3T3 Cells↗
PubMed2001

Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials.

PURPOSE: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. PATIENTS AND METHODS: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials. RESULTS: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] = 0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR = 0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio = 0.67). CONCLUSION: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.

Antineoplastic Agents, Hormonal↗
PubMed2001

Simultaneous multi-site recordings of neural activity with an inline multi-electrode array and optical measurement in rat hippocampal slices.

Understanding neuronal network function requires multi-site recording. An optical imaging method using voltage-sensitive dyes (VSD) is one such suitable method. It is also important to complement this technique with methods that measure other physiological parameters of neuronal network activity. We aimed to develop a multi-channel electrode method that would easily permit the simultaneous optical imaging of neural activity in vitro. There are several multi-electrode systems; some of these are commercially available, but they are not easy to use and are also expensive. We developed a novel, less expensive, stainless steel inline electrode array that utilizes the standard etching method of circuit board manufacturing. This method, along with widely available computer drawing software, allowed us to produce electrode arrays with uniform quality in electrical characteristics and shapes. The electrode array was designed so that it could easily substitute for single electrode systems without modifying the conventional set-up used for electrophysiological measurements and optical recordings. Simultaneous measurement of evoked neural activities in area CA1 of the rat hippocampal slice with our optical imaging method using the VSD Di-4-ANEPPS is demonstrated in this paper. The electrode array was also used as a stimulating electrode, and the evoked response was measured by the optical recording method. The results demonstrate the advantages of simultaneous recordings obtained by these complementary multi-site recording methods in vitro.

Animals↗
PubMed2001

Decrease in intraoperative brain surface temperature in patients with subarachnoid haemorrhage.

BACKGROUND: Recent experimental and clinical evidence of hypothermic protection against neuronal injury creates new interests regarding human brain temperature. However, very little information is available for the brain temperature under certain pathological conditions. In this study, intra-operative brain temperature in patients with subarachnoid haemorrhage (SAH) is particularly addressed. METHODS: Brain surface temperature and oxygen saturation of jugular bulb (SjO2) were monitored during early surgery undergone within 48 hours after the onset in patients with SAH (n = 16). Those were also measured in patients with unruptured aneurysms during elective surgery as control (n = 15). FINDINGS: The brain surface temperature was significantly lower in SAH than control (35.3 +/- 0.8 vs. 36.1 +/- 0.5 degrees C, P < 0.01). The reduction in brain surface temperature was correlated with the severity of the Hunt and Kosnik's aneurysmal grade (r = 0.837, P < 0.01). SjO2 was significantly lower in SAH than control (51.5 +/- 7.3 vs. 68.5 +/- 7.6%, P < 0.01), and was positively correlated with brain surface temperature (r = 0.642, P < 0.01). INTERPRETATION: These results suggest that the brain temperature and/or the temperature gradient within the brain may be altered in an early period after SAH. Since brain temperature is determined by cerebral blood flow (CBF), metabolism, temperature of both circulating blood and surrounding environment, the brain surface temperature reduction may be explained by depressed CBF and metabolism in SAH.

Aneurysm, Ruptured↗
PubMed2001

Insulin resistance and coronary risk factors in Japanese type 2 diabetic patients with definite coronary artery disease.

Insulin resistance is known as an important risk factor for coronary artery disease (CAD). However, CAD-related mortality in Japanese type 2 diabetics is lower than in Caucasians. To investigate whether insulin resistance is related to CAD in Japanese type 2 diabetics, we measured insulin sensitivity and several coronary risk factors in Japanese patients with type 2 diabetes with and without CAD. Thirty-three patients with definite CAD and 33 age- and sex-matched patients without CAD (control) were studied. Insulin sensitivity was assessed by the K index of insulin tolerance test (KITT). Clinical characteristics, classical risk factors, lipoprotein (a), and insulin sensitivity were compared between the two groups. Patients with CAD had a significantly longer duration of diabetes (9.0 +/- 1.4 vs. 5.5 +/- 0.9 years, P < 0.05, respectively), were mostly hypertensive (69.7 vs. 39.4%, P < 0.05), and more likely to be treated with insulin (45.5 vs. 18.2%, P < 0.05) compared with the control. Concerning the metabolic parameters, patients with CAD had a significantly higher insulin resistance than control (2.40 +/- 0.15 vs. 3.23 +/- 0.17%/min, P < 0.01, respectively), higher triglyceride (1.39 +/- 0.10 vs. 1.05 +/- 0.05 mmol/l, P < 0.05), lower HDL cholesterol (1.05 +/- 0.05 vs. 1.28 +/- 0.06 mmol/l, P < 0.05), and higher lipoprotein (a) (27.5 +/- 4.3 vs. 17.4 +/- 2.0 mg/dl, P < 0.05). Multiple logistic regression analysis indicated that hypertension, insulin resistance, high lipoprotein (a) and triglyceride, and low HDL cholesterol were independently related to CAD. Our results suggest that insulin resistance per se is a significant risk factor for CAD in Japanese patients with type 2 diabetes.

Aged↗
PubMed2001

Assessing the aromatic potential of Cabernet Sauvignon and Merlot musts used to produce rose wine by assaying the cysteinylated precursor of 3-mercaptohexan-1-ol.

The development of a method for assaying S-3-(hexan-1-ol)-L-cysteine, the cysteinylated precursor of 3-mercaptohexan-1-ol (P-3MH), in must has made it possible to study its impact on the aromatic potential of Merlot and Cabernet Sauvignon grape varieties used to produce rose wines in Bordeaux. The original feature of this method is the purification of very small volumes of must (500 microL) containing P-3MH by affinity chromatography and gas-phase chromatography coupled with mass spectrometry of the purified precursor in trimethylsilylated derivative form. Assays of the cysteinylated precursor in Merlot and Cabernet Sauvignon grapes showed that it was mainly located in the grape skins (60%). Prolonged juice-skin contact increased the must's P-3MH content, and this phenomenon was more marked at higher temperatures. Assessment of the aromatic potential of must used to produce rose wines by chemical analysis of an S-cysteine conjugate is mentioned for the first time.

Cysteine↗
PubMed2001

Formation of furfurylthiol exhibiting a strong coffee aroma during oak barrel fermentation from furfural released by toasted staves.

Furfurylthiol (FFT) is formed in white wines during alcoholic fermentation in the barrel from the furfural released by toasted staves. The quantity of furfural released into the must has a decisive effect on the quantity of FFT in the finished wine. Wines fermented in new barrels thus contain larger quantities of FFT than those fermented in used barrels. Fermentation conditions favorable to an excess production of H(2)S (hydrogen sulfide) by the yeast promote the formation of this volatile thiol. The presence of this volatile thiol in white wines is, therefore, closely related to the yeast's sulfur metabolism.

Coffee↗
PubMed2001

Fas/FasL mediated apoptosis of thyrocytes in Graves' disease.

We examined in the present study the possible involvement of Fas and its ligand (FasL) in the process of Graves' disease. Immunohistochemical analysis showed that few normal thyrocytes expressed Fas but many thyrocytes in Graves' disease expressed this molecule. The percentage of FasL-positive thyrocytes in Graves' thyroids was, however, less than in normal thyroids. Several apoptotic thyrocytes and infiltrating mononuclear cells (MNCs) were detected scattered throughout Graves' thyroid tissues and abundant proliferating cell nuclear antigen (PCNA)-positive thyrocytes were present. Apoptotic cells, as well as PCNA-positive cells, were scarcely detectable in normal thyroid glands, however. In vitro treatment of thyrocytes by IL-1beta a cytokine found to be expressed in Graves' thyroid glands, increased Fas but reduced FasL expression. IL-1beta-stimulated thyrocytes became sensitive to apoptosis by anti-Fas IgM monoclonal antibody (mAb). Activated T cells, which strongly expressed FasL, showed cytotoxic activity toward IL-1beta-stimulated thyrocytes but not toward unstimulated thyrocytes. This cytotoxic activity involved the Fas/FasL pathway. Importantly, unstimulated thyrocytes could kill activated, but not resting, T cells. IL-1beta-stimulated thyrocytes, with down-regulated FasL expression, could not efficiently kill activated T cells. The cytotoxic activity of unstimulated thyrocytes toward activated T cells was inhibited by anti-FasL mAb. Interestingly, unstimulated thyrocytes induced apoptosis in IL-1beta-stimulated thyrocytes but not in unstimulated thyrocytes. These interactions were also blocked by anti-FasL mAb. Our results suggest that the apoptotic cell death of both thyrocytes and infiltrating MNCs found in Graves' thyroid glands is regulated by IL-1beta through Fas/FasL interactions.

Apoptosis↗
PubMed2001

Development of low-turnover bone diseases after parathyroidectomy and autotransplantation.

Parathyroidectomy and immediate autotransplantation (PTX-AT) has been shown to decrease bone pain and increase bone mineral density. However, adynamic bone disease (ABD) has been predicted to develop if the serum intact parathyroid hormone (i-PTH) level remains lower than normal for a long period of time. Therefore, we investigated the bone histology of patients whose serum i-PTH levels did not increase over 70 pg/mL for 1 year after PTX-AT. Four chronic hemodialysis patients were investigated. The serum intact osteocalcin (i-OC) level was measured and histomorphometry for cancellous bone was performed 1 year after the operation. Tetracycline hydrochloride was administered in the 12 weeks after PTX-AT. The serum i-PTH levels were 20.5 +/- 15.0 pg/mL and i-OC levels were 19.5 +/- 0.9 ng/mL. Histomorphometric analyses showed the osteoclast surface to be 0.1% in two cases and 0% in the other two cases, the eroded surface was 7.7 +/- 6.1%, and the fibrosis volume and osteoblast surface were 0% in all four cases. Osteoid volume, osteoid surface and osteoid thickness were lower in cases 1-3, but higher in case 4. All tetracycline labelings were in contact with the mineralization front in cases 1 and 3, but some were not in cases 2 and 4. Serum i-PTH and i-OC levels indicated that ABD developed in these four cases. Histomorphometric analyses revealed that ABD developed in case 1, while either ABD or low-turnover osteomalacia developed in cases 2 and 4, and low-turnover osteomalacia was observed in case 3 after PTX-AT. In conclusion, i-PTH should not be maintained at lower levels to avoid low-turnover bone diseases.

Bone Diseases, Metabolic↗
PubMed2001

Correction of hyperglycaemia reduces insulin resistance and serum soluble E-selectin levels in patients with Type 2 diabetes mellitus.

AIMS: To investigate the effects of glycaemic control on insulin sensitivity and serum concentrations of soluble vascular cell adhesion molecule (sVCAM)-1 and E-selectin (sE-selectin) in patients with Type 2 diabetes mellitus. To examine whether reductions in serum adhesion molecule levels correlate with improvement in insulin resistance. METHODS: A total of 54 patients with Type 2 diabetes were treated for 4 weeks with either diet alone, sulphonylurea or insulin. Fasting glucose, insulin sensitivity, lipids, sVCAM-1, and sE-selectin levels were measured before and after treatment. RESULTS: All treatment modalities successfully corrected hyperglycemia. Reductions in blood glucose levels resulted in improvement in insulin sensitivity (diet KITT 2.40 +/- 0.26-3.09 +/- 0.36, P < 0.01; sulphonylurea 2.24 +/- 0.16-2.94 +/- 0.18, P < 0.01; insulin 1.68 +/- 0.27-2.16 +/- 0.22%/min, P < 0.05), and decrease in sE-selectin levels (diet 88.4 +/- 14.9-66.2 +/- 10.8, P < 0.05; sulphonylurea 85.1 +/- 11.6-59.8 +/- 7.8, P < 0.01; insulin 84.4 +/- 8.7-66.8 +/- 7.4 ng/ml, P < 0.01), but no change in sVCAM-1 levels. There was a significant correlation between the degree of decrease in sE-selectin levels and improvement in insulin sensitivity (r = -0.38, P < 0.01). CONCLUSIONS: Correction of hyperglycaemia, independent of treatment modality, resulted in improvement of insulin resistance and decrease in sE-selectin levels. These changes might, in part, contribute to reduce the risk of diabetic microvascular and macrovascular complications in patients with Type 2 diabetes mellitus.

Biomarkers↗
PubMed2001

Comparison of lymphocyte depletion and clinical effectiveness on filtration leukocytapheresis in patients with rheumatoid arthritis.

We evaluated the relationship between the clinical benefit of filtration leukocytapheresis (LCP) and the number of removed leukocytes in patients with rheumatoid arthritis (RA). LCP was performed in 31 drug-resistant RA patients. LCP was carried out 3 times with 1 week separating each session. Assessment of RA before and after LCP showed a substantial and rapid improvement in tender joint counts, swollen joint counts, and patients' and physicians' assessments. Careful analysis indicated that 19 of 31 patients with RA showed > or = 20% improvement following LCP therapy. The number of leukocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. No adverse reactions or complications were noted. There was no significant difference in any indices of clinical activity and the removal rates of leukocytes between responders and nonresponders. The total numbers of removed lymphocytes in responders were significantly higher than those in nonresponders (responders 64.1 x 10(8) versus nonresponders 50.7 x10(8), p < 0.05). The relationship between clinical effectiveness and the number of removed granulocytes and monocytes was not statistically significant. Our results suggest that filtration LCP to remove leukocytes from the peripheral blood, especially lymphocytes, exerts an immunomodulatory effect in patients with RA.

Adult↗