PubMed Health⌕ Search

Biomedical subjects

H Iwase

Publications and source records attributed to H Iwase.

At least 19 recordsLinked to original sources

Experimental fragmentation studies with 12C therapy beams.

High-energy beams of (12)C ions in the range of 80-430 MeV u(-1) delivered by the heavy-ion synchrotron SIS-18 are used for radiotherapy of deep-seated localized tumors at the treatment unit at GSI Darmstadt. In order to improve the physical database, the fragmentation characteristics along the penetration path in tissue were investigated experimentally by using a water phantom as tissue-equivalent absorber. Measurements were performed at specific energies of 200 and 400 MeV u(-1) of the incident (12)C ions and at six different depths before and behind the Bragg peak. Secondary fragments with nuclear charges Z(f) = 1-5 were identified by scintillation detectors using DeltaE-E and time-of-flight techniques. The preliminary results include energy- and angular distributions, fragment yields, build-up curves and attenuation of the primary carbon projectiles.

Animals↗

Comprehensive study of urinary cortisol metabolites in hyperthyroid and hypothyroid patients.

OBJECTIVE: To further analyse the significance and mutual relationship of thyroid function-linked alterations in cortisol metabolism that have been separately and variously reported. PATIENTS AND MEASUREMENTS: Twenty-four-hour urine samples from 21 patients with hyperthyroidism (Graves' disease), 16 patients with hypothyroidism (Hashimoto's thyroiditis), 21 healthy age- and sex-matched controls for hyperthyroidism, and 16 healthy age- and sex-matched controls for hypothyroidism were evaluated for 6beta-hydroxycortisol (6beta-OHF), tetrahydrocortisol (THF), tetrahydrocortisone (THE), allo-tetrahydrocortisol (allo-THF), urinary free cortisol (UFF), urinary free cortisone (UFE) and 17-hydroxycorticosteroid (17-OHCS). RESULTS: Urinary 17-OHCS, THE and allo-THF levels increased considerably in hyperthyroid patients compared to the controls, while UFF and THF showed no difference between the two groups. Urinary 6beta-OHF was significantly lower in the hyperthyroid patients than in the controls. Both the urinary allo-THF + THF/THE and the UFF/UFE ratios were significantly lower in the hyperthyroid patients than in the controls, whereas only the former was significantly higher in the hypothyroid patients than in the controls. The urinary allo-THF/THF ratio was significantly higher in the hyperthyroid patients and significantly lower in the hypothyroid patients than in the controls. In an analysis of pooled subjects including all groups (n = 64), free T4 levels correlated negatively (P < 0.0001) with the urinary allo-THF + THF/THE ratio but not with the UFF/UFE ratio. The serum levels of free T4 correlated positively (P < 0.0001) with the urinary allo-THF/THF ratio. CONCLUSION: The thyroid hormones seem to affect the total 11beta-HSD activity (allo-THF + THF/THE) more strongly than the renal 11beta-HSD2 activity (UFF/UFE). 5alpha-reductase activity (allo-THF/THF) is also enhanced in hyperthyroidism, while the reduction of urinary 6beta-OHF in hyperthyroidism might be a secondary effect of the altered activity of the total 11beta-HSD and 5alpha-reductase.

17-Hydroxycorticosteroids↗

Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer.

Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P<0.0001), ER (P=0.02), and progesterone receptor (P=0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P=0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive, had significantly better response to endocrine therapy (P=0.04), and longer survival after relapse (P=0.0003), than those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that the expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.

Adult↗

Simulations of an accelerator-based shielding experiment using the particle and heavy-ion transport code system PHITS.

In order to estimate the biological effects of HZE particles, an accurate knowledge of the physics of interaction of HZE particles is necessary. Since the heavy ion transport problem is a complex one, there is a need for both experimental and theoretical studies to develop accurate transport models. RIST and JAERI (Japan), GSI (Germany) and Chalmers (Sweden) are therefore currently developing and bench marking the General-Purpose Particle and Heavy-Ion Transport code System (PHITS), which is based on the NMTC and MCNP for nucleon/meson and neutron transport respectively, and the JAM hadron cascade model. PHITS uses JAERI Quantum Molecular Dynamics (JQMD) and the Generalized Evaporation Model (GEM) for calculations of fission and evaporation processes, a model developed at NASA Langley for calculation of total reaction cross sections, and the SPAR model for stopping power calculations. The future development of PHITS includes better parameterization in the JQMD model used for the nucleus-nucleus reactions, and improvement of the models used for calculating total reaction cross sections, and addition of routines for calculating elastic scattering of heavy ions, and inclusion of radioactivity and burn up processes. As a part of an extensive bench marking of PHITS, we have compared energy spectra of secondary neutrons created by reactions of HZE particles with different targets, with thicknesses ranging from <1 to 200 cm. We have also compared simulated and measured spatial, fluence and depth-dose distributions from different high energy heavy ion reactions. In this paper, we report simulations of an accelerator-based shielding experiment, in which a beam of 1 GeV/n Fe-ions has passed through thin slabs of polyethylene, Al, and Pb at an acceptance angle up to 4 degrees.

Aluminum↗

Comparison between calculation and measured data on secondary neutron energy spectra by heavy ion reactions from different thick targets.

Measured neutron energy fluences from high-energy heavy ion reactions through targets several centimeters to several hundred centimeters thick were compared with calculations made using the recently developed general-purpose particle and heavy ion transport code system (PHITS). It was confirmed that the PHITS represented neutron production by heavy ion reactions and neutron transport in thick shielding with good overall accuracy.

Computer Simulation↗

Detection of identical JC virus DNA sequences in both human kidneys.

We studied JC virus (JCV) DNA sequence diversity among kidneys derived from cadavers with various causes of death. The 610-bp JCV DNA sequences we evaluated were identical not only among specimens derived from the same kidney but also among those derived from both kidneys of the same cadaver. Because the left and right kidneys are anatomically independent, our findings suggest that the viremia that has been proposed to occur after primary infection distributes the same JCV strain to both kidneys.

Adult↗

Clinical significance of AIB1 expression in human breast cancer.

AIB1 (amplified in breast cancer 1) is a member of the steroid receptor coactivator family and is a key factor in enhancing estrogen-dependent transcription. To evaluate the clinical significance of AIB1 in breast cancer, we performed Southern blot analysis of the AIB1 gene on 124 human breast cancer tissues. We also performed reverse transcription-polymerase chain reaction and semi-quantitative analysis of AIB1 mRNA expression on 58 of the tissues, and immunohistochemical detection of AIB1 protein on 115 of the tissues. On Southern blot analysis, the AIB1 gene was amplified in only two of the 124 breast cancer cases. On semi-quantitative analysis, the relative expression level of AIB1 normalized to that of GAPDH varied from 0.247 to 7.721 (median = 0.94), and was not correlated with any clinico-pathological factors. Although most of the breast cancer cells revealed cytoplasmic staining of AIB1, only 16% (18 in 115) showed nuclear staining of AIB1 protein. AIB1 nuclear expression was correlated with positivity for estrogen receptor alpha (P = 0.022). Those patients with tumor samples that showed nuclear staining of AIB1 tended to be successfully treated by endocrine therapy in comparison with those who did not show nuclear staining of AIB1. In conclusion, AIB1 nuclear expression was correlated with the estrogen receptor alpha status, and patients with AIB1 nuclear expression tended to be successfully treated by hormonal therapy.

Adult↗

Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery.

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of antiangiogenic factors should be a viable approach for cancer gene therapy. In this study, we investigated whether intravenous administration of endostatin gene complexed with a cationic vector (GL67/DOPE or PEI22K) could inhibit the development of lung tumors in mice injected i.v. with NFSa Y83 fibrosarcoma cells (5 x 10(5)) which frequently form lung metastasis. mRNA and protein of the transfected gene were produced in the lung and other organs of the transfected mice as assessed by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. Single intravenous injection of the endostatin gene (60 microg) complexed with either GL67/DOPE or PEI22K on day 3 or day 7 after fibrosarcoma cell inoculation significantly inhibited tumor formation in the lung as evidenced by the reduced number of lung tumors and lung weight, and prolonged survival of the endostatin gene-transfected mice compared with control mice. These findings suggested that the endostatin gene therapy, using cationic vector-mediated intravenous gene transfer, might be a feasible strategy for organ-targeted prevention and regulation of possible disseminated cancers.

Animals↗

Appropriate cerebral perfusion pressure during rewarming after therapeutic hypothermia.

This study evaluated the cerebral ischemic parameters during the rewarming period after therapeutic hypothermia to determine the critical cerebral perfusion pressure (CPP) threshold to avoid ischemic deterioration. Cat experimental head injury was induced by inflation of an epidural rubber balloon to maintain intracranial pressure at 30 mmHg under hypothermia. During the rewarming period, CPP was maintained at > or = 120 mmHg, 90 mmHg, and 60 mmHg by controlling the blood pressure. CBF, CMRO2, AVDO2, and cerebral venous oxygen saturation (ScvO2) were measured. Brain extracellular glutamate concentrations were also measured by a dialysis electrode. Histological preparations of all brains were examined under an electron microscope. The cerebral metabolic parameters in animals with CPP of more than 90 mmHg returned to the base values after rewarming. However, ScvO2 was significantly lower (27 +/- 6%) and AVDO2 was significantly higher (9.4 +/- 1.8 ml/100 g/min) after rewarming in the animals with CPP = 60 mmHg, which indicated misery perfusion. Animals with CPP = 60 mmHg also showed increased extracellular glutamate concentration and histological ischemic damage (mitochondrial swelling). CPP of 60 mmHg during the rewarming period is associated with irreversible ischemia, which indicates continuation of cerebral vasoconstriction. Therefore, a CPP of greater than 90 mmHg is required to avoid cerebral ischemia.

Animals↗

JC virus genotyping offers a new means of tracing the origins of unidentified cadavers.

There has been no reliable means of tracing the origins of unidentified cadavers but the recent finding that JC virus (JCV) can serve as a means of elucidating human migrations suggested that this virus may also be useful to trace the origins of unidentified cadavers. DNA samples extracted from renal tissue and urine were used as the template for PCR amplification of a 610 bp region (IG region) of the viral genome. We detected JCV DNA in 45% of the renal samples and in 33% of the urine samples and was detectable even 10 days after death. The sequences of the amplified IG regions could be used to determine the genotypes. We conclude that the JC virus genotype is a new marker useful for tracing the origins of unidentified cadavers.

Cadaver↗

Evaluation of oestrogen receptor beta wild-type and variant protein expression, and relationship with clinicopathological factors in breast cancers.

We addressed the clinicopathological significance of the oestrogen receptor (ER) beta protein, including an ERbeta variant, ERbetacx, in normal human breast and breast cancer. The reverse transcriptase-polymerase chain reaction (RT-PCR) showed that wild-type ERbeta (ERbetaw) mRNA expression was higher in normal than cancer tissues, and that ERbetacx mRNA was higher in cancer than in normal tissues. Immunohistochemistry of 22 normal breast tissues and 57 breast cancers was performed with three different ERbeta antibodies and one ERbetacx antibody. All normal breast samples showed staining with the three ERbeta antibodies, suggesting that ERbetaw might have a physiological role in oestrogen signalling in the normal breast. In breast cancer, expression of the ERbetaw protein correlated well with the expression of the ERalpha and progesterone receptor (PgR), as well as histological grade (HG), and tended to indicate a better prognosis than when ERbetaw was absent. Thirty-one (54%) breast cancer samples contained ERbetacx, whereas the corresponding tissue for normal breast samples stained positive in only two (9%).

Adult↗

Hamatometacarpal fracture-dislocation: distinctive three dimensional computed tomographic appearance.

We report here two fully documented cases of hamatometacarpal fracture-dislocation following trauma and treated in our hospital. In our cases, the patients suffered hamate fracture in association with metacarpal dislocation. In the first case, a dorsal oblique fracture of the hamate was associated with a dorsal dislocation of the base of the fourth metacarpal. In the second case, a dorsal oblique fracture of the hamate was not associated with a dorsal dislocation of the base of the fifth metacarpal. This diagnosis should be suspected on initial review of plain radiographs, which must include an oblique view because of diagnostic difficulty for this injury. We recommend three dimensional computed tomography (3D-CT) in any patient presenting with pain after blunt trauma to the hand to prevent in diagnosis. Open reduction and internal fixation of the fracture is indicated and relevant for displaced fracture.

Adult↗

Recurrent palmar dislocation of the distal radioulnar joint. A case report.

Recurrent palmar dislocation of the distal radioulnar joint is not a common injury. We report one case in a 73-year-old female. This injury was incorrectly diagnosed at the first presentation because there has been no distinct deformity at the wrist and extension-flexion was normal. The need for proper physical examination and accurate radiographic positioning is stressed. Distal diaphysis resection combined with distal radioulnar arthrodesis (modified Sauve-Kapandji procedure) was the preferred method of treatment in an old patient. Two years after the injury, the patient was asymptomatic.

Age Factors↗

Expression, function, and clinical implications of the estrogen receptor beta in human lung cancers.

The higher frequency of human lung adenocarcinoma in females than in males, strongly suggests the involvement of gender dependent factors in the etiology of this disease. This is the first investigation of estrogen receptor (ER) beta in human lung. Immunohistochemical staining revealed ERbeta expression in normal lung and in atypical adenomatous hyperplasia (AAH), considered as a precancerous lesion for adenocarcinomas. Adenocarcinomas showed significantly higher expression of ERbeta than squamous cell carcinomas. On the contrary, ERalpha expression was not detected in all cases. The functional integrity of ERbeta such as the binding ability to estrogen responsive element (ERE) and transcriptional activity was confirmed using a human lung cancer cell line, RERF-LC-OK. Colony formation of this cell was significantly reduced in the presence of pure antiestrogen. We conclude that ERbeta, but not ERalpha, is present in lung tissues with an important physiological function in normal lung. Furthermore, ERbeta may play a role in growth and development of adenocarcinomas.

Adenocarcinoma↗

Immobilization stress-induced thymocyte apoptosis in rats.

Immobilization of rats is a well known model of emotional stress. We studied apoptosis in rat thymocytes during immobilization for 2-8 hours (h). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells increased with time of immobilization. The positive cells increased significantly after 2 h and comprised about 33% of total cells after 8 h. The apoptotic cells aggregated as scattered foci predominantly in the cortex of the thymus and diffusely distributed with time of the stress. The DNA laddering also increased with time of immobilization, which was inhibited by a glucocorticoid receptor antagonist, RU-486. These results suggest that the emotional stress evoked by immobilization induces thymocyte apoptosis through glucocorticoid overflow.

Animals↗