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Biomedical subjects

T Nagasaka

Publications and source records attributed to T Nagasaka.

At least 19 recordsLinked to original sources

Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. The present study aimed to investigate IDO expression and its prognostic significance in endometrial cancer. Indoleamine 2,3-dioxygenase expression in endometrial cancer tissues (n = 80) was immunohistochemically scored as four groups (IDO-, 1+, 2+, and 3+). The high IDO expression (IDO2+ or 3+) in tumour cells was found in 37 (46.3%) of the 80 cases, and was positively correlated with surgical stage, myometrial invasion, lymph-vascular space involvement, and lymph node metastasis, but not with the histological grade. Patients with high IDO expression had significantly impaired overall survival and progression-free survival (PFS) (P = 0.002 and P = 0.001, respectively) compared to patients with no or weak expression of IDO (IDO- or 1+). The 5-year PFS for IDO-/1+, 2+, and 3+ were 97.7, 72.9, and 36.4%, respectively. Even in patients with early-stage disease (International Federation of Gynecology and Obstetrics I/II, n = 64), the PFS for IDO2+/3+ was significantly poor (P = 0.001) compared to that for IDO-/1+. On multivariate analysis, IDO expression was an independent prognostic factor for PFS (P = 0.020). These results indicated that the high IDO expression was involved in the progression of endometrial cancer and correlated with the impaired clinical outcome, suggesting that IDO is a novel and reliable prognostic indicator for endometrial cancer.

Biomarkers, Tumor↗

Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival.

Angiotensin II, a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT(1)R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT1R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT1R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT1R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n = 67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type 1 angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT1R, the overall survival and progression-free survival were significantly poor (P = 0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT1R, although VEGF, but not AT1R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT1R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.

Disease Progression↗

Confocal endomicroscopy for the diagnosis of gastric cancer in vivo.

BACKGROUND AND STUDY AIMS: Advances in endoscopy have led to imaging of the details of the gastric mucosa, but the histological diagnosis usually has to be confirmed by endoscopic biopsy. A method of confocal endomicroscopy that has recently been developed allows the observation of living cells in vivo. Several investigators have reported that the technique is of value, but there have as yet been no studies describing its application in gastric cancer. PATIENTS AND METHODS: Twenty-seven patients with early gastric cancer underwent confocal endomicroscopy (Pentax EG-3870CIK; Pentax, Tokyo, Japan). After intravenous administration of fluorescein sodium, confocal images obtained from the normal mucosa and from cancerous lesions were interpreted by two pathologists independently and compared with the histological findings, including CD34 immunostaining of biopsy specimens or resected specimens from the same sites. RESULTS: Fluorescein yielded high-quality confocal images of the gastric mucosa; if cancer could be targeted (59%) images were mostly graded good. The images corresponded to the hematoxylin-eosin staining of transverse sections of specimens from the same sites. In the results for the interpretation by the two pathologists, the accuracy for the diagnosis of gastric cancer was 94.2% (pathologist A), and 96.2% (pathologist B), respectively. The accuracy decreased substantially when poor images and inaccessible lesions were included. CONCLUSIONS: Confocal endomicroscopy is useful in the diagnosis of gastric cancer but good quality images cannot always be obtained. In the future, it may allow virtual biopsy and help reduce unnecessary biopsies.

Adenocarcinoma↗

Predicting struvite formation for phosphorus recovery from human urine using an equilibrium model.

Interest in phosphorus recovery from urine diverted from faeces has been growing recently. Phosphorus in urine can be precipitated out as struvite (MgNH4PO4 x 6H2O) with addition of magnesium salt under alkaline conditions. Struvite formation, however, should be more well understood for its practical application. We predicted the struvite formation with a development of a new equilibrium model. The model considered the formation of eight different kinds of precipitates, including struvite, with effects of ionic strength and temperature. In addition, experiments on struvite formation in urine were conducted for the model validation. The model prediction of struvite formation had good agreement with the experimental results. The optimum pH to form struvite was predicted to be 9.4-9.7. In order to precipitate 99% of phosphate in urine with 1.5 fold Mg concentration to PO4-P, the pH value was necessary to be more than 8.1 based on the model prediction.

Humans↗

Are anemic patients more sensitive to calcineurin inhibitors?

A calcineurin inhibitor (CNI) is characterized by high affinity binding to red blood cells. There is a possibility that hematocrit levels might affect the immunosuppressive effects of cyclosporine (CsA). The purpose of this study was to examine whether the treatment with CNI was more effective in preventing acute rejection in anemic compared with nonanemic patients and to find a suitable method to monitoring immunosuppression. Ninety-five living donor renal transplant recipients who were treated with CsA were divided into five groups depending on their Ht levels. The incidences of biopsy-proven acute rejection were 1/8 (12.5%), 8/31 (25.8%), 6/28 (21.4%), 10/22 (45.5%), and 2/6 (33.3%) for Ht < or = 25%, 25% < Ht < or = 30%, 30% < Ht < or = 35%, 35% < Ht < or = 40%, and 40% < Ht, respectively. In vitro IL-2 mRNA inhibition tests were performed to evaluate lymphocyte function after stimulation of whole-blood with phorbol myristate acetate and Ca-ionophore in the presence of various concentrations of CsA. Whole blood CsA levels causing 50% inhibition of IL-2 mRNA (IC50) were 256, 310, 175, and 55 ng/mL for Ht 50%, 40%, 30%, and 20%, respectively. It is speculated that plasma concentrations of CsA may increase at low Ht levels, because lower incidences of acute rejection and lower IC50 values of CsA were observed in the anemic state. When the dosage of CsA was adjusted to its whole-blood concentration, the anemic state is likely to enhance the immunosuppressive effect of CsA. A pharmacodynamic study, such as the IL-2 mRNA inhibition test, is preferable for CsA monitoring.

Anemia↗

Feasibility of rapid-sequence 31P magnetic resonance spectroscopy in cardiac patients.

PURPOSE: To determine the clinical feasibility of rapid-sequence phosphorus-31 magnetic resonance spectroscopy (31P-MRS) of the heart with cardiac patients using a 1.5T clinical MR system. MATERIAL AND METHODS: Twenty cardiac patients, i.e. dilated cardiomyopathy (DCM) 13 cases, hypertrophic cardiomyopathy (HCM) 3 cases, hypertensive heart diseases (HHD) 3 cases, and aortic regurgitation (AR) 1 case were examined using rapid cardiac 31P-MRS. Complete three-dimensional localization was performed using a two-dimensional phosphorus chemical-shift imaging sequence in combination with 30-mm axial slice-selective excitation. The rapid-sequence 31P-MRS procedure was phase encoded in arrays of 8 x 8 steps with an average of 4 acquisitions. The total examination time, including proton imaging and shimming, for the rapid cardiac 31P-MRS procedure, ranged from 10 to 15 min, depending on the heart rate. Student's t test was used to compare creatine phosphate (PCr)/adenosine triphosphate (ATP) ratios from the cardiac patients with those of the control subjects (n = 13). RESULTS: The myocardial PCr/ATP ratio obtained by rapid 31P-MRS was significantly lower (P < 0.001) in DCM patients (1.82 +/- 0.33, mean +/- SD), and in patients with global myocardial dysfunction (combined data for 20 patients: 1.89 +/- 0.32) than in normal volunteers (2.96 +/- 0.59). These results are similar to previous studies. CONCLUSION: Rapid-sequence 31P-MRS may be a valid diagnostic tool for patients with cardiac disease.

Adenosine Triphosphate↗

Human papillomaviruses of the mucosal type are present in some cases of extragenital Bowen's disease.

BACKGROUND: Bowen's disease in the genital area is generally considered to be caused by mucosal high-risk human papillomaviruses (HPVs). However, the detection rate and spectrum of HPVs in extragenital Bowen's disease are various and it is not clear to what extent HPV is involved in its pathogenesis. OBJECTIVES: To assess the degree of association of HPV in extragenital cases by examining detection rates, types, quantities and localization of HPV. METHODS: A polymerase chain reaction (PCR) approach that we had previously established, which can give sensitive detection of a broad range of HPVs from cutaneous [including epidermodysplasia verruciformis-related HPVs (EV-HPVs)] to mucosal HPVs, was applied to samples from 41 patients with extragenital Bowen's disease and normal skin samples from 48 individuals. Semiquantitative L1-PCR and tyramide-based in situ hybridization (ISH) were also employed for positive cases. RESULTS: HPVs belonging to the mucosal high-risk group were detected in three patients with Bowen's disease (7%; two HPV 16 and one HPV 33), with 10(1)-10(3) copy equivalents per diploid amount of cellular DNA. They were distributed among most nuclei of tumour cells but in none of the cells of adjacent normal skin. HPVs belonging to the cutaneous group were detected in two patients (5%; HPV 27 and HPV 76) at 10(-2)-10(-3) copy equivalents, the same level as in a normal skin specimen positive for type 23 EV-HPV. No positive signals were observed by ISH. CONCLUSIONS: HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease.

Aged↗

Critical progressive small-graft injury caused by intrasinusoidal pressure elevation following living donor liver transplantation.

In adult-to-adult living liver transplantation, small-for-size graft syndrome sometimes occurs. The relationship between the hemodynamic changes and histologic findings has not been studied in patients with failure of small-for-size grafts. We analyzed the relationship between the postoperative hemodynamic changes and pathologic findings in patients with small-for-size grafts that ended in graft failure. From March 1999 to December 2002, adult-to-adult living-donor liver transplantation with small-size grafts (graft volume/standard liver volume less than 40%) was performed in eight patients. Three patients died from graft failure caused by overperfusion, which was diagnosed from pathologic findings. We analyzed the relation between hepatic hemodynamic parameters, such as portal venous blood velocity or splenic arterial pulsatility index, and histologic changes in patients with graft failure. Severe portal hyperperfusion (90 cm/sec at the umbilical portion) was observed on postoperative day 1. Among patients with graft failure, critical hemodynamic changes, such as sudden onset of extremely deteriorated portal venous blood flow, occurred during the early postoperative period (postoperative day 5, 3, 6, respectively). Histologic examination revealed vacuolar changes in the cytoplasm of hepatocytes, and submassive necrosis indicated intrasinusoidal pressure elevation. These changes were not observed in the biopsy obtained soon after reperfusion. In conclusion, critically decreased vascular beds may cause intrasinusoidal pressure elevation and sinusoidal circulatory disturbances.

Adult↗

Rapid-sequence phosphorus-31 magnetic resonance spectroscopy of the human heart using a 1.5-T clinical system.

PURPOSE: To compare a 'standard' slow phosphorus-31 magnetic resonance spectroscopy (31P-MRS) sequence with two faster sequences in phantoms and healthy volunteers using a 1.5-T clinical system. MATERIAL AND METHODS: Complete 3D localization was performed using a 2D phosphorus chemical-shift imaging sequence in combination with 30-mm axial slice-selective excitation. Two 31P-MRS rapid sequences (RS8-4: 8 x 8 phase-encoding, with an average of 4 acquisitions, and RS16-1: 16 x 16 phase-encoding, 1 acquisition) were compared with the standard sequence (StdP: 16 x 16 phase-encoding, with an average of 8 acquisitions) in phantom and healthy volunteers. RESULTS: Acquisition time for the 31P-MRS procedure with StdP, RS8-4, and RS16-1 in the healthy volunteer studies ranged from 30 to 45, 3 to 5, and 3 to 5 minutes, respectively. Metabolite measurements of healthy volunteers obtained from 31P-MRS using RS8-4 correlated with values obtained using StdP (PCr r2=0.63, P<0.001; ATP r=0.41, P<0.01 and PCr/ATP ratio r2=0.25, P<0.05). There was no correlation between StdP and RS16-1 for either ATP or the PCr/ATP ratio (r2=0.03, P=0.60, and r2=0.11, p=0.26, respectively). Reproducibility (intensity of phosphorus signal) with RS16-1 was worse than that of RS8-4 or StdP. CONCLUSION: 31P-MRS using RS8-4 may be a valid diagnostic tool for patients with cardiac diseases.

Adult↗

Assessment of para-aortic lymph nodes by intraoperative sonography in gynecological malignancies: a preliminary report.

OBJECTIVE: To investigate the usefulness of intraoperative sonography for the assessment of para-aortic lymph nodes in gynecological malignancies. METHODS: The assessment of para-aortic lymph node swelling by computed tomography (CT), palpation during surgery and intraoperative sonography was performed in 43 women with a gynecological malignancy. The sensitivity, specificity and predictive values of each technique for assessment of node metastasis were examined in the 33 women who underwent para-aortic lymphadenectomy. For each of the three assessment techniques, the number of para-aortic lymphadenectomies that would have been performed and the number of women who would have had missed metastasis were evaluated assuming a para-aortic lymphadenectomy would be performed only when swollen nodes were detected. RESULTS: Para-aortic nodes were assessed to be swollen by CT, palpation, and intraoperative sonography, respectively, in one, six and 10 of 43 women in total, and in one, six and nine of the 33 women who underwent para-aortic lymphadenectomy. The sensitivity and negative predictive value of intraoperative sonography were 100%, while the specificity and positive predictive value of CT were 100%. If para-aortic lymphadenectomy had been performed only when swollen nodes were detected by intraoperative sonography, the number performed would have decreased from 33 to nine without missing lymph-node metastasis. CONCLUSION: Intraoperative sonography has potential for the assessment of para-aortic lymph nodes in gynecological malignancies.

Aorta↗

Telomerase, p53 and PCNA activity in osteosarcoma.

AIMS: The aim of this study was to investigate telomerase activity and to assess the correlation between telomerase activity, tumor proliferative activity and p53 overexpression in osteosarcoma tumor samples. METHODS: Using a telomerase polymerase chain reaction-enzyme-linked immunoassay based on the telomeric repeat amplification protocol method, we examined telomerase activity in 26 primary osteosarcoma specimens. P53 overexpression was identified using immunohistochemical staining, and tumor proliferative activity was assessed by immunohistochemical staining of PCNA. RESULTS: Telomerase activity was detected at a relatively low level in five of 26 osteosarcoma tissue specimens. P53 was detected in eight of 21 cases. There was no significant correlation between telomerase activity and p53 overexpression (p=0.325). There was a significant correlation between PCNA staining and telomerase activity (p=0.0075). CONCLUSION: Difference between the telomerase activity and p53 overexpression in osteosarcoma suggests that p53 and telomerase may not cooperate in tumor proliferation. Correlation of telomerase activity to PCNA expression suggests that telomerase activity may also useful for evaluate proliferative activity in osteosarcoma.

Adolescent↗

Involvement of cytotoxic granules in the apoptosis of aplastic anaemia.

To study the involvement of cytotoxic granules in apoptosis of aplastic anaemia (AA), we analysed bone marrow clot sections of AA for apoptosis and perforin, granzyme B and T-cell intracellular antigen-1 (TIA-1) expression. Perforin, TIA-1 expression and apoptosis were significantly increased in AA patients compared with control subjects, but granzyme B was not. TIA-1 was significantly correlated with apoptotic cells of AA. No correlation was found between perforin and apoptotic cells of AA. These results suggest that perforin and TIA-1 play a role in the pathogenesis of AA. TIA-1 is implicated as an effector in the apoptosis of AA.

Adolescent↗

Age and duration related changes in muscle sympathetic nerve activity in Parkinson's disease.

OBJECTIVE: To clarify the characteristics of sympathetic vasomotor function in Parkinson's disease by sympathetic neurographic analysis. METHODS: Muscle sympathetic nerve activity (MSNA) was recorded using a microneurographic technique at rest and during head up tilt in 18 patients with idiopathic Parkinson's disease and 21 healthy controls. RESULTS: Heart rate and blood pressure at rest did not differ between index and control subjects. The increase in these variables and MSNA in response to tilting was slightly blunted in the Parkinson's group. Resting MSNA showed a negative correlation with age in patients with Parkinson's disease (p<0.05) and a positive correlation with age in controls (p<0.01). There was a negative correlation between duration of disease or disability levels and MSNA (p<0.01). CONCLUSIONS: Sympathetic vasomotor function may be related to age and disease duration in Parkinson's disease.

Age Factors↗

Ipsilateral thalamic MRI abnormality in an epilepsy patient.

In a 19-year-old patient with status epilepticus arising in the right parietal neocortex, unenhanced ictal MRI showed abnormalities mainly in the right cerebral cortex, contralateral cerebellum, and ipsilateral thalamus. The thalamus is considered a key site of functional abnormality in this patient.

Adult↗

Brain activation during the fist-edge-palm test: a functional MRI study.

The purpose of our study is to clarify, using functional MRI, brain regions activated during the fist-edge-palm task (FEP) compared to relatively simple hand motor tasks using either the right or the left hand in right-handed normal volunteers. The FEP was introduced to detect a disorder of voluntary movement, and it is believed to be closely related to contralateral frontal lobe damage. However, this assumption still remains controversial. Ten subjects participated in this study. Hand motor tasks were as follows: (1) the FEP, in which the subjects were requested to place their hand in three different positions sequentially: a fist resting horizontally, a palm resting vertically, and a palm resting horizontally; (2) a fist-palm task (FP), in which the subjects were asked to clench and unclench their fist alternately; and (3) a control task requiring the subjects to knock lightly with their clenched fist. The contralateral sensomotor and premotor areas were activated in the FP with the right hand and the contralateral sensorimotor, premotor, and supplementary motor areas (SMA) were activated in the FP with the left hand. In the FEP with either hand, bilateral premotor and left parietal areas and ipsilateral cerebellum were also activated as well as contralateral sensorimotor area and SMA. Our results suggest that successful performance of the FEP requires the participation of more brain areas than FP, which may explain why some patients without frontal lobe damage failed to perform the FEP.

Adult↗