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Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 217 records · Page 12Linked to original sources

Association of serum tumour necrosis factor-alpha with serum low-density lipoprotein-cholesterol and blood pressure in apparently healthy Japanese women.

1. The pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha is considered to be involved in the development of atherosclerosis by inducing local inflammatory responses in the vascular wall. Because TNF-alpha is also known to affect lipid and glucose metabolism, the association between the circulating concentration of TNF-alpha and atherogenic risk factors was examined in 82 apparently healthy Japanese women (aged 19-69 years; mean age 48.5 years). 2. The mean (+/-SD) serum TNF-alpha concentration was 2.7+/-0.9 pg/mL (range 1.4-5.9 pg/mL). The TNF-alpha concentration showed significant correlations with age (r = 0.28; P = 0.01), body mass index (r = 0.27; P = 0.01), the waist-hip ratio (r = 0.41; P = 0.0002), percentage body fat (r = 0.30; P = 0.006), systolic (r = 0.32; P = 0.004) and diastolic (r = 0.24; P = 0.03) blood pressure, total cholesterol (r = 0.27; P = 0.02) and low-density lipoprotein-cholesterol (LDL-C; r = 0.36; P = 0.001), while the correlations with high-density lipoprotein-cholesterol (r = -0.20; P = 0.08) and insulin resistance estimated by the homeostasis model assessment (HOMA(IR); r = 0.16; P = 0.15) were not statistically significant. 3. When adjusted for age and menopause, TNF-alpha was significantly associated with systolic blood pressure (r = 0.25; P = 0.02) and LDL-C (r = 0.27; P = 0.02). The association between TNF-alpha and LDL-C remained significant when adjustment was made for age, menopause and the waist-hip ratio (r = 0.24; P = 0.03). 4. Our results indicate that TNF-alpha may play a role in modulating blood pressure and LDL-C.

Adult↗

Effects of milrinone on left ventricular end-systolic pressure-volume relationship of rat hearts in situ.

1. We have already shown that the left ventricular (LV) end-systolic pressure-volume relationship (ESPVR) of rat hearts in situ is an upward convex curve and that LV end- systolic pressure (ESP(mLVV)) and the systolic pressure-volume area (PVA(mLVV)) at a mid-range LV volume (mLVV) sensitively reflect acute changes in LV contractility and work capability. Milrinone is a non-glycosidic, non-sympathomimetic drug that increases myocardial cAMP concentrations by selective inhibition of cardiac phosphodiesterase III. Therefore, milrinone could act on the entire cardiovascular system and cause an increase in inotropy, arterial vasodilatation and venodilatation. The aim of the present study was to investigate whether the approach we have recently instituted is able to detect the effects of milrinone on the entire cardiovascular system. 2. We measured simultaneously, in anaesthetized rats, continuous LV pressure using a catheter-tip micromanometer and LV volume by LV volumetry using a conductance catheter. We obtained steady state LV pressure-volume loops and intermittently obtained the LV ESPVR by gradual occlusion of the ascending aorta. We then evaluated LV function by assessing milrinone-induced changes in the ESPVR (i.e. ESP(mLVV) and PVA(mLVV)) and vasodilator actions by assessing milrinone-induced changes in ESP(ESV) and effective arterial elastance (Ea), defined as the ESP(ESV)/stroke volume ratio. 3. Milrinone (total dose 49.5 microg; infusion rate 3.3-6.7 microg/min, 7-10 microg/kg per min; blood concentration 53.9 ng/mL) largely shifted the ESPVR upwards and, thus, significantly increased end-systolic pressure (ESP(0.08)) and the systolic pressure-volume area (PVA(0.08)) at a mid-range LV volume (= 0.08 mL/g myocardium). Milrinone also significantly decreased LV ESP(ESV) and decreased Ea, although these decreases were not significant. 4. The results of the present study suggest that our own recently instituted approach to evaluate LV function by measuring LV pressure-volume loops and ESPVR succeeded in detecting a cardiotonic action of milrinone with arterial vasodilatation in normal rat hearts.

Animals↗

Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma.

AIM: The aim of this study is to assess the poly ADP-ribosylation activity in human hepatocellular carcinoma (HCC) and in liver cirrhosis (LC) as compared to the activity in normal livers (NL). METHODS: Hepatocellular carcinoma and LC tissues were sampled from 19 patients with HCC. Normal liver tissue was obtained from 19 patients with metastatic liver cancer. Poly ADP-ribosylation activity of these tissues was measured by using [32P]-adenylate nicotinamide adenine dinucleotide (NAD)-incorporation into the 116-kDa protein. Nicotinamide adenine dinucleotide glycohydrolase activity of these tissues was determined with thin layer chromatography. The immunohistochemical expression of Ki-67 was also assessed as a parameter of cell proliferative activity. RESULTS: The poly ADP-ribosylation of the 116 kDa protein was significantly increased in patients with HCC and LC as compared with NL (P<0.0001, P<0.05, respectively) and was inhibited by poly (ADP-ribose) polymerase inhibitors in a dose-dependent manner. There was no significant difference in NAD glycohydrolase activity among the three groups. A significant correlation was found between the Ki-67 positive cell rate and the relative radioactivity of poly ADP-ribosylation in HCC patients (r=0.794, P<0.0001). The poly ADP-ribosylation of the 116 kDa protein of LC was significantly higher in patients who had recurrences of HCC after hepatic resection than in patients without recurrence (P<0.05). CONCLUSION: Poly ADP-ribosylation of the 116 kDa protein in HCC patients might be enhanced with its proliferative activity, and poly ADP-ribosylation of the same protein in LC patients might be a useful parameter of carcinogenic potential for predicting HCC recurrence after hepatectomy in patients who have had HCC.

Adult↗

Blastic natural killer cell lymphoma arising from the mediastinum with terminal deoxynucleotidyl transferase expression.

Blastic natural killer (NK) cell lymphoma/leukemia is a relatively rare NK cell malignancy. We report the second case of blastic NK cell lymphoma arising from the mediastinum with an aggressive clinical course. The patient was a 63-year-old Japanese man with an anterior mediastinum tumor. The biopsy specimen showed diffuse proliferation of tumor cells with frequent mitotic figures and apoptotic bodies. Both angiocentric features and small foci of coagulative necrosis were found in this section. The tumor cells had medium to large nuclei with a fine chromatin pattern, inconspicuous nucleoli and scanty cytoplasm. The nuclear contour was oval to moderately irregular, showing slight pleomorphism as compared with typical lymphoblastic lymphoma. The tumor cells were positive for CD2, CD56 and terminal deoxynucleotidyl transferase, but negative for other T-cell antigens, B-cell antigens and myeloid markers. In situ hybridization for Epstein-Barr virus encoded small ribonucleic acid 1 was negative.

Apoptosis↗

Thymidine phosphorylase expression causes both the increase of intratumoral microvessels and decrease of apoptosis in human esophageal carcinomas.

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor, is expressed at higher levels in tumor tissues compared to the adjacent normal tissues in a variety of human carcinomas. The higher expression is associated with an increase of intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. We examined the role of dThdPase in apoptosis, IMVD, P53 expression and patient prognosis of human stages II and III esophageal squamous cell carcinomas (SCC). dThdPase expression was noted in 52 of the 78 esophageal SCC (66.7%), regardless of tumor stages and histologic grades. Mean IMVD was 117.9 +/- 32.6 in the dThdPase-positive cases and 103.1 +/- 21.5 in the dThdPase-negative cases, the value being significantly higher in the former (P < 0.05). Similarly, median (range) apoptotic index (AI: percentage of apoptotic cells) was significantly lower in the dThdPase-positive SCC, 1.8 (0.4-6.5), than in the dThdPase-negative SCC, 3.7 (0.6-7.0) (P < 0.01). AI and IMVD showed a significant inverse correlation (r = - 0.31, P = 0.005). There was also no significant difference in the frequency of P53 expression between the dThdPase-positive SCC and the negative SCC. No statistical difference was noted regarding the postoperative survival rate between the dThdPase-positive and the negative SCC. Although dThdPase expression was not associated with patient prognosis, the expression provided an advantage for tumor growth of human esophageal SCC, not only by increasing the intratumoral microvessels, but also attenuation of apoptosis, which might occur via a p53 gene-independent pathway.

Apoptosis↗

Aberrant expression of Pax-2 mRNA in renal cell carcinoma tissue and parenchyma of the affected kidney.

BACKGROUND: Pax proteins are transcription factors that demonstrate oncogenic properties and appear to play a crucial role in ontogenesis. Pax-2 is expressed in early kidney organogenesis, Wilms' tumor and renal cell carcinoma. In order to determine whether the expression of Pax-2 mRNA is a frequent and specific event in renal cell carcinoma, its expression in nephrectomized specimens and cell lines was investigated. METHODS: The expression of Pax-2 mRNA was examined by reverse transcription polymerase chain reaction in 55 nephrectomized specimens, nine renal parenchyma specimens from patients without renal cell carcinoma and 16 cell lines from various malignant diseases. RESULTS: All tumor tissue specimens expressed Pax-2 mRNA. In addition, 38 of 55 specimens from the renal parenchyma of the affected kidney expressed Pax-2 mRNA. In contrast, only two of the nine kidney specimens from patients without renal cell carcinoma expressed Pax-2 mRNA, indicating that expression of this protein is significantly higher in renal cell carcinoma (P < 0.01). All three cell lines from renal cell carcinoma expressed Pax-2. In contrast, Pax-2 was only expressed in two of three cell lines from transitional cell carcinoma and in none of the other lines. CONCLUSION: The results indicate that Pax-2 expression is a frequent and highly specific event in renal cell carcinoma.

Carcinoma, Renal Cell↗

Assessment of renal function with color Doppler ultrasound in autosomal dominant polycystic kidney disease.

BACKGROUND: Measurement of renal blood flow by color Doppler ultrasound is useful for assessment of renal function in a variety of renal disorders. In autosomal dominant polycystic kidney disease (ADPKD), however, it might be difficult to visualize interlobar arteries because of deformity of renal structure. To evaluate the usefulness of color Doppler in ADPKD, parameters determined by blood flow examination were compared with the results of ordinal renal function tests. METHODS: Twenty-one patients with ADPKD were examined by color Doppler ultrasound measurement. In each patient, 10 interlobar arteries in both kidneys were investigated. Minimum blood flow velocity (Vmin), maximum blood flow velocity (Vmax), mean blood flow velocity (Vmean), acceleration, resistive index and pulsatility index were measured in relation to the results of creatinine clearance, serum creatinine, blood urea nitrogen and 15 and 120 min values of the phenolsulfonphthalein test. RESULTS: In all patients, interlobar arteries were able to be visualized and blood-flow profile was measured. Although variations of Vmin, Vmax, Vmean and acceleration were relatively large, the resistive index and pulsatility index varied little in each kidney. Mean values of Vmin (P < 0.005), Vmean (P < 0.05), resistive index (P < 0.005) and pulsatility index (P < 0.005) were well correlated to creatinine clearance with statistical significance. CONCLUSIONS: In ADPKD, color Doppler ultrasound measurement is a useful method for assessment of renal function and could be used for monitoring the dynamic state of renal blood flow as a non-invasive technique.

Aged↗

Endocrine therapy for recurrence after definitive radiotherapy in patients with prostate cancer.

BACKGROUND: Long-term results were analyzed to evaluate the role of endocrine therapy in the management of local and distant recurrence of prostate cancer following external radiation therapy. METHODS: Between 1976 and 1994, 92 patients with untreated prostate cancer underwent external beam radiation therapy alone. Endocrine therapy had been started when relapse was evident. RESULTS: Failure was seen in 35 of 92 patients: 10 local, 19 distant and six biochemical failures. Endocrine treatment was performed in 28 patients with nine local and 19 distant failures. The cancer-specific survival rate from the endocrine treatment was 54.5% at 5 years. Prostate-specific antigen level in 20 of 20 patients (100%) decreased to below the normal limit 3 months after the start of endocrine therapy. In univariate analysis, T classification was the most significant variable for cancer-specific survival from the initial treatment. CONCLUSIONS: A favorable outcome was achieved by endocrine therapy in patients who had relapsed after external beam radiation monotherapy. Even the recurrent tumor had a sensitivity to androgen. Patients with locally advanced disease (T2b and T3) had poorer prognosis than those with minimally extended disease (T1b and T2a).

Aged↗

Postnatal development of the testis in Japanese children based on observations of undescended testes.

BACKGROUND: Little is known about the morphological aspects of the postnatal development of the testis in Japanese children. By investigating the normal development of the testis, clinicians in urology can give better strategies to their patients. In addition, the pattern of development will improve the understanding of the effect of xenoestrogens. METHODS: Biopsied testis samples of 68 patients with undescended testes aged between 2 and 21 years were examined by light microscopy. Nineteen patients with normal histology of the bilateral testes were selected for this study. For light microscopy, paraffin sections were stained with hematoxylin and eosin. In addition, using electron microscope, Epon sections stained with lead citrate and uranyl acetate were observed. Semi-thin sections stained with toluidine blue were also used for light microscopy. RESULTS: Gonocytes were observed in the testis of the 2-year-old boys. Spermatocytes developed by 4 years of age and spermatids developed by 11 years of age. The immature Sertoli-Sertoli ectoplasmic junction was observed as early as 4 years of age, and it was completed by 9 years of age. Mature myoid cells were observed by the age of 13 years. Immature Leydig cells were found at 7 years of age and the cells matured by 13 years of age. CONCLUSION: A pattern of postnatal development of the testis in Japanese children was presented.

Adolescent↗

Prostate adenocarcinoma producing syndrome of inappropriate secretion of antidiuretic hormone.

The syndrome of inappropriate secretion of antidiuretic hormone (ADH) was recognized in a 68-year-old man with a poorly differentiated metastatic adenocarcinoma of the prostate. Elevated levels of ADH were found in the tissues of the primary tumor and lymph node metastasis. The patient's clinical course is detailed and the pathophysiology of this syndrome is discussed. To our knowledge, this case is the ninth reported case of syndrome of inappropriate secretion of ADH with adenocarcinoma of the prostate. Antidiuretic hormone activity was proven in only three cases including this case.

Adenocarcinoma↗

Ser-59 is the major phosphorylation site in alphaB-crystallin accumulated in the brains of patients with Alexander's disease.

The phosphorylation state of alphaB-crystallin accumulated in the brains of two patients with Alexander's disease (one infantile and one juvenile type) was determined by means of SDS-PAGE or isoelectric focusing of soluble and insoluble fractions of brain extracts and subsequent western blot analysis with specific antibodies against alphaB-crystallin and each of three phosphorylated serine residues. The level of mammalian small heat shock protein of 25-28 kDa (Hsp27) in the same fraction was also estimated by western blot analysis. The majority of alphaB-crystallin was detected in the insoluble fraction of brain homogenates and phosphorylation was preferentially observed at Ser-59 in both cases. A significant level of phosphorylation at Ser-45 but not Ser-19 was also detected. Hsp27 was found at considerable levels in the insoluble fractions. alphaB-crystallin and phosphorylated forms were detected in the cerebrospinal fluid of patient with the juvenile type. AlphaB-crystallin and phosphorylated forms were also detectable at considerable levels in the insoluble fraction of brain homogenates from patients with Alzheimer's disease and aged controls. The phosphorylation site was mostly at Ser-59 in all cases. Immunohistochemically, alphaB-crystallin was stained in Rosenthal fibers in brains of patients with Alexander's disease and their peripheral portions were immunostained with antibodies recognizing phosphorylated Ser-59. These results indicate that the major phosphorylation site in alphaB-crystallin in brains of patients with Alexander's disease or Alzheimer's disease as well as in aged controls is Ser-59.

Adult↗

Human cystinuria-related transporter: localization and functional characterization.

BACKGROUND: Cystinuria has been proposed to be an inherited defect of apical membrane transport systems for cystine and basic amino acids in renal proximal tubules. Although the mutations of the recently identified transporter BAT1/b(0,+)AT have been related to nontype I cystinuria, the function and localization of human BAT1 (hBAT1)/b(0,+)AT have not been well characterized. METHODS: The cDNA encoding hBAT1 was isolated from human kidney. Fluorescence in situ hybridization was performed to map the hBAT1 gene on human chromosomes. Tissue distribution and localization of expression were examined by Northern blot and immunohistochemical analyses. hBAT1 cDNA was transfected to COS-7 cells with rBAT cDNA, and the uptake and efflux of 14C-labeled amino acids were measured to determine the functional properties. The roles of protein kinase-dependent phosphorylation were investigated using inhibitors or activators of protein kinases. RESULTS: The hBAT1 gene was mapped to 19q12-13.1 on the human chromosome, which is the locus of nontype I cystinuria. hBAT1 message was expressed predominantly in kidney. hBAT1 protein was localized in the apical membrane of proximal tubules in human kidney. When expressed in COS-7 cells with a type II membrane glycoprotein rBAT (related to b(0,+)-amino acid transporter), hBAT1 exhibited the transport activity with the properties of amino acid transport system b(0,+), which transported cystine as well as basic and neutral amino acids presumably via a substrate exchange mechanism. BAT1-mediated transport was reduced by the protein kinase A activator and enhanced by the tyrosine kinase inhibitor. CONCLUSIONS: hBAT1 exhibited the properties expected for a transporter subserving the high-affinity cystine transport system in renal proximal tubules. The hBAT1 gene was mapped to the locus of nontype I cystinuria, confirming the involvement of hBAT1 in cystinuria.

ATP-Binding Cassette Transporters↗

Changes in nitric oxide synthesis and epileptic activity in the contralateral hippocampus of rats following intrahippocampal kainate injection.

PURPOSE: To investigate the effects of nitric oxide (NO) on seizure activity observed in brain areas that are remote from a primary epileptic focus. METHODS: Following an injection of kainate (concentration 1 mg/ml, volume 1 microl) in the rat hippocampus, we measured NO synthesis in the contralateral hippocampus and epileptic activity by electroencephalogram (EEG). The NO end products, nitrite and nitrate, were measured by in vivo microdialysis combined with an automated NO end-product analyzer and then used as indices of NO synthesis. We also assessed the effect of a specific inhibitor of neuronal NO synthase (NOS) on both the epileptic activity and NO synthesis in the contralateral hippocampus. For this assessment, we administered 7-nitroindazole (7-NI) (50 mg/kg) intraperitoneally 30 min before the kainate injection. RESULTS: Epileptic discharges in the contralateral hippocampus were frequently observed 90 min after unilateral hippocampus kainate injection. The duration of these discharges gradually increased until 240 min after the kainate injection. The NO end-product levels increased immediately after kainate injection and continued to increase gradually throughout the experiments, to a maximum of 213% of the base level. This elevation of NO end products was followed by epileptic discharges. Both the seizure activity and the elevation of contralateral hippocampus NO end-product levels were markedly attenuated in the animals that received 7-NI. CONCLUSIONS: The results suggest that remote seizure activity caused by the transneuronal spread of kainate-induced discharges may be related to NO derived from neuronal NOS.

Animals↗

Iron deposition in renal biopsy specimens from patients with kidney diseases.

This study was performed to investigate the correlation between clinical parameters and grading of iron deposition in renal biopsy specimens from 102 patients with various kidney diseases. Iron deposition in renal tissues was detected by Berlin blue staining. The extent of iron staining was semiquantitatively graded as negative (Fe(-)), grade 0, or positive (Fe(+)), including faint, grade 1; moderate, grade 2; or severe, grade 3, by light microscopy. Thirty-four of 102 patients (33%) showed positive iron staining. Fe(+) patients had various renal diseases, mainly consisting of 12 patients with immunoglobulin A nephropathy and 5 patients with benign nephrosclerosis. Mean arterial pressure (MAP), serum creatinine (sCr) levels, incidence of hematuria, and urinary N-acetylbeta-D-glucosaminidase (u-NAG) levels in Fe(+) patients were significantly greater than those in Fe(-) patients, and u-NAG levels correlated positively with the extent of iron deposition. Study patients were tentatively divided into two groups according to the extent of iron deposition: group A, patients with grades 2 and 3 staining, and group B, patients with grades 0 and 1 staining. In group A, MAP, sCr level, urinary protein excretion, and the incidence of hematuria were significantly greater than in group B. Our results suggest that the amount of iron deposition in renal tissue may contribute to the progression of chronic renal disease and may be an early and sensitive indicator of renal damage in certain renal diseases.

Acetylglucosaminidase↗

Destruction of acetabular bone caused by early failure of a constrained acetabular component.

Use of a constrained acetabular component is 1 option for the treatment of dislocation after total hip arthroplasty. We report a case of a constrained acetabular component that resulted in postoperative early fixation loss and required revision 12 days after primary surgery. The superoposterior wall of the acetabulum was destroyed by the migrated acetabular component. Sharp ends of screws with a metal shell may have plowed up acetabular bone gradually after fixation loss of the component. This failure illustrates the potential risk of using a constrained acetabular component for total hip arthroplasty.

Acetabulum↗

The sphericity of the bearing surface in total hip arthroplasty.

This study evaluated the sphericity of bearing surfaces in total hip arthroplasty. The out-of-roundness of metal femoral heads, the inner surface of polyethylene liners, and commercially available ball bearings was measured. The hip prostheses were obtained directly from the manufacturers. The sphericity of the bearing surfaces was significantly inferior to that of the ball bearings. The sphericity of the femoral head on the sagittal plane was inferior to that on the transverse plane. Several significant differences were found among different manufacturers. The sphericity of the femoral head on the sagittal plane and that of polyethylene significantly improved in 1999 and 2000 compared with those in 1995. Further improvement is desirable, however, because good sphericity is expected to prolong the functional performance of the prosthesis after total hip arthroplasty.

Analysis of Variance↗

Functional magnetic resonance imaging-controlled neuronavigator-guided brain surgery: a case report.

The effectiveness of functional magnetic resonance imaging (f-MRI)-controlled and navigator-guided brain surgery for a patient with a recurrent astrocytoma is demonstrated. Preoperative f-MRI was performed in order to identify the motor area and ensure that the tumour was in the left prefrontal area. A more aggressive operation was planned for the recurrent tumour. The f-MRI data were input to the MKM navigation system and during the operation the contours of the tumour and motor area were visualised b y the microscope of the navigation system. The tumour and surrounding gliotic brain tissue were removed completely. The diagnosis was a grade III astrocytoma. The combination of the navigation system and f-MRI was useful for preoperative design of the surgical strategy, and tumour orientation during the operation, enabling aggressive surgery to be performed without functional deficits ensuing.

Adult↗

Detection of craniospinal dissemination of intracranial germ cell tumours based on serum and cerebrospinal fluid levels of tumour markers.

Nineteen intracranial germ cell tumours treated during the past 11 years were evaluated retrospectively. The tumours were classified into three groups according to the level of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) in serum and cerebrospinal fluid, and the optimal treatment for each group was determined. Group A consisted of patients with normal titres of AFP and HCG, group B of patients with relatively high titres (< 10 times normal), and group C comprised patients with higher titres ( 10 times normal levels). In group A, an appropriate field and dose of irradiation was necessary to prevent craniospinal dissemination. In group B, none of four patients who underwent total or subtotal resection of the tumour had craniospinal disseminatio n or tumour recurrence, whereas dissemination occurred in four further patients, including two who had received radiochemotherapy only, and two who had undergone partial resection of the tumour. While patients in group C had dissemination at the time of initial diagnosis, most patients in group B developed dissemination more than 10 months after initial treatment, suggesting that the type of treatment received as first line therapy is important in patients in this group. The prognosis of patients in group C, however, was unaffected by the priority given to either surgery, radiation or chemotherapy as first line treatment. Craniospinal dissemination can be prevented in patients with germ cell tumours who have a relative increase in levels of AFP and HCG by aggressive removal of the tumours as first line therapy, regardless of the type of adjuvant therapy given.

Adolescent↗