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Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 559 records · Page 31Linked to original sources

Adjuvant regional chemotherapy after hepatic resection for colorectal metastases.

BACKGROUND: This study explored the possibility of achieving a better survival rate and reduced recurrence in the remaining liver in patients with colorectal hepatic metastases undergoing hepatic resection. Adjuvant postoperative regional chemotherapy was administered via the hepatic artery or the portal vein. METHODS: A retrospective study was performed on 174 patients after hepatic resection for colorectal metastases. These comprised 78 patients who had hepatic artery infusion (HAI) chemotherapy (HAI group), 30 who had portal vein infusion (PVI) chemotherapy (PVI group) and 66 who had no regional chemotherapy (resection alone group). The three groups were compared with one another in terms of complications, survival rate and patterns of recurrence. RESULTS: Severe complications did not occur at any point during adjuvant HAI or PVI chemotherapy. The 5-year disease-free survival rate of patients in the HAI, PVI and resection alone groups were 35, 13 and 9 per cent respectively, including six hospital deaths. Patients in the HAI group showed significantly improved recurrence rates in the remaining liver compared with the resection alone group (P = 0.03), and more prolonged disease-free and overall survival than those in the PVI (P = 0.01 and P = 0.02 respectively) and resection alone (P = 0.0001 and P = 0.0006 respectively) groups. CONCLUSION: This study suggests that adjuvant HAI chemotherapy after hepatic resection may have therapeutic potential for improved management of patients with colorectal metastases.

Aclarubicin↗

Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with extensive tumour thrombus through the hepatic vein.

BACKGROUND AND AIMS: Advanced hepatocellular carcinoma (HCC) with extensive tumour growth through the hepatic vein still has an extremely poor prognosis, even after cancer chemotherapy and/or transarterial embolization. Although aggressive surgical treatments using extracorporeal circulation and liver transplantation have been performed by some authors, the reported results were still unsatisfactory. In this study, we report the favourable result of hepatic artery chemoembolization and subsequent surgical resection in three patients with advanced HCC with extensive tumour thrombus through the hepatic vein. METHODS AND RESULTS: Three irresectable patients with HCC with extensive tumour thrombus through the hepatic vein underwent hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam. After the reduction of tumour extent with hepatic artery chemoembolization, two of the three patients underwent surgical resection. These two patients are still alive at 59 and 21 postoperative months, respectively. In the other case, the extent of the tumour and functional reserve of the liver prevented us from performing surgical resection, but the patient is doing well 62 months after the initial treatment. CONCLUSIONS: Hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam might be an effective treatment for irresectable advanced HCC with extensive tumour thrombus into the inferior vena cava or the right atrium through the hepatic vein. Radical surgical resection might be applicable for selected patients without high surgical risk after reducing tumour extent by hepatic artery chemoembolization.

Aclarubicin↗

Thymidine phosphorylase expression in human colorectal mucosa, adenoma and carcinoma: role of p53 expression.

The enzyme, thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), which acts as a potent angiogenic factor. The present study immunohistochemically examined the expression of dThdPase in human colorectal mucosa, adenomas and carcinomas, as well as six cultured colorectal carcinoma cell lines, in terms of intratumoral microvessel density (IMVD) and P53 expression. Thymidine phosphorylase was observed in lymphocytes, fibroblasts and macrophages, as well as smooth muscle cells and Schwann cells in the peripheral nerve fibers. The dThdPase-positive stromal cells apparently outnumbered the normal epithelial cells, adenoma and carcinoma cells with dThdPase. Weak but obvious cytoplasmic immunoreactivity was noted in a few normal colonic epithelia, predominantly the upper surface area, while a few adenoma cells showed weak nuclear immunostaining for dThdPase in six (24%) of the 25 colonic adenomas. Expression of dThdPase was noted in 33 (73.3%) of the 45 Dukes A and B, 14 (51.9%) of the 27 Dukes C and 14 (56.0%) of the 25 Dukes D carcinomas. The mean IMVD was 84.0 +/- 26.2 in the 36 dThdPase-negative carcinomas and 97.9 +/- 31.6 in the 61 dThdPase-positive carcinomas, the value being significantly higher in the latter group (P < 0.05). The frequency of dThdPase expression was significantly lower in the P53-negative carcinomas than in the positive carcinomas (P < 0.05). Western blot analysis showed the highest expression of dThdPase in LoVo carrying the wild-type p53 gene, followed by Colo201, Colo320, DLD-11 and WiDr carrying the mutated gene. These results indicate that: (i) the main source of dThdPase is stromal cells, including lymphocytes and macrophages in both colorectal normal and carcinoma tissues; (ii) dThdPase may take part in the induction of intratumoral microvessels, regardless of tumor stage; and (iii) expression might be modulated by not only P53 but also other molecules.

Adenoma↗

Evaluation of functional bladder capacity in Japanese children.

BACKGROUND: Functional bladder capacity is a very important factor in the diagnosis of children with voiding disorders. Because Japanese children are thought to have somewhat smaller functional bladder capacity compared with Western children, the convenient formula (so-called Koff formula) bladder capacity (in ounces) = age (in years)+ 2 is not suitable for use in Japanese children. METHODS: We measured the bladder capacities of 131 Japanese children aged 5-15 years without clinical voiding pattern abnormalities to develop a practical guideline for the prediction of normal bladder capacity for age. RESULTS: An approximate formula relates age and bladder capacity as: bladder capacity (mL) = 25 x (age (years) + 2). CONCLUSIONS: The formula presented is thought to be a useful guide for the diagnosis of small, normal or large bladder capacity and offers information on voiding disorders in Japanese children.

Adolescent↗

Pattern of progression and survival in hormonally treated metastatic prostate cancer.

BACKGROUND: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. METHODS: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM ) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. RESULTS: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. CONCLUSIONS: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.

Aged↗

External beam radiation monotherapy for prostate cancer.

BACKGROUND: To clarify the implications and limitations of external beam radiation monotherapy for localized prostate cancer, the long-term outcomes and prognostic factors were investigated. METHODS: Between 1976 and 1994, 91 patients with untreated prostate cancer were treated with external beam radiation therapy alone. Thirty-two were classified as T1b, eight were T2a, four were T2b and 47 were T3. Pelvic lymphadenectomy was carried out in 69 cases; 57 were staged as pN0, eight were pN1, four were pN2 and 22 were pNX. Linac X-rays were used in 55 cases, fast neutron in 15 and a combination of the two in 21. No other therapy was given until relapse and when relapse was evident endocrine therapy was started. RESULTS: The observation period ranged from 3 to 206 months with a median of 78 months. Local control rate and disease-free, cause-specific and overall survivals at 10 years were 74.0, 49.6, 74.2 and 39.2%, respectively. By univariate analysis, T category, pN category and histologic grade were significant prognostic indicators for disease-free survival. Multivariate analysis revealed that T category was an independent prognostic factor. In T2b and T3 diseases, pN0/1 patients demonstrated significantly better disease-free survival than pNX. CONCLUSIONS: A favorable long-term outcome was achieved by external beam radiation monotherapy in patients with minimally extended prostate cancer (T1b and T2a). For locally advanced disease (T2b and T3), staging pelvic lymphadenectomy would be useful for the selection of patients.

Adenocarcinoma↗

Radiotherapy for local progression in patients with hormone-refractory prostate cancer.

PURPOSE: The aim of the present study was to investigate the effect of radiotherapy on the local progression of hormone-refractory prostate cancer. METHODS: From 1986 to 1995, 38 patients were diagnosed with local progression without distant progression after hormonal therapy at Chiba University Hospital. Eleven cases were treated with irradiation for local progression. External beam irradiation was delivered to the prostate at a dose of 50-66.6 Gy. RESULTS: In patients treated with radiotherapy, the duration from initial treatment to local recurrence was 6-80 months (mean +/- SD: 33.9 +/- 22.9 months). The follow-up period after irradiation was 7-64 months (mean +/- SD; 25.4 +/- 18.8 months). Three and 5 year cause-specific survival rates from radiotherapy were 46.2 and 23.1%, respectively. Radiotherapy had a marked effect on symptoms associated with local progression and no patients suffered from the symptoms after the radiotherapy. Complications of radiotherapy were limited. CONCLUSIONS: In patients with hormone refractory local progression without distant progression, low morbidity, low mortality radiotherapy offers a variable therapy to other palliative treatments because radiotherapy is able to control local symptoms for a long period of time.

Aged↗

Metanephric adenoma of the kidney.

BACKGROUND: Metanephric adenoma is a rare renal neoplasm that is histologically and clinically unique. We found this neoplasm in a 62-year-old female, whose renal tumor was incidentally detected on abdominal ultrasound examination. METHODS/RESULTS: Ultrasound, computed tomography and magnetic resonance imaging were compatible with those of renal cell carcinoma. With a diagnosis of renal cell carcinoma, right partial nephrectomy was performed. This tumor showed histologic similarity to developing metanephric tubular epithelium. It was composed of uniformly small epithelial cells, which formed tubules. CONCLUSIONS: The patient has been well and healthy for 20 months after surgery. The unique features of metanephric adenoma should be clinically and pathologically recognized because of its invariably benign course.

Adenoma↗

Prognosis of patients with T4 prostate carcinoma.

BACKGROUND: The clinical course of patients with T4 prostate carcinoma was examined in order to consider whether there are alternative treatment options besides androgen ablation therapy. METHODS: From 1986 to 1995 at Chiba University Hospital, there were 22 cases of T4 prostate carcinoma. Sixteen cases had no bone metastasis at initial diagnosis. Tumor grade and response of prostate-specific antigen (PSA) to endocrine treatment were evaluated in these 16 cases. RESULTS: Four patients had moderately differentiated and 12 had poorly differentiated adenocarcinoma. For initial treatment, all patients received endocrine therapy. Anti-androgen therapy was effective in 15 cases and the 5 year cause-specific and progression-free survival rates were 72.1 and 38.1%, respectively. Patients with moderately differentiated tumors tended to have a longer disease-free period than those with poorly differentiated tumors (P = 0.047). CONCLUSIONS: Endocrine therapy was effective in patients with T4 tumors. It was suggested that aggressive local treatment (i.e. radiotherapy) in combination with endocrine therapy may be considered if the patients had no distant metastases and had a long life expectancy.

Adenocarcinoma↗

Responses of heat shock proteins hsp27, alphaB-crystallin, and hsp70 in rat brain after kainic acid-induced seizure activity.

We determined the changes in the levels of the mammalian small heat shock protein of 25-28 kDa (hsp27) and the hsp alphaB-crystallin in various regions of rat brain after kainic acid-induced seizure activity by means of specific immunoassays. The levels of hsp27 in the hippocampus and entorhinal cortex were markedly increased and reached a maximum (1.5-2 microg/mg of protein) 2-4 days after the seizure. The levels of hsp27 in these regions were considerably high even 10 days after the seizure. A marked increase in levels of mRNA for hsp27 was also observed in the hippocampus of rats 1-2 days after the seizure. A severalfold increase in the levels of alphaB-crystallin was observed in the hippocampus and entorhinal cortex of rats 2 days after the seizure. However, the maximum levels were <50 ng/mg of protein. The levels of protein sulfhydryl group and glutathione were significantly reduced in the hippocampus of rats at 24 h after the seizure, which might have enhanced the expressions of hsp27 and alphaB-crystallin. The expression of inducible mammalian hsp of 70 kDa (hsp70) was also enhanced in the hippocampus of rats after the seizure, as detected by western and northern blotting analyses. Immunohistochemically, an intensive staining of hsp27 was observed in both glial cells and neurons in the hippocampus, piriform cortex, and entorhinal cortex of rats with kainic acid-induced seizure. However, in the cerebellum, where the receptors for kainic acid are also rich, hsp27 was barely induced in the same rats. This might be due to high levels of the cerebellar calcium-binding proteins parvalbumin and 28-kDa calbindin-D, which might have a protective effect against the kainic acid-inducible damage.

Animals↗

Cell cycle inhibitors (p27Kip1 and p21CIP1) cause hypertrophy in LLC-PK1 cells.

BACKGROUND: Angiotensin II has been reported to induce renal tubular hypertrophy, but the mechanisms of this hypertrophy are not well known. We evaluated the roles of cyclin-dependent kinase (CDK) inhibitors in renal tubular hypertrophy. METHODS: To elucidate whether CDK inhibitors cause renal tubular hypertrophy, we produced adenovirus vectors containing coding sequences of the CDK inhibitors p27Kip1 (AxCAp27), p21CIP1 (AxCAp21), and p16INK4 (AxCAp16), and we investigated the effect of these gene transfers on epidermal growth factor (EGF)-induced proliferation in LLC-PK1 cells. We evaluated the cell cycle and hypertrophy by measurements of the [3H]-leucine and [3H]-thymidine incorporation, the protein:DNA ratio, flow cytometry, and CDK4 and CDK2 kinase assays. RESULTS: AxCAp27 and AxCAp21 caused significant increases in [3H]-leucine incorporation and the protein:DNA ratio but did not change the [3H]-thymidine incorporation. Conversely, AxCAp16 inhibited EGF-stimulated [3H]-thymidine incorporation but did not change the [3H]-leucine incorporation. AxCAp27, AxCAp21, and AxCAp16 all inhibited EGF-stimulated CDK4 kinase activity (to 15.6, 14.1, and 21.9% of control, respectively). Forward light-scatter analysis demonstrated that AxCAp27 and AxCAp21 increased the cell size but that AxCAp16 effected no change in cell size. CONCLUSION: These findings suggest that p27Kip1 and p21CIP1 may play an important role in hypertrophy of renal tubule cells by reducing pRb phosphorylation. On the other hand, p16INK4 was not found to cause hypertrophic changes in EGF-treated LLC-PK1 cells.

Adenoviridae↗

Profile of circulating levels of interleukin-1 receptor antagonist and interleukin-6 in colorectal cancer patients.

BACKGROUND: Circulating levels of pro-inflammatory cytokines are associated with the disease status of cancer patients. We investigated the profile of circulating levels of interleukin (IL)-6 and its antagonist in colorectal cancer patients. METHODS: Serum concentrations of interkeukin-1 receptor antagonist (IL-1ra) and IL-6 in 80 colorectal cancer patients and tissue concentrations of IL-1ra and IL-6 in 60 primary colorectal cancers and normal colonic mucosas were determined. The serum concentration of immunosuppressive acidic protein (IAP) was also determined. RESULTS: The serum concentrations of IL-1ra and IL-6 in the patients were significantly higher than those in the controls. The serum concentration of IL-1ra in the patients was associated with clinicopathologic factors including tumor size, liver metastasis, lymph node metastasis, vessel involvement, or serum level of carcinoembryonic antigen. Although the serum IL-1ra level increased in keeping with the increase of serum IL-6, the net balance between IL-1ra and IL-6 was significantly lower than that in the controls. The serum IL-1ra to IL-6 ratio decreased in association with the patient's age, the rate of loss of body weight and the serum level of IAP. Although the serum level of IL-6 correlated with the IL-6 concentration in the cancer tissue, the serum level of IL-1ra did not correlate with the IL-1ra concentration in this tissue. CONCLUSIONS: Serum IL-1ra, induced systemically by a marked activation of the IL-6 network in cancer tissue, may be a potent index that evaluates disease progression of colorectal carcinoma. Decreased serum IL-1ra to IL-6 ratio may reflect the deterioration of the systemic anti-inflammatory response that is associated with aging, tumor-related malnutrition, or immunosuppression.

Adult↗

Clinical features and surgical outcome in patients with asymptomatic meningiomas.

The clinical features and surgical outcomes of 108 patients with an asymptomatic meningioma were studied in patients who were admitted to any neurosurgical institute in the Yamaguchi prefecture in the southern part of Japan between 1986 and 1995. Their clinical characteristics were compared with 414 patients with symptomatic meningiomas over the same period. Asymptomatic patients were older than symptomatic patients, although not significantly so. Tumours were located in the right cerebral hemisphere (46 versus 31%, p = 0.003) more frequently in asymptomatic than in symptomatic patients. Four of 75 surgically-treated asymptomatic patients had a poor outcome, including two with severe disability and two deaths. Such outcomes did not differ significantly in frequency compared with those of 356 surgically-treated symptomatic patients which included 11 with severe disability and 11 deaths. Postoperative morbidity and mortality in asymptomatic patients are not negligible. Poor outcome was associated with more advanced age and with midline tumours.

Adolescent↗

Hydrogen peroxide-induced apoptosis in HL-60 cells requires caspase-3 activation.

Apoptosis has been associated with oxidative stress in biological systems. Caspases have been considered to play a pivotal role in the execution phase of apoptosis. However, which caspases function as executioners in reactive oxygen species (ROS)-induced apoptosis is not known. The present study was performed to identify the major caspases acting in ROS-induced apoptosis. Treatment of HL-60 cells with 50 microM hydrogen peroxide (H2O2) for 4 h induced the morphological changes such as condensed and/or fragmented nuclei, increase in caspase-3 subfamily protease activities, reduction of the procaspase-3 and a DNA fragmentation. To determine the role of caspases in H2O2-induced apoptosis, caspase inhibitors, acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-cmk), acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) and acetyl-Val-Glu-Ile-Asp-aldehyde (Ac-VEID-CHO), selective for caspase-1 subfamily, caspase-3 subfamily and caspase-6, respectively, were loaded into the cells using an osmotic lysis of pinosomes method. Of these caspase inhibitors, only Ac-DEVD-CHO completely blocked morphological changes, caspase-3 subfamily protease activation and DNA ladder formation in H2O2-treated HL-60 cells. This inhibitory effect was dose-dependent. These results suggest that caspase-3, but not caspase-1 is required for commitment to ROS-triggered apoptosis.

Amino Acid Chloromethyl Ketones↗

Anti-tumor polysaccharide from the mycelium of liquid-cultured Agaricus blazei mill.

Anti-tumor active polysaccharide against Sarcoma 180 was isolated by DEAE-Sepharose CL-6B and Sepharose 4B column chromatography from the hot-water soluble fraction of the mycelium of liquid-cultured Agaricus blazei mill. This polysaccharide did not react with antibodies of anti-tumor polysaccharides such as lentinan, gliforan, and FIII-2-b which is one of anti-tumor polysaccharides from Agaricus blazei. Moreover, the analyses of 13C-NMR and GC-MS suggested that this polysaccharide was preliminarily glucomannan with a main chain of beta-1,2-linked D-mannopyranosyl residues and beta-D-glucopyranosyl-3-O-beta-D-glucopyranosyl residues as a side chain. This polysaccharide was completely different from the anti-tumor polysaccharide from fruiting body of Agaricus blazei, beta-1,6-glucan.

Agaricus↗

Effects of mild hypothermia on the cortical release of excitatory amino acids and nitric oxide synthesis following hypoxia.

Studies concerning neurotransmitter release following cerebral hypoxia are scarce, and the effects of mild hypothermia on hypoxia-induced neurotransmitter release are unknown. The purpose of this study was to investigate changes in excitatory amino acid (EAA) concentrations and nitric oxide (NO) synthesis following cerebral hypoxia in rats, and the effects of mild hypothermia on both. Cerebral hypoxia (PaO2, 30-40 mm Hg) was induced in each rat for 60 min. Cerebral blood flow (CBF) was measured by laser-Doppler flowmetry, and the extracellular concentrations of EAAs and NO end-products (nitrite and nitrate) were measured by in vivo microdialysis in normothermic (37 degrees C) and hypothermic (32 degrees C) rats. In both groups, CBF showed modest increases during hypoxia and returned to baseline during reoxygenation. The EAA levels of the normothermic rats increased markedly after hypoxia induction and returned to baseline levels during reoxygenation. Hypothermia abolished these increases completely. The NO end-product levels under normothermic conditions declined slightly during hypoxia, and then increased transiently during reoxygenation. Hypothermia appeared to attenuate the NO end-product level and to delay the peak. When the relationship between glutamate and the NO end-products was examined on an individual-animal basis, glutamate release did not parallel NO synthesis. The results indicate that hypothermic neuroprotection during cerebral hypoxia may be attributable to the amelioration of damage by reduction of presynaptic EAA release. Although it is unclear from the present results alone whether endothelial NO synthase, neuronal NO synthase or both caused the elevation of the NO end-products during reoxygenation, it is possible that the attenuation and delay of the peak of the NO end-product level plays a role in protection from NO-induced neuronal damage.

Animals↗

Temporal and spatial profile of apoptotic cell death in transient intracerebral mass lesion of the rat.

Apoptosis is involved in the pathogenesis of cerebral ischemia. Previous studies have confirmed that the brain surrounding an intracerebral hematoma develops ischemia. We investigated the number and distribution of cells exhibiting DNA fragmentation with apoptotic morphology in the transient intracerebral mass lesion to determine whether apoptosis contributed to the lesion progress after intracerebral hemorrhage (ICH). Transient intracerebral mass was created by inflation of a microballoon for 10 min (group A) or 2 h (group B) in the caudoputamen in rats, and brains were examined 1, 3, 6, 24, and 48 h after microballoon deflation. The lesion volume was calculated using parallel coronal sections with cresyl violet staining. Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine (dUTP)-biotin nick end labeling (TUNEL) was used to detect cells undergoing DNA fragmentation. Immunohistochemistry for Fas antigen was also done to ascertain molecular mechanisms of apoptosis. Histological examination of hematoxylin and eosin-stained sections showed the typical appearance of neuronal necrosis in the caudoputaminal lesion. Lesion volume in the caudoputamen gradually increased as time advanced from 1 to 48 h. Cells stained heavily by TUNEL with apoptotic morphology were detected in the lesion, but not in the inner boundary zone of the lesion. The number of these cells significantly increased from 6 to 24 h in each experimental group (p < 0.05). The cells with positive immunoreactivity for Fas antigen was prominently observed in the lesion at 6 h. The distribution of apoptotic cells and the rapid increase in the number of apoptotic cells after 24 h propose that apoptotic cell death may contribute to lesion core formation but not to gradual development of the lesion.

Analysis of Variance↗