Search PubMed⌕ Search

Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 1,477 records · Page 82Linked to original sources
PubMedDate not supplied

Heterogeneity of drug susceptibility of mouse active anaphylactic shock.

To determine the main mediators for mouse anaphylactic shock, the suppression of active anaphylactic shock by cyproheptadine, an antagonist of histamine/serotonin, and CV-6209, an antagonist of platelet-activating factor (PAF), was systematically evaluated using various mouse strains. The suppression was quite heterogeneic depending on the mouse strain and method for sensitization. When sensitization was done with bovine serum albumin (BSA) plus Bordetella pertussis organisms, anaphylactic shock in C57BL/6N mice was suppressed by cyproheptadine but not by CV-6209. In contrast, shock in C3H/HeN and WBB6F1-W/Wv mice was suppressed by CV-6209 but not by cyproheptadine. Shock in BALB/c mice was suppressed by both agents but that in WBB6F1-(+)/+ mice was not at all by either one. DS and BDF1 mice showed differences due to the length of the sensitization period; shock was not suppressed by cyproheptadine with a shorter sensitization (9 to 11 days) but clearly suppressed with prolonged sensitization of 14 to 15 days. Shock in DS, WBB6F1-(+)/+ and BDF1 mice, which was not suppressed by either agent alone, was strongly suppressed by the combination of the two agents. In animals which had been sensitized with BSA emulsified with Freund's complete adjuvant (FCA) and given DL-propranolol as a shock potentiator, a similar pattern of drug susceptibility as that in the pertussis-vaccinated animals was obtained in general, although a discrepancy was seen with regard to the suppression of CV-6209 in C3H/HeN and BDF1 mice. Synergistic suppression by CV-6209 and cyproheptadine was also very clear with the WBB6F1-(+)/+ mice sensitized using FCA. In addition, results quite similar to those with cyproheptadine were obtained with the other two antihistamines, triprolidine almost devoid of antiserotonin activity and oxatomide, in testing with BDF1 mice sensitized using Bordetella pertussis organisms. From these findings, the conclusion is that histamine and PAF play major roles solely or in combination in mouse active anaphylactic shock.

Anaphylaxis↗
PubMedDate not supplied

High-dose ifosfamide, carboplatin and etoposide with autologous peripheral blood progenitor cell transplantation for small-cell lung cancer.

BACKGROUND: We investigated the feasibility and efficacy of high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide (HD-ICE) facilitated by autologous peripheral blood progenitor cell transplantation (ABPCT) for the treatment of small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eleven patients aged 44 to 63 years old (5 with extensive disease [ED] and 6 with limited disease [LD]) were entered into this study. Induction chemotherapy consisted of 3 to 4 cycles of cisplatin and irinotecan for ED-SCLC, and cisplatin and etoposide for LD-SCLC. Patients with LD-SCLC received concurrent chest radiotherapy along with the first cycle of induction chemotherapy. After induction therapy, peripheral blood progenitor cells (PBPC) were collected following G-CSF administration during a recovery phase from high-dose etoposide (1,500 mg/m2). Eight patients (4 with ED and 4 with LD) with adequate organ function were treated with HD-ICE (15 g/m2 ifosfamide, 1,200 mg/m2 carboplatin and 1,500 mg/m2 etoposide) followed by ABPCT. RESULTS: Hematologic recovery was rapid and non-hematological toxicities were acceptable without treatment-related mortality. In ED-SCLC, all of the 4 patients achieved complete response (CR) or near CR but developed a relapse of the disease. In LD-SCLC, 2 of 4 patients with LD-SCLC are alive in continuous CR for 18 and 21 months after the beginning of induction therapy. CONCLUSIONS: Despite a limited number of patients and short follow-up time, these preliminary results indicate that marrow-ablative therapy (HD-ICE) supported by ABPCT is feasible in the treatment of elderly patients with LD- and ED-SCLC.

Adult↗
PubMedDate not supplied

Effect of docetaxel with cisplatin or vinorelbine on lung cancer cell lines.

Docetaxel shows substantial activity against lung cancer. To find the optimal drug combination for docetaxel, we evaluated the effects of cisplatin, etoposide, mitomycin C, irinotecan, vindesine, and vinorelbine using three human lung cancer cell lines, ABC-1, EBC-1, and SBC-3. Drug cytotoxicity was determined by MTT assay. Tumor cells were incubated for 96 hours in the presence of docetaxel and each of the test drugs stated above. The combined drug interaction was evaluated by median-effect plot analysis and improved IC50-isobologram analysis. Both methods showed strong antagonism (subadditive or protective effect) between docetaxel and etoposide when tested on ABC-1 and EBC-1 cells. Docetaxel and cisplatin displayed additive effects on all cell lines tested, when evaluated by improved IC50-isobologram analysis. The combination of docetaxel and vinorelbine exerted synergistic effect on the growth inhibition of SBC-3 cells, which showed a wide range of fractional cytotoxicity when analyzed by median-effect plot and supraadditive when analyzed by improved IC50-isobologram. These observations suggest a possibility that docetaxel can be used in combination with vinorelbine or cisplatin in the treatment of lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Local recurrence of breast cancer demonstrated on 99mTc-MIBI scintigraphy.

We present a postmastectomy patient in whom a mass was palpated in the chest wall. It appeared to be difficult to determine whether the chest wall mass was local recurrence of breast cancer or granulation induced by mastectomy on computed tomography (CT). The mass was successfully demonstrated on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy as an area of increased accumulation, and was considered to be a recurrent tumor. Surgical resection was performed, and the mass was histopathologically proven to be recurrence. 99mTc-MIBI scintigraphy may contribute to the detection of local recurrence or distant metastasis in addition to the diagnosis of primary breast cancer and axillary metastasis.

Breast Neoplasms↗
PubMedDate not supplied

In vitro evaluation of antimicrotubule agents in human small-cell lung cancer cell lines.

BACKGROUND: The improvement of treatment outcome of small-cell lung cancer (SCLC), and search for new effective drugs and to overcome drug-resistance are essential. MATERIALS AND METHODS: We evaluated the cytotoxicity of antimicrotubule agents to seven human SCLC cell lines consisting of one cell line (SBC-3) established from a previously untreated patient as a representative of drug-sensitive cell line, three cell lines (SBC-2, SBC-4, and -7) derived from treated patients as representatives of intrinsic drug-resistance cell lines, and three drug-resistant sublines (SBC-3/ADM, SBC-3/ETP, and SBC-3/CDDP) selected by continuous exposure of the SBC-3 cell line to increasing concentrations of doxorubicin, etoposide, or cisplatin as representatives of acquired drug-resistant cell lines. RESULTS: IC50 values for SBC-2, -3, -4, and -7 cells of antimicrotubule agents were markedly lower than those of doxorubicin, etoposide, and cisplatin. Both SBC-3/ADM and SBC-3/ETP subline were highly resistant to paclitaxel, docetaxel, vinorelbine, vincristine, vindesine, and vinblastine. However, an SBC-3/ADM subline was not fully cross-resistant to rhizoxin, and an SBC-3/ETP subline was as sensitive to rhizoxin as an SBC-3 cell line. A cisplatin-resistant subline, SBC-3/CDDP, showed no cross-resistance to the antimicrotubule agents. CONCLUSION: These results suggest that antimicrotubule agents are useful for SCLC, and rhizoxin may be particularly effective in the salvage treatment of refractory or relapsed patients.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Experimental and clinical studies on liver regeneration following transcatheter portal embolization.

BACKGROUND/AIMS: We studied compensatory hypertrophy following transcatheter portal embolization experimentally in dogs and clinically under the condition of cholestasis. METHODOLOGY: Experimental study: Sixteen dogs were used for this study. Transcatheter portal embolization was performed in the left lobes (70% of the total liver) using Gelfoam powder in dogs with 2-week obstructive jaundice. Liver weight, liver blood flow and the intracellular adenosine triphosphate content of isolated hepatocytes were measured after transcatheter portal embolization. Clinical Study: transcatheter portal embolization of the right portal branch was performed in 13 patients with cancer of the biliary tract and 3 patients with hepatocellular carcinoma before (extended) right lobectomy, using Gelfoam powder and thrombin. Six patients who had a total bilirubin level > 5 mg/dLunderwent a percutaneous transhepatic biliary drainage before transcatheter portal embolization. Liver function tests, a volumetric study with computed tomography and immunohistochemical staining for profilerating cell nuclear antigen and apoptosis in the resected livers were performed. RESULTS: Experimental study: The weight ratio of the non-embolized lobes to the total liver, 2 weeks after transcatheter portal embolization in the dogs with jaundice, was significantly lower than that of the normal dogs with transcatheter portal embolization (40.5 +/- 4.5% vs. 47.6 +/- 3.2%), but significantly larger than that of the dogs without transcatheter portal embolization. The cellular adenosine triphosphate content and tissue blood flow in the embolized lobes were significantly lower than those in the nonembolized lobes in the normal and cholestatic livers. Clinical study: The postoperative course in all patients was uneventful, with no serious complication or liver dysfunction. Extended right lobectomy with caudate lobectomy was equivalent to 65% before transcatheter portal embolization and to 56% after, transcatheter portal embolization owing to compensatory hypertrophy of the left lobe. However, there was no significant difference in liver volume in the patients with or without obstructive jaundice. Apoptosis was observed in the embolized lobe. CONCLUSIONS: Preoperative transcatheter portal embolization with percutaneous transhepatic biliary drainage for the purpose of liver regeneration would be useful for treating extended hepatectomy with obstructive jaundice.

Animals↗
PubMedDate not supplied

Detection of occult tumor cells in peripheral blood from patients with small cell lung cancer by reverse transcriptase-polymerase chain reaction.

The reverse transcriptase-polymerase chain reaction (RT-PCR) of tumor-specific or -associated genes is a sensitive assay for detecting a minimal number of tumor cells in peripheral blood (PB) or bone marrow (BM). In this study, we determined whether mRNA of bombesin receptors is detectable in PB or peripheral blood progenitor cell (PBPC) samples from patients with small cell lung cancer. Among three bombesin-like peptide receptors, we used the neuromedin B receptor (NMB-R) gene as a target, because of the most frequent expression on SCLC cell lines. The lower limit of detection was one tumor cell in one million normal PB cells and there was no detection in normal PB or BM cells unlike a cytokeratin 19 gene. The NMB-R gene was detected in 14 (31.8%) of 44 PB samples from patients with SCLC at diagnosis and 2 (15.4%) of 13 samples of PBPC collected during a recovery phase after chemotherapy followed by administration of G-CSF (filgrastim). At diagnosis, patients whose PB was positive for the NMB-R gene had a significantly shorter survival than those who were negative. Our observation suggests that this assay may be useful in diagnosing metastatic disease and monitoring minimal residual disease in patients with SCLC.

Aged↗
PubMedDate not supplied

A case of jugular foramen chordoma with extension to the neck: CT and MR findings.

We describe a case of jugular foramen chordoma with extracranial extension into the carotid, parapharyngeal, and perivertebral spaces through the jugular foramen. Although this type of extension is unusual, the differential diagnosis of head and neck tumors includes unusual extension of chordoma as well as extension of meningioma and neurinoma from the posterior skull base.

Aged↗
PubMedDate not supplied

Successful treatment with concurrent chemoradiotherapy followed by surgery for a patient with thymic adenocarcinoma.

Most neoplasms arising from the thymic epithelium are considered to be 'thymomas', which are composed of cytologically benign, neoplastic epithelial cells and nonneoplastic lymphocytes. In contrast, thymic epithelial neoplasms displaying cytologically malignant features have recently been classified as thymic carcinomas of various types of histology. However, primary thymic adenocarcinoma is extremely rare and only four cases of it have been reported in the literature. We report a rare case of primary thymic adenocarcinoma of 4-year complete remission with concurrent chemoradiotherapy followed by surgery. A 61-year-old Japanese man was referred to us complaining of facial edema and general fatigue. Computed tomography scans revealed a huge mass in the anterior mediastinum obstructing the superior vena cava. He was diagnosed with thymic adenocarcinoma on needle biopsy. He was treated with induction chemoradiotherapy consisting of cisplatin, 5-FU and concurrent thoracic radiation, which yielded a partial response. He then underwent surgical resection of the remaining mass. However, pathologic examination of the resected mass revealed no malignant cells. The patient is doing well without symptoms or signs of relapse 53 months after diagnosis.

Adenocarcinoma↗
PubMedDate not supplied

Generation of cytotoxic T lymphocytes against autologous lung cancer cells resistant to apoptosis.

BACKGROUND: [corrected] Non-small cell lung cancer (NSCLC) is resistant to conventional treatment; so the development of a new therapy is urgent. MATERIALS AND METHODS: 50 patients with NSCLC and malignant effusion were enrolled in this study. Seventeen autologous lung cancer cell lines were established. Peripheral lymphocytes and irradiated autologous tumor cell lines were co-cultured to generate cytotoxic T lymphocytes (CTL). Expression of apoptosis-related molecules were analysed by RT-PCR or FACS. RESULTS: CTL lines were established in 2 patients. Both CTL lines were CD3+, CD8+ and MHC class I-restricted T cells and showed cytotoxic activities not only against autologous tumor cell lines but against allogenic cancer cell lines. Two lung cancer cell lines were established from one patient before and after cisplatin-based chemotherapy. The tumor cell line established after chemotherapy was apoptosis-resistant, but was sensitive to cytotoxicity of CTL. CONCLUSION: CTL-based immunotherapy may be one of the candidates for future therapies against NSCLC.

Adult↗
PubMedDate not supplied

Connective tissue growth factor is directly related to liver fibrosis.

BACKGROUND/AIMS: Connective tissue growth factor is a mitogenic, chemotactic, and cell matrix-inducing factor for fibroblasts, and is exclusively and directly induced by transforming growth factor-beta 1. In skin fibrosis, connective tissue growth factor is thought to be a downstream effector of transforming growth factor-beta 1 that is directly involved in the proliferation of connective tissue cells and the accumulation of matrix. Our aim is to confirm the involvement of connective tissue growth factor in liver fibrosis. METHODOLOGY: Specimens obtained from autopsy of 12 patients with normal liver (n = 3), hepatocellular carcinoma (n = 3), liver cirrhosis secondary to alcoholic abuse (n = 3), or viral hepatitis (n = 3), were used for digoxigenin labeled in situ hybridization. RESULTS: Abundant connective tissue growth factor messages were detected in the fibrotic area between cirrhotic nodules. Hepatocytes did not show any signals even when they became carcinomas. Normal livers showed few or no signals. CONCLUSIONS: These results confirmed the direct relationship between connective tissue growth factor gene expression and liver fibrotic change.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Differential diagnosis of small hepatocellular carcinoma and borderline lesions and therapeutic strategy.

BACKGROUND/AIMS: To investigate imaging characteristics and surgical results of adenomatous hyperplasia and early-stage hepatocellular carcinoma. METHODOLOGY: A retrospective study set in the First Department of Surgery, University of Tokushima, Japan. From 1994 to 1997, 33 patients with 55 small hepatocellular carcinomas (< or = 3 cm) and 10 borderline lesions (3 adenomatous hyperplasia, 5 atypical adenomatous hyperplasia, 2 atypical adenomatous hyperplasia with focal malignancy) were enrolled for this study. The detectability of these lesions on imaging was evaluated. Cumulative survival and disease-free survival rates were also calculated. RESULTS: Twenty-eight patients were incidentally diagnosed on ultrasonography during follow-up study for chronic disease. In the conventional studies, detection rates of ultrasonography, computed tomography and angiography for small hepatocellular carcinomas and borderline lesions were 76% 80%, 33% 10% and 36% 20%, respectively. Magnetic resonance imaging, intraoperative ultrasonography, helical computed tomography and portal angiographic computed tomography showed better results of 67% 20%, 100% 90%, 70% 50% and 74% 56%, respectively. On differential diagnosis, the ratio of echo level in small hepatocellular carcinomas was significantly higher than that in borderline lesions. The 3-year and 5-year survival rates for all patients were 61% and 41%, while disease-free survival rates at the corresponding times were 15% and 7%, respectively. A total of 25 patients (76%) developed intrahepatic recurrence during a mean follow-up of 33.8 months, although there was no recurrent lesion in 4 adenomatous hyperplasia patients treated with microwave coagulation therapy and ethanol injection intraoperatively. CONCLUSIONS: For tumors larger than 1 cm in diameter, the detection rates with various diagnostic modalities were rather high. However, the differential diagnosis of borderline lesions from small hepatocellular carcinomas could be based on pathologic studies only. Early detection of small hepatic lesions and treatment by methods such as resection or ethanol injection are of critical importance in improving long-term survival.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Clarification of risk factors for hepatectomy in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatic resection is still associated with a higher morbidity than other major abdominal surgery. The aim of this study was to define risk factors for postoperative morbidity, and to evaluate the plasma cytokine pattern to detect early postoperative infection in patients with hepatocellular carcinoma. METHODOLOGY: One hundred and thirty-nine hepatic resections for hepatocellular carcinoma over a 10-year period from 1987 to 1997 were performed. Preoperative and intraoperative predictors of morbid outcomes were analyzed using multiple regression in a stepwise, logistic model. The postoperative concentrations of interleukin-6, interleukin-8, granulocytecolony stimulating factor, endotoxin and hepatocyte growth factor were measured in 32 patients following hepatic resection. RESULTS: Mortality rate within 30 postoperative days was 2.2%, with morbidity occurring in 40.2%. Significant pre- and intraoperative predictors for morbidity were ICGR15 and the presence of liver cirrhosis. Changes of interleukin-6, interleukin-8, granulocytecolony stimulating factor and endotoxin levels were not consistent with the occurrence of postoperative complications. However, the postoperative peak hepatocyte growth factor levels were positively correlated with morbidity. CONCLUSIONS: ICGR15 and presence of liver cirrhosis had a marked effect on the incidence of postoperative complications after hepatectomy for hepatocellular carcinoma. An increase of serum hepatocyte growth factor level could be used to detect complications in the early postoperative period, but the inflammatory cytokine response after hepatectomy did not relate to an increased complication rate.

Adult↗
PubMedDate not supplied

Simple hypothermic retrograde cerebral perfusion during aortic arch surgery.

We have found that retrograde cerebral perfusion can be performed by simply elevating central venous pressure during aortic arch surgery. During hypothermia (15 degrees C) venous blood rich in oxygen perfuses the brain, while the lower half of the body is perfused with the descending aorta occluded. Fourteen cases of aortic arch aneurysm (11 males, 3 females) were treated by this method and evaluated. Median and lateral thoracotomies were performed in 6 and 8 cases, respectively. Cerebral circulatory arrest time was 65 +/- 14 min (32-93 min), and significant oxygen and lactate extraction were noted in the brain. Eleven cases showed no neurologic deficit, but loss of consciousness due to other causes occurred in 3. In conclusion, this method maintained the aerobic metabolism of the brain and protected it during prolonged cerebral circulatory arrest, simplifying the procedure and permitting both median and lateral approaches.

Age Factors↗
PubMedDate not supplied

Phytotherapeutic compound YHK exerts an inhibitory effect on early stage of experimentally-induced neoplastic liver lesions.

The aim of this study was to investigate the effects of the herbal compound YHK on hepatocarcinogenesis induced by diethylntrosamine (DEN) in Sprague Dawley rats. Rats were randomly divided into 3 groups and followed up for 15 weeks. Groups 1 was given standard food and represented the healthy control. Liver preneoplastic foci were induced using the DEN method in groups 2 and 3 (20 rats each). However, group 3 was concomitantly given 50mg/kg/day of YHK. For quantitative assessment of liver preneoplastic foci, the placental form of glutathione-S-transferase (GST-P) positive foci were measured using immunohistochemical staining and image analysis. Treatment using DEN caused a significant decrease in body weight and increase in liver weight compared to the control group while concomitant supplementation with YHK prevented body weight loss and liver weight increase. As compared to DENonly treated rats, the group given YHK showed a significant decrease in the number, size and volume of GSTP- positive foci. Moreover, co-administration of YHK significantly reduced the incidence, number, size and volume of hepatocellular carcinoma. Anti-inflammatory, anti-fibrotic as well as antioxidative properties of this compound are mechanisms which are likely to be advocated for to explain its protective effect. It is concluded that herbal compound YHK by preventing hepatocarcinogenesis in DEN-induced liver preneoplastic lesions in rats has the potential to a large clinical application as a functional food.

Animals↗