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Biomedical subjects

M Ueno

Publications and source records attributed to M Ueno.

At least 37 records · Page 2Linked to original sources

Comparison of two-year and five-year tamoxifen use in Japanese post-menopausal women.

AIM: Large multicenter, randomized trials have revealed the advantages of using tamoxifen for 5 years vs 2 years in breast cancer patients. The aim of this report is to confirm the optimal duration of tamoxifen administration in a study of Japanese breast cancer patients. METHODS: Japanese post-menopausal estrogen receptor-positive breast cancer patients treated with mastectomy were randomly assigned to either a 5-year or 2-year course of tamoxifen. The primary endpoint was disease-free survival, with secondary endpoints of overall survival and a reduction in the development of metachronous contra-lateral breast cancer. RESULTS: A total of 256 breast cancer patients were randomized to a 5-year or 2-year tamoxifen administration group. After a median follow-up time of 81 months, there were no significant differences seen in terms of disease-free or overall survival (p=0.65 and 0.56, respectively). Furthermore, the impact of the 5-year use of tamoxifen on the development of contra-lateral breast cancer did not reach statistical significance (p=0.0511). However, 5-year tamoxifen use was closely associated with gynaecological complications (p=0.0081). CONCLUSION: We could not show a beneficial effect of using tamoxifen for 5 years over 2 years in Japanese estrogen receptor-positive patients. This is likely due to the small number of patients enrolled in our study; however, racial disparity may influence this result. A reevaluation is necessary to study the advantages of the 5-year use of tamoxifen in the Japanese racial subgroup.

Adult↗

Pathological study on the relationship between C4d, CD59 and C5b-9 in acute renal allograft rejection.

In order to evaluate the activation or inhibition of the later phases of classical complement cascade in renal allograft presenting with acute rejection, particularly with C4d deposition on the peritubular capillary (PTC), we observed the expression of CD59 and C5b-9 on the PTC. Subjective cases were divided into two groups, an acute rejection group, of 4 males and 6 females, and a normal donor group, of 5 males and 5 females. Renal biopsies were performed at the onset of acute rejection and at the transplant operation, before reperfusion. C4d deposition on PTC was found in three of 10 cases (30%) with biopsy proven acute rejection, whereas CD59 on PTC was positively expressed in all of the rejection cases. Although C5b-9 was not observed on PTC in the acute rejection group, it was intensively deposited on the tubular basement membrane (TBM) in five cases, including the three with positive C4d on PTC. In the normal donor group, CD59 on PTC was intensively observed, whereas C5b-9 was weakly expressed on TBM. CD59, a complement regulatory factor, works as an inhibitory factor against the formation of C5b-9, a membrane attack complex. From our data, we noted the dissociation between the depositions of C4d and C5b-9 on PTC. The substantially expressed CD59 on PTC may affect this dissociation between C4d and C5b-9 on PTC. The intensive deposition of C5b-9 on TBM in acute rejection cases may suggest an independent immunological injury attacking tubular cells.

Acute Disease↗

Transforming growth factor-beta1 gene polymorphism modifies the histological and clinical manifestations in Japanese patients with IgA nephropathy.

Transforming growth factor (TGF)-beta1, a multifunctional cytokine, which regulates proliferation and differentiation of a variety of cell types, has the central role in the development and progression of renal injury in both animal models and human. Although it has been suggested that genetic variations in the TGF-beta1 gene are associated with the activity of the gene product, their clinical significance in glomerular disease is unknown. We investigated whether the polymorphisms of C-509T and T869C in TGF-beta1 account for interindividual variation in manifestations of IgA nephropathy (IgAN) using 626 Japanese subjects including 329 patients with histologically proven IgAN and 297 healthy controls with normal urinalysis. The frequencies of genotypes, alleles, and major haplotypes were similar between the patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium, and the major haplotypes were C-C and T-T, which accounted for more than 95% of the total. In patients with -509CC and in those with the 869CC, urinary protein excretion was higher than in those with other genotypes, whereas no difference in other clinical manifestations was noted. Moreover, patients with -509CC and those with 869CC genotypes presented with a significant higher score of mesangial cell proliferation than in those with other genotypes. These results suggest that TGF-beta1 gene polymorphisms are specifically associated with heavy proteinuria and mesangial cell proliferation in Japanese patients with IgAN, although they do not confer susceptibility to this disease.

Adult↗

Peroxisome proliferator-activated receptor gamma C161T polymorphisms and survival of Japanese patients with immunoglobulin A nephropathy.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays an important role in lipid metabolism, insulin sensitivity, atherogenesis, and immune regulation. A genetic polymorphism (C161T) at exon 6 of PPAR gamma gene (PPARG) was reported to be associated with the onset of coronary artery disease. However, there has been no report of an association with renal disease. Genomic DNAs were isolated from 225 Japanese patients with histologically confirmed immunoglobulin A nephropathy (IgAN). The PPARG C161T genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. The association of the polymorphism with renal prognosis in IgAN patients was analyzed using the Kaplan-Meier method and Cox proportional hazard regression model. The PPARG polymorphism was not associated with the renal survival rate. However, when patients were stratified into those either with or without hypertension at the time of diagnosis, the renal survival of the CT/TT genotypes was significantly better in those without hypertension than those with the CC genotype. We report that the PPARG C161T polymorphism is associated with the survival of IgAN patients without hypertension. The T allele of the polymorphism might have a protective effect on the progression of IgAN.

Adult↗

Esophageal carcinoma with tracheal stenosis due to tumor invasion and long survival after chemoradiotherapy.

For patients who have esophageal carcinoma with tracheal invasion surgery is usually not indicated because operative complications are considerable and the prognosis is poor. We experienced complete regression of a large esophageal carcinoma with tracheal stenosis due to tumor invasion without tracheo-esophageal fistula. Irradiation of 68 Gy was delivered to a long T field from the neck to the lower thoracic esophagus, and was combined with chemotherapy using cisplatin and 5-fluorouracil. The tumor decreased markedly in size and the tracheal stenosis resolved. The patient has survived for 4 years, although second primary early esophageal carcinoma and hypopharyngeal carcinoma were detected 2 years after his initial chemoradiotherapy. Although the prognosis of advanced esophageal carcinoma with invasion of other organs is usually poor, the effect of chemoradiotherapy can sometimes be dramatic and a good result can be achieved in such patients.

Combined Modality Therapy↗

Prolactin-signal transduction in neonatal rat pancreatic islets and interaction with the insulin-signaling pathway.

During pregnancy, pancreatic islets undergo structural and functional changes in response to an increased demand for insulin. Different hormones, especially placental lactogens, mediate these adaptive changes. Prolactin (PRL) mainly exerts its biological effects by activation of the JAK2/STAT5 pathway. PRL also stimulates some biological effects via activation of IRS-1, IRS-2, PI 3-kinase, and MAPK in different cell lines. Since IRS-2 is important for the maintenance of pancreatic islet cell mass, we investigated whether PRL affects insulin-signaling pathways in neonatal rat islets. PRL significantly potentiated glucose-induced insulin secretion in islets cultured for 7 days. This effect was blocked by the specific PI 3-kinase inhibitor wortmannin. To determine possible effects of PRL on insulin-signaling pathways, fresh islets were incubated with or without the hormone for 5 or 15 min. Immunoprecipitation and immunoblotting with specific antibodies showed that PRL induced a dose-dependent IRS-1 and IRS-2 phosphorylation compared to control islets. PRL-induced increase in IRS-1/-2 phosphorylation was accompanied by an increase in the association with and activation of PI 3-kinase. PRL-induced IRS-2 phosphorylation and its association with PI 3-kinase did not add to the effect of insulin. PRL also induced JAK2, SHC, ERK1 and ERK2 phosphorylation in neonatal islets, demonstrating that PRL can activate MAPK. These data indicate that PRL can stimulate the IRSs/PI 3-kinase and SHC/ERK pathways in islets from neonatal rats.

Animals↗

Pulmonary adenocarcinoma with osteoblastic bone metastases in a cat.

A 12-year-old male cat with depression and dyspnoea was presented for investigation. Radiography and computed tomography revealed hydrothorax and solid masses involving the sternum, ribs and thoracic vertebrae. The cat died two days after first presentation, and postmortem examination revealed lung masses and proliferative bony lesions. Histologically, a neoplastic proliferation of epithelial cells was seen in the lungs, with a large amount of collagen and deposits of cholesterin. The bone lesions were also composed of neoplastic epithelial cells and abundant calcified osteoid, without atypia. A diagnosis of pulmonary adenocarcinoma with osteoblastic bone metastases was made. This is the first reported case of osteoblastic metastases in the cat.

Adenocarcinoma↗

Developmental changes in gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica) hypothalamo-hypophysial system.

We previously isolated a novel dodecapeptide containing a C-terminal -Arg-Phe-NH(2) sequence, SIKPSAYLPLRF-NH(2) (RFamide peptide), from the Japanese quail (Coturnix japonica) brain. This novel quail peptide was shown to be located in neurons of the paraventricular nucleus (PVN) and their terminals in the median eminence (ME), and to decrease gonadotropin release from cultured anterior pituitary in adult birds. We therefore designated this peptide gonadotropin-inhibitory hormone (GnIH). Furthermore, a cDNA encoding the GnIH precursor polypeptide has been characterized. To understand the physiological roles of this peptide, in the present study we analyzed developmental changes in the expressions of GnIH precursor mRNA and the mature peptide GnIH during embryonic and posthatch ages in the quail diencephalon including the PVN and ME. GnIH precursor mRNA was expressed in the diencephalon on embryonic day 10 (E10) and showed a significant increase on E17, just before hatch. GnIH was also detected in the diencephalon on E10 and increased significantly around hatch. Subsequently, the diencephalic GnIH content decreased temporarily, and again increased progressively until adulthood. GnIH-like immunoreactive (GnIH-ir) neurons were localized in the PVN on E10, but GnIH-ir fibers did not extend to the ME. However, GnIH-ir neurons increased in the PVN on E17, just before hatch, and GnIH-ir fibers extended to the external layer of the ME, as in adulthood. These results suggest that GnIH begins its function around hatch and acts as a hypothalamic factor to regulate gonadotropin release in the bird.

Animals↗

A proposal on the hard tissue remineralization in osteoarthritis of the knee joint investigated by FT-IR spectrometry.

An investigation was performed on hard tissues of the affected area in the cases of osteoarthritis of the knee joint by using Fourier transform infrared spectroscopy (FT-IR) to obtain the information on components and characteristics of the compounds in the hard tissues at the molecular level. Biological specimens used were: normal cortical bone, normal cancellous bone, sclerotic area of the affected site (subchondral bone), osteophyte and cartilage of the affected joint. FT-IR spectra of these specimens were measured and spectroscopic characteristics of various types of hard tissues were quantified. As the result of the analysis, signal ratio of PO4(3-) to amide I (PO4(3-)/amide I) was 0 in cartilage, and the ratio was at the highest in normal cortical bone of the ulna, being as high as 1.82. The signal ratio of the sclerotic area of the affected site was 1.69, and this was higher than the values in osteophyte (1.44) or cancellous bone of the tibia (1.61). It is inferred from these data that the degree of remineralization was considerably higher in osteoarthritis of the knee joint. On the other hand, in the osteophyte, which is frequently seen in the radiography of osteoarthritis, it was 1.44 for the attached osteophyte and 1.37 for the detached osteophyte, and these values were lower compared with the values in the sclerotic area of the affected site (1.69). From these results, it appears that remineralization of mineral components is very likely to occur under the acidic conditions in the articular region in this disease. We propose that the mechanism of hard tissue formation in the knee joint of osteoarthritis is a form of remineralization.

Aged↗

Learning curve of video-assisted thoracoscopic esophagectomy and extensive lymphadenectomy for squamous cell cancer of the thoracic esophagus and results.

BACKGROUND: The efficacy of thoracoscopic radical esophagectomy for cancer of the thoracic esophagus and the learning curve required have yet to be clearly established. METHODS: Eighty treatment-naive patients with esophageal cancer without contiguous spread underwent esophageal mobilization and extensive mediastinal lymphadenectomy through a 5-cm minithoracotomy and four trocar ports. The outcomes in the first 34 patients (group 1) and the last 46 patients (group 2) were compared. RESULTS: There were no differences in background or clinicopathologic factors between the two groups. The duration of the thoracoscopic procedure and blood loss were less (p <0.0001), the incidence of postoperative pulmonary infection was less (p = 0.0127), and the number of mediastinal nodes retrieved was greater (p = 0.0076) in group 2. Multivariate analysis demonstrated that surgical experience (number of cases performed) predicted the risk of pulmonary infection (p = 0.0331). CONCLUSION: Video-assisted thoracoscopic radical esophagectomy can be performed with safety and efficacy comparable to those of open esophagectomy. Morbidity decreases with the surgeon's experience.

Adult↗

Video-assisted thoracoscopic esophagectomy and radical lymph node dissection for esophageal cancer. A series of 75 cases.

BACKGROUND: The efficacy of thoracoscopic radical esophagectomy for cancer has yet to be established, mainly because previous reports have not included a sufficient number of cases. METHODS: Seventy-five treatment-naive patients with esophageal cancer without contiguous spread underwent esophageal mobilization and extensive mediastinal lymphadenectomy through a 5-cm mini-thoracotomy and four trocar ports. RESULTS: Video-assisted thoracoscopic surgery was performed without major intraoperative complications or emergency conversion to open surgery. We retrieved 34.1+/-13.0 mediastinal nodes, including 11.5+/-3.8 tracheobronchial nodes and 6.2+/-3.0 recurrent laryngeal nodes. Mean time of operation and blood loss were less in the last 39 patients than the first 36 (186.7+/-25.3 min and 165.4+/-101.8 g vs 270. 2+/-96.0 min and 421.5+/-31.2 g, respectively: p <0.0001 and p <0.001). Pulmonary morbidity was 5% in the later 39 patients. Survival was 90%, 80%, and 57% at 1, 2, and 5 years after surgery. CONCLUSION: Thoracoscopic radical esophagectomy has less morbidity and comparable survival to conventional surgery, after a moderate amount of experience. Mini-thoracotomy is essential to perform the procedure safely and effectively.

Adult↗

High efficiency gene transfer to human CD34+ cells.

We have previously reported the development of improved MLV-based retroviral vectors whose prototype is entitled MT (Kim et al, J. Virol. 72:994-1044; Yu et al, Gene Therapy 7:797-804). The MT vector does not contain any viral coding sequences, and thus the possibility of homologous recombination between the vector and the packaging genome is virtually nil. Indeed, in a shotgun RCR detection assay, an MT-based vector did not produce any RCR. On the contrary, the MFG vector, containing parts of all three viral coding sequences (gag, pol, and env), generated a significant number of RCR. In addition to being safe, MT-based vectors produce levels of gene expression and viral titer comparable to or higher than other vectors currently available within the community. Based on this vector, we have constructed a number of retroviral vectors that can be used for the treatment of a variety of human diseases. Our major target diseases are those that can be treated with or the status of which can be significantly improved with bone marrow transplantation. To obtain the most significant therapeutic effects, it is necessary to achieve the highest possible gene delivery efficiency, drive the highest level of gene expression, and prevent expression of the inserted therapeutic gene from being negatively influenced by the genome environment. To these ends, we compared various LTRs for their effects on the level of gene expression, tested the effect of cis-acting elements that may influence chromatin structure or position effect of the inserted gene, and studied different transduction conditions for their gene delivery efficiency. Data recently obtained from these experiments will be presented.

Antigens, CD34↗

Polychlorinated dibenzo-p-dioxin and dibenzofuran concentrations in serum samples of workers at intermittently burning municipal waste incinerators in Japan.

OBJECTIVES: To find whether or not incinerator workers employed at intermittently burning municipal incineration plants are exposed to high concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). METHODS: 20 Workers employed at three municipal waste incineration plants (incinerator workers) and 20 controls were studied. The previous job, dietary, smoking, and body weight and height were obtained from a questionnaire survey. Concentrations of PCDDs and PCDFs were measured in serum samples of the workers and the deposited dust of the plants. The influence of occupational exposure on concentrations of PCDDs and PCDFs in serum samples was examined by multiple regression analysis. RESULTS: Dust analysis showed that dominant constituents were octachlorodibenzo-p-dioxin (OCDD) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) among the PCDDs, and 1,2,3,4,6,7,8-heptachlorodibenzofuran (HpCDF) and octachlorodibenzofuran (OCDF) among the PCDFs. The toxicity equivalents (TEQs) of summed PCDDs and PCDFs in the deposited dust were 0.91, 33, and 11 ng TEQ/g, respectively, for plants I, II, and III. The means of TEQ in serum samples of summed PCDDs and PCDFs in the incinerator workers and controls were 22.8 and 16.4 pg TEQ/g lipid for area I, 29.4 and 19.3 pg TEQ/g lipid for area II, and 22.8 and 24.9 pg TEQ/g lipid for area III, which were almost the same as for the general population of Japan. No significant differences in the TEQ of PCDDs and TEQ of PCDDs and PCDDs were found between the incinerator workers and the controls. However, the TEQ of PCDFs was significantly higher among the incinerator workers in areas I and II, and the 1,2,3,4,6,7,8-HpCDF concentration was also significantly higher for all three areas. When the occupational exposure index for each constituent of PCDDs and PCDFs was defined as the product of the duration of employment at the incineration plant and the concentration of the constituent in the deposited dust, multiple regression analysis showed that the concentrations of HxCDF, HpCDF, and TEQ of PCDFs in serum samples increased with the occupational exposure index. The multiple regression analysis also suggested that significant factors affecting the concentrations in serum samples were area for HxCDD, age for TCDD, PeCDD, PeCDF, TEQ of PCDDs, TEQ of PCDFs, and TEQ of summed PCDDs and PCDFs, and BMI for HxCDD, HpCDD, and OCDD. CONCLUSION: This study showed that incinerator workers employed at intermittently burning incineration plants were not necessarily exposed to high concentrations of PCDDs and PCDFs. However, the increases in the concentrations in serum of HxCDF, HpCDF and TEQ of PCDFs with the occupational exposure index suggest that the incinerator workers had inhaled dust containing PCDDs and PCDFs during their work.

Adult↗

Functional analysis of the effect of the posterior stabilising cam in two total knee replacements. A comparison of the Insall/Burstein and Bisurface prostheses.

The Bisurface knee prosthesis (BP) has a posterior stabilising cam (ball-and-socket joint) in the mid-posterior region of the femorotibial joint in an attempt to improve the range of movement. Based on an in vitro weight-bearing study contact areas of the Insall/Burstein 2 (IB2) and the BP knee were compared using pressure-sensitive films. The stability afforded by the cam was evaluated by means of dislocation distances in the vertical and horizontal planes. Significant adverse anterior translation in mid-flexion was not observed with the BP knee since the cam was effective above 60 degrees of flexion. At flexion of 60 degrees or more, the total contact areas were larger, as the cam represented a weight-bearing surface. The dislocation distances for the BP knee compared favourably with those for the IB2 knee. We conclude that the cam of the BP knee allows good movement, stability and wear.

Arthroplasty, Replacement, Knee↗

Expression of ribosomal protein L4 (rpL4) during neurogenesis and 5-azacytidine (5AzC)-induced apoptotic process in the rat.

5-Azacytidine (5AzC) induces neuronal apoptosis in rat and mouse fetuses. 5AzC also induces apoptosis in undifferentiated PC12 cells, and ribosomal protein L4 (rpL4) mRNA expression increases prior to apoptosis. To clarify the roles of rpL4 during neurogenesis, we first examined the distribution of rpL4 mRNA in the developing rat brain by in situ hybridization and RT-PCR, and compared the results to the distribution of TUNEL- or PCNA-positive cells. rpL4 mRNA expression was strong in the ventricular zone (VZ), subventricular zone (SVZ), cortical plate (CP), cerebral cortex, granule cell layer (GCL), pyramidal cell layer (Py) and external granular layer (EGL) during embryonic and early postnatal days, and it was remarkably weakened thereafter. A lot of PCNA-positive cells were observed in VZ, SVZ, and EGL during embryonic and early postnatal days, and such distribution of PCNA-positive cells was almost identical to rpL4 mRNA distribution. Only few TUNEL-positive cells were observed in VZ, SVZ, cerebral cortex, EGL, and hippocampus during embryonic and early postnatal days, and the regions with TUNEL-positive cells were not identical to rpL4 mRNA distribution. Next, the changes of rpL4 mRNA expression in the brain of 5AzC-treated rat fetuses were examined by in situ hybridization and RT-PCR. Apoptotic cells appeared at 9 to 24 hours after treatment (HAT). However, the rpL4 mRNA expression was unchanged during the apoptotic process. From the results, it is suggested that rpL4 would have certain roles in cell proliferation and differentiation during neurogenesis, but have no roles in 5AzC-induced apoptosis in the fetal brain.

Animals↗

Effect of methylprednisolone on phospholipase A(2) activity and lung surfactant degradation in acute lung injury in rabbits.

Glucocorticoids are the most potent and widely used anti-inflammatory agents, but they are not particularly effective against early phase of acute respiratory distress syndrome. We investigated whether methylprednisolone, a synthetic glucocorticoid, could inhibit increase of phospholipase A(2) activity in the lung and lead to protection against a model of acute respiratory distress syndrome in rabbits. Infusion of oleic acid (0.1 ml/kg/h, i.v. for 2 h) provoked pulmonary hemorrhage and edema, protein leakage and massive neutrophil infiltration, resulted in severe hypoxemia and impaired lung compliance, accompanying the increase of phospholipase A(2) activity and interleukin-8, and degradation of surfactant in the bronchoalveolar lavage fluid. Infusion of methylprednisolone (60 mg/kg/h, i.v. for 30 min before the oleic acid and then 0.5 mg/kg/h, i.v. for 6 h) did not improve the above described lung injury induced by oleic acid, nor did it suppress phospholipase A(2) activity and degradation of surfactant in bronchoalveolar lavage fluid, while it strongly reduced interleukin-8 levels in both plasma and bronchoalveolar lavage fluid. We conclude that methylprednisolone did not attenuate oleic acid-induced acute lung injury and this can be explained partly by its failure to reduce the increase of phospholipase A(2) activity and the surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early acute respiratory distress syndrome.

Animals↗