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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 91 records · Page 5Linked to original sources

A case of endocrine ductal carcinoma of the breast.

A case of endocrine ductal carcinoma of the breast is presented. A 65-year-old woman was admitted with complaints of left breast mass and pain. Physical examination, mammography, ultrasonography, and computed tomography showed a mass 5 cm in diameter in the left breast suggestive of breast cancer, and incisional biopsy confirmed ductal carcinoma. Auchincloss's mastectomy was performed. The tumor, 4.0 x 3.8 cm in size, consisted of a relatively uniform proliferation of tumor cells with round nuclei and abundant eosinophilic cytoplasm. Immunohistochemically, tumors cells were positive for chromogranin A, synaptophysin, and neuron-specific enolase. Endocrine ductal carcinoma with invasion was diagnosed. No lymph node metastasis was observed, and estrogen and progesterone receptors were positive.

Aged↗

A patient with type I CD36 deficiency whose myocardium accumulated 123I-BMIPP after 4 years.

A 73-year-old man with aortic regurgitation was examined by 123I-alpha-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial single photon emission computed tomography (SPECT) in 1995. Myocardial accumulation was not evident on either the early or the delayed image obtained 15 minutes and 3 hours, respectively, after injecting 123I-BMIPP. Flow cytometric analysis of CD36 expression in monocytes and platelets identified a type I CD36 deficiency. The patient was hospitalized for severe heart failure in 1999. Upon admission, the cardiothoracic ratio on chest X-rays was 73%, and the left ventricular end-diastolic diameter on echocardiograms was enlarged to 77 mm. On the second day, we performed 123I-BMIPP myocardial SPECT. Myocardial accumulation was evident in the delayed, but not in the early image. We repeated 123I-BMIPP myocardial SPECT on the 10th day after admission. Myocardial accumulation was evident on both early and delayed images. 99mTc-tetrofosmin myocardial SPECT was immediately performed after 123I-BMIPP myocardial SPECT to distinguish myocardial from pooling images in the left ventricle, but, because the images from both 99Tc-tetrofosmin and 123I-BMIPP myocardial SPECT were idential, we considered that the 123I-BMIPP myocardial SPECT images reflected the actual myocardial condition. The CD36 molecule transports long-chain fatty acid (LCFA) on the myocardial membrane, but 123I-BMIPP scintigraphy does not show any myocardial accumulation in patients with type I CD36 deficiency, indicating that myocardial LCFA uptake occurs through CD36 on the human myocardial membrane. Even though our patient had type I CD36 deficiency, BMIPP was uptaken by the myocardium during heart failure, suggesting a variant pathway on the human myocardial membrane for LCFA uptake.

Aged↗

Assessment of ampulla (Takotsubo) cardiomyopathy with coronary angiography, two-dimensional echocardiography and 99mTc-tetrofosmin myocardial single photon emission computed tomography.

UNLABELLED: We studied the causative mechanism of ampulla (Takotsubo) cardiomyopathy. METHODS: We examined 7 patients with ampulla cardiomyopathy by means of coronary angiography, two-dimensional echocardiography and 99Tc-tetrofosmin myocardial SPECT at the time of emergency admission (acute phase), at 3 to 5 days after the attack (subacute phase) and at 1 month after the attack (chronic phase). The left ventricle was divided into 9 regions on two-dimensional echocardiograms and 99mTc-tetrofosmin myocardial SPECT images, then the degree of abnormalities in each region was scored in four grades from normal (0) to severely abnormal (3). We injected nicorandil into the coronary arteries and determined the elevation in the ST segment before and after administration. RESULTS: Coronary angiography did not show stenotic lesions in any patient. The acute, subacute and chronic phase myocardial perfusion scores on 99mTc-tetrofosmin myocardial SPECT were 11.2 +/- 3.4, 2.7 +/- 2.3 and 0.4 +/- 0.5, respectively, and wall motion scores on echocardiograms were 13.0 +/- 3.6, 4.4 +/- 2.2 and 0.6 +/- 0.6, respectively, indicating improvement in all scores during the subacute phase (p < 0.01). The elevation in the ST segment (mm) on the electrocardiogram was improved from 8.3 +/- 2.7 to 4.9 +/- 1.9 after the administration of nicorandil (p < 0.05). CONCLUSION: These findings indicated that coronary microvascular spasm is one causative mechanism of ampulla cardiomyopathy.

Acute Disease↗

Analysis of T cell receptor V(beta) gene expression and clonality in bronchoalveolar fluid lymphocytes from a patient with chronic eosinophilic pneumonitis.

Chronic eosinophilic pneumonitis (CEP) is characterized by longstanding respiratory symptoms accompanied by a massive pulmonary eosinophil infiltration. T lymphocytes in bronchoalveolar lavage (BAL) from patients with chronic eosinophilic pneumonitis are considered to recognize unknown antigens. To analyze the pathogenesis of CEP, we examined the T cell receptor (TCR) repertoire and T cell clonotype of BAL lymphocytes and peripheral blood lymphocytes (PBLs) in a 66-year-old woman patient with CEP. The expression of TCR BV gene was analyzed by the family PCR method using specific primers for 20 TCR BV genes and BC gene. The clonotype of BAL and peripheral T cells was examined by the PCR-single-strand conformation polymorphism (SSCP) method. Functional sequences of some T cell clones were also carried out. A TCR repertoire of BAL T cells was heterogeneous as well as PBLs. However, SSCP analysis showed that distinct T cell clonotypes were detected in BAL T cells, TCR BV3, BV4, BV6, BV8, BV9, BV14, and BV18-positive T cell clones especially, expanded clonally in BAL from the patient. Sequencing analysis showed that GVD, LGG, RDXS, and SSG amino acid sequence motif were found in the CDR3 in lung-specific T cells. BAL-specific T cell clones accumulated in the patient with CEP. Thus, we can conclude that BAL T cells are induced by the antigen-driven stimulation and these cells might play a crucial role in the generation of CEP.

Aged↗

Cross-phylum regulatory potential of the ascidian Otx gene in brain development in Drosophila melanogaster.

The origin of molecular mechanisms of cephalic development is an intriguing question in evolutionary and developmental biology. Ascidians, positioned near the origin of the phylum Chordata, share a conserved set of anteroposterior patterning genes with vertebrates. Here we report the cross-phylum regulatory potential of the ascidian Otx gene in the development of the Drosophila brain and the head vertex structures. The ascidian Otx gene rescued the embryonic brain defect caused by a null mutation of the Drosophila orthodenticle (otd) gene and enhanced rostral brain development while it suppressed trunk nerve cord formation. Furthermore, the ascidian Otx gene restored the head vertex defects caused by a viable otd mutation, ocelliless, via specific activation and repression of downstream regulatory genes. These cross-phylum regulatory potentials of the ascidian Otx gene are equivalent to the activities of the Drosophila and human otd/Otx genes in these developmental processes. These results support the notion that basal chordates such as ascidians have the same molecular patterning mechanism for the anterior structures found in higher chordates, and suggest a common genetic program of cephalic development in invertebrate, protochordate and vertebrate.

Amino Acid Sequence↗

Hyaluronic acid secretion during carbon dioxide pneumoperitoneum and its association with port-site metastasis in a murine model.

BACKGROUND: The mechanism of port-site metastasis after laparoscopic cancer surgery is unclear. This study aimed to determine whether carbon dioxide (CO2) pneumoperitoneum caused an increase in hyaluronic acid, which is secreted from mesothelial cells of the peritoneal cavity, and to assess the risk for port-site metastasis using a murine pneumoperitoneal model. METHODS: Sandwich-binding protein assay was used to measure the concentration of hyaluronic acid in the peritoneal cavity at 6, 12, 18, 24, 48, and 72 h after CO2 pneumoperitoneum or laparotomy for 30 min. The concentrations of hyaluronic acid during pneumoperitoneum were compared among different gases (CO2, helium, air), intervals (5, 30, 60 min), and pressures (0-2, 4-6, 8-10 mmHg). To investigate the effects of exogenous hyaluronic acid, the development of port-site metastasis was examined using mouse adenocarcinoma cell-line colon 26 cells. RESULTS: The intraperitoneal concentration of hyaluronic acid after CO2 pneumoperitoneum had increased already at 6 h, had reached the maximum level at 24 h, and had begun to decrease at 72 h. The concentration of hyaluronic acid at 24 h and 48 h in the CO2 pneumoperitoneum group was higher than that in the laparotomy group. This increase in hyaluronic acid also was found during helium and air pneumoperitoneum, and the concentration of hyaluronic acid in the peritoneal cavity was at its maximum when CO2 pneumoperitoneum lasted 30 min at 4 to 6 mmHg. The frequency of port-site metastasis was the highest when hyaluronic acid was injected during CO2 pneumoperitoneum (100%). CONCLUSIONS: In a murine model, the intraperitoneal concentration of hyaluronic acid was significantly increased after CO2 pneumoperitoneum, and the increase was more evident than that after laparotomy. Increased hyaluronic acid during pneumoperitoneum may be associated with port-site metastasis after laparoscopic cancer surgery.

Adenocarcinoma↗

Surgery for gastric cancer: 10-year experience worldwide.

To demonstrate recent experience of gastric cancer surgery worldwide and to evaluate modern strategies for the treatment of gastric cancer, we investigated the English-language literature of the past 10 years, based on papers published in well-known medical journals. In many countries, the increased detection of early gastric cancer, advanced operative procedures, and careful postoperative management have improved the surgical results of gastric cancer over the years. Although randomized controlled trials in Europe showed no survival benefit of D2 resection over D1 resection, the results must be interpreted with caution and cannot be extrapolated to Japanese patients, because the morbidity and mortality after D2 gastrectomy in Japan are much less than those after D1 gastrectomy in Europe. Recently, less invasive treatments, including endoscopic mucosal resection and laparoscopic gastrectomy, have become feasible for patients with early gastric cancer, but their risks and benefits compared with traditional gastrectomy are unclear.

Gastrectomy↗

Gastrectomy for a patient with early gastric cancer and human immunodeficiency virus (HIV) infection.

Gastric cancer associated with human immunodeficiency virus (HIV) infection is rare, and mostly results in a poor outcome. We report a patient with HIV infection and early gastric cancer successfully treated by gastrectomy. A 49-year-old man with a 6-year history of HIV infection underwent gastric fiberscopy, and a IIc-type depressed lesion was detected in the gastric antrum. With a diagnosis of early gastric cancer, we abided strictly by standard precautions for patients with HIV infection and carried out Billroth I gastrectomy. Histologic examination revealed that the lesion (which measured 0.9 x 0.4 cm in size), was well differentiated tubular adenocarcinoma confined to the mucosa. A review of the literature disclosed that this is the first reported case of early gastric cancer associated with HIV infection.

Adenocarcinoma↗

Pattern of lymph node micrometastasis and prognosis of patients with colorectal cancer.

BACKGROUND: Studies of lymph node micrometastases in patients with colorectal cancer have ignored the prognostic significance of the number and level of lymph node micrometastases. The aim of this study was to clarify the prognostic significance of the status of lymph node micrometastases in histologically node-negative colorectal cancer. METHODS: We used immunohistochemistry with anti-cytokeratin antibody CAM5.2 to examine 1013 lymph nodes in 42 patients (12 recurrent and 30 nonrecurrent) with histologically determined Dukes' B colorectal cancer. Five serial 6-microm sections were used for immunohistochemical staining. The frequency, tumor cell pattern, and number and level of lymph node micrometastases were compared between the recurrent and nonrecurrent groups. RESULTS: Micrometastasis was confirmed in 16% (59/373) of lymph nodes in the recurrent group and 12% (77/640) of lymph nodes in the nonrecurrent group, and the frequency of lymph node micrometastases was 92% (11/12) in the recurrent group and 70% (21/30) in the nonrecurrent group. The tumor cell pattern in the metastatic lymph nodes was similar in the recurrent and nonrecurrent groups. Micrometastasis in four or more lymph nodes occurred more frequently in the recurrent group than in the nonrecurrent group (58% vs. 20%, P < .05), and micrometastasis to N2 or higher nodes occurred more frequently in the recurrent group than in the nonrecurrent group (92% vs. 47%, P < .01). CONCLUSIONS: The number and level of positive micrometastatic lymph nodes was significantly correlated with postoperative recurrence of histologically determined Dukes' B colorectal cancer. This parameter is a useful prognostic indicator in histologically node-negative colorectal cancer and is helpful in planning adjuvant chemotherapy.

Aged↗

Hepatitis C virus core particle detected by immunoelectron microscopy and optical rotation technique.

Hepatitis C Virus (HCV) are 55-65 nm spherical particles, but the internal structure of the virion remains to be clarified. To clarify the morphology of HCV core particles, we performed an immune electron microscopy (IEM) using plasma samples from two blood donors with high HCV RNA titers and a detergent-treated anti-HCV core antibody-free plasma sample with high HCV RNA titer (1.5x10(8) copies/ml). Spherical particles, with 33-40 nm in diameter (an average diameter of 37 nm) were found in 1.22-1.25 g/ml fractions after sucrose density gradient centrifugation by conventional electron microscopy (EM). IEM using rabbit polyclonal antibody (RR8) specific to the putative HCV core protein and goat anti-rabbit IgG colloidal gold particles revealed that these spherical particles specifically reacted with RR8. This finding indicates that the spherical particles are naked HCV core particles. Some of the HCV core particles had an icosahedron-like structure. Optical rotation technique showed that the HCV core particle exhibits six-fold symmetry and that the length of regular hexagon side is approximately 20 nm. These findings showed that HCV core particles are spherical particles of 33-40 nm in diameter and that HCV core particles may possess an icosahedron-like structure and a buoyant density of 1.22-1.25 g/ml.

Journal Article↗

Protection of T cells from radiation-induced apoptosis by Cepharanthin.

Cepharanthin (CE) is a medicine that contains several biscoclaurine alkaloids. We examined the effects of CE on radiation-induced T cell apoptosis. Radiation induced apoptosis on T cells in a dose-dependent manner, while CE inhibited radiation-induced apoptosis. CE also attenuated the cytotoxic effects of radiation on the proliferative response of T cells. CE inhibited not only the loss of mitochondrial transmembrane potential but also the activation of caspase 3 in irradiated T cells. Radiation plus CE induced the up-regulation of Bax and the down-regulation of Bcl-2 in T cells in comparison with radiation alone. These results suggest that CE inhibits the signal transduction pathway of apoptosis induced by radiation, regardless of the expression of Bcl-2 or Bax.

Adult↗

Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein.

PURPOSE: MDR1 P-glycoprotein (P-gp) plays an important role in determining drug disposition. The purpose of the present study was to establish in vitro models to predict the in vivo function of P-gp. METHODS: As an in vitro method, the transcellular transport of 12 compounds across the monolayer of Caco-2- and MDR1-transfected cells was examined. The ability of these compounds to stimulate the ATP hydrolysis was also determined using the isolated membrane fraction expressing P-gp. As a parameter to describe the in vivo P-gp function, we calculated the brain-to-plasma concentration ratio of compounds in mdr1a/1b knockout mice divided by the same ratio in wild type mice. RESULTS: A good correlation was observed between the in vitro flux ratio across the monolayer and in vivo P-gp function for 12 compounds. Although all compounds that stimulated ATP hydrolysis were significantly transported by P-gp, some compounds were transported by P-gp without significantly affecting ATP hydrolysis. CONCLUSION: Collectively, the in vitro flux ratio across monolayers of P-gp-expressing cells may be used to predict in vivo P-gp function. The extent of ATP-hydrolysis in vitro may also be a useful parameter for in vivo prediction, particularly for eliminating P-gp substrates in high-throughput screening procedures.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Increased lymphoid MxA expression in acute asthma exacerbation in children.

BACKGROUND: Although the association between acute asthma exacerbation and viral infection has been well documented, virus identification rates vary. It has recently been reported that the expression of MxA protein in lymphocytes, inducible by type I interferons, can serve as a sensitive marker for viral infection in the host. The objective was to determine the contribution of viral infection to precipitation of asthma attacks in children. METHODS: We studied 186 asthmatic children, aged 0-12 years, over a 1-year period to evaluate MxA protein levels in peripheral blood lymphocytes by using a flow cytometric analysis in whole blood. RESULTS: Of all the subjects, 80 (47%) exhibited significantly elevated levels of MxA expression in lymphocytes, presumably indicating the states of viral infection. The association of viral infections with acute asthma exacerbation seemed to be marked in younger children: enhanced MxA expression was seen in 73.3% of infants (aged 0-1 year), 49.5% of toddlers (aged 2-5 years), and 26% of schoolchildren (aged 6-12 years). Seasonal changes in the frequency of viral infection associated with deterioration were also observed. CONCLUSIONS: Flow cytometric assay of MxA protein expression in whole blood appears to be an easy and useful method to evaluate viral infections in acute asthma exacerbation.

Acute Disease↗

Comparison of plasma alpha glutathione S-transferase concentrations during and after low-flow sevoflurane or isoflurane anaesthesia.

BACKGROUND: We evaluated the effect of low-flow sevoflurane anaesthesia, in which compound A is generated, and isoflurane anaesthesia, in which compound A is not generated (n=13 in each group), on hepatocellular integrity using alpha glutathione S-transferase (GST). Alpha GST is a more sensitive and specific marker of hepatocellular damage than is aminotransferase activity and correlates better with hepatic histology. METHODS: Sevoflurane or isoflurane were delivered without nitrous oxide with a fresh gas flow of 1 l/min. Concentrations of compound A in the circuit were measured hourly, and plasma alpha GST concentrations were measured perioperatively. RESULTS: Mean duration of anaesthesia was 338+/-92 min in the sevoflurane group and 320+/-63 min in the isoflurane group. Mean compound A concentration in the sevoflurane group was 28.6+/-9.0 ppm. There was no significant difference in alpha GST concentrations between the sevoflurane and isoflurane groups during or after anaesthesia. CONCLUSION: These results indicate that low-flow sevoflurane and isoflurane anaesthesia have the same effect on hepatic function, as assessed by plasma alpha GST concentrations.

Adult↗

Midkine and cyclooxygenase-2 promoters are promising for adenoviral vector gene delivery of pancreatic carcinoma.

Midkine (MK), a heparin binding growth factor, and cyclooxygenase-2 (COX-2), a key enzyme in the conversion of arachidonic acid to prostaglandin, are both up-regulated at the mRNA or protein level in many human malignant tumors. Here, we investigated the tumor specificity of both MK and COX-2 promoters in human pancreatic cancer, with the aim to improve the selectivity of therapeutic gene expression. We constructed recombinant adenoviral (Ad) vectors containing either the luciferase (Luc) reporter gene under the control of the COX-2 or MK promoter or the herpes simplex virus thymidine kinase (HSV Tk) gene under the control of the COX-2 promoter and compared the expression with the cytomegalovirus (CMV) promoter. AdMKLuc achieved moderate to relatively high activity upon infection to both primary and established pancreatic carcinoma cells. Of the two COX-2 promoter regions (COX-2M and COX-2L), both revealed a high activity in primary pancreatic carcinoma cells, whereas in the established pancreatic carcinoma cell lines, COX-2L has an approximately equal high activity compared to CMV. In addition, both AdCOX-2M Tk and AdCOX-2L Tk induced marked cell death in response to ganciclovir (GCV) in three of four established pancreatic carcinoma cell lines. From these results, and because it has been reported that AdMKTk and AdCOX-2L Tk in combination with GCV did not reveal significant liver toxicity, we conclude that the MK as well as the COX-2 promoters are promising tumor-specific promoters for Ad vector-based gene therapy of pancreatic cancer.

Adenoviridae↗

A novel system for mitigation of ectopic transgene expression induced by adenoviral vectors.

Adenoviral (Ad) vectors are good candidates for gene therapy in view of their high in vivo gene delivery efficiency. However, greater control over the tissue distribution of transgene expression is required to avoid potentially deleterious effects in non-target organs. In this regard, the liver is particularly at risk due to the high natural tropism of Ad for this organ, where dose limiting toxicity has been seen due to toxic transgene expression. We hypothesized that the cre/loxP system could be utilized to reduce unintended transgene expression at this site. This concept was tested using an Ad vector (AdLCLLL) carrying a reporter gene cassette in which the promoter and luciferase gene were flanked by LoxP sequences. Co-administration of this vector with a second vector carrying the cre recombinase gene in vitro and in vivo resulted in specific down-regulation of transgene expression. This novel approach thus has the potential to improve the safety of gene therapy strategies that rely upon the delivery of genes which may be hepatotoxic.

Adenoviridae↗

Risk factors for complications following resection of large gastric cancer.

BACKGROUND: Although there is a low mortality rate after gastrectomy in Japan, most studies include many early gastric cancers. There have been few studies on the morbidity after gastrectomy for advanced gastric cancer. The aim of this study was to clarify the characteristics and risk factors for postoperative complications after resection of large gastric cancers based on three clinical factors: patient, operation and tumour. METHODS: A retrospective study was carried out on 97 patients with a gastric tumour measuring 10 cm or more in diameter. Postoperative complications were recorded and the patients were divided into two groups: 38 with complications and 59 without. Patient, operative and tumour findings were compared between the two groups. RESULTS: Overall morbidity and mortality rates were 39 and 7 per cent respectively. The most frequent complication was pleural effusion (17 per cent), followed by anastomotic leakage (14 per cent), abdominal abscess (12 per cent), wound infection (12 per cent), pancreatic leakage (8 per cent) and peritonitis (6 per cent). Risk factors associated with postoperative complications were operating time (400 versus 337 min, P < 0.01), blood loss (1338 versus 782 ml, P < 0.01), pancreatic invasion (26 versus 8 per cent, P < 0.05) and raised serum carcinoembryonic antigen (CEA) level (5 ng/ml or greater) (36 versus 17 per cent, P < 0.05), independent of patient age, nutritional status, type of gastrectomy, splenectomy or pancreatectomy, extent of lymph node dissection, tumour location, size and stage of disease. CONCLUSION: Even in Japan, the morbidity of gastrectomy for large gastric cancer is high and associated with operating time, blood loss, pancreatic invasion and serum CEA level.

Blood Loss, Surgical↗