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Biomedical subjects

T Sawada

Publications and source records attributed to T Sawada.

At least 55 records · Page 3Linked to original sources
PubMed2003

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↗
PubMed2003

High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis.

OBJECTIVE: We investigated the rheumatoid arthritis (RA) diagnostic performances of anti-cyclic citrullinated peptide antibody (anti-CCP) and antifilaggrin antibody (AFA) in comparison with RF and matrix metalloproteinase-3 (MMP-3). METHODS: We used a second generation enzyme-linked immunosorbent assay (ELISA) kit for the detection of anti-CCP. We constructed recombinant human filaggrin, which was citrullinated in vitro by human peptidylarginine deiminase, and subsequently used it as the coating antigen for AFA-ELISA. A total of 549 RA patients and 208 other rheumatic disease patients were included in the study. RESULTS: The specificities of anti-CCP (88.9%) and AFA (94.7%) were superior to those of RF (81.7%) and MMP-3 (49.5%). The sensitivity of anti-CCP (87.6%) was superior to all others. However, the sensitivity of AFA (68.7%) was inferior to those of RF (69.8%) and MMP-3 (75.7%). Furthermore, receiver operating characteristic curves of anti-CCP and AFA passed closer to the upper left corner than those of RF and MMP-3, and the areas under the curves (AUC) of AFA and anti-CCP were significantly larger. In addition, the AUC of anti-CCP was significantly larger than that of AFA. CONCLUSION: ELISA detection of antibodies to citrullinated antigens, especially a second generation anti-CCP, showed higher discriminative ability than other assays, including RF, and would be useful to aid the diagnosis of RA in clinical practice.

Adult↗
PubMed2003

Clinicopathological significance of hypoxia-inducible factor-1alpha expression in human pancreatic carcinoma.

AIMS: The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) plays a key role in the cellular adaptation to hypoxia and the activation of several genes that have been implicated in tumour growth. The aim of this study was to investigate the clinicopathological significance of HIF-1alpha expression in pancreatic carcinoma. METHODS AND RESULTS: We investigated HIF-1alpha expression immunohistochemically in pancreatic carcinoma tissues and regional lymph node metastasis. In cases of pancreatic ductal carcinoma, the relationship between HIF-1alpha expression and various clinicopathological parameters including cellular proliferation, apoptosis, and microvessel density, was also examined. Over-expression of HIF-1alpha was frequently (29 of 49 cases, 59.2%) detected in pancreatic carcinoma and regional lymph node metastasis (19 of 25 cases, 76.0%), whereas HIF-1alpha expression was almost absent in non-cancerous pancreatic tissues. HIF-1alpha expression was significantly associated with tumour size (P = 0.023) and advanced TNM stage (stage I/II versus stage III, P = 0.039; stage I/II versus stage IV, P = 0.027). Moreover, HIF-1alpha expression positively correlated with cellular proliferation (P = 0.024) and microvessel density/neo-angiogenesis (P = 0.038), but not with apoptosis. CONCLUSIONS: HIF-1alpha may play a critical role in the progression of pancreatic carcinoma.

Adenocarcinoma, Papillary↗
PubMed2003

Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis.

Fas/Fas ligand (FasL) interaction has been implicated in the pathogenesis of various diseases. To clarify the involvement of Fas/FasL in the pathogenesis of intestinal inflammation, we investigated the preventive and therapeutic effects of neutralizing anti-FasL monoclonal antibody (MAb) on the development of chronic colitis induced by adaptive transfer of CD4+CD45RBhigh T cells to SCID mice. Administration of anti-FasL MAb from 1 day after T cell transfer (prevention study) resulted in a significant improvement of clinical manifestations such as wasting and diarrhea. However, histological examination showed that mucosal inflammation in the colon, such as infiltration of T cells and macrophages, was not improved by the anti-FasL MAb treatment. In vitro studies showed that anti-FasL MAb did not inhibit IFN-gamma production by anti-CD3/CD28-stimulated lamina propria CD4+ T cells but suppressed TNF-alpha and IL-1beta production by lamina propria mononuclear cells. Therapeutic administration of anti-FasL MAb from 3 wk after T cell transfer also improved ongoing wasting disease but not intestinal inflammation. These results suggest that the Fas/FasL interaction plays a critical role in regulating systemic wasting disease but not local intestinal inflammation.

Adoptive Transfer↗
PubMed2002

Thoracoscopic internal mammary sentinel node biopsy for breast cancer.

Sentinel node (SN) biopsy has changed the management of breast cancer. This pilot study assessed the utility of lymphatic mapping and thoracoscopic SN biopsy for internal mammary node (IMN) staging. Forty-nine breast cancer patients underwent lymphatic mapping using 99mTc-tin colloid. Patients with IMSNs underwent thoracoscopic biopsy. Lymphoscintigraphy showed IMSNs in 15 of 49 cases (31%). The incidence of IMN drainage was relationed to age and tumor location; 50% of patients younger than age 40 and 43% with tumors located in inner quadrants had IMN drainage. The thoracoscopic procedure was performed in 11 of 15 patients, and 18 IMSNs were removed; the time of the procedure ranged from 20 to 60 min. No patients had complications from the procedure. Two of 11 patients (18%) had IMSN metastasis, and one of them had only IMN metastasis. Lymphatic mapping and the thoracoscopic approach were useful for IMSN biopsy. They may enable the physician to make an appropriate treatment decision for breast cancer.

Adult↗
PubMed2002

Ultrastructure of basement membranes in developing shark tooth.

Based on studies of the tooth of largely mammalian species, the dental basement membranes are shown to be specialized for various roles significant in the development and maintenance of the tooth. Comparative studies with the nonmammalian tooth will facilitate further clarification of the mechanisms of mammalian tooth formation. In this study, basement membranes of the shark tooth in successive developmental stages was ultrastructurally examined for elucidation of their roles in odontogenesis. Teeth of a shark, Cephaloscyllium umbratile, were processed for thin section electron microscopy. Throughout the developmental stages the lamina densa of the basement membrane was made up of a fine network of "cords," irregular anastomosing strands known to be the major component of mammalian basement membranes. In the presecretory stage of the shark tooth, dental papilla cells were immobilized for their differentiation into odontoblasts by means of the binding of their processes to numerous narrow extensions of the lamina densa of the inner dental epithelium. In the secretory stage, a number of cords of the widened lamina densa were extended towards and bound to tubular vesicles of the forming enameloid. During the mineralization stage, fragments of the degrading enameloid matrix appeared to be moving through the lamina densa to the epithelial cells for processing. In the maturation stage, half of the lamina densa facing the enameloid was mineralized forming an advancing edge of mineralization of the enameloid. It provided strong binding and smooth transition of organic to mineral phase which may allow transportation of substances across the phases for enameloid maturation in a way similar to that reported in the mammalian tooth. These observations indicate that basement membranes of the developing shark tooth, as those in the mammalian tooth, play various roles, including anchoring, firm binding, and possible mediation of the transport of substances that are known to be vital for the development of the tooth.

Animals↗
PubMed2002

Cytogenetic analysis of infantile neuroblastomas by comparative genomic hybridization.

Neuroblastomas are heterogeneous tumors. Their clinical behavior varies from spontaneous regression to malignant progression. To investigate the cytogenetic heterogeneity of infantile neuroblastomas, we employed comparative genomic hybridization (CGH). To characterize chromosomal imbalances in 35 infantile neuroblastomas, we performed CGH and compared our results with those of other clinical and biological studies. The most frequent genetic imbalances were found in chromosome 17 (43%), including whole chromosome 17 gains in eight patients (23%) and 17q gains in seven patients (20%). A 1p loss and a 2p gain were detected in six patients each (17%). Losses of 11q and 14q were detected in two patients (6%) and one (3%) patient, respectively. The number of gains of 17q were significantly higher in DNA diploid tumors than in aneuploid tumors (P=0.006). Conversely, whole chromosome 17 gains were not found in DNA diploid tumors and/or MYCN amplification. Interestingly, nine of 17 tumors that were histologically evaluated showed a spontaneous regression and did not demonstrate any partial chromosomal abnormalities (i.e. 17q gain, 1p loss, 2p gain, 11q loss and 14q loss). These results suggest that a gene on chromosome 17q is associated with neuroblastoma progression. Finally, our observations indicate that the chromosomal imbalances observed in infantile neuroblastomas are different from those observed in older patients.

Blotting, Southern↗
PubMed2002

Effects of subminimal inhibitory concentrations of amoxicillin against Actinobacillus pleuropneumoniae.

The bactericidal effects of amoxicillin at below minimum inhibitory concentration (MIC) against Actinobacillus pleuropneumoniae NB001 were studied in vitro and in vivo. In vivo, the efficacy of amoxicillin on experimentally induced A. pleuropneumoniae infection in disease-free pigs was evaluated. Nine pigs were divided into three groups and all three groups were housed in the same room. Group I pigs were given long-acting amoxicillin injection 22 h prior to A. pleuropneumoniae challenge. Group II pigs were also A. pleuropneumoniae challenged but not given long-acting amoxicillin. Group III pigs were not treated. In vitro, A. pleuropneumoniae growth was suppressed in porcine blood with amoxicillin at below MIC. In vivo, clinical signs of disease were absent or mild in group I during 50 h post-challenge, and serum amoxicillin concentration was already less than MIC from 15 h post-challenge. Infected group II controls were severely affected by the infection, and mortality reached 100% within 50 h post-challenge. All non-treated pigs in group III became infected with NB001 from infected control pigs, and they displayed severe clinical signs of disease within 24 h post-challenge of groups I and II, and died within 50 h post-challenge of groups I and II.

Actinobacillus Infections↗
PubMed2002

Ventricular activation and recovery measured in electrocardiographic limb leads correlate with measurements from specific areas in body surface mapping.

AIMS: Dispersion of ventricular depolarization-repolarization in 12-lead electrocardiograms (ECGs) has been reported to provide noninvasive information on arrhythmogenicity. However, there are two methods to calculate the dispersion from ECGs including and excluding limb leads. The aim of this study was to examine whether temporal parameters from limb leads represent activation and repolarization of a particular part of the body surface. METHODS AND RESULTS: We compared the temporal parameters of activation time (AT), activation-recovery interval (ARI), and recovery time (RT) from limb leads of ECGs with those from an 87-lead body surface maps. The study population consisted of 50 normal subjects (25 men and 25 women, 19.4 +/- 1.6 years). The temporal parameters in leads I, II, and III were highly (r > 0.9) correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. The temporal parameters in leads aVR, aVL, and aVF showed a significant correlation (r > 0.8) with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. The mean AT, ARI, and RT from each limb lead of ECG were almost the same as those of unipolar leads over the corresponding areas of the body surface. CONCLUSIONS: These findings suggest that ATs, ARIs, and RTs from limb leads may represent those from unipolar leads of particular areas over the body surface in normal subjects. The temporal parameters from limb leads of ECGs may provide information on activation and repolarization as well as the precordial leads of ECGs.

Adolescent↗
PubMed2001

Identification of a new synaptic vesicle protein 2B mRNA transcript which is up-regulated in neurons by amyloid beta peptide fragment (1-42).

The treatment of Alzheimer's disease (AD) remains a major challenge because of the incomplete understanding of the triggering events that lead to the selective neurodegeneration characteristic of AD brains. Here we describe a new transcript of synaptic vesicle protein 2B (SV2Bb) mRNA that is up-regulated at mRNA level in neurons by amyloid beta peptide (Abeta) fragment (1-42). In comparison to SV2B this new mRNA encodes for the same protein but it has an elongated 3'-untranslated region (3'UTR) that contains several AU-rich (AUR) cis-acting elements which are probably involved in posttranscriptional regulating of SV2Bb translation. In conclusion, alteration of SV2B(b) expression appears to be involved in processes of neuronal degeneration.

3' Untranslated Regions↗
PubMed2001

Change in concentrations of luteinizing hormone subunit messenger ribonucleic acids in the estrous cycle of beef cattle.

Changes in the concentrations of LH subunit messenger ribonucleic acids (mRNAs) and in the LH content of the anterior pituitary of beef cattle were studied during the estrous cycle. Japanese beef cows were classified according to the expected day of the estrous cycle: stage I (early-luteal phase, days 1-4; day 1=day of ovulation), stage II (early-mid-luteal phase, days 5-10), stage III (late-mid-luteal phase, days 11-17) and stage IV (follicular phase, days 18-20), according to the morphology of the ovaries. The anterior pituitaries of the cows were collected and the levels of alpha and LHbeta subunit mRNAs were determined by slot-blot analyses. The LH content of the anterior pituitary was measured by radioimmunoassay. The level of alpha subunit mRNA in the pituitary of cows was highest in stage I and decreased significantly by stage II (P<0.05); thereafter it tended to increase. The level of LHbeta subunit mRNA did not change significantly during the estrous cycle. The LH content of the pituitary of cows was low in stage I and tended to increase by stage II, then to decrease from stage II to III, and to increase significantly from stage III to IV (P<0.05). These results suggest that the highest levels of gene expressions of alpha subunit in the anterior pituitary occur in the early-luteal phase of beef cows, while the LH content is increased most in the follicular phase. The enhanced gene expressions of common alpha subunit in the early-luteal phase could be important in replenishing the bovine anterior pituitary with LH, which is depleted of hormone by the LH surge or the enhanced pulsatile release.

Animals↗
PubMed2001

In vivo gene transfer to cerebral white matter lesions with a recombinant adenovirus vector.

Ischemic white matter lesions have been reported in rats after bilateral common carotid ligation (BCAL). Previously, comparing normotensive rats (WKY) with spontaneously hypertensive rats (SHR), we too found that sustained moderate ischemia with spontaneous hypertension accelerated the formation of ischemic white matter lesions. In this study, we explored the feasibility of gene therapy for lesioned white matter by means of an adenovirus vector expressing a reporter gene, LacZ. Using sham-operated and hypoperfused SHR as well as sham-operated and hypoperfused WKY, we demonstrated that (i) adenovirus vectors could deliver a foreign gene into oligodendrocytes and astrocytes in the cerebral white matter; (ii) the transduction efficiency was most effective in SHR after BCAL; and (iii) the level of alpha(V)-integrin was significantly correlated with adenoviral transduction efficiency.

Adenoviridae↗
PubMed2001

Serovars of Erysipelothrix species isolated from the tonsils of healthy cattle in Japan.

Serovars of 79 Erysipelothrix isolates recovered from the tonsils of healthy slaughtered cattle over a 1-year period in Japan were determined by an agar double-diffusion precipitation system using typing sera representing all the known serovars, 1 through 23 and type N, of Erysipelothrix. A total of 43 out of the 79 Erysipelothrix isolates could be classified into nine serovars but the remaining 36 isolates were untypable. Of 42 isolates identified as Erysipelothrix rhusiopathiae, 4, 6, 2, 3, 1,12, 13 and 1 isolates belonged to serovars 1b, 2, 5, 9, 12, 13, 19 and 21, respectively. One isolate belonged to Erysipelothrix tonsillarum serovar 3.

Animals↗
PubMed2001

Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances.

To detect and quantitate uneven cell surface molecules, such as blood group antigens on a blood cell and immunoglobulin molecules on a mast cell, an improved method of thermal lens microscopy was employed. The antigen molecules were immunologically stained with their antibodies, which were labeled with colloidal gold. Since the surface of the biological cells was not flat but spherical, the focal point of the probe laser beam inevitably deviated from the sample surface on the moving stage. Therefore, the deviation of the focal point of the probe beam was corrected by adjusting the phase of the signal. Using this technique, a three-dimensional antigen distribution on each cell surface was imaged. Despite the convex surface of cells, labeled colloidal gold was correctly quantified. In the measurement of erythrocyte antigens, a small quantity of Lewis antigens was successfully detected on the umbilical cord erythrocytes. Immunoglobulin E on a mast cell, derived from the allergic human mucosa fungus, was also observed by this method, and the distribution of IgE molecules on the cell surface was quantitatively imaged. A thermal lens microscope, which measures spherical samples correcting the deviation, made it possible for us to observe and assay the substances on biological specimens that have complicated forms, such as living cells in vivo or in situ.

Antigens, Surface↗
PubMed2001

The effect of transforming growth factor-alpha on the progression of decidualization in rats.

Although transforming growth factor-alpha (TGF-alpha), one of the epidermal growth factor (EGF) family of growth factors, is expressed in the rat decidual cells, its roles in decidualization remain to be elucidated. This study examined the effect of TGF-alpha on the progression of decidualization and a possibility for involvement of prostaglandins (PGs) in its action. Pseudopregnant rats were ovariectomized and given endometrial trauma on Day 5 (vaginal plug = Day 1) and were daily treated with 2 mg progesterone thereafter. Immunocytochemical localization of EGF receptor was distinctly evident in the decidual, stromal and epithelial cells on Day 7. Continuous infusion of TGF-alpha (500 pg/h) into the uterine lumen from Day 7 significantly increased weights of the uterine horns with deciduomata on Day 9. Although injection on Day 7 of indomethacin, an inhibitor of PGs synthesis, decreased the uterine weight, this effect was overridden by the continuous infusion of this growth factor. These results demonstrated the stimulatory action of TGF-alpha on the progression of decidualization. Further, TGF-alpha increased the secretion of prostaglandin E in cultured decidual and/or stromal cells dose-dependently, suggesting the possibility that PGs mediate the action of this growth factor.

Animals↗
PubMed2001

Enhanced VEGF production and decreased immunogenicity induced by TGF-beta 1 promote liver metastasis of pancreatic cancer.

TGF-betas are multifunctional polypeptides that regulate cell growth and differentiation, extracellular matrix deposition, cellular adhesion properties, angiogenesis and immune functions. In this study, we investigated the effect of TGF-beta1 on liver metastasis and its mechanism by using human pancreatic cancer cell lines Panc-1, Capan-2, and SW1990. Capan-2 and SW1990 cells demonstrated enhanced liver metastatic potential by in vivo splenic injection with TGF-beta1. Consequently, we examined the role of TGF-beta1 on in vitro angiogenesis and received cytotoxicity by peripheral blood mononuclear leukocytes (PBMLs). While TGF-beta1 slightly decreased cell proliferation, it also upregulated VEGF production in all cancer cells examined. The binding of PBMLs to cancer cells and cancer cell cytotoxicity during co-culture with PBMLs were remarkably decreased by treatment with TGF-beta1. Panc-1 cells revealed no liver metastasis despite their high immunogenetic and angiogenetic abilities, which was attributed to a lack of expression of the cell surface carbohydrates that induce attachment to endothelial cells. We concluded that the presence of TGF-beta1 in the microenvironment of tumour site might play an important role in enhancing liver metastasis of pancreatic cancer by modulating the capacity of angiogenesis and immunogenicity.

Animals↗