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Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 109 records · Page 6Linked to original sources

Quantification of TGF-beta1 mRNA along rat nephron in obstructive nephropathy.

Unilateral ureteral obstruction (UUO) leads to interstitial fibrosis of the obstructed kidney, and transforming growth factor-beta1 (TGF-beta1) is thought to play an important role in this process. Although increased TGF-beta1 mRNA expression in the obstructed kidney has been demonstrated, the source of the increased TGF-beta1 remains to be elucidated. To determine the precise localization of TGF-beta1 in the obstructed kidney, we examined TGF-beta1 mRNA expression using in situ hybridization and competitive RT-PCR in rats with UUO. In situ hybridization demonstrated that TGF-beta1 mRNA expression was preferentially increased in tubular epithelial cells and to a lesser degree in infiltrating macrophages in obstructed kidneys. Quantitative analysis using competitive RT-PCR in microdissected nephron segments revealed that levels of TGF-beta1 mRNA in obstructed kidneys relative to control kidneys increased significantly in proximal tubules, thick ascending limbs of Henle, and distal convoluted tubules, whereas those in glomeruli and collecting ducts did not change significantly. Of the tubular segments, the proximal tubules appeared to predominantly contribute to increased TGF-beta1 mRNA. Our findings suggest that renal tubules, particularly proximal tubules, are the main contributors to increased TGF-beta1 mRNA expression in obstructed kidneys and to the subsequent interstitial fibrosis.

Animals↗

The expression of thymidine phosphorylase suppresses spontaneous apoptosis of cancer cells in esophageal squamous cell carcinoma.

OBJECTIVE: Thymidine phosphorylase (TP) is an enzyme which converts thymidine to thymine. TP is expressed in a variety of human carcinomas and is known to be a potent angiogenic factor. A recent in vitro study indicated that TP is involved in the intracellular apoptotic signal transduction pathway. The aim of this study was to investigate the correlations between the expression of TP, microvessel density (MVD) and the occurrence of spontaneous apoptosis in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of TP, intratumoral MVDs and percentages of apoptotic cancer cells, expressed by the apoptotic index (AI), of 155 tumors from 155 patients with ESCC were analyzed by immunohistochemistry and compared. RESULTS: Positive TP expression in cancer and stromal cells was detected in 89 (57.4%) and 104 (67.1%) cases, respectively. The mean MVD and mean AI of the 155 tumors were 288/mm(2) (range: 36-668/mm(2)) and 2.1% (range: 0-20.4%). The mean MVD of 104 tumors with TP-positive stromal cells (336/mm(2)) was higher than that of 51 tumors with TP-negative stromal cells (188/mm(2), p < 0.001). However, the mean MVD of 89 tumors with TP-positive cancer cells (293/mm(2)) did not differ from that of 66 tumors with TP-negative cancer cells (280/mm(2), p = 0.509). On the other hand, the mean AI of 89 tumors with TP-positive cancer cells (1.2%) was lower than that of 66 tumors with TP-negative cancer cells (3.4%, p < 0.001). However, the mean AI of 104 tumors with TP-positive stromal cells (1.9%) did not differ from that of 51 tumors with TP-negative stromal cells (2.6%, p = 0.058). No significant correlation between the MVDs and the AIs was observed (rho = -0.067, p = 0.409). CONCLUSION: In ESCC, TP may play an important role in tumor progression by increasing microvessels and suppressing apoptosis of cancer cells.

Aged↗

Clinicopathological findings in patients with gastric adenocarcinoma with familial aggregation.

BACKGROUND/AIMS: The clinicopathological characteristics of gastric cancer (GC) with a positive family history of site-specific GC have not been well discussed. The aim of this study was to estimate the risk of familial aggregation of GC in a hospital-based case-control study and to analyze the clinicopathological characteristics of GC with familial aggregation of GC. METHODS: Our series was comprised of 926 histologically confirmed patients with GC (588 males and 338 females) and 2,052 non-cancer outpatients between 1985 and 1996. The odds ratios (ORs), as estimators of relative risks, together with the corresponding 95% confidence intervals (CIs) for a family history of GC and for a family history of other cancers were calculated. Moreover, the clinicopathological findings of patients with GC who had a GC family history were compared with those of patients with GC who had no GC family history. RESULTS: A positive family history of GC was associated with a statistically significant increase in the risk of GC (OR = 2.15; 95% CI = 1.77-2.63), while no association was observed between the risk of GC and a family history of other cancers (OR = 1.11; 95% CI = 0.91-1.36). The incidence of a multifocal occurrence of GCs was higher in patients with a family history of GC (19.4%) than in patients without a family history of GC (12%, p = 0.005). The risk (OR) of occurrence of multiple cancers in the stomach in patients who had a family history of GC was 1.77 (95% CI = 1.19-2.64). CONCLUSIONS: Our results suggest that a family history of GC seemed to be a risk factor for the development of GC. Further, a family history of GC was found to be associated with a multifocal occurrence of GC.

Adenocarcinoma↗

Local immune response in squamous cell carcinoma of the uterine cervix.

The role of Langerhans cells as antigen-presenting cells was examined in cervical carcinomas. Frozen samples were obtained from 34 women with stage Ib and II cervical carcinomas. Langerhans cells (CD1), T lymphocytes (CD4 and CD8), B lymphocytes (CD22), and natural killer (CD57, NK) cells were all quantitatively assessed in cervical carcinomas using immunohistochemical methods. These results were related to the MHC class I and II expression on the tumor cells. The majority of Langerhans cells were distributed among cancer cells and they were positively correlated with CD4+, NK and B cells in cervical carcinomas. This is suggestive of the presence of local immune response. The numbers of Langerhans, CD4+, CD8+ and NK cells did not significantly correlate with age at operation, lymph node metastases or depth of cervical wall invasion. The downregulation of MHC class I expression found in 8 (24%) carcinomas was not associated with the decrease in the number of immunologic cells. The upregulation of MHC class II expression found in 26 (76%) carcinomas was significantly associated with the increase in the number of Langerhans cells (p < 0.007). However, the association between the upregulation of MHC-II expression and CD4+ cells did not reach statistical significance (p < 0.07). This is probably due to a small case in this study. MHC-II-restricted immunity may partly contribute to the local immune response in stages Ib and II squamous cell carcinoma of the uterine cervix.

Adult↗

Clinicopathological significance of cathepsin D expression in gastric adenocarcinoma.

OBJECTIVE: An estrogen-regulated lysosomal protease, cathepsin D, has been detected in a variety of tissues. This proteinase has been described as closely associated with tumor progression and metastasis in malignant tumors. The purpose of this study was to determine the clinicopathological and prognostic significance of cathepsin D expression in gastric adenocarcinoma. METHODS: In a consecutive series of 478 patients with gastric carcinoma (median follow-up period: 93 months, range: 1-285 months), cathepsin D expression in tumors was quantitatively analyzed with immunohistochemistry using a monoclonal antibody against cathepsin D (clone: 1C11). The percentage of cathepsin-D-positive cancer cells (the CD index) was calculated. In addition, the amount of cathepsin-D-positive stromal cells was evaluated; three grades (high, intermediate, and low) were used for the classification. RESULTS: The mean CD index of 478 tumors was 12.8% (range: 0-100%, median: 8%). The mean CD index of diffuse-type gastric carcinomas (14.9%) was significantly higher than that of intestinal-type carcinomas (10.1%, p < 0.0001). Cathepsin D expression of cancer cells was significantly associated with the depth of tumor invasion in both types. The percentage of tumors with high cathepsin D expression in stromal cells was significantly higher in well-differentiated tumors (25.5%) than in moderately differentiated (12.8%) or in poorly differentiated tumors (19.1%). Cathepsin D expression of stromal cells was significantly associated with the depth of tumor invasion in the intestinal type, in contrast to the diffuse type. Highly expressed cathepsin D in cancer cells was associated with a poor prognosis in both types of carcinoma, but in stromal cells highly expressed cathepsin D was associated to a poor prognosis in the intestinal type only. CONCLUSION: These results indicate that cathepsin D expression in cancer cells may play an important role in tumor progression in diffuse-type gastric carcinoma, whereas in the intestinal type of carcinoma, cathepsin D expression in stromal cells may play an important role in tumor progression.

Adenocarcinoma↗

Mechanism of burn injury during magnetic resonance imaging (MRI)--simple loops can induce heat injury.

To determine the mechanism of burn injury associated with magnetic resonance imaging (MRI), the induced current in the loops of a conductive lead was measured. Seven types of loops with effective areas within the range from 100 to 12 000 cm2 were made and then each loop was placed in the bore of a whole-body MR system at 0.5 T and MRI was carried out. During radio frequency (RF) irradiation, an induced voltage was observed in loops that were placed with their axes parallel to the linearly polarized transmitting RF field. The voltage had a sincfunction characteristic and was within the range 55-235 V at the RF pulse sequence for usual MR imaging. When the axis was vertical, negligible current was observed. A resistor inserted into the circuit of a 30 x 40 cm loop sparked and burned out. Simple loops of conductive material may result in the induction of a large and potentially hazardous voltage in the imaging system. Self-resonance of such a loop may add greatly to hazards by increasing the effective coupling to the RF transmitter. Also, impedance matching of the inserted resistor with the impedance of the loop increases the dissipated power at the resistor.

Burns, Electric↗

Characterization of anti-myocardial autoantibodies in Japanese patients with dilated cardiomyopathy.

Few previous reports have comprehensively screened all the anti-myocardial autoantibodies (AMCA) in relation to other clinical profiles in patients with idiopathic dilated cardiomyopathy (IDC), so the present study used both immunohistochemistry (FITC) and immunoblotting (IB) for screening patients with IDC in order to characterize the clinical significance of AMCA. Sera were collected from 100 patients with IDC and age-matched 100 healthy control subjects (CTL). For FITC, an unfixed frozen section of human myocardium was used for the standard indirect immunofluorescence; for IB, total cardiac homogenates of the same myocardium were blotted to serum at 2 sets of dilution (1:200 and 1:10,000). The positive rates of AMCA detection for each method were as follows (IDC vs CTL); 39% vs 6% for FITC, 38% vs 4% for IB (1:200), and 10% vs 0% for IB (1:10,000). Fifty-nine patients with IDC and 8 CTL were positive for AMCA by either method, and 18 patients with IDC and 2 CTL were positive for AMCA by both methods. IB-positivity at 1:200 was an independent predictor by multiple logistic regression analysis of non-sustained ventricular tachycardias as well as left ventricular end-diastolic diameter and plasma norepinephrine concentration.

Adult↗

Diabetic ketoacidosis associated with recurrent pulmonary edema and rhabdomyolysis in a patient with Turner's syndrome.

Turner's syndrome is a condition involving total or partial absence of one X chromosome and has been associated with a number of diseases including non insulin dependent diabetes mellitus, abnormalities of glucose metabolism and hypothreosis. There have been many case reports in which Turner's syndrome is associated with type 2 diabetes, but the association with type 1 diabetes and/or life threatening complications is very rare. We present an unusual case of a patient with Turner's syndrome who has type 1 diabetes and is complicated with ketoacidosis, severe acute and recurrent pulmonary edema and rhabdomyolysis.

Acidosis↗

Lung lesions induced by intratracheal instillation of vanadium pentoxide powder in rats.

To clarify acute toxicity and histopathological changes in the lung after exposure to V2O5 powder, rats (SD, male, n=66) were observed for 4 weeks after an intratracheal administration of V2O5 powder (geometric mean diameter 0.31 microm, geomertic standard deviation sigmag=2.19) at three doses (0.88, 3.0, 13.0 mg/kg body weight). The histopathological lung lesions were developed dose-dependently, and characterized by exudative inflammation, injury of alveolar macrophages, and swelling and mucous degeneration in the broncho-bronchiolar epithelia. Growth rate of the V2O5 powder-instilled rat was also retarded dose-dependently. The V2O5 powder used was composed of not coagulated but well dispersed particles consisting of vanadium pentoxide of more than 99.8% (w/w) with vanadium tetraoxide of less than 0.2%. The V2O5 powder was found to be 8 times more soluble in an artificial biological fluid "Gamble's solution" than in a pure water. From the present findings as well as those from the related literature, it was inferred that the histopathological lesions induced by the intratracheally instilled V2O5 powder are caused not only by the V2O5 particles per se but also by vanadium ions dissolved from the particles into the lung fluid.

Air Pollutants, Occupational↗

Expression of the SART3 antigens in oral cancers.

It was previously reported that SART3 is a tumor-rejection antigen recognized by HLA-A24-restricted cytotoxic T lymphocytes (CTLs). This study investigated expression of the SART3 antigen in oral cancer as a candidate of tumor antigens for use in specific immunotherapy. The SART3 antigen was detected in all of the oral cancer cell lines tested, 24 of 31 (77%) oral cancer tissue samples, 0 of 3 oral benign tumors and 0 of 3 normal oral tissues. Oral cancer cell lines had the ability to stimulate IFN-gamma production by the HLA-A24-restricted and SART3-specific CTLs that were established from the peripheral blood mononuclear cells (PBMCs) of an esophageal cancer patient. Therefore, the SART3 antigen could be an appropriate vaccine candidate for a large number of oral cancer patients.

Antigens, Neoplasm↗

Color/power Doppler sonographic differential diagnosis of superficial lymphadenopathy: metastasis, malignant lymphoma, and benign process.

OBJECTIVE: Differentiation of lymph nodes as metastasis, malignant lymphoma, and benign lesions by gray scale and color/power Doppler ultrasonography has been reported. In this study we sought to determine patterns of abnormal vascularity, the relationship between diagnostic criteria and node size, and which vessel in the node was best suited for Doppler spectral analysis. Extrahilar vessels, defined as vessels entering through the lymphatic surface and not through the hilus, were also investigated. METHODS: One hundred twenty-nine nodes were examined by color/power Doppler ultrasonography. RESULTS: Extrahilar vessels were seen in 85.4% of metastatic, 40.5% of lymphomatous, and 7.7% of benign nodes regardless of node size. The mean pulsatility index and resistive index values of metastatic nodes were higher than those of benign nodes regardless of their size. Those of lymphoma were intermediate compared with the others. CONCLUSIONS: A pulsatility index greater then 1.3 and a resistive index greater than 0.72 suggested malignancy as measured from any vessel.

Breast Neoplasms↗

[YAG laser-induced reperfusion of photothrombotic middle cerebral artery occlusion in rats].

The laser-driven photochemical occlusion of middle cerebral artery(MCA) is much easier, and less traumatic than standard electrocautery or even clip methods, while the infarct size is fairly reproducible. This study aimed to establish the system for YAG laser-induced reperfusion of photothrombotic MCA occlusion. Male spontaneously hypertensive rats(5-7 months old, 350-450 g) were anesthetized with halothane, endotracheally intubated, and mechanically ventilated. The photosensitizing dye rose bengal(20 mg/kg body weight) was administered intravenously over 90 sec starting simultaneously with 3 min of krypton laser irradiation(568 nm, 20 mW). The irradiated middle cerebral artery was completely occluded by an intraluminal thrombus. A YAG laser operating at 355 nm(16 mW, 15 Hz) was focused with a cylindrical lens and positioned with a mirror onto the occluded distal MCA. This YAG laser irradiation for approximately 3 min caused reperfusion of the thrombosed distal MCA. We demonstrated a novel method of reperfusion in the photothrombotic MCA occlusion model. This reperfusion model should facilitate study of the therapeutic window for reversibility in thrombotic stroke.

Animals↗

Correlation between spontaneous apoptosis and the expression of angiogenic factors in advanced gastric adenocarcinoma.

The aim of this study was to investigate whether angiogenic factors influence the occurrence of spontaneous apoptosis in advanced gastric cancer. The apoptotic indices (AIs) of 97 tumors from 97 patients with advanced gastric cancer (pT3, pN0, pM0, Stage II) were analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) method. Intratumoral microvessel densities (IMVDs) of tumors stained with anti-CD34 monoclonal antibody were quantified under x 200 magnification using computer-assisted image analysis. The expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF), thymidine phosphorylase (dThdPase), transforming growth factor-alpha (TGF-alpha), and p53 were analyzed immunohistochemically and compared with IMVDs and AIs. The mean IMVD of the 97 tumors was 365/mm2 (range 147-990/mm2). The mean AI of tumors was 2.1% (range 0-11.3%). A significant inverse correlation between the AIs and the IMVDs was shown (p = -0.278, P = 0.0064). The mean IMVDs of tumors with high expressions of dThdPase, TGF-alpha, or p53 were significantly higher than those of tumors with low expressions of these factors. The mean AI of tumors with high expressions of dThdPase was significantly lower than that of tumors with low expressions of dThdPase (P = 0.023). However, no significant correlations were detected between AIs and the expression levels of VEGF, TGF-alpha, or p53. In gastric cancer, dThdPase may play an important role in tumor progression by increasing microvessels and by suppressing apoptosis of cancer cells.

Adenocarcinoma↗

Thiopental enhances human platelet aggregation by increasing arachidonic acid release.

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30-300 microM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5-15 microM), epinephrine (0.1-20 microM) arachidonic acid (0.5-1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30-500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 microM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental (> or = 100 microM). Thiopental (> or = 100 microM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 microM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 microM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.

Arachidonic Acid↗

[Immunohistochemical study of dihydropyrimidine dehydrogenase (DPD) and p53 in biopsied specimens of esophageal cancer before chemoradiotherapy].

We studied whether the immunohistochemical status of dihydropyrimidine dehydrogenase (DPD) and p53 can be used to predict the sensitivity to chemoradiotherapy (CRT) in patients with esophageal cancer. In 19 patients who did not undergo preoperative CRT, the immunoreactivity of DPD and p53 in biopsied specimens correlated well with those in surgically resected specimens (DPD: 100%, p53: 73%). Fifteen patients were treated with 5-FU (250-300 mg/body/day: day 1-5, 8-12), low-dose cisplatin (10 mg/body/day: day 1, 8) and radiotherapy (30-40 Gy). The response rate (CR + PR) for CRT in these patients was 40%. All tumors that showed CR or PR demonstrated low expression of DPD. However, all tumors with high DPD expression showed MR or NC. However, the expression of p53 did not correlate with the response rate for CRT. Therefore, the effect of CRT for esophageal cancer may be predicted by immunohistochemical examination of DPD in biopsied tumor specimens.

Antineoplastic Combined Chemotherapy Protocols↗

[Two cases of effective weekly paclitaxel administration for metastatic breast cancer].

We report two cases of effective weekly paclitaxel (TXL) administration for metastatic breast cancer. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. Case 1: A 66-year-old woman was treated with adriamycin, cyclophosphamide, doxifluridine (5'-DFUR), fadrozole, medroxyprogesterone acetate (MPA) and pamidronate for pleural, mediastinal and supraclavicular lymph nodes and skull metastases. She complained of hoarseness and supraclavicular and mediastinal lymph nodes had developed, for which she received weekly TXL administration. Metastatic lymph nodes had disappeared 3 months after administration. Case 2: A 61-year-old woman was treated with CMF therapy, 5'-DFUR, tamoxifen, MPA fadrozole and pamidronate for bone metastasis and local recurrence. She received weekly TXL administration for an axillary recurrence and contralateral supraclavicular lymph node metastases. Metastatic and recurrent lesions had disappeared 3 months after administration. The toxic events were leukopenia (grade 1) and peripheral neuropathy (grade 1). No major adverse effects were observed in either case.

Aged↗