Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 91 records · Page 5Linked to original sources

PubMed2001

Serum p53 antibody as a useful marker for monitoring of treatment of superficial colorectal adenocarcinoma after endoscopic resection.

BACKGROUND: Mutation of the p53 gene is a genetic alteration found in human cancers. Overexpression of p53 has been found to induce antibody production in serum, and, recently, the simple detection of serum antibody has been made possible. The aim of this study was to evaluate the potential role of serum p53 antibody in the early diagnosis of superficial colorectal cancer and in the monitoring of its treatment after endoscopic resection. METHODS: In a prospective study, our subjects were 27 patients with superficial colorectal adenocarcinomas, whose results were compared with those in 38 patients with benign adenomas; all patients were treated by endoscopic resection. The correlation between serum p53 antibody levels before and within 3 weeks after resection was determined, using an immunoassay. Immunohistological staining for p53 was also performed, and its sensitivity was compared with that of two other tumor markers. RESULTS: Preoperatively, serum p53 antibody was detected in 63.0% (17/27) patients with adenocarcinoma and in 2.6% (1/38) patients with adenoma, showing a significant difference (P < 0.001). However, the two other markers carcinoembryonic antigen (CEA) and carbohydrate antigen CA19-9, showed no significant difference between superficial colorectal adenocarcinoma and adenoma. The serum p53 antibody status was strongly correlated with p53 immunostaining in adenocarcinoma (P = 0.0065), but there was no significant correlation in adenoma (P = 0.973). Sixteen (94.1%) of 17 seropositive adenocarcinoma patients, showed negative conversion after complete tumor resection, and all these 16 patients remained seronegative. CONCLUSION: The detection of serum p53 antibody is expected to serve as a new genetic marker, determined by serological analyses, for aiding in the early diagnosis of superficial colorectal cancer and indicating its local curability after endoscopic treatment.

Adenocarcinoma↗

PubMed2001

Phytochrome-mediated control of COP1 gene expression in rice plants.

We isolated a COP1 cDNA from rice and found that it could complement the Arabidopsis cop1-4 mutant. The putative rice COP1 protein has the Ring-finger, coiled-coil. and WD-40 repeat domains, which are also conserved in pea, tomato, and mammalian COP1 proteins. The degree of overall identity between rice COP1 and Arabidopsis COP1 is 73%, and the similarity value is 83%. Expression of rice COP1 was detected in almost all plant tissues, with the level being relatively higher in calli and very low in etiolated leaves. The expression level was positively controlled by light in etiolated and green leaves. At the end of the light period, expression of the gene in green leaves could be down-regulated by far-red light. This far-red light effect could be prevented by subsequent irradiation with red light. These results indicate that phytochrome regulates rice COP1 expression.

Amino Acid Sequence↗

PubMed2001

Indications for curative resection of advanced gallbladder cancer with hepatoduodenal ligament invasion.

PURPOSE: Hepatoduodenal ligament invasion (HLI) is an inhibiting factor for the curative resection of advanced gallbladder cancer. The aim of this study was to clarify the indications for surgical resection in patients with advanced gallbladder cancer with and without HLI by analyzing outcomes. METHODS: The subjects were 58 patients with advanced gallbladder cancer who underwent aggressive resection, and 20 nonresected patients diagnosed as haring HLI. The presence of stromal cancerous infiltration at six sites in the hepatoduodenal ligament was investigated. The extent of cancer spread was classified into two grades by the number of sites where cancer cells detected: low grade, one or two invasion sites; high grade, three or more sites. RESULTS: Pancreatoduodenectomy, vascular reconstruction, and extensive hepatectomy were frequently performed in the patients with HLI. The cumulative 5-year-survival rate of the HLI patients was 10.9%, significantly worse than that of the resected patients without HLI (46.6%; P < 0.01). Patients with paraaortic lymph node metastasis died within 1 year. The cumulative 5-year-survival rate after curative resection was 38.1%, significantly better than that after noncurative resection (0%; P < 0.05). The survival was significantly worse in patients with high-grade invasion than in these with low-grade invasion (P < 0.05), being equivalent to that in the nonresection patients. Of four factors, operative curability, hepatic lobectomy, HLI grade, and paraaortic lymph node metastasis, the HLI grade and hepatic lobectomy were considered to be significant prognostic factors by Cox's multivariate analysis (backward stepwise method). CONCLUSIONS: Aggressive surgical resection for curative purposes should be limited to patients with low-grade HLI and metastasis-negative paraaortic lymph nodes.

Adult↗

PubMed2001

Adjuvant therapies using biliary stenting for malignant biliary obstruction.

The aim of this study was to analyze the patency of expandable metallic stents in malignant biliary obstruction and to evaluate the efficacy of adjuvant therapy accompanied by biliary stenting. We analyzed 29 patients in whom bile duct stenting was performed for malignant biliary obstruction. Their types of disease were: hilar ductal carcinoma (n = 8), gallbladder carcinoma (n = 11), and pancreatic carcinoma (n = 10). Initially, 46 expandable metallic stents were placed in 29 patients. In 23 of the 29 patients, adjuvant therapy was administered. Seventeen patients underwent radiotherapy, and 16 patients received various systemic chemotherapies. In principle, hyperthermia was performed twice a week, simultaneously with radiotherapy. Patient survival and the probability of stent patency were calculated using actuarial life table analysis. There was no significant difference in stent patency among the patients according to type of disease. Hyperthermia did not influence the stent patency rate. The median stent patency time was significantly greater in the chemo-radiation group than in the no-adjuvant therapy group: 182 days versus 68 days, respectively (P = 0.017). Moreover, a significant increase was seen in the median survival time in the chemo-radiation group: 261 days versus 109 days (P = 0.0337). Complications occurred in 9 patients (31.0%). Stent occlusion occurred in 6 patients (20.7%), with all of these patients managed successfully using a transhepatically placed new expandable metallic stent, employing the stent-in-stent method. Stent migration occurred in 2 patients after radiotherapy. Adjuvant therapies such as radiotherapy and systemic chemotherapy, in combination with stent insertion, resulted in an increase in the patency period of expandable metallic stents and in increased patient survival time.

Aged↗

PubMed2001

Presence of serum p53 antibodies is associated with decreased in vitro chemosensitivity in patients with esophageal cancer.

Resistance to chemotherapy remains a serious problem inhibiting the successful treatment of advanced esophageal cancer. A number of studies have revealed that p53 genetic alteration and protein overexpression can predict chemosensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conducted to examine whether analysis of serum p53 Abs could predict the chemosensitivity of esophageal cancer. Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 19 patients with esophageal squamous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues were also analyzed for chemosensitivity by the histoculture drug response assay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5-FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 protein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibition index of patients positive for p53-Abs was significantly lower than that of patients negative for p53-Abs (P < 0.001). This tendency was also observed in the inhibition index to 5-FU. The presence of serum p53-Abs was associated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, the detection of serum p53-Abs is suggested to be useful for predicting chemosensitivity in patients with esophageal cancer.

Aged↗

PubMed2001

Preclinical study of adenoviral p53 gene therapy for esophageal cancer.

An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%-80% at 100 plaque-forming units (PFU)/cell and 80%-100% at 300PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer.

Adenoviruses, Human↗

PubMed2001

Long-term outcomes of immunosuppressed renal transplant recipients with malignancies.

This study analyzes ten cases of malignancy in a cohort of 183 renal transplant recipients, examining surgical management, postoperative immunosuppressive therapy, and long-term outcome. One of these ten patients, who had malignant lymphoma of the jejunum, died of the neoplasm, but the other nine patients did not show any signs of tumor recurrence after removal. All of these nine patients, except for one who had transplant renal cell carcinoma (RCC), received the same dose of immunosuppressive agents after surgery for the malignant disease. Seven patients were still alive at the time of this report, six of whom had good transplant renal function. The findings of this study indicate that even if immunosuppressive agents predispose to the development of cancer, it is not necessary to reduce their dose after removal of the tumor.

Adult↗

PubMed2001

Successful surgical treatment of renal cell carcinoma in a transplanted kidney from a cadaveric donor: report of a case.

Posttransplant renal cell carcinoma (RCC) usually arises in the native kidneys of renal transplant recipients rather than in the transplanted kidney. This report describes a case of RCC that developed in the transplanted cadaveric kidney in a 37-year-old male recipient 9 months after transplantation. An en bloc radical transplant nephrectomy was performed, and he has subsequently remained stable on hemodialysis for 3 years without any sign of recurrence.

Adenocarcinoma↗

PubMed2001

Factors Influencing Visual Acuity Following Vitrectomy for Exudative Age-related Macular Degeneration.

Purpose: We investigated the influence of various factors on visual results in patients undergoing surgical removal of choroidal neovascular membranes (CNVM) caused by age-related macular degeneration (AMD).Subjects and Methods: This study was performed in 55 eyes of 55 patients who underwent surgical removal of CNVM for AMD and followed them for 6 months or more. The criterion for surgical eligibility was active subfoveal choroidal neovascular membrane of 0.5 or more disc diameter above the retinal pigment epithelium with visual acuity of 0.3 or worse. We investigated the influence of various factors on the logarithm of the minimum angle of resolution (log MAR) final visual acuity. The factors were age, symptom duration, preoperative log MAR visual acuity, CNVM diameter, mean deviation with visual field analyzer, previous laser treatment, posterior vitreous detachment, findings of indocyanine green angiography, operative complications, and recurrence of CNVM.Results: Better preoperative visual acuity, shorter symptom duration, and smaller CNVM diameter were correlated with better postoperative final visual acuity.Conclusions: Surgical excision of subfoveal CNVM may be the better therapeutic choice in selected cases with AMD.

Journal Article↗

PubMed2001

Putidaredoxin-cytochrome P450cam interaction.

Cytochrome P450cam (P450cam) catalyzes the monooxygenation of D-camphor. During the enzymatic reaction, oxyferrous, D-camphor-bound P450cam forms a binary complex with reduced putidaredoxin as an obligatory reaction intermediate. We have found that reduced putidaredoxin undergoes EPR-detectable conformational changes upon formation of the intermediate complex and also upon formation of a binary complex with CO- or NO-ferrous, D-camphor-bound P450cam. The structural changes in putidaredoxin are almost identical irrespective of the ligand bound to P450cam, and distinct from and significantly larger than those induced by unliganded ferrous P450cam. The binary complex formation also induce conformational alterations in the CO- and NO-ferrous, D-camphor-bound P450cam, thereby evoking simultaneous changes in the structure of the two proteins. A molecular basis and roles of such structural changes in the D-camphor monooxygenation are discussed.

Bacterial Proteins↗

PubMed2001

Intratubular calcification in a post-renal transplanted patient with secondary hyperparathyroidism.

In this article, we present a case in which marked intratubular calcification occurred in the transplanted kidney. The patient received living renal transplantation without control of severe secondary hyperparathyroidism, and the tacrolimus hydrate was used as an immunosuppressive agent, the adverse effects of which can induce intratubular calcification. Biopsy of the renal allograft revealed many intratubular calcifications in the cortex region of the specimen, although the histological grade was borderline for the Banff classification. The pathogenic causes of intratubular calcification were difficult to distinguish from the adverse effects of tacrolimus and the uncontrolled hyperparathyroidism.

Biopsy↗

PubMed2001

Hypertrophic pachymeningitis with anti-neutrophil cytoplasmic antibody (p-ANCA), and diabetes insipidus.

We treated a patient with idiopathic cranial hypertrophic pachymeningitis and elevated serum titer of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactive against myeloperoxidase. This 67-year-old man showed multiple cranial nerve-palsies, central diabetes insipidus (DI), and an intrasellar mass. DI and intrasellar mass had been present for 3 years, and DI had been well controlled by intranasal desmopressin. His nerve-palsies were most likely caused by thickened dura matter detected by the brain MRI. Granuloma may develop in the sella, and MRI findings in our patient are compatible to it. Corticosteroid and oral cyclophosphamide therapy improved his neurological symptoms and serum p-ANCA level with showing good correlation. DI improved temporally for 2 months. Few other cases of hypertrophic pachymeningitis with elevated p-ANCA have been reported, however the etiology is unknown. As p-ANCA antibodies have been detected in many of vasculitides, microvasculitis may be involved in some cases of idiopathic hypertrophic pachymeningitis.

Aged↗

PubMed2001

Activation of potassium conductance by ophiopogonin-D in acutely dissociated rat paratracheal neurones.

1. The effect of ophiopogonin-D (OP-D), a steroidal glycoside and an active component of Bakumondo-to, a Chinese herbal antitussive, on neurones acutely dissociated from paratracheal ganglia of 2-week-old Wistar rats was investigated using the nystatin-perforated patch recording configuration. 2. Under current-clamp conditions, OP-D (10 microM) hyperpolarized the paratracheal neurones from a resting membrane potential of -65.7 to -73.5 mV. 3. At the concentration of 1 microM and above, OP-D concentration-dependently activated an outward current accompanied by an increase in the membrane conductance under voltage-clamp conditions at a holding potential of -40 mV. 4. The reversal potential of the OP-D-induced current (I(OP-D)) was -79.4 mV, which is close to the K(+) equilibrium potential of -86.4 mV. The changes in the reversal potential for a 10 fold change in extracellular K(+) concentration was 53.1 mV, indicating that the current was carried by K(+). 5. The I(OP-D) was blocked by an extracellular application of 1 mM Ba2+ by 59.0%, but other K(+) channel blockers, including 4-aminopyridine (3 mM), apamin (1 microM), charybdotoxin (0.3 microM), glibenclamide (1 microM), tolbutamide (0.3 mM) and tetraethylammonium (10 mM), did not inhibit the I(OP-D). 6. OP-D also inhibited the ACh- and bradykinin-induced depolarizing responses which were accompanied with firing of action potentials. 7. The results suggest that OP-D may be of benefit in reducing the excitability of airway parasympathetic ganglion neurones and consequently cholinergic control of airway function and further, that the hyperpolarizing effect of OP-D on paratracheal neurones via an activation of K(+) channels might explain a part of mechanisms of the antitussive action of the agent.

Action Potentials↗

PubMed2001

Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion gene transfer (uracil phosphoribosyl transferase and herpes simplex virus thymidine kinase).

Advanced esophageal cancers are highly malignant and frequently resistant to 5-fluorouracil (5-FU). Escherichia coli uracil phosphoribosyltransferase (UP) is a pyrimidine salvage enzyme that alters 5-FU metabolism and sensitivity. A recombinant adenovirus encoding the UP gene (AxCA.UP) has been applied in gastric cancer gene therapy to sensitize cancer cells to lower concentrations of 5-FU. We have generated a recombinant adenovirus (AxCA.UT) encoding UP and herpes simplex virus thymidine kinase fusion protein (UT) to examine whether it would enhance the antitumor activity of AxCA.UP treatment. AxCA.UT treatment significantly enhanced the sensitivity of human esophageal cancer cells to and significantly enhanced the growth inhibition effects of UP gene therapy in vitro. Moreover, both 5-FU and ganciclovir showed bystander effects on growth inhibition. In an in vivo study, the therapeutic outcome of AxCA.UT treatment significantly enhanced the antitumor activity of AxCA.UP treatment. These observations suggest that AxCA.UT may be useful in esophageal cancer gene therapy.

Adenoviridae↗

PubMed2001

Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process.

BACKGROUND: There is controversy regarding the exact localization and roles of osteopontin (OPN), a multipotential chemokine, in renal injury. There is little information on the expression and role of OPN in gentamicin-induced acute tubular necrosis (ATN) and its recovery process. METHODS: A severe ATN model was made using male Wistar rats by injecting gentamicin (150 mg/kg/day) for five days and limiting the provision of water. The expression and localization of OPN mRNA and protein, ED1 as a macrophage marker, proliferating cellular nuclear antigen (PCNA), CD44 as an OPN receptor, megalin as a proximal tubule marker, and their relationships to each other were examined from the early tubular necrotic period to the late recovery period by Northern blotting, in situ hybridization, and double immunohistochemical staining. RESULTS: In the gentamicin group, OPN mRNA and protein were expressed in only the PCNA-positive proliferating cortical distal tubules, not in the necrotic proximal tubules, until day 6 after the first administration, but were found markedly in PCNA-positive regenerative proximal and distal tubules on days 10, 15, and 30. The localization of PCNA-positive cells was almost always accompanied with the up-regulated expression of OPN using quantitative analysis (P < 0.01). CD44 expression was markedly up-regulated in the renal cortical tubular epithelium from days 6 to 30. In the control group, no expression of OPN and CD44 in the cortical area was found throughout the experimental period. CONCLUSIONS: These results suggested that OPN is related to the proliferation and regeneration of tubular epithelial cells after tubular damage.

Animals↗

PubMed2001

Novel glomerular lipoprotein deposits associated with apolipoprotein E2 homozygosity.

BACKGROUND: Hyperlipoproteinemia is occasionally associated with severe glomerular injury caused by abnormal accumulation of lipid in glomeruli, which occurs in conditions such as lipoprotein glomerulopathy (LPG). This study investigates the cases of two siblings with homozygous apolipoprotein (apo) E2 who show unique histologic features, massive proteinuria, and dysbetalipoproteinemia. METHODS: Histologic studies were performed using renal biopsy specimens. Plasma lipoproteins were extensively characterized. The exons of the apo E genes were sequenced to avoid missing any mutations. RESULTS: Histologically, the siblings' condition resembled LPG by light microscopy studies. Electron microscopy studies revealed large lipoid deposits in the paramesangium, subendothelium, and subepithelium of the glomeruli, which were different from LPG in terms of not forming the layered structure resembling a fingerprint even in large lipoprotein thrombi, and mesangial foam cells. Immunohistochemically, the lipoid deposits contained apo E and apo B. These patients did not have either diabetic nephropathy or other known forms of glomerulonephritis. The sequence of exons of the apo E genes revealed homozygosity for apo E2 in both cases. CONCLUSION: The extensive lipoprotein deposition in glomeruli, which resembles LPG, can also occur in apo E2 homozygous individuals, but in a distinct fashion. Because the two cases were siblings, they may have other shared alleles, in addition to the apo E2 allele, that negatively affect processing of lipoproteins and lead to abnormal accumulation of lipoprotein deposits in glomeruli.

Amino Acid Sequence↗

PubMed2001

Apoptosis and epithelial phagocytosis in mitomycin C-treated human pulmonary adenocarcinoma A549 cells.

Fate of human cancer cells damaged by mitomycin C was investigated by electron microscopy. In a monolayer culture of pulmonary adenocarcinoma A549 cells, the antitumor drug mitomycin C induced dilation of the smooth endoplasmic reticulum and Golgi apparatus. Simultaneously, the myelin figures, autophagosomes and dense tonofilament bundles were formed in the cytosol. Nuclear changes also included nucleolar condensation, as well as the disappearance of the karyosomes and thinned marginal heterochromatins. These nuclei came to be rigid and densely chromatic, finally resulting in apoptosis. There was no alteration in the mitochondria or rough endoplasmic reticulum. Meanwhile, some remaining intact A549 cells extended their cytoplasm toward detached cells and engulfed them. These results indicate that mitomycin C induces apoptosis in A549 cells and concurrently stimulates epithelial phagocytotic activity against their own damaged cells.

Adenocarcinoma↗

PubMed2001

Idiopathic submucosal hematoma of esophagus complicated by dissecting aneurysm, followed-up endoscopically during conservative treatment.

Submucosal hematoma of the esophagus is encountered as a rare complication of endoscopic treatment for esophageal varices, but is seen more often with the increasing frequency of endoscopic applications. Idiopathic submucosal hematoma is a rarer event and in most cases sudden intense vomiting has been postulated as its cause. We report here the case of such a patient whose condition was complicated by a dissecting aneurysm. During conservative treatment, careful follow-up was required to differentiate the submucosal hematoma from an aorto-esophageal fistula.

Aged↗