Retroviral vectors transfer functional MHC class II heterodimers into bone marrow: a genetic approach to tolerance induction.
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3T3 Cells↗
Biomedical subjects
H Shimada
Publications and source records attributed to H Shimada.
Apoptosis of hepatocytes is a main cause of inducing lethal hepatic failure after excessive hepatectomy in rats.
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Animals↗
Role of protein kinase a pathway in epidermal growth factor-induced liver cell repair.
To gain a better understanding of the mechanisms that control the repair process in the injured liver, the actions of epidermal growth factor (EGF) and protein kinase A (PKA) were studied. Normal rat liver cells (clone 9) were grown to confluence. Standardized excisional wounds were made with a razor blade. The extent of hepatocyte migration into the wound was measured and determined at specific time intervals using a computerized digital analyzing system. Immunostaining of F-actin was performed with a fluorescein-labeled phalloidin. EGF significantly stimulated liver cell migration, whereas specific EGF-neutralizing antibody inhibited the EGF-induced migration. Agents that activate PKA at different stages of the PKA activation pathway, including 3-isobutyl-1-methylxanthine (IBMX), forskolin, and cholera toxin, inhibited EGF-induced migration. EGF triggered formation of actin stress fibers. PKA-activating agents inhibited actin stress fiber formation and stretching of cells at the wound margin. The following conclusions were drawn: (1) In excisional wounds of hepatocyte monolayers, both EGF and PKA exert action on actin microfilaments, which are stretched by EGF and inhibited by PKA; (2) the enhanced repair of wounded hepatocyte monolayers by EGF is blocked by activation of the PKA pathway at various levels; and (3) these actions of EGF and PKA indicate their important regulatory roles in controlling the rate of hepatocyte migration and restitution following the creation of excisional wounds.
Animals↗
Exercise-induced cerebral deoxygenation among untrained trekkers at moderate altitudes.
The pathophysiology of altitude-related disorders in untrained trekkers has not been clarified. In the present study, the effects of workload on cardiovascular parameters and regional cerebral oxygenation were studied in untrained trekkers at altitudes of 2700 m and 3700 m above sea level. We studied 6 males and 4 females at each altitude, and their average ages were 31.3+/-7.1 y at 2700 m and 31.2+/-6.8 y at 3700 m, respectively. The resting values of heart rate and mean blood pressure were not significantly different at 2700 m and 3700 m than at sea level. However, increases in these values after exercise were more prominent at high altitudes (heart rate increase = 51.6% at 2700 m and 70.4% at 3700 m; mean blood pressure increase: 19.0% at 2700 m and 17.2% at 3700 m). In addition, post-exercise blood lactate concentration was significantly higher at 3700 m than at sea level or at 2700 m (i.e., 7.6 mM at 3700 m, 3.8 mM at 2700 m, and 4.17 mM at 0 m, respectively). Exercise induced an acute reduction in the arterial oxygen saturation value (SpO2) at 2700 m and 3700 m (i.e., 11.2% reduction at 2700 m and 9.4% at 3700 m), whereas no changes were observed at sea level. The resting values of regional oxygen saturation (rSO2)--measured by a near infra-red spectrophotometer at sea level, 2700 m, and 3700 m-were nearly identical. Exercise at sea level did not reduce this value. In contrast, we observed a decrease in rSO2 after subjects exercised at 2700 m and 3700 m (i.e., 26.9% at 2700 m and 48.1% at 3700 m, respectively). The rSO2 measured 2 min and 3 min after exercise at 3700 m was significantly higher than the preexercise value. From these observations, we concluded that alterations in cardiovascular parameters were apparent only after an exercise load occurred at approximately 3000 m altitude. Acute reduction in cerebral regional oxygen saturation might be a primary cause of headache and acute mountain sickness among unacclimatized trekkers.
Acclimatization↗
An infant with neuroblastoma and MYCN amplification found through mass screening.
PURPOSE: This report describes an extremely rare case of an infant with neuroblastoma involving MYCN amplification found through mass screening (MS). PATIENT: An 8-month-old boy was referred to our hospital after screening for neuroblastoma showed positive results. A firm tumor was found above his left kidney and completely resected. RESULTS: The tumor arose from the left adrenal gland. The disease was classified as stage I according to the International Neuroblastoma Staging System. Although the tumor showed a favorable histology, MYCN was amplified to 20 copies. After surgery, the infant underwent chemotherapy, but a new mass in the right adrenal gland was found. After chemotherapy, the tumor was excised. Despite several courses of chemotherapy, multiple metastases in both lung fields appeared. More intensive chemotherapy and allogenic peripheral blood stem cell transplantation were performed, but the infant died from pulmonary hemorrhage after the transplantation. CONCLUSIONS: The majority of patients with neuroblastoma found through MS have a good outcome. However, some patients have poor prognostic factors, like our patient with MYCN amplification. There is a need to develop a suitable protocol for babies with high risk features younger than 1 year of age found through MS.
Adrenal Gland Neoplasms↗
Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival.
PURPOSE: The goal of this study was to determine the incidence of metastatic sites in neuroblastoma and the extent to which metastatic sites correlate with age, tumor biology, and survival. PATIENTS AND METHODS: All 648 patients with stage IV and IVS neuroblastoma registered on Children's Cancer Group protocols 3881 and 3891 were analyzed. Metastatic site data were provided by treating institutions and reviewed in patients with central nervous system (CNS), intracranial, lung, or "other" metastases. RESULTS: The incidence of metastatic sites at diagnosis was 70.5% in bone marrow, 55.7% in bone, 30.9% in lymph nodes, 29.6% in liver, 18.2% in intracranial and orbital sites, 3.3% in lung, and 0.6% in CNS. Event-free survival (EFS) was decreased in patients with bone, bone marrow, CNS, intracranial/ orbital, lung, and pleural metastases, and improved in those with liver and skin metastases. In infants, MYCN amplification and unfavorable Shimada histopathology correlated with increased frequencies of bone and intracranial or orbital metastases. In older patients, MYCN amplification correlated with increased frequencies of intracranial or orbital, liver, and lung metastases. Multivariate analysis revealed that metastatic site is not an independent prognostic factor. CONCLUSIONS: Metastatic pattern in neuroblastoma differs with age and correlates with tumor biological features and EFS. These correlations could reflect changes in host or tumor biological features with age resulting in differences in metastatic capacity or tumor affinity for specific sites.
Adolescent↗
Detection of preoperative serum anti-p53 antibodies in gastric cancer.
The presence of circulating anti-p53 antibodies (p53Ab) was investigated in 81 gastric cancer patients by ELISA. Preoperatively, anti-p53Ab were revealed in 13 cases (16%), including 3 early gastric cancers. No significant correlation of p53Ab with patient age, sex, pathological parameters and tumor markers, such as CEA and CA19-9 was observed, although p53Ab positivity tended to be associated with a higher rate of lymph node metastases (p = 0.073). We have found no significant correlation between p53Ab and poor survival rate (p = 0.325). In conclusion, we have observed that p53Ab are detectable in gastric cancer patients, even at early stages of disease, however, p53Ab have not served as a predictor of poor prognosis in gastric cancer in this series.
Adenocarcinoma↗
Beneficial effect of hyperbaric oxygen therapy on liver regeneration after 90% hepatectomy in rats.
BACKGROUND/AIMS: Hyperbaric oxygen therapy (HBOT) has been reported to augment oxygen delivery to ischemic tissues and improve the liver dysfunction in clinical cases. HBOT was performed after 90% hepatectomy in rats to determine its effect on the regeneration of remnant liver. METHODS: After 90% hepatectomy was performed in 8-week-old male Wistar rats, the animals were subdivided into an HBOT (2 atm abs., 80% O2, 1 h/day, 3 days) group and a non-HBOT group. Members of both groups were sacrificed, usually every 4 h until a maximum of 50 h after hepatectomy, and the liver regeneration rate, the proportion of PCNA-positive cells and the ATP volume in the remnant tissues were examined. RESULTS: In the HBOT group, the liver regeneration rate at 36 h and 50 h after operation and the proportion of PCNA positive cells at 8 h was significantly increased compared with the non-HBOT group. The ATP volume in the remnant livers in the HBOT group was also significantly increased at 12 h. CONCLUSION: HBOT augmented liver regeneration after hepatectomy by stabilization of energy metabolism induced by oxygen delivery in rats.
Animals↗
Antitumor effect of murine colon carcinoma cells retrovirally transduced with interleukin-4 and granulocyte macrophage-colony stimulating factor genes.
We have investigated the antitumor effect of murine colon carcinoma cells developed to produce cytokines. Retrovirally transduced cells were inoculated into syngeneic mice, and their survivals were examined. Inoculation of interleukin-4 (IL-4)- or granulocyte macrophage-colony stimulating factor (GM-CSF)-producing cells alone did not affect the survival of the mice. In the tumors derived from an admixture of IL-4 and GM-CSF producers, however, regression developed spontaneously, and prolonged survival of the challenged mice was consequently observed. Histological examination revealed predominant infiltration of neutrophils around the tumor of a mixed population of IL-4 and GM-CSF producers.
Animals↗
Efficacy of lansoprazole against peptic ulcers induced by non-steroidal anti-inflammatory drugs: endoscopic evaluation of ulcer healing.
Beyond the obvious step of limiting use of non-steroidal anti-inflammatory drugs (NSAIDs), the treatment of ulcers induced by NSAIDs remains controversial. We evaluated the efficacy of the proton-pump inhibitor lansoprazole on NSAID-induced ulcers. Ulcers were endoscopically diagnosed in 47 NSAID users. These patients received 30 mg/day lansoprazole, orally, for 6 or 8 weeks (6 weeks for duodenal ulcers and 8 weeks for other ulcers). Ulcer healing was assessed using an established classification system. The presence of immunoglobulin G antibody against Helicobacter pylori was also evaluated. The antibody was present in the sera of 51% of patients (24/47). Most of the ulcers reached scarring stages S1 (healing) or S2 (good healing), and the S2 healing rate was 35%. Two H. pylori seropositive patients did not reach these stages; their ulcers were improved by H. pylori eradication therapy, followed, in one case, by medication with misoprostol. Lansoprazole seemed to be useful for most patients with NSAID-induced ulcers, but a few needed additional treatments.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Expression of beta 1 integrins (very late antigens-4 and -5) on myeloma cells and clinical correlates in patients with multiple myeloma.
beta 1 Integrins are considered to be essential for the differentiation of bone-marrow B cells through an interaction with fibronectin-expressed bone-marrow stromal cells. The expression of very late antigens-4 (VLA-4) and -5 (VLA-5) by CD38bright bone-marrow cells in patients with multiple myeloma was measured by flow cytometry using specific monoclonal antibodies. The percentage of CD38bright bone-marrow cells appeared to correlated with that of bone-marrow plasma cells as judged by examination of bone-marrow smears (r = 0.911, P < 0.0001). Expression of VLA-4 and VLA-5 by CD38bright cells varied between patients, but the expression of VLA-4 was always equal to or greater than that of VLA-5. The ratio of VLA-4 to VLA-5 expression (VLA-4:VLA-5 ratio) was calculated and compared with the clinical features of the myeloma patients. A high VLA-4:VLA-5 ratio (> 2.0) was associated with the presence of plasmacytomas and urinary Bence-Jones protein was more common in this group. No other correlations between the clinical features of the disease and the expression of beta 1 integrins were found.
ADP-ribosyl Cyclase↗
Preoperative factors influencing visual outcome following surgical excision of subfoveal choroidal.
PURPOSE: To evaluate long-term visual acuity outcomes and the influences of various preoperative factors on visual outcome in patients undergoing surgical removal of choroidal neovascular neovascularization (CNV) caused by age-related macular degeneration (ARMD). METHODS: The authors studied 146 eyes of 146 patients who were followed for at least 1 year after surgical excision of CNV associated with ARMD. Surgical indications included subfoveal active CNV localized mainly above the retinal pigment epithelium (RPE) and a standard Japanese decimal visual acuity of 0.3 or worse. CNV above the RPE was diagnosed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography. CNVs were divided into completely classic CNV or mainly classic CNV. The relationships of the post-operative logarithm of the minimum angle of resolution (logMAR) visual acuity with preoperative logMAR visual acuity, the shortest distance from the center of the foveal avascular zone to the CNV margin, CNV size, and age were analyzed. RESULTS: Final logMAR visual acuity was improved (defined as a logMAR visual acuity increase of 0.2 or more) in 78 eyes (54%), stable in 47 (32%), and worsened in 21 (14%). Stepwise regression identified CNV size as a significant factor influencing final logMAR visual acuity (R2 = 0.213, p<0.0001), while preoperative logMAR visual acuity, shortest distance from the center of the foveal avascular zone to the CNV margin, and age showed no significant correlation with final logMAR visual acuity. Surgical complications included retinal detachment in six eyes (4%), subretinal hematoma in four eyes (2%), macular hole in three (2%), and proliferative vitreoretinopathy in two (1%). CNV recurred postoperatively in 18 eyes (12%). In 92 eyes with completely classic CNV, visual acuity was improved in 57 (62%), stable in 27 (29%), and worsened in 8 (9%). In 54 eyes with mainly classic CNV, visual acuity was improved in 21(39%), stable in 20 (37%), and worsened in 13 (24%). CONCLUSIONS: Surgical excision of CNV for ARMD was effective for completely classic CNV, and better postoperative visual acuity was achieved in cases of small CNV. Given the fact that photodynamic therapy (PDT) has only been used in Japan since 2004, future study should compare PDT and surgical excision in Japanese subjects for relative merits against surgical risk and postoperative complications, to define indications for PDT and surgical excision.
Aged↗
A pathology database system for autopsy diagnoses using free-text method.
Using natural language a computerized indexing and retrieval system was developed on a commercial database program, DATATRIEVE (Digital Equipment Corporation, Japan). Summarized anatomical diagnoses of nearly 4000 autopsy cases have been registered over a 13-year period at Tokyo Metropolitan Geriatric Hospital. There were 187,367 words in the pathological diagnoses with 4689 distinct words excluding articles, prepositions and conjunctions. 'Atrophy', 'congestion' and 'metastasis' were the most frequent words with frequencies of 4335, 3377, and 3373, respectively. Distinct clinical diagnoses were 2497, among which 'pneumonia', 'hypertension' and 'DIC' predominated. Each step of retrieval by character strings from the sequential data file requires less than a minute.
Aged↗
The elevated mRNA content as a potential indicator of precancerous states of the gallbladder mucosa in patients with pancreaticobiliary maljunction.
Pancreaticobiliary maljunction (PBM) patients have a high incidence of cancer in the gallbladder. In the present study, we showed that precancerous lesions in the gallbladder of PBM such as hyperplasia or metaplasia, indicated high concentration of the amount of total mRNA. The mRNA content could be easily measured by our new technique utilizing a GenePlate, which is a poly (dT) oligonucleotide immobilized plastic plate, and Yoyo-1, a fluorescent DNA intercalator. To standardize the mRNA contents, we utilized which was defined as the ratio of total mRNA contents to total nucleic acids in a same sample. The mRNA index of the proliferating cells was significantly higher than that of the resting cells, and the mRNA index of cancer cells, such as gastric cancer, colon cancer, bile duct cancer, and gallbladder cancer also showed significantly higher concentration than that of normal mucosa. In the study of precancerous lesion, PBM, the mRNA index was significantly higher than that of mild cholecystitis but less than that of gallbladder cancer, suggesting that in the gallbladder mucosa of PBM, a precancerous state was able to be diagnosed by the mRNA index.
Animals↗
Detection of serum p53 antibodies in patients with esophageal squamous cell carcinoma: correlation with clinicopathologic features and tumor markers.
The significance of serum p53-Abs in patients with esophageal squamous cell carcinoma was determined. Examination of clinicopathological features and assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty-three (58%) of 57 patients were positive for serum p53-Abs, however, no relation with cancer progression existed. Fourteen of the 33 sero-positive patients revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears to be a useful marker for the detection of esophageal squamous cell carcinoma.
Aged↗
Thymidine phosphorylase expression and effect of doxifluridine: a phase II study.
Doxifluridine (5'-DFUR), an active intermediate metabolite of capecitabine, is converted to 5-fluorouracil by thymidine phosphorylase (TP). We used immunohistochemical staining to investigate the relation between TP expression and 5'-DFUR effects in 40 patients with advanced/recurrent lung metastases from colorectal cancer. Cox regression analysis suggested that TP-positive cancer cells (risk ratio 3.72), were independent factors in survival whereas factors in progression-free survival were TP-positive cancer cells (2.93), and TP-positive stromal cells (0.24). It is suggested that TP expression in cancer cells and in stromal cells are opposite prognostic factors in patients treated with 5'-DFUR.
Adult↗
Production of lycopene by the food yeast, Candida utilis that does not naturally synthesize carotenoid.
The Erwinia uredovora crtE, crtB, and crtI genes, which are responsible for the synthesis of carotenoid lycopene from farnesyl pyrophosphate, were expressed in Candida utilis under the control of the promoters and terminators derived from the C. utilis GAP, PGK, and PMA genes, respectively. The yeast transformant carrying the carotenoid biosynthesis genes produced 758 microg/g dry weight of lycopene along with 407 microg/g dry weight of phytoene in the stationary phase. It was observed in the C. utilis transformant that ergosterol content was decreased to 65% of that in the parent strain that accumulated 6.04 mg/g dry weight of ergosterol. It is therefore possible that the carbon flux for the ergosterol biosynthesis has been branched at farnesyl pyrophosphate to generate a new pathway for the lycopene production in this yeast transformant.
Anticarcinogenic Agents↗
Sialyl Lewis X expression in vascular permeating lesions as a factor for predicting colorectal cancer metastasis.
BACKGROUND/AIMS: To evaluate the potential of sialyl Lewis X (SLX) expression for predicting residual liver recurrence, we examined the vascular permeating lesions surrounding the metastatic liver tumors for SLX as a marker of residual liver recurrence. METHODOLOGY: Twenty-eight cases of metastatic liver tumors of colorectal cancers were examined using SLX monoclonal antibody for SLX expression in surrounding vascular permeating lesions. RESULTS: The cumulative residual liver recurrence rate in cases positive for SLX (SLX(+)) expression in the vascular permeating lesions surrounding the metastatic liver tumor was significantly higher than in the negative cases (p < 0.05). Furthermore, logistic regression analysis revealed that SLX positivity in the lesions surrounding the metastatic liver tumor was an important discriminant for residual liver recurrence (p = 0.0197). CONCLUSIONS: These results indicated that SLX expression in vascular permeating lesions surrounding the metastatic liver tumor is a predictive factor for residual liver recurrence.
Biomarkers, Tumor↗