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Biomedical subjects

N Ando

Publications and source records attributed to N Ando.

At least 73 records · Page 4Linked to original sources
PubMed1996

Hypoxia precedes the development of experimental preretinal neovascularization.

BACKGROUND: Although the mechanism of preretinal neovascular growth in the cell-injected rabbit eye model is not known, it has been proposed that the initial vasodilation and eventual development of neovascularization may be attributable to inflammatory mediators. However, an alternative explanation involving hypoxia has not been considered. The purpose of this study was to measure preretinal oxygen tension prior to the development of preretinal neovascularization in the cell-injected rabbit eye. METHODS: In the rabbit, intravitreous injections of 250,000 homologous dermal fibroblasts were performed on one eye; the fellow (control) eye was injected with vehicle. Preretinal oxygen tension over the myelin wing was measured using 19F-NMR spectroscopy of a 30-microliters droplet of perfluorocarbon previously injected into the preretinal vitreous. RESULTS: Compared to control eyes, fibroblast-injected eyes showed a 1.7-fold decrease in preretinal oxygen tension from the first time studied (1 day after cell injection) through the development of visible neovascularization. Hypoxia occurred without coexisting ophthalmoscopic evidence of vascular occlusion or, on days 1 and 3 after cell injection, retinal detachment. CONCLUSION: This result demonstrates for the first time that preretinal hypoxia precedes the development of preretinal neovascularization in the fibroblast-injected rabbit eye.

Animals↗
PubMed1996

Meanings of c-erbB and int-2 amplification in superficial esophageal squamous cell carcinomas.

BACKGROUND: Accumulation of genetic abnormalities is linked to the development and progression of cancer. We therefore analyzed the correlation between the clinical characteristics of superficial esophageal squamous cell carcinoma patients and oncogene amplifications. METHODS: Between 1980 and 1991, there were 63 cases of superficial esophageal carcinoma (Tis and T1 cancer) at Keio University Hospital. The T1 cases were divided into two groups: T1a cases, in which the tumor had invaded the lamina propria, and T1b cases, in which the tumor had invaded the submucosa. DNA was isolated from paraffin-embedded blocks. Oncogene amplification was determined by slot-blot hybridization. RESULTS: Amplification of int-2 and c-erbB was detected in 14 and 5, respectively, of the 54 cases. Three of 12 T1b patients with int-2 amplification died of distant organ metastasis. The survival rate for the group with int-2 amplification was significantly lower than that without int-2 amplification. All 4 T1b patients with c-erbB amplification had lymph node metastasis at operation. CONCLUSIONS: These findings mean that genetic abnormalities are a useful marker for treating patients with superficial esophageal squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed1996

Drug sensitivity testing for clinical samples from oesophageal cancer using adhesive tumour cell culture system.

A total of 83 specimens of surgically resected tumours from 78 patients with oesophageal cancer were assayed for drug sensitivity using an adhesive tumour cell culture system (LifeTrac CSA assay). Seventyone of 83 specimens had a sufficient number of cells to permit growth in culture and 57 of 71 (80%) were evaluable for drug response. Cells (3 x 10(3) ml-1 well-1) were cultured for 14 days and exposed to drugs on days 3-8. Growing cells were confirmed as cancer cells by immunohistochemical staining. IC90 values against several anti-cancer drugs were determined and population distributions of IC90 for each drug served as the basis for judging sensitivity. The 10th percentiles of IC90 (microgram ml-1) for CDDP, 5-FU, DOX, CPM, MTX, VP16, IFOS, VDS, BLM and CDDP + 5-FU were 0.3, 0.16, 0.005, 0.9, 0.006, 0.09, 0.8, 0.006, 0.04 and 0.15 + 0.09 respectively. The population distribution of IC90 against each drug showed a specific pattern that was very similar among histopathological gradings and stages of the disease. This system appeared to be a clinically applicable drug sensitivity test for human oesophageal cancer.

Antineoplastic Agents↗
PubMed1996

Phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus: nine Japanese institutions trial.

A phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus was carried out cooperatively by nine Japanese institutions. Forty-five patients with thoracic advanced squamous cell carcinoma, who had T4 tumor or distant lymph node metastasis (M1(LYM)), were enrolled in the study for treatment with cisplatin (70 mg/m2) on days 1 and 36, and 5-fluorouracil infusion (700 mg/m2) on days 1-4 and 36-39 sandwiched around external beam irradiation (60 Gy over 6 weeks). Of the 45 evaluable patients, 37 (84.1%) completed the treatment. The overall response rate was 64.4%, and the complete response rate 8.9%. The median duration of response was 125.0 days for patients who achieved complete and partial response. The 50% median survival time was 215 days. There was one toxicity-related death due to radiation pneumonitis. The major form of toxicity exceeding grade 2 was myelosuppression and anorexia, but grade 4 toxicity was also observed (2 pulmonary, 1 severe hypoxemia, 1 severe cardiac failure and 1 mental disturbance). The results showed that this form of chemoradiotherapy had a satisfactory effect and might be useful for treatment of inoperable advanced esophageal cancer.

Adult↗
PubMed1996

Rapid diagnosis of methicillin-resistant Staphylococcus aureus bacteremia by nested polymerase chain reaction.

OBJECTIVE: The purpose of this study was to establish a rapid and sensitive diagnostic method for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in postoperative patients. SUMMARY BACKGROUND DATA: As a result of diffusion and abuse of third-generation cephalosporin antibiotics in the 1980s in Japan, an outbreak of MRSA infection has been posed. In the field of surgery, severe postoperative infections with MRSA such as MRSA bacteremia, which may lead to multiple organ failure, have emerged with a high mortality. METHODS: Thirty-five patients with high fever (above 38.5 C) or watery diarrhea or both within 2 weeks after gastrointestinal major surgery and 6 healthy volunteers were examined. Nested polymerase chain reaction was used to detect mecA and toxic shock syndrome toxin-1 (TSST-1) genes in blood specimens. RESULTS: The mecA and TSST-1 genes were not detected in the blood samples of any of the six healthy volunteers. In all 12 samples from which MRSA colonies were isolated by blood culture, mecA and TSST-1 genes were detected. Although it took at least 48 hours to identify MRSA by the blood culture method, the presence of mecA and TSST-1 genes was determined by nested polymerase chain reaction method within only 3 to 4 hours after blood sampling. CONCLUSIONS: This method, as a sensitive and rapid monitoring system for MRS bacteremia, would be clinically beneficial for prevention of cross infection and for early determination of appropriate treatment for infected patients.

Bacteremia↗
PubMed1996

Case report: lymphangioma of the oesophagus endoscopically resected.

Lymphangioma of the oesophagus is an extremely rare entity, with only nine cases having been reported worldwide. We report on a 52-year-old woman with oesophageal lymphangioma, diagnosed using endoscopic ultrasonography and endoscopically resected. No case of malignant transformation of the lymphangioma has been reported in the literature. Endoscopic resection seems to be a minimally invasive method that is appropriate both for the removal of the tumour and precise diagnosis.

Endoscopy↗
PubMed1996

Role of interleukin-4 and vascular cell adhesion molecule-1 in selective eosinophil migration into the airways in allergic asthma.

Recent in vitro studies have suggested that interleukin-4 (IL-4) may be involved in the preferential migration of eosinophils into the airways in allergic asthma through its capacity to selectively increase vascular cell adhesion molecule-1 (VCAM-1) expression on vessels. To test this hypothesis, we studied the expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on vascular endothelium in bronchial mucosal biopsies from 20 allergic asthmatics using an immunohistochemistry technique and related the observations to IL-4 levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to eosinophil infiltration in the bronchial mucosa. IL-4 was detectable in BAL fluid from nine subjects (range, 15.1 to 110 pg/ml in 20-fold concentrated BAL fluid) (IL-4-positive asthmatics) but unmeasurable in the remaining 11 subjects (IL-4-negative asthmatics). The IL-4-positive asthmatics showed a significantly increased expression of VCAM-1 but not E-selectin and ICAM-1 on vessels as compared with both IL-4-negative asthmatics (P < 0.001) and diseased control subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated with BAL IL-4 levels (rs = 0.89; P < 0.0001). Moreover, there was a significant correlation between the endothelial expression of VCAM-1 and the number of eosinophils, but not neutrophils, in the bronchial submucosa (r2 = 0.76; P < 0.001). A significant correlation was also found between BAL IL-4 levels and the number of eosinophils. These results suggest that IL-4 is a VCAM-1-selective activator also in human airways and the VCAM-1-dependent pathways play a role in selective migration of eosinophils into the airways in allergic asthma, and support the hypothesis described above.

Adult↗
PubMed1996

Effects of steroids on the lung accumulation of neutrophil and monocyte in rabbits with endotoxemia.

STUDY OBJECTIVE: To determine the effects of steroids on the lung accumulation of polymorphonuclear leukocytes (PMNs) and monocytes in rabbits with endotoxemia. DESIGN: A prospective, randomized, controlled animal trial. SETTING: Surgical research laboratory, Keio University School of Medicine. SUBJECTS: Twenty-four female Japanese white rabbits. INTERVENTIONS: Rabbits with endotoxemia were pretreated with steroids sufficient to inhibit the production of tumor necrosis factor (TNF) and to prevent the fall of BP. MEASUREMENTS AND RESULTS: The circulating leukocyte counts and the leukocyte accumulation in the lung were evaluated. Endotoxin caused a rapid decrease in circulating PMNs and monocytes followed by an 8-fold greater accumulation of PMNs (p < 0.001) and a 6.5-fold greater accumulation of monocytes (p < 0.05). Steroids failed to inhibit this initial drop of PMNs and monocytes. However, steroids inhibited the PMN accumulation in the lung by 50% (p < 0.05), without inhibiting the monocyte accumulation in the lung. CONCLUSIONS: These findings suggest that the lung accumulation of PMNs is dependent on TNF or other inflammatory mediators that are inhibited by steroids while the lung accumulation of monocyte is not.

Animals↗
PubMed1996

Further evidence for prognostic significance of epidermal growth factor receptor gene amplification in patients with esophageal squamous cell carcinoma.

To determine the value of epidermal growth factor receptor (EGFR) gene amplification as a biological prognostic indicator in patients with esophageal squamous cell carcinoma, the EGFR gene amplification was determined by slot-blot hybridization using DNA extracted from formalin-fixed and paraffin-embedded blocks of tissues from 107 patients with esophageal squamous cell carcinoma who had undergone curative surgery. Results were analyzed by both univariate and multivariate statistical analysis. EGFR gene amplification greater than 3-fold was detected in the primary tumors of 13 (12%) of the 107 cases. The cumulative survival rate for patients with EGFR gene amplification in the primary tumors was significantly lower than that for patients without amplification (P < 0.001). A significant correlation was observed between extensive lymph node involvement at the time of surgery and EGFR gene amplification (P < 0.05). In the multivariate analysis, EGFR gene amplification (P = 0.015) and vascular invasion (P = 0.003) proved to retain independent prognostic values. These results suggest that EGFR gene amplification may be a useful biological marker for the prediction of lymph node metastasis and a poorer prognosis of esophageal squamous cell carcinoma.

Adult↗
PubMed1996

Cyclin D1 amplification as a new predictive classification for squamous cell carcinoma of the esophagus, adding gene information.

The cyclin D1, referred to as PRAD-1, has been mapped to the 11q13 region, and its expression has been detected in squamous cell lines and several primary esophageal carcinomas. We assessed cyclin D1 amplification in 122 squamous cell carcinomas of the esophagus. Samples for DNA extraction were obtained from formalin-fixed paraffin-embedded specimens, and 10 microgram of each DNA sample were subjected to slot blot analysis. The presence of more than three gene copies was considered evidence of gene amplification. Amplification of cyclin D1 was detected in 28 (23%) of 122 cases of squamous cell carcinoma of the esophagus. There were no significant differences between the clinicopathological background factors in groups positive and negative for cyclin D1 amplification, but the survival rate of patients exhibiting amplification was significantly lower (P < 0.001). The groups were stratified according to the pN (pathological N category) factor and pT (pathological T category) factor in the TNM classification, and the cumulative survival rates in the amplification groups were always significantly lower. Amplification of cyclin D1 was correlated with distant organ metastasis after curative operations, but there was no significant difference in lymph node recurrence rates of patients with or without amplification. Cyclin D1 amplification had the second highest partial regression coefficient in the multivariate analysis, after the pN factor. Amplification of cyclin D1 was independent of the TNM classification as a prognostic factor, and was a useful marker for predicting outcome and distant organ metastasis in patients with squamous cell carcinoma of the esophagus. It appears that appropriate treatment can be selected by evaluating both TNM factors and cyclin D1 amplification.

Adult↗
PubMed1995

Structural changes in the oviductal wall during passage of unfertilized cumulus-oocyte complexes in mice.

BACKGROUND: Little information is available on the structural relationship of cumulus-oocyte complexes and the oviductal wall during the transport of cumulus-oocyte complexes. METHODS: To this end, morphological changes of the oviductal wall during the passage of unfertilized cumulus-oocyte complexes were examined chronologically in ICR mice 25-27 days of age injected with PMSG and hCG. Mice were sacrificed at 12, 14, 16, 18, and 24 hr after the injection of hCG to remove oviducts, and the height of mucosal folds, muscle layers, and epithelial cells was measured in the serial sections stained with hematoxylineosin or colloidal iron. RESULTS: The height of the mucosal fold and muscle layer where cumulus-oocyte complexes were located was less than that of the adjacent portions. At 12-18 hr of hCG injection (approximately 2-8 hr after ovulation), the ova with surrounding cumulus cells lie free in a wide lumen, and the muscular tissue consists of only 2 or 3 layers of cells, arranged mostly longitudinally. However, a neighboring portion without cumulus-oocyte complexes, where the folds meet in the middle, appreciably restricts the free space in the lumen. After 24 hr of hCG administration, structural changes in the oviductal wall, where cumulus-oocyte complexes were located, were no longer apparent. The number of cumulus cells surrounding the oocyte decreased during the passage through the oviduct. At 12-18 hr after hCG injection, approximately 140 cells were identified in the largest cross section of a cumulus-oocyte complex, but after 24 hr of hCG administration (approximately 14 hr after ovulation), an oocyte was surrounded with only approximately 25 cells. CONCLUSIONS: These results indicate that oocyte-cumulus cell complexes influence the structure of the oviductal wall during the passage in the oviduct.

Animals↗
PubMed1995

Structural changes in the oviductal wall during the passage of unfertilized cumulus-oocyte complexes in mice.

BACKGROUND: Little information is available on the structural relationship of cumulus-oocyte complexes and the oviductal wall during the transport of cumulus-oocyte complexes. Then, morphological changes of the oviductal wall during the passage of unfertilized cumulus-oocyte complexes was examined chronologically in ICR mice 25-27 days of age injected with PMSG and hCG. METHODS: Mice were sacrificed at 12, 14, 16, 18, and 24 hr after the injection of hCG to remove oviducts, and the height of mucosal folds, muscle layers, and epithelial cells were measured in the serial sections stained with hematoxylin-eosin or colloidal iron. RESULTS: The height of the mucosal fold and muscle layer where cumulus-oocyte complexes were located was less than that of the adjacent portions. At 12-18 hr of hCG injection (about 2-8 hr after ovulation), the ova with surrounding cumulus cells lie free in a wide lumen, and the muscular tissue consists of only 2 or 3 layers of cells, arranged mostly longitudinally. However, a neighboring portion without cumulus-oocyte complexes, where the folds meet in the middle, appreciably restricts the free space in the lumen. After 24 hr of hCG administration, structural changes in the oviductal wall, where cumulus-oocyte complexes were located, were no longer apparent. The number of cumulus cells surrounding the oocyte decreased during the passage through the oviduct. At 12-18 hr after hCG injection, about 140 cells were identified in the largest cross section of a cumulus-oocyte complex, but, after 24 hr of hCG administration (about 14 hr after ovulation), an oocyte was surrounded with only about 25 cells. CONCLUSIONS: These results indicate that oocyte-cumulus cell complexes influence the structure of the oviductal wall during the passage in the oviduct.

Animals↗
PubMed1995

Antimicrotubule effects of the novel antitumor benzoylphenylurea derivative HO-221.

The antitumor action of HO-221, a novel benzoylphenylurea derivative, was studied. The in vitro cytotoxic strength of HO-221 was investigated, as measured by IC50 values, compared with those of other drugs with different action mechanisms, using Chinese hamster lung (CHL) cells, mouse leukemia L1210 cells and human promyelocytic leukemia HL-60 cells. Morphological alterations following treatment were observed under a phase contrast microscope, and the mitotic index was determined at regular intervals to check for accumulation of metaphase cells. HO-221 was found to have a very strong toxic effect on all cell types, equal to that of the spindle poisons used as controls. HO-221 also produced the same specific morphological changes as the spindle poisons, with a significant accumulation of metaphase cells. A chromosome analysis of treated cells showed that HO-221 frequently induced polyploid and aneuploid cells, but without accompanying chromosome-breaking activity. An in vivo mouse bone marrow micronucleus assay was also carried out. The assay allowed the in vivo identification of a chromosome breaker or a spindle poison through the measurement of the relative sizes of micronuclei produced and erythrocytes. HO-221 was found frequently to induce relatively large micronuclei, an action regarded as specific to spindle poisons. It was thus demonstrated that HO-221 acts as a spindle poison both in vitro and in vivo. In order to investigate the mechanism of this action, a study of tubulin assembly using purified calf brain tubulin was carried out, which demonstrated clearly that HO-221 inhibits microtubule assembly. A detailed investigation of the action mechanism of HO-221 as a spindle poison is now called for.

Animals↗
PubMed1995

Effect of endogenous and exogenous EGF on the growth of EGF receptor-hyperproducing human squamous cell carcinoma implanted in nude mice.

The effect of epidermal growth factor (EGF) on the biological behaviour of human tumours in vivo is still controversial. We investigated the effect of EGF on the growth of an EGF receptor-hyperproducing human epidermoid carcinoma, A431 tumour, and on a human small-cell lung carcinoma, H69 tumour, without detectable EGF receptor by using sialoadenectomised (sialex) mice as an endogenous EGF-suppressed animal model. The plasma EGF concentration in the sialex athymic mice was significantly lower than that in the sham-operated mice (P < 0.05). After exogenous EGF replacement with an implanted minipump, the plasma EGF concentration was significantly increased in both groups (P < 0.05). There was no significant difference between the body weight growth curves of sialex and sham-operated mice with and without EGF treatment. The tumour weight of A431, both estimated and measured in sialex mice, was significantly lower than that in sham-operated control mice (P < 0.05), and the growth of A431 tumour was significantly increased by exogenous EGF treatment (P < 0.05). Mitotic activity of these tumours detected by immunohistochemical staining for incorporated bromodeoxyuridine indicated a mitosis-stimulatory effect of endogenous and exogenous EGF on A431 tumours. In contrast to these findings on A431 tumours, a growth-stimulatory effect of endogenous and exogenous EGF was not observed in the H69 tumour. These results suggest a growth-promoting effect of physiological levels of endogenous EGF on EGF receptor-hyperproducing human tumours in vivo.

Animals↗
PubMed1995

Cloning and characterization of the A-factor receptor gene from Streptomyces griseus.

A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) and its specific receptor protein control streptomycin production, streptomycin resistance, and aerial mycelium formation in Streptomyces griseus. The A-factor receptor protein (ArpA) was purified from a cell lysate of S. griseus IFO 13350. The NH2-terminal amino acid sequences of ArpA and lysyl endopeptidase-generated fragments were determined for the purpose of preparing oligonucleotide primers for cloning arpA by the PCR method. The arpA gene cloned in this way directed the synthesis of a protein having A-factor-specific binding activity when expressed in Escherichia coli under the control of the T7 promoter. The arpA gene was thus concluded to encode a 276-amino-acid protein with a calculated molecular mass of 29.1 kDa, as determined by nucleotide sequencing. The A-factor-binding activity was observed with a homodimer of ArpA. The NH2-terminal portion of ArpA contained an alpha-helix-turn-alpha-helix DNA-binding motif that showed great similarity to those of many DNA-binding proteins, which suggests that it exerts its regulatory function for the various phenotypes by directly binding to a certain key gene(s). Although a mutant strain deficient in both the ArpA protein and A-factor production overproduces streptomycin and forms aerial mycelium and spores earlier than the wild-type strain because of repressor-like behavior of ArpA, introduction of arpA into this mutant abolished simultaneously its streptomycin production and aerial mycelium formation. All of these data are consistent with the idea that ArpA acts as a repressor-type regulator for secondary metabolite formation and morphogenesis during the early growth phase and A-factor at a certain critical intracellular concentration releases the derepression, thus leading to the onset of secondary metabolism and aerial mycelium formation. The presence of ArpA-like proteins among Streptomyces spp., as revealed by PCR, together with the presence of A-factor-like compounds, suggests that a hormonal control similar to the A-factor system exists in many species of this genus.

4-Butyrolactone↗
PubMed1995

Relative contributions of thalamic reticular nucleus neurons and intrinsic interneurons to inhibition of thalamic neurons projecting to the motor cortex.

1. Intracellular responses to stimulation of the cerebral cortex (Cx) and cerebellum were analyzed in thalamocortical neurons (TCNs) in the ventroanterior-ventrolateral (VA-VL) complex of the thalamus and neurons in the thalamic reticular nuclei (RNs) of anesthetized cats, and the contribution of reticular nucleus neurons (RNNs) and thalamic interneurons (TINs) to cerebral and cerebellar inhibition of TCNs was determined. 2. Single TCNs projecting to area 4 or 6 received convergent monosynaptic excitatory and disynaptic inhibitory inputs from both the dentate nucleus (DN) and the interpositus nucleus (IN). These TCNs also received monosynaptic excitatory postsynaptic potentials (EPSPs) and disynaptic inhibitory postsynaptic potentials (IPSPs) from the pericruciate cortex (areas 4 and 6). Each TCN received the strongest excitatory and inhibitory inputs from the cortical area to which that TCN projected, and weaker inhibitory inputs from adjacent cortical areas. 3. RNNs were identified morphologically by intracellular injection of horseradish peroxidase (HRP). Stimulation of the brachium conjunctivum (BC) evoked disynaptic EPSPs with a long decay phase in RNNs in the anterior ventrolateral part of the RN. Single RNNs received convergent disynaptic excitatory inputs from both the DNA and the IN. Stimulation of the Cx produced monosynaptic long-lasting EPSPs with two different latencies in these RNNs: early EPSPs with latencies of 0.9-2.1 ms and late EPSPs with latencies of 1.8-3.5 ms. Collision experiments with BC- and Cx-evoked EPSPs in RNNs indicated that BC-evoked disynaptic EPSPs and Cx-evoked early EPSPs were produced by axon collaterals of TCNs to RNNs. The latencies of the Cx-evoked late EPSPs in RNNs were almost identical to those of Cx-evoked monosynaptic EPSPs in TCNs, indicating that corticothalamic neurons (CTNs) exert monosynaptic excitatory effects on RNNs and TCNs. 4. Stimulation of the Cx produced IPSPs in TCNs with short latencies of 1.8-2.7 ms and longer latencies of > or = 2.8 ms. The Cx-evoked early IPSPs with latencies of 1.8-2.7 ms were mediated by RNNs. The origin of Cx-evoked late IPSPs with latencies of > or = 2.8 ms in TCNs was twofold, Cx-induced early IPSPs in TCNs were facilitated by conditioning cortical stimulation that induced late IPSPs in the TCNs. The same conditioning cortical stimulation also facilitated BC-evoked disynaptic IPSPs. The time course of this facilitatation indicated that CTNs produce long-lasting excitation in TINs. These results indicated that Cx-evoked IPSPs with latencies of > 2.7 ms were mediated at least in part by RNNs and inhibitory TINs in the VA-VL complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗