[A case of Brown-Séquard syndrome caused by demyelinating disease].
Explore the source record for details and available documents.
Brown-Sequard Syndrome↗
Biomedical subjects
I Kinoshita
Publications and source records attributed to I Kinoshita.
Altered retinoblastoma protein expression in nonsmall cell lung cancer: its synergistic effects with altered ras and p53 protein status on prognosis.
BACKGROUND: Inactivation of the retinoblastoma (Rb) gene has been documented in various types of cancer, including lung cancer. Alterations of the p53 and ras genes are also common features in the molecular biology of lung carcinoma, and the authors of this article have reported previously on the prognostic significance of both of them. In the present study, the authors evaluated the prognostic significance of the loss of Rb protein expression alone, then performed a combined analysis of Rb protein and ras p21 status (Rb/ras) as well as an analysis of Rb and p53 protein status (Rb/p53) in patients with nonsmall cell lung cancer (NSCLC). METHODS: Ninety-one patients with NSCLC underwent potentially curative resection between 1977 and 1988, 65 of whom received postoperative combination chemotherapy. Tumor specimens were analyzed for Rb protein expression by immunohistochemistry. Univariate and multivariate analyses were performed to assess the association between Rb protein expression and survival. RESULTS: Nineteen (21%) of the 91 NSCLCs showed negative Rb protein expression. Positive or negative Rb protein expression (Rb+ or Rb-) as an individual factor was not statistically correlated with survival or prognosis in this cohort of NSCLC patients, although a tendency among Rb- patients to do worse was observed. The authors then combined the Rb protein status with previously studied results of ras p21 and p53 protein expression in the same tumor specimens, and compared the prognosis between the individuals with theoretically the best pattern of gene expression in their tumors and those with theoretically the worst pattern of expression, i.e., Rb+/ras- versus Rb-/ras+ and Rb+/p53- versus Rb-/p53+. In patients with adenocarcinoma, those with Rb-/ras+ tumors survived for a significantly shorter period after surgery (13% 5-year survival) than those with Rb+/ras- tumors (82% 5-year survival) (P = 0.01). Similarly, patients with Rb-/p53+ tumors survived for a significantly shorter period (20% 5-year survival) compared with those who had Rb+/p53- tumors (73% 5-year survival) (P = 0.008). Rb/ras status was a significant prognostic factor (P = 0.02 by univariate analysis, P = 0.048 by multivariate analysis), and Rb/p53 status tended to be significant as a prognostic factor (P = 0.04 by univariate analysis, P = 0.08 by multivariate analysis). In patients with squamous cell carcinoma, neither Rb/ras nor Rb/p53 status was a significant prognostic factor in this cohort. CONCLUSIONS: These results suggest that combined immunohistochemical analyses of Rb and ras p21 proteins and of Rb and p53 proteins may indicate their potentially synergistic effects on survival and prognosis. These analyses may also be useful for stratifying patients with adenocarcinoma of the lung into different prognostic groups and identifying populations with different risks of recurrence. Larger prospective studies with Stage I NSCLC patients are necessary to confirm the current findings.
Adenocarcinoma↗
Impaired learning of active avoidance in water-intoxicated rats.
Brain edema is an important clinical condition. Pathophysiological findings on behavioral changes may be helpful for a comprehensive understanding of brain edema. However, only few reports on behavioral studies of brain edema have so far appeared. Experiments using psychological techniques on animals are rather time-consuming and may not be suitable for the study of transient conditions, as brain edema caused by trauma, vascular accidents, or others. We have developed a method for avoidance learning of rats using a running wheel apparatus with computer assistance. This model was employed in studies on brain edema from water introxication in rats. As a result, avoidance learning was significantly impaired by water intoxication. Either direct overhydration of the brain or indirect effects, as a decrease in cerebral blood flow, or both, are suggested as mechanisms underlying the impairment of behavior.
Animals↗
Does small-dose gamma-ray radiation induce endogenous antioxidant potential in vivo?
The induction of in vivo antioxidant potential following small doses of gamma-ray irradiation was investigated in C57BL/6 mice. The antioxidant capacity of various organs was assessed in terms of the scavenging activity of cytosol fractions against 1,1-diphenyl-2-picrylhydrazyl (DPPH), a chemically stable radical. Significant elevations in the scavenging activity were recognized in several organs, including the liver, pancreas and brain, soon after post-irradiation with 50 cGy of gamma-ray. These increases persisted for 24 h. gamma-Radiation of the liver at 25-50 cGy elevated its cytosolic antioxidant capacity, but this was lowered at 200 cGy. In order to assess which antioxidants underlie this phenomenon, the content of a reduced form of glutathione (GSH) in liver was assayed as a function of time after gamma-irradiation at a dose of 50 cGy. The GSH content was significantly increased from 6 h after irradiation, and this change was consistent with that of the total radical scavenging potency of the liver against DPPH. Further, the elevation of GSH content was accompanied by elevated GSSG reductase activity induced by gamma-irradiation.
Animals↗
Altered p16INK4 and retinoblastoma protein status in non-small cell lung cancer: potential synergistic effect with altered p53 protein on proliferative activity.
p16INK4 protein (p16) and retinoblastoma protein (pRB), like p53 protein, are important tumor suppressors that regulate the cell cycle. We immunohistochemically examined fresh-frozen specimens of 114 resected non-small cell lung cancers (NSCLCs) for loss of p16 and pRB expression, together with aberrant accumulation of p53 protein and the proliferative activity determined by the Ki-67 index. Three pRB-positive tumors were uninterpretable for p16 status. Of the remaining 111 tumors, 30 (27%) lacked p16 expression, and 10 (9%) lost pRB expression. No tumors showed coincident loss of both proteins, supporting the hypothesis that they function in a single pathway. Of 25 tumors, including 4 p16-negative tumors, examined by Southern blot analysis, only 2 p16-negative tumors were considered to have reduced gene dosage consistent with possible homozygous deletion of the CDKN2 gene encoding p16, suggesting that immunohistochemistry is a sensitive and suitable method to screen for p16 alteration. Loss of p16 expression did not correlate with any clinical factors or p53 status, whereas loss of pRB expression correlated with heavy smoking (P = 0.03 by Fisher's exact test and P = 0.01 by the multivariate logistic regression analysis). Proliferative activity was considerably higher in p53-positive tumors than in p53-negative tumors (P < 0.001). Loss of p16 or pRB expression was associated with a further increase in proliferative activity in the p53-positive tumors (P = 0.009) but not with proliferative activity in the p53-negative tumors. These results suggest that alteration of the p16/pRB pathway is relatively frequently involved in the development and progression of NSCLCs and that its effect on the proliferative activity is potentially synergistic with altered p53 protein.
Aged↗
Mechanism of increasing dystrophin-positive myofibers by myoblast transplantation: study using mdx/beta-galactosidase transgenic mice.
Female mdx/mdx mice were crossed with non-dystrophic transgenic males expressing the beta-galactosidase (beta-gal) gene under a muscle-specific promoter (TnILacZ1/29). All male offspring were mdx mice and about 50% of them also expressed the beta-gal gene. The beta-gal/mdx mice were selected as recipients for the transplantation of myoblasts from non-transgenic normal BALB/c mice. When host muscles were not irradiated before myoblast transplantation, 4.6% of the muscle fibers in host muscles were dystrophin positive 1 month after transplantation. Most of these dystrophin-positive muscle fibers were also beta-gal positive. About one quarter of these fibers are the result of reverse mutations; most of them have, however, been produced by fusion of donor myoblasts with host muscle fibers or with host myoblasts. The virtual absence of beta-gal-negative fibers indicates that there were no exclusively donor-donor fusions. When host muscles were irradiated before myoblast transplantation, roughly the same percentage (5.5%) of dystrophin-positive fibers were formed in the injected muscle, but 42% of them were beta-gal negative. These beta-gal-negative dystrophin-positive muscle fibers were formed by the exclusive fusion of donor myoblasts with one another rather than with host cells. This clearly indicates that myoblast transplantation can form completely new muscle fibers or muscle fiber segments when host satellite cell proliferation is reduced by irradiation. These newly formed muscle fibers had, however, a small diameter and additional myoblast transplantation may be required to increase their size. This situation has some similarities with findings in Duchenne muscular dystrophy patients of more than 6 years of age, who also have a limited proliferation capacity of their satellite cells.
Animals↗
Successive injections in mdx mice of myoblasts grown with bFGF.
We studied the effects of single and repeated sets of injections in the same muscle of mdx mice of myoblasts grown with or without a high concentration 100 ng ml-1 of basic fibroblast growth factor (bFGF). The injected myoblasts were obtained from non-dystrophic transgenic mice expressing the beta-galactosidase gene under the control of a muscle-specific promoter. In these experiments, the host muscle was not irradiated to prevent muscle regeneration by host myoblasts. The host muscle was not damaged before myoblast transplantation with notexin, marcaïne or cold to trigger a regeneration-degeneration cycle. Without such pretreatments, the first set of injections of myoblasts grown without bFGF produced only 8% beta-galactosidase-positive and dystrophin-positive muscle fibers 1 month after transplantation. The percentage of muscle fibers containing the donor reporter gene increased, however, to 26% following a second set of injections in the same muscle. The percentage of muscle fibers expressing the donor reporter gene was significantly higher when the myoblasts were grown with a high dose of bFGF. Indeed the first set of injections produced 34% beta-gal-positive fibers while a second set of injections raised this percentage to 54%. In all cases, the percentage of dystrophin-positive fibers was similar to that of beta-gal-positive fibers. Therefore a high percentage of muscle fibers of donor origin can be obtained without preliminary damaging treatments of the mdx muscle when myoblasts grown with bFGF are injected several times. The effects of bFGF is not produced by increasing the percentage of myoblasts in a primary muscle culture since improvement of myoblast transplantation was obtained with a pure myoblast clone even with a lower concentration (10 ng ml-1) of bFGF.
Animals↗
Partial laminin alpha2 chain restoration in alpha2 chain-deficient dy/dy mouse by primary muscle cell culture transplantation.
Laminin-2 is a component of skeletal and cardiac basal lamina expressed in normal mouse and human. Laminin alpha2 chain (LAMA2), however, is absent from muscles of some congenital muscular dystrophy patients and the dystrophia muscularis (dy/dy) mouse model. LAMA2 restoration was investigated following cell transplantation in vivo in dy/dy mouse. Allogeneic primary muscle cell cultures expressing the beta-galactosidase transgene under control of a muscular promoter, or histocompatible primary muscle cell cultures, were transplanted into dy/dy mouse muscles. FK506 immunosuppression was used in noncompatible models. All transplanted animals expressed LAMA2 in these immunologically-controlled models, and the degrees of LAMA2 restoration were shown to depend on the age of the animal at transplantation, on muscle pretreatment, and on duration time after transplantation in some cases. LAMA2 did not always colocalize with new or hybrid muscle fibers formed by the fusion of donor myoblasts. LAMA2 deposition around muscle fibers was often segmental and seemed to radiate from the center to the periphery of the injection site. Allogeneic conditionally immortalized pure myogenic cells expressing the beta-galactosidase transgene were characterized in vitro and in vivo. When injected into FK506-immunosuppressed dy/dy mice, these cells formed new or hybrid muscle fibers but essentially did not express LAMA2 in vivo. These data show that partial LAMA2 restoration is achieved in LAMA2-deficient dy/dy mouse by primary muscle cell culture transplantation. However, not all myoblasts, or myoblasts alone, or the muscle fibers they form are capable of LAMA2 secretion and deposition in vivo.
Age Factors↗
Myoblast transplantation in monkeys: control of immune response by FK506.
Myoblasts were grown from monkey muscle biopsies and infected in vitro with a defective retroviral vector containing a cytoplasmic beta-galactosidase (beta-gal) gene. These myoblasts were then transplanted to 14 different monkeys, 6 of which were immunosuppressed with FK506. Without immunosuppression, only a few myoblasts and myotubes expressing beta-gal were observed 1 week after the transplantation, but no cells expressing beta-gal were observed after 4 weeks. This result was attributed to immune responses since infiltration by CD4+ or CD8+ lymphocytes was abundant 1 week after transplantation but not after 4 weeks. The expression of interleukin 6 (IL-6), interleukin 2 (IL-2), granulocyte/macrophage colony stimulating factor (GM-CSF), transforming growth factor-beta (TGF-beta) and granzyme B mRNAs was increased in the myoblast-injected muscle indicating that the infiltrating lymphocytes were activated. Moreover, antibodies against the donor myoblasts were detected in 3 out of 6 cases. When the monkeys were immunosuppressed with FK506, muscle fibers expressing beta-galactosidase (beta-gal) were present 1, 4 and 12 weeks after the transplantation. There was neither significant infiltration by CD4 or CD8 lymphocytes, nor antibodies detected. The mRNA expression of most cytokines was significantly reduced as compared to the nonimmunosuppressed monkeys. These results indicate that FK506 is effective in controlling short-term immune reactions following myoblast transplantation in monkeys and suggest that it may prove useful for myoblast transplantation in Duchenne Muscular Dystrophy patients.
Animals↗
DNA sequence from a fossil pollen of Abies spp. from Pleistocene peat.
DNA was amplified from individual fossil pollen grains of Abies spp. (Pinaceae), which have been detected from Pleistocene peaty deposits (at least 150,000 years old). To identify the species of the fossil pollen by DNA analysis, the region indicating the species-specific sequence was searched among extant Abies species and the spacer region between rrn5 and trnR in chloroplast DNA was sequenced for four grains of the fossil pollen. Three pollen samples produced the same sequence as extant Abies species. The sequence for the remaining sample differed from that of extant Abies by one substitution. This study showed not only a successful DNA analysis from a single grain of fossil pollen but also a new method to identify the species of fossil pollen for the pollen analysis field.
Base Sequence↗
Prognostic significance of p53 and ras p21 expression in nonsmall cell lung cancer.
BACKGROUND: Alterations of the p53 gene are one of the most common genetic changes in various types of cancer, including lung cancer. Abnormalities in the ras genes, including point mutations and overexpression, are another common feature in the molecular biology of lung cancer and are associated with a poorer prognosis. The authors' purpose was to determine expression of the mutated p53 gene in nonsmall cell lung cancer (NSCLC) specimens that were studied for expression of ras p21 and to document whether altered p53 expression was also an important factor for survival. METHODS: Ninety-six patients with NSCLC underwent surgical resection between 1977 and 1985, 63 of whom received postoperative combination chemotherapy. None received radiation therapy. Tumor specimens were analyzed for altered p53 expression by immunohistochemistry. Univariate and multivariate analyses were performed to assess the association between p53 expression and survival. RESULTS: Fifty-six (58%) of 96 tumor specimens showed altered p53 expression, and 91 patients were analyzed for survival. Altered p53 expression did not correlate with clinicopathologic characteristics except for postsurgical pathologic tumor (pT) classification. The patients with altered p53 expression survived for a significantly shorter period after surgery than those without p53 expression, including all patients who underwent resection and potentially curative resection (P = 0.02 and P = 0.048, respectively, generalized Wilcoxon test). Multivariate analysis showed independent prognostic significance for altered p53 expression (hazard ratio [HR] = 1.72, P = 0.04) and surgical cure (HR = 4.69, P < 0.001). The combined analysis of mutated p53 and ras p21 expression in the same tumor specimens revealed that patients with p53- and ras p21-negative tumors survived the longest among those with different p53 and ras p21 features (P = 0.005, generalized Wilcoxon test). CONCLUSION: Altered p53 expression is a significant and independent negative prognostic factor for patients with surgically resected NSCLC: Combined immunohistochemical analysis of mutated p53 and ras p21 expression can divide patients with NSCLC into more accurate prognostic groups. If the current findings can be confirmed in larger prospective studies, combined immunohistochemical analysis of mutated p53 and ras p21 expression can be a useful clinical tool for stratifying patients with NSCLC into accurate prognostic groups and for identifying the population with a different risk of recurrence.
Aged↗
Increased granzyme B mRNA after alloincompatible myoblast transplantation.
Normal C57BL/10SnJ myoblasts were transplanted into the tibialis anterior of C57BL/10SnJ, C57BL/ScSn mdx, or BALB/c mice. These transplantations allowed us to investigate the immune response not only against MHC but also against dystrophin introduced in the dystrophic muscles by such transplantations. Recently, our group reported following myoblast transplantations cellular infiltration of the host muscle by class II MHC cells, macrophages, and lymphocytes expressing CD4 or CD8 and IL-2 receptors. In the present study, activation of these infiltrating lymphocytes was investigated by measuring the expression of granzyme B mRNA. We used reverse-transcriptase polymerase chain reaction to detect granzyme B mRNA at various intervals after myoblast transplantations. To standardize the results, the mRNA were reverse transcribed using an oligo (dt) so that beta-actin mRNA could also be amplified from the same cDNA preparation. Granzyme B mRNA was increased for at least 3 weeks after MHC alloincompatible grafts. The absence of increased granzyme B expression after allocompatible transplantation in mdx mice suggests that dystrophin is not sufficiently immunogenic to induce short term acute rejection. These results indicate that lymphocytes infiltrated in muscles injected with histoincompatible myoblasts are activated and sustain the requirement for an adequate immunosuppression after such transplantations.
Animals↗
Inhibition of proliferation by L-myc antisense DNA for the translational initiation site in human small cell lung cancer.
We evaluated the antiproliferative effect of L-myc antisense DNA in NCI-H209, a human small cell lung cancer (SCLC) cell line overexpressing the L-myc gene. The synthetic DNA used in the present study was oligodeoxynucleoside phosphorothioate, which showed rapid incorporation into NCI-H209 cells and localized mainly in the cell nucleus and weakly in the cytoplasm. The exposure of this cell line to L-myc antisense DNA covering the translational initiation site of L-myc proteins inhibited the cell proliferation in a dose-dependent sequence-specific manner. Furthermore, the growth inhibition by this antisense DNA was correlated with the level of L-myc expression in three SCLC cell lines, NCI-H209, NCI-H510, and NCI-H82. In Western blot analysis, expression of the L-myc proteins was down-regulated in the antisense-treated cells compared with control-treated cells in NCI-H209. Together with unique characteristics of the L-myc gene, including: (a) a frequently amplified and overexpressed state in SCLC; and (b) very restricted and low-level expression in human adult tissues, the present data indicate that L-myc is a good candidate for the target gene for antisense DNA therapy based on molecular biological diagnosis in SCLC.
Base Sequence↗
Successful myoblast allotransplantation in mdx mice using rapamycin.
Explore the source record for details and available documents.
Animals↗
Pretreatment of myoblast cultures with basic fibroblast growth factor increases the efficacy of their transplantation in mdx mice.
The effect of pretreatment of cultures with basic fibroblast growth factor (bFGF) on myoblast allotransplantation to C57BL/10ScSn mdx/mdx mouse (mdx mouse) muscles not previously damaged and not irradiated was studied. Transgenic CD1 mice which have a beta-galactosidase gene under the control of the promoter of the quail fast skeletal muscle troponin I gene, were used as donors. The myoblasts were grown with 100 ng/mL bFGF during the last 2 days before injecting them in the left tibialis anterior (TA) muscles of mdx mice. Myoblasts from the same primary cultures were also grown without bFGF and injected in the right TA muscles as control. The recipient mice were immunosuppressed with FK 506. Twenty-eight days after myoblast transplantation, the percentage of beta-galactosidase-positive fibers was significantly higher (more than fourfold) following culture with bFGF than without bFGF. Almost all beta-galactosidase-positive fibers were also dystrophin positive. Direct intramuscular injections of bFGF or of Hank's balanced salt solution (HBSS) at the time of myoblast transplantation and at several intervals afterwards were also investigated. The percentage of beta-galactosidase-positive fibers did not differ significantly following intramuscular injection of bFGF from controls injected with HBSS. In vitro, this high concentration of bFGF significantly reduced the formation of myotubes, and the percentage of mononuclear cells which were myoblasts was significantly increased by 34%. These observations alone do not account for the fourfold increase in transplantation success. The presence of bFGF in the culture did not significantly increase the cell survival 3 days after their transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis.
To determine if L-arginine, a precursor of the endothelium-derived relaxing factor, restores endothelium-dependent dilation in human coronary arteries, we studied 21 patients in whom the lumina of the coronary arteries were angiographically smooth or slightly irregular and in whom there was a constrictor response to acetylcholine (ACh) in the left anterior descending coronary artery or the circumflex coronary artery. We examined the response to intracoronary ACh before and after infusion of L-arginine by measuring coronary diameter with quantitative angiography. Intracoronary injection of ACh produced vasoconstriction in the majority of patients with coronary risk factors. The percentage diameter change in smooth segments in patients with entirely smooth coronary arteries (group 1, n = 44) from baseline was -20.7% +/- 17.4%. During systemic infusion of L-arginine, the constrictor response to ACh in these segments was significantly attenuated (-2.2% +/- 15.1% from baseline, p < 0.01, ACh alone vs ACh during L-arginine infusion). In smooth segments in patients with luminal irregularities in the other coronary arteries (group 2, n = 19), ACh produced a marked constriction (-32.5% +/- 22.5% from baseline, p < 0.05, group 1 vs group 2). Infusion of L-arginine also attenuated ACh-induced vasoconstriction in these segments (-9.7% +/- 14.1% from baseline, p < 0.01, ACh vs ACh during L-arginine infusion). In segments with irregular lumina (group 3, n = 26), ACh produced more prominent vasoconstriction. The percentage diameter change was -40.9% +/- 26.5% from baseline (p < 0.01 vs group 1).(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Coronary angioplasty of chronic total occlusions with bridging collateral vessels: immediate and follow-up outcome from a large single-center experience.
OBJECTIVES: The purpose of the present study was to assess the effect of bridging collateral vessels on the success of coronary angioplasty of chronic total occlusions in the context of state of the art technology and operator skill. BACKGROUND: Coronary angioplasty of chronic total occlusions has been associated with relatively low success rates. Because the presence of bridging collateral vessels in chronic total occlusion has been reported to be the major predictive factor in procedural failure, angioplasty is often not recommended in patients with such vessels. METHODS: Three hundred ninety-seven consecutive patients undergoing coronary angioplasty for chronic total occlusion were classified into two groups. Patients in group I had chronic total occlusion with bridging collateral vessels (97 patients, 109 total occlusions), and patients in group II had chronic total occlusion without such vessels (300 patients, 324 total occlusions). RESULTS: The mean +/- SD duration of occlusion was 46 +/- 66 months (range 2 to 170) in group I and 27 +/- 39 months (range 2 to 112) in group II (p < 0.05, high power value 0.83, group I vs. group II). Angioplasty for single-vessel disease was performed in a smaller proportion of patients in group I than in group II (22% vs. 36%, p < 0.05; power value 0.77). Procedural success was achieved in 82 chronic total occlusions in group I and 270 chronic total occlusions in group II (75% vs. 83%, p = 0.07; power value 0.53). The rates of restenosis and reocclusion were 54% and 16%, respectively, for group I and 56% and 13%, respectively, for group II (p = 0.76, 0.46; power value 0.51, 0.47). Complications were minor with no Q wave infarction or requirement for urgent bypass surgery in either group. Of 81 patients with unsuccessful coronary angioplasty, 1 patient from group I (1%) and 3 patients from group II (1%) required pericardiocentesis because of cardiac tamponade. Guide wire manipulation did not impair the flow of bridging collateral channels in group I. CONCLUSIONS: Coronary angioplasty can open chronic total occlusions, with or without bridging collateral channels, for safe and effective recanalization without major complications.
Aged↗
Cyclophosphamide immunosuppression does not permit successful myoblast allotransplantation in mouse.
Cyclophosphamide immunosuppression does not permit successful myoblast allotransplantation in mouse. Myoblast transplantation is a potential treatment for Duchenne muscular dystrophy. In one clinical trial, Duchenne patients were immunosuppressed with cyclophosphamide. We report here that myoblasts from transgenic mice expressing the beta-galactosidase reporter gene transplanted in mdx mice failed to form new muscle fibres when cyclophosphamide (2 or 10 mg kg-1 per day) was used for immunosuppression. At the lowest dose of cyclophosphamide (2 mg kg-1 per day), some mdx recipient mice formed antibodies against donor myoblasts; however, no humoral immune reaction was observed at the highest dose (10 mg kg-1 per day). The failure of transplantation under cyclophosphamide treatment was attributed to the low immunosuppressive activity at a low dose and to the toxic action of a high dose of this drug. These results could explain the lack of success of myoblast transplantation in a previous clinical trial.
Animals↗