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Comparison of two different doses of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced emesis. | given intravenously as a single dose before the CDDP infusion. From days 2-5; all patients received oral ondansetron 8 mg twice daily. Seventy-five patients (38 in the 8 mg group and 37 in the 24 mg group) were evaluable for analysis. Among these; there were 24 patients who received ifosfamide (IFO) on the 2nd day of treatment; these patients were evaluated separately for delayed emesis. Complete protection from acute emesis was obtained in 26 (68.4%) and 26 (70.3%) patients; in the two groups; respectively | 8978584 | [
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Comparison of two different doses of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced emesis. | . Complete protection against acute nausea was achieved in 23 (60.5%) and 24 (64.9%) patients; respectively. With respect to the delayed emesis; complete protection was achieved in 14 (56%) and 13 (50%) patients not receiving IFO and in 4 (30.8%) and 3 (27.3%) of those receiving IFO. The figures for the delayed nausea were: 12 (48%) and 13 (50%); 2 (15.4%) and 2 (18.2%); respectively. Similar protection against emesis and nausea was recorded during the second cycle of chemotherapy. Both regimens have the sa | 8978584 | [
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Comparison of two different doses of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced emesis. | me efficacy and thus; taking into account the cost-effectiveness; 8 mg of ondansetron plus dexamethasone in a single intravenous dose should be used for the prevention of high-dose CDDP-induced emesis. | 8978584 | [
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A randomised, double-blind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy. | A double-blind; parallel-group study in 189 ovarian cancer patients compared the efficacy of ondansetron 8 mg i.v. (OND) and metoclopramide 60 mg i.v. (MET) both in combination with dexamethasone 20 mg i.v. in the prevention of carboplatin-induced emesis. On day 1; complete or major control of emesis (0-2 emetic episodes) was observed in 97% patients from the OND group compared with 74% patients from the MET group (p < 0.001). Similarly; a worst-day analysis over days 1-3 showed complete or major control of | 8978585 | [
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A randomised, double-blind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy. | emesis in 87% patients (OND) compared wth 66% patients (MET) (p < 0.001). Similar findings in favour of the OND group were observed for nausea grade on day 1 and the worst-day grade during days 1-3. OND was better tolerated than MET. Fewer patients from the OND group (13%) reported adverse events compared with the MET group (21%). Extrapyramidal type symptoms were observed in 6 (6%) patients from the MET group (paraesthesia; involuntary movement of the jaw and tongue; and restlessness); compared with none | 8978585 | [
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A randomised, double-blind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy. | from the OND group. Ondansetron plus dexamethasone is a highly effective and well-tolerated treatment and is significantly superior to metoclopramide plus dexamethasone in the prevention of carboplatin-induced emesis. | 8978585 | [
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Chemotherapy-induced spontaneous pneumothorax in a patient with bulky mediastinal lymphoma: a rare oncologic emergency. | Chemotherapy-induced spontaneous pneumothorax (SP) has been described sporadically in chemosensitive tumors; particularly sarcoma; with multiple lung metastases. We present a patient who developed SP following rapid regression of bulky mediastinal lymphoma. Immediately on chest tube insertion; the lung recovered and further chemotherapy could be delivered uneventfully. We suggest that (1) chemotherapy-induced SP should be included amongst oncologic emergencies and that (2) a high degree of awareness of this | 8978586 | [
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Chemotherapy-induced spontaneous pneumothorax in a patient with bulky mediastinal lymphoma: a rare oncologic emergency. | complication is required. | 8978586 | [
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Brachytherapy for penile cancer using silicon mold. | We analyzed the treatment results of 15 patients with penile cancer treated by afterloading brachytherapy with a silicon-made mold we devised. The group included 8 patients with T1; 5 with T2 and 2 with T3 tumors; and inguinal lymph node metastases were noted in 4 patients. The total dose of brachytherapy ranged from 32 to 74 Gy with or without an electron beam boost. The median dose rate was 200 cGy/h ranging from 100 to 350 cGy/h. Local control was achieved in 12 of the 15 patients (80%); and was related | 8978588 | [
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Brachytherapy for penile cancer using silicon mold. | to the T category; with 100% of T1 and 80% of T2; in contrast to 0% of T3 tumor. Three patients with partial response or residual tumor underwent amputation. Local recurrence was recognized in 1 patient with a T2 tumor; but salvaged by surgery. Penis conservation was achieved in 11 of 15 patients (73%). Of the 4 patients with inguinal lymph node metastases; 3 were controlled by surgery and radiation therapy. The other with a T3 tumor died from the disease. Brachytherapy with a mold for penile cancer was con | 8978588 | [
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Brachytherapy for penile cancer using silicon mold. | sidered to be the first choice for penis-conserving therapy; and the patients with T1 and T2 tumors have good indications for this method of treatment. | 8978588 | [
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Carboplatin as an anticancer agent for transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. | Transcatheter arterial chemoembolization (TACE) is a conservative treatment in patients with hepatocellular carcinoma (HCC). In the present study; 30 patients with unresectable HCC underwent TACE using carboplatin (300 mg); and their clinical results were evaluated. After TACE; 18 (60.0%) of 30 patients demonstrated tumor size reduction rates > or = 50%. Of 23 patients with pretreatment serum alpha-fetoprotein (AFP) levels >20 ng/ml (cutoff); 14 (60.9%) showed AFP reduction > or = 75%. The 1-; 2-; 3- and 4- | 8978589 | [
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Carboplatin as an anticancer agent for transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. | year survival rates were 82.9; 68.1; 45.1 and 37.6%; respectively. The median survival was 2.3 years. The only notable adverse reaction accompanying TACE was a transient myelosuppression. Carboplatin is thought to be a useful anticancer agent in patients with HCC treated with TACE. | 8978589 | [
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Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report. | Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemotherapy. The major limiting toxicity was myelotoxicity. Recently; the role of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced neutropenic sepsis has been well established. In this study; we tested whether recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow function in both previously untreated and pretreated metastatic NPC patients receiving intensive chemotherapy. Twelve pati | 8978590 | [
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Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report. | ents with distant metastatic disease; 5 newly diagnosed (group A) and 7 pretreated patients (group B); were enrolled to receive BEC (bleomycin; epirubicin and cisplatin); followed by rhG-CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles. Four patients in group A completed the treatment as scheduled while only 2 patients in group B did. After the first treatment cycle; 6 patients (50%) had grade III-IV myelosuppression. Five of the patients were from group B. The mean values of t | 8978590 | [
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Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report. | he white cell count nadir were 2;680 (range 1;200-3;700) in group A and 1;343 (range 400-2;900) in group B (p = 0.0386). Neutropenia-associated fever occurred in 7 patients; 6 of whom had received previous treatment. There were 2 deaths due to toxicity; and both patients had liver metastases within 6 months following radiation. After 24 months of follow-up; only 1 patient is still alive. Our preliminary results suggest that in previously treated metastatic NPC patients; bone marrow suppression is still the | 8978590 | [
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Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report. | major limiting toxic side effect of aggressive chemotherapy; especially for those patients with liver recurrences within 6 months after irradiation and despite rhG-CSF support. | 8978590 | [
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Follow-up study in head and neck cancer: cure rate according to tumor location and stage. | The purpose of this clinical study was to analyze a long-term follow-up of all the patients with head and neck cancer in our institution. Between 1973 and 1993; 1;355 consecutive cases of head and neck cancerwere diagnosed; treated and followed up regularly. All were subjected to a multidisciplinary approach; and followed up until death or for 10 years with no event of disease. The local relapse rate was 20% and the node-regional relapse rate 15%. Distant metastases were observed in 6% of the patients mainl | 8978591 | [
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Follow-up study in head and neck cancer: cure rate according to tumor location and stage. | y arising from the nasopharynx (23%) followed by the hypopharynx (11%). The main organ involved was the lung (50%). Median follow-up of the group was 10 years (range 4 months to 15 years). Cancer cure was observed after 5 years in glottic and supraglottic laryngeal carcinoma; oral and nasopharyngeal cancer and after 2.5 years in patients with cancer of the oropharynx and hypopharynx. The highest cure rate was 80% in the glottis; followed by 70% in the supraglottic area; 45% in the mouth; 30% in the nasophar | 8978591 | [
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Follow-up study in head and neck cancer: cure rate according to tumor location and stage. | ynx; 25% in the oropharynx; and 20% in the hypopharynx. A second primary tumor was observed in 7% of the patients and a third primary in 0.6% of the patients. Only in 7 patients; the second or third primary was seen after 5 years of follow-up. Curability should be observed after 5 years from definitive therapy of glottic; supraglottic; oral and nasopharyngeal and earlier in oropharyngeal and hypopharyngeal cancer. Further follow-up should be discontinued. Second and third neoplasias are the main problems af | 8978591 | [
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Follow-up study in head and neck cancer: cure rate according to tumor location and stage. | ter 5 years of follow-up but their incidence is low. | 8978591 | [
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'Spontaneous' regression of advanced leiomyosarcoma of the urinary bladder. | A case of advanced leiomyosarcoma of the urinary bladder is reported in a 25-year old man who; in a short time; experienced a complete 'spontaneous' regression of his fatal illness. He first presented with severe haemoperitoneum resulting from an unresectable bleeding tumour of the urinary bladder. Debulking surgery was performed; followed by salvage chemotherapy. Histological and ultrastructural examinations of the tumour confirmed a poorly differentiated leiomyosarcoma. The residual disease failed to resp | 8978587 | [
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'Spontaneous' regression of advanced leiomyosarcoma of the urinary bladder. | ond to salvage chemotherapy; but regressed 'spontaneously' 5 months after cessation of therapy. The patient is alive without evidence of disease 51 months after the diagnosis. This remarkable phenomenon and relatively long survival in a poor-risk leiomyosarcoma of the urinary bladder has never been reported previously. | 8978587 | [
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CYFRA 21-1: an indicator of survival and therapeutic effect in lung cancer. | CYFRA 21-1 is a new tumor marker using two different monoclonal antibodies which recognize the divergent epitope on the N- or C-terminal region of domain 2 of cytokeratin 19 fragment; respectively. In this study; we investigated the relationship between levels of CYFRA 21-1 and survival duration; as well as the efficacy of chemotherapy associated with changes in CYFRA 21-1. Serum samples were obtained from 87 patients with nonoperable lung cancer (35 cases with squamous-cell carcinoma; 33 with adenocarcinom | 8978592 | [
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CYFRA 21-1: an indicator of survival and therapeutic effect in lung cancer. | a; 3 with large-cell carcinoma; and 16 with small-cell carcinoma). The cutoff point was set at 3.5 ng/ml. In a CYFRA 21-1 assay; significantly more patients with squamous-cell carcinoma and adenocarcinoma were positive compared to patients with small-cell and large-cell carcinomas (p = 0.0017). Following chemotherapy; blood levels of CYFRA 21-1 decreased significantly in responders versus nonresponders (p = 0.0246). A significant correlation was noted between survival periods and pretreatment levels of CYFR | 8978592 | [
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CYFRA 21-1: an indicator of survival and therapeutic effect in lung cancer. | A 21-1 (p = 0.0036). The present study suggests that CYFRA 21-1 might be useful as a possible indicator of survival and therapeutic effect for lung cancer. | 8978592 | [
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Immunohistochemical analysis of nucleoside diphosphate kinases in oral squamous cell carcinomas. | The nm23 gene is a potential metastasis suppressor gene originally identified using a murine melanoma cell line. The nm23 proteins are nucleoside diphosphate (NDP) kinases; and there are two isotypes in human and other mammalian cells. Immunohistochemical analysis with anti-rat NDP kinase (NDP kinase alpha; NDP kinase beta) monoclonal antibodies was performed in deparaffinized sections of 56 specimens of oral squamous cell carcinoma. Detection of these NDP kinases in tissue samples was correlated with clini | 8978595 | [
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Immunohistochemical analysis of nucleoside diphosphate kinases in oral squamous cell carcinomas. | cal and histopathological factors. The NDP kinase A (nm23 H1 protein)-positive group was apt to have a lower frequency of neck metastasis than the negative one (p < 0.01). Consequently; it is suggested that NDP kinase A might be a metastasis suppressor factor that may be useful for predicting tumor metastases in patients with oral squamous cell carcinoma. | 8978595 | [
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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 th | 8978596 | [
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Antitumor effect of murine colon carcinoma cells retrovirally transduced with interleukin-4 and granulocyte macrophage-colony stimulating factor genes. | e 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. | 8978596 | [
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Combination effect of anti-Fas antibody and chemotherapeutic drugs in ovarian cancer cells in vitro. | To clarify the significance of the Fas antigen (Ag) in gynecologic tumors; its expression in gynecologic cancer cell lines was examined. The Fas Ag was expressed in 6 of 15 cell lines. Five of 8 ovarian cancer cell lines but none of 4 choriocarcinoma cell lines expressed the Fas Ag. In drug-resistant cell lines derived from one of the Fas-positive cells; its expression was not lost after development of resistance to cisplatin; SN-38 or etoposide; but its expression was absent in the cell line resistant to A | 8978593 | [
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Combination effect of anti-Fas antibody and chemotherapeutic drugs in ovarian cancer cells in vitro. | driamycin. The effect of the anti-Fas antibody (Ab) was then studied. Apoptosis was induced in 7 of 9 Fas-positive cell lines; whereas the remaining two cell lines were unaffected. Furthermore; the combination effect of the anti-Fas Ab and drugs was examined in an ovarian cancer cell line and its drug-resistant variants; and a synergistic effect was observed. These results suggest important roles of the Fas Ag in ovarian cancer and the potential for overcoming drug resistance by a combination of the anti-Fa | 8978593 | [
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Effects of cisplatin on testicular tissue and the Leydig cell-pituitary axis. | The mechanisms responsible for the rapid increases in levels of gonadotropin and steroid hormones upon administration of cisplatin to rats are not clearly understood. In the present study; the morphologic effects of cisplatin on the testis and the relationship of these changes to serum hormone levels were studied in adult rats. Upon administration of a single dose (5 mg/kg) of cisplatin; the levels of testosterone in the peripheral blood decreased and the level of luteinizing hormone (LH) increased. After 3 | 8978597 | [
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Effects of cisplatin on testicular tissue and the Leydig cell-pituitary axis. | days; significant damage to the germinal epithelium became detectable by morphologic examination. In Leydig and Sertoli cells; dilatation of the endoplasmic reticulum; structural changes in mitochondria and an increase in the numbers of inclusion bodies were detected. Although blood-testis barriers between Sertoli cells were normal; the relationship between germinal cells and the relationship between germinal cells and Sertoli cells were distorted. It is concluded that damage to Leydig cells and withdrawal | 8978597 | [
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Effects of cisplatin on testicular tissue and the Leydig cell-pituitary axis. | of the controlling effects of the germinal epithelium on the LH-Leydig cell axis could explain the changes in serum hormone levels. | 8978597 | [
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Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications. | The serum levels of lysosomal cathepsin B and L and Stefin A; an intracellular inhibitor of these proteolytic enzymes; were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p < 0.001). However no difference was observed between HCC and LC groups. Interestingly; a significant relationship was evi | 8978598 | [
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Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications. | denced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p < 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as compared to normal subjects or LC patients (p < 0.001) and significantly correlated with the number of malignant lesions (r = 0.49; p = 0.001). Stefin A serum levels were increased in HCC and LC patients as compared to healthy subjects (p < 0.02). However; these levels were significantly higher in the LC group as compared to the HCC | 8978598 | [
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Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications. | group (p < 0.05). In cancer patients; a significant relationship was observed between Stefin A serum content and tumor size (r = 0.35; p < 0.05); number of neoplastic lesions (r = 0.556; p < 0.001) and serum alpha-fetoprotein (r = 0.38; p < 0.01). These data suggest that cathepsin B and L and Stefin A may be potentially useful as additional biochemical parameters to monitor the therapeutic response of these diseases to clinical treatments and to identify patients with cirrhosis developing precancerous lesio | 8978598 | [
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Slow increase in intranuclear and cytosolic free calcium concentrations in L929 cells is important in tumour necrosis factor-alpha-mediated cell death. | The potential involvement of cellular calcium in the signalling pathway of tumour necrosis factor-alpha (TNF) was assessed in L929 cells using 45Ca2+ and confocal laser scanning microscopy with fluorescence calcium indicators. Our data indicate that the effect of TNF on intracellular Ca2+ mobilization is a slow process with no discernible increase in the cytosolic free Ca2+ concentration ([Ca2+]c) and intranuclear Ca2+ level ([Ca2+]n) within the 1st min of TNF (25 ng/ml) administration. However; prolonged e | 8978594 | [
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Slow increase in intranuclear and cytosolic free calcium concentrations in L929 cells is important in tumour necrosis factor-alpha-mediated cell death. | xposure (2 h) of L929 cells to TNF brought about pronounced increase in cytosolic and intranuclear [Ca2+] even in the absence of external Ca2+. The increase in intracellular [Ca2+] was more apparent when cells were treated with thapsigargin; an inhibitor of microsomal Ca2+-ATPase. Interestingly; most of the Ca2+ released was around and confined to the nucleus. Following the pretreatment of cells with thapsigargin; a synergistic killing effect was obtained when cells were cultured with TNF. The use of 45Ca2+ | 8978594 | [
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Slow increase in intranuclear and cytosolic free calcium concentrations in L929 cells is important in tumour necrosis factor-alpha-mediated cell death. | also revealed that TNF enhanced the 45Ca2+ uptake in a time-dependent manner. Calcium channel blockers; verapamil and diltiazem; could alleviate both the TNF-mediated 45Ca2+-uptake and killing activity. Our results therefore suggest that an increase in cellular Ca2+ is a crucial factor in the TNF cytotoxicity. | 8978594 | [
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] |
p53 protein expression in gastrointestinal lymphomas. | We investigated the p53 protein expression in gastrointestinal lymphomas (GIL). Paraffin-embedded samples of 52 patients were examined for this purpose. The avidin-biotin Complex method was used for immunostaining. Nine of the 52 samples (17.3%) showed p53 staining. There was no relationship between the p53 protein expression and clinical characteristics; such as stage; disease localization and tumor burden. Complete remission was higher in patients not expressing this protein; and the p53 protein was more | 8978599 | [
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p53 protein expression in gastrointestinal lymphomas. | frequently expressed in intermediate and high grade histopathology than low grade lymphomas; but there was no statistically significant difference between the two groups (p = 0.008). Interestingly; patients expressing the p53 protein were younger than the ones not expressing it (30.7 +/- 14.1 vs. 43.6 +/- 15.7 years). We conclude that the p53 protein expression in GILs may be a poor prognostic indicator due to a lower response rate to chemotherapy. | 8978599 | [
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The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. | Autosomal dominant polycystic kidney disease (ADPKD) is a common disease and an important cause of renal failure. It is characterized by considerable intrafamilial phenotypic variation and focal cyst formation. To elucidate the molecular basis for these observations; we have developed a novel method for isolating renal cystic epithelia from single cysts and have used it to show that individual renal cysts in ADPKD are monoclonal. Loss of heterozygosity was discovered within a subset of cysts for two closely | 8978603 | [
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The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. | linked polymorphic markers located within the PKD1 gene. Genetic analysis revealed that it was the normal haplotype that was lost. This study provides a molecular explanation for the focal nature of cyst formation and a probable mechanism whereby mutations cause disease. The high rate at which "second hits" must occur to account for the large number of cysts observed suggests that unique structural features of the PKD1 gene may be responsible for its mutability. | 8978603 | [
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Eomesodermin, a key early gene in Xenopus mesoderm differentiation. | Eomesodermin (Eomes) is a novel Xenopus T-domain gene. In normal development; it is expressed in mesodermal cells in a ventral-to-dorsal gradient of increasing concentration. It reaches its peak expression 1-2 hr before any other known panmesodermal gene. It is strongly inducible by normal vegetal cells and by mesoderm-inducing factors. Ectopic expression of Eomes in animal caps induces the transcription of nearly all mesodermal genes in a concentration-dependent way. Overexpression of Eomes dorsalizes vent | 8978604 | [
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Eomesodermin, a key early gene in Xenopus mesoderm differentiation. | ral mesoderm; inducing gsc and changing cell fate to muscle and notochord. Blocking the function of Eomes causes gastrulation arrest and defective mesoderm-dependent gene activation. We propose that Eomes fulfills an essential function in initiating mesoderm differentiation and in determining mesodermal cell fate. | 8978604 | [
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Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. | During nervous system development; spinal commissural axons project toward floor plate cells and trochlear motor axons extend away from these cells. Netrin-1; a diffusible protein made by floor plate cells; can attract spinal commissural axons and repel trochlear axons in vitro; but its role in vivo is unknown. Netrin-1 deficient mice exhibit defects in spinal commissural axon projections that are consistent with netrin-1 guiding these axons. Defects in several forebrain commissures are also observed; sugge | 8978605 | [
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Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. | sting additional guidance roles for netrin-1. Trochlear axon projections are largely normal; predicting the existence of additional cues for these axons; and evidence is provided for a distinct trochlear axon chemorepellent produced by floor plate cells. These results establish netrin-1 as a guidance cue that likely collaborates with other diffusible cues to guide axons in vivo. | 8978605 | [
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Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. | Nitric oxide (NO) has been implicated in hippocampal long-term potentiation (LTP); but LTP is normal in mice with a targeted mutation in the neuronal form of NO synthase (nNOS-). LTP was also normal in mice with a targeted mutation in endothelial NOS (eNOS-); but LTP in stratum radiatum of CA1 was significantly reduced in doubly mutant mice (nNOS-/eNOS-). By contrast; LTP in stratum oriens was normal in the doubly mutant mice. These results provide the first genetic evidence that NOS is involved in LTP in s | 8978606 | [
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Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. | tratum radiatum and suggest that the neuronal and endothelial forms can compensate for each other in mice with a single mutation. They further suggest that there is also a NOS-independent component of LTP in stratum radiatum and that LTP in stratum oriens is largely NOS independent. | 8978606 | [
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Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. | Nitric oxide (NO) has been proposed to act as a retrograde messenger during long-term potentiation (LTP) in the CA1 region of hippocampus; but the inaccessibility of the presynaptic terminal has prevented a definitive test of this hypothesis. Because both sides of the synapse are accessible in cultured hippocampal neurons; we have used this preparation to investigate the role of NO. We examined LTP following intra- or extracellular application of an NO scavenger; an inhibitor of NO synthase; and a membrane- | 8978607 | [
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Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. | impermeant NO donor that releases NO only upon photolysis with UV light. Our results indicate that NO is produced in the postsynaptic neuron; travels through the extracellular space; and acts directly in the presynaptic neuron to produce long-term potentiation; supporting the hypothesis that NO acts as a retrograde messenger during LTP. | 8978607 | [
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A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. | We describe the phenotype of gene-targeted mice lacking the putative chemokine receptor BLR1. In normal mice; this receptor is expressed on mature B cells and a subpopulation of T helper cells. Blr1 mutant mice lack inguinal lymph nodes and possess no or only a few phenotypically abnormal Peyer's patches. The migration of lymphocytes into splenic follicles is severely impaired; resulting in morphologically altered primary lymphoid follicles. Furthermore; activated B cells fail to migrate from the T cell-ric | 8978608 | [
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A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. | h zone into B cell follicles of the spleen; and despite high numbers of germinal center founder cells; no functional germinal centers develop in this organ. Our results identify the putative chemokine receptor BLR1 as the first G protein-coupled receptor involved in B cell migration and localization of these cells within specific anatomic compartments. | 8978608 | [
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The Drosophila beaten path gene encodes a novel secreted protein that regulates defasciculation at motor axon choice points. | In the Drosophila embryo; at specific choice points along the major motor nerves; subsets of motor axons defasciculate and then steer into their muscle target regions. Here we describe the analysis of beaten path (beat); a gene required for the selective defasciculation of motor axons at these choice points. In beat mutant embryos; motor axons fail to defasciculate and bypass their targets. This phenotype is suppressed by mutations in FasII and conn; two genes encoding cell adhesion molecules expressed on m | 8978609 | [
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The Drosophila beaten path gene encodes a novel secreted protein that regulates defasciculation at motor axon choice points. | otor axons; suggesting that beat provides an antiadhesive function. beat encodes a novel secreted protein that is expressed by motoneurons during outgrowth. Rescue and ectopic expression experiments support the model that Beat protein is secreted by motor axons where it functions to regulate their selective defasciculation at specific choice points. | 8978609 | [
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A Drosophila neurexin is required for septate junction and blood-nerve barrier formation and function. | Septate and tight junctions are thought to seal neighboring cells together and to function as barriers between epithelial cells. We have characterized a novel member of the neurexin family; Neurexin IV (NRX); which is localized to septate junctions (SJs) of epithelial and glial cells. NRX is a transmembrane protein with a cytoplasmic domain homologous to glycophorin C; a protein required for anchoring protein 4.1 in the red blood cell. Absence of NRX results in mislocalization of Coracle; a Drosophila prote | 8978610 | [
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A Drosophila neurexin is required for septate junction and blood-nerve barrier formation and function. | in 4.1 homolog; at SJs and causes dorsal closure defects similar to those observed in coracle mutants. nrx mutant embryos are paralyzed; and electrophysiological studies indicate that the lack of NRX in glial-glial SJs causes a breakdown of the blood-brain barrier. Electron microscopy demonstrates that nrx mutants lack the ladder-like intercellular septa characteristic of pleated SJs (pSJs). These studies identify NRX as the first transmembrane protein of SJ and demonstrate a requirement for NRX in the form | 8978610 | [
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A Drosophila neurexin is required for septate junction and blood-nerve barrier formation and function. | ation of septate-junction septa and intercellular barriers. | 8978610 | [
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Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. | Arterial smooth muscle cells (SMCs) are arrested in the G1 phase of the cell cycle on polymerized type I collagen fibrils; while monomer collagen supports SMC proliferation. Cyclin E-associated kinase and cyclin-dependent kinase 2 (cdk2) phosphorylation are inhibited on polymerized collagen; and levels of the cdk2 inhibitors p27Kip1 and p21Cip1/Waf1 are increased compared with SMCs on monomer collagen. p27Kip1 associates with the cyclin E-cdk2-p21Cip1/Waf1 complex in SMCs on polymerized collagen. Monovalent | 8978611 | [
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Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. | blocking antibodies to alpha2 integrins; integrins that mediate adhesion to both forms of collagen; mimic these effects on monomer collagen. Furthermore; polymerized collagen rapidly suppresses p70 S6 kinase; a possible regulator of p27Kip1. Thus; fibrillar collagen specifically regulates early integrin signaling that may lead to up-regulation of cdk2 inhibitors and inhibition of SMC proliferation. | 8978611 | [
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Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. | Sexual orientation and courtship behavior in Drosophila are regulated by fruitless (fru); the first gene in a branch of the sex-determination hierarchy functioning specifically in the central nervous system (CNS). The phenotypes of new fru mutants encompass nearly all aspects of male sexual behavior. Alternative splicing of fru transcripts produces sex-specific proteins belonging to the BTB-ZF family of transcriptional regulators. The sex-specific fru products are produced in only about 500 of the 10(5) neu | 8978612 | [
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Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. | rons that comprise the CNS. The properties of neurons expressing these fru products suggest that fru specifies the fates or activities of neurons that carry out higher order control functions to elicit and coordinate the activities comprising male courtship behavior. | 8978612 | [
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branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. | The molecular basis for patterning of complex organ structures like the lung and insect tracheal system is unknown. Here; we describe the Drosophila gene branchless (bnl) and demonstrate that it is a key determinant of the tracheal branching pattern. bnl is required for tracheal branching and is expressed dynamically in clusters of cells surrounding the developing tracheal system at each position where a new branch will form and grow out. Localized misexpression of bnl can direct branch formation and outgro | 8978613 | [
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branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. | wth to new positions. Generalized misexpression activates later programs of tracheal gene expression and branching; resulting in massive networks of branches. bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase; an FGF receptor homolog expressed on developing tracheal cells. The results suggest that this FGF pathway specifies the tracheal branching pattern by guiding tracheal cell migration during primary branch | 8978613 | [
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branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. | formation and then activating later programs of finer branching at the ends of growing primary branches. | 8978613 | [
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Induction of large DNA palindrome formation in yeast: implications for gene amplification and genome stability in eukaryotes. | Many amplified genes; including some oncogenes; are organized as large inverted repeats. How such giant palindromes are generated remains largely unknown. Recent studies of a palindrome in the ciliate Tetrahymena suggest a novel mechanism that requires chromosome breakage next to short inverted repeats. The prevalence of short inverted repeats in eukaryotic genomes raises the interesting possibility that this process may occur widely as a response to chromosome damage. Here we demonstrate that in Saccharomy | 8978615 | [
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Induction of large DNA palindrome formation in yeast: implications for gene amplification and genome stability in eukaryotes. | ces cerevisiae; large DNA palindromes are formed efficiently; probably by intramolecular recombination; when a double-strand break is introduced next to short inverted repeats. These results suggest a general mechanism for large palindromic DNA formation and reveal an important new source of genome instability resulting from chromosome breakage at selective sites. | 8978615 | [
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Chromatid segregation at anaphase requires the barren product, a novel chromosome-associated protein that interacts with Topoisomerase II. | We have isolated a Drosophila gene; barren (barr); required for sister-chromatid segregation in mitosis. barr encodes a novel protein that is present in proliferating cells and has homologs in yeast and human. Mitotic defects in barr embryos become apparent during cycle 16; resulting in a loss of PNS and CNS neurons. Centromeres move apart at the metaphase-anaphase transition and Cyclin B is degraded; but sister chromatids remain connected; resulting in chromatin bridging. This phenotype is similar to that | 8978614 | [
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Chromatid segregation at anaphase requires the barren product, a novel chromosome-associated protein that interacts with Topoisomerase II. | described in TOP2 mutants in yeast. Barren protein localizes to chromatin throughout mitosis. Colocalization and biochemical experiments indicate that Barren associates with Topoisomerase II throughout mitosis and alters the activity of Topoisomerase II. We propose that this association is required for proper chromosomal segregation by facilitating the decatenation of chromatids at anaphase. | 8978614 | [
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A tyrosyl-tRNA synthetase recognizes a conserved tRNA-like structural motif in the group I intron catalytic core. | The Neurospora crassa mitochondrial (mt) tyrosyl-tRNA synthetase (CYT-18 protein) functions in splicing group I introns; in addition to aminoacylating tRNA(Tyr). Here; we compared the CYT-18 binding sites in the N. crassa mt LSU and ND1 introns with that in N. crassa mt tRNA(Tyr) by constructing three-dimensional models based on chemical modification and RNA footprinting data. Remarkably; superimposition of the CYT-18 binding sites in the model structures revealed an extended three-dimensional overlap betwe | 8978617 | [
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A tyrosyl-tRNA synthetase recognizes a conserved tRNA-like structural motif in the group I intron catalytic core. | en the tRNA and the group I intron catalytic core. Our results provide insight into how an RNA-splicing factor can evolve from a cellular RNA-binding protein. Further; the structural similarities between group I introns and tRNAs are consistent with an evolutionary relationship and suggest a general mechanism for the evolution of complex catalytic RNAs. | 8978617 | [
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] |
Pathogenesis and pathology of focal malformations of cortical development and epilepsy. | This article reviews the pathogenesis and pathology of the most common focal malformations of cortical development in association with epilepsy. The classification of these disorders is reviewed in the context of new developments in the areas of diagnosis and genetics. The major pathological substrates and the possible mechanisms of these malformations are discussed. The possible mechanisms of epileptogenesis in the context of focal malformations are complex and poorly understood at present. Advances in thi | 8978619 | [
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Pathogenesis and pathology of focal malformations of cortical development and epilepsy. | s area promise to enhance our understanding of the basic mechanisms of epilepsy. | 8978619 | [
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Transcription activation at class II CAP-dependent promoters: two interactions between CAP and RNA polymerase. | At Class II catabolite activator protein (CAP)-dependent promoters; CAP activates transcription from a DNA site overlapping the DNA site for RNA polymerase. We show that transcription activation at Class II CAP-dependent promoters requires not only the previously characterized interaction between an activating region of CAP and the RNA polymerase alpha subunit C-terminal domain; but also an interaction between a second; promoter-class-specific activating region of CAP and the RNA polymerase alpha subunit N- | 8978616 | [
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Transcription activation at class II CAP-dependent promoters: two interactions between CAP and RNA polymerase. | terminal domain. We further show that the two interactions affect different steps in transcription initiation. Transcription activation at Class II CAP-dependent promoters provides a paradigm for understanding how an activator can make multiple interactions with the transcription machinery; each interaction being responsible for a specific mechanistic consequence. | 8978616 | [
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Neuroimaging of focal malformations of cortical development. | Neuroimaging is playing an increasingly important role in the evaluation of patients with malformations of cerebral cortical development. In this review; the authors address optimal neuroimaging of cortical malformations using x-ray computed tomography; single-photon-emission computed tomography; positron emission tomography; magnetic resonance imaging; and magnetic resonance spectroscopy. Initially; the authors discuss the strengths and weaknesses of the various imaging techniques. This is followed by a di | 8978620 | [
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Neuroimaging of focal malformations of cortical development. | scussion of the clinical and neuroimaging characteristics of several different imaging manifestations of focal malformations of cortical development; including polymicrogyria; focal subcortical heterotopia; schizencephaly; focally thickened gyri; focally irregular gyri; hemimegalencephaly; and transmural dysplasia. The authors intend that; after reading this review; the reader will have a better understanding of the optimal neuroimaging techniques for evaluating these malformations and their many neuroimagi | 8978620 | [
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Value of full-field visual evoked potentials for retrochiasmal lesions. | Some abnormalities in the P100 on monocular stimulation have been said to indicate retrochiasmal abnormalities. This study was undertaken to evaluate the reliability of visual evoked potentials (VEPs) for this purpose. We retrospectively reviewed VEPs that could be interpreted as indicative of a retrochiasmal lesion; based on an amplitude asymmetry of >50% between the P100 recorded on the left and right occipital regions. The abnormality had to be present on both left and right monocular stimulation (uncros | 8978622 | [
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Value of full-field visual evoked potentials for retrochiasmal lesions. | sed pattern). Studies were conducted in accordance with the guidelines of the American Electroencephalographic Society. Findings on magnetic resonance (MR) imaging were analyzed. For comparison; we also studied a control group of 30 patients with normal VEPs. During a 16-month period; we identified 15 patients who fulfilled the aforementioned criteria and who had undergone an MR scan of the brain. Eight scans were normal and seven were abnormal. Of the seven abnormal scans; five revealed multiple periventri | 8978622 | [
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Value of full-field visual evoked potentials for retrochiasmal lesions. | cular white matter lesions in both hemispheres suggestive of multiple sclerosis: one a single punctate white matter lesion in the left frontal corona radiata; and one multiple white matter lesions in the basal ganglia; brainstem; and cerebellum but not in the hemispheres. In the control group with normal VEPs; nine had at least one hemispheric lesion on MR scans. This yielded a positive predictive value of 33%. The negative predictive value was 70%; sensitivity 36%; and specificity 68%. Because of a high ra | 8978622 | [
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Value of full-field visual evoked potentials for retrochiasmal lesions. | te of false positives; full-field VEPs were not reliable in predicting retrochiasmal lesions. | 8978622 | [
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EEG features of focal malformations of cortical development. | Recent advances in neuroimaging have allowed the detection and characterization of focal malformations of cortical developmental in a significant proportion of patients with epilepsy; many of whom were previously labelled as cryptogenic; allowing a better description of the associated electroencephalogram (EEG) features. Alpha activity is usually preserved; although superficial gyral abnormalities are often associated with overlying localized polymorphic delta activity; and occasionally abnormal fast activi | 8978621 | [
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EEG features of focal malformations of cortical development. | ty. Most affected patients with epilepsy show interictal spikes. These are often broadly concordant with the structural abnormality but may show a wider anatomic distribution and be multifocal; or occasionally appear only in anatomically distant sites. In many patients the spikes are frequent and sometimes they occur continuously or in long trains. EEG findings are often stable over time; but some patients only show the development of slow wave changes or interictal spikes when followed serially for several | 8978621 | [
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EEG features of focal malformations of cortical development. | years. A small proportion of patients with focal malformations of cortical development have EEG features mimicking idiopathic generalized epilepsy; and occasionally patients exhibit continuous generalized spike and slow wave activity in sleep. Electrocorticography studies confirm the often widespread nature of interictal spiking; but may also show highly epileptogenic patterns recorded directly from dysplastic cortex. The intrinsic epileptogenicity of areas of cortical developmental abnormalities has also | 8978621 | [
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EEG features of focal malformations of cortical development. | been demonstrated by chronic intracranial studies and in vitro recordings of slices obtained from resected human dysplastic cortex. In this regard such developmental abnormalities are fundamentally different from acquired lesions such as tumors/vascular anomalies that usually exert their effects through changes in adjacent cortex. | 8978621 | [
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Alpha frequency, reaction time, and the speed of processing information. | Several experiments indicate that alpha frequency is significantly correlated with the speed of information processing; as measured by reaction times. These data imply that alpha frequency is a timing mechanism for cognitive processes. However; this interpretation contradicts the well-accepted view that there is no single alpha rhythm; but instead an entire population of different alpha oscillations. We present arguments and report data in the attempt to demonstrate that this paradox can be resolved if diff | 8978623 | [
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Alpha frequency, reaction time, and the speed of processing information. | erent states of alpha oscillations are distinguished. The results of the present study show that during a state of desynchronization; task-related shifts in alpha frequency are not "real" because they are not related to reaction times. Instead; they most likely reflect power changes in different frequency bands. | 8978623 | [
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Periodic lateralized epileptiform discharges--a critical review. | It is the purpose of this review to critically consider and organize the literature dealing with the ephemeral electroencephalographic (EEG) pattern periodic lateralized epileptiform discharges (PLEDs). Although the retrospective nature of these studies limits their ability to discuss accurately the clinical and pathophysiological aspects of this EEG entity; the available data strongly emphasize stroke as the dominant etiology and its high association with seizures. Recent evidence; particularly from functi | 8978624 | [
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Periodic lateralized epileptiform discharges--a critical review. | onal neuroimaging studies; strongly suggests that PLEDs might reflect a key pattern for focal hyperexcitability in the penumbra zone of ischemic stroke. The authors prefer to consider PLEDs as an EEG signature of a dynamic pathophysiological state in which unstable neurobiological processes create an ictal-interictal continuum; with the nature of the underlying neuronal injury; the patient's preexisting propensity to have seizures; and the co-existence of any acute metabolic derangements all contributing to | 8978624 | [
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Periodic lateralized epileptiform discharges--a critical review. | whether seizures occur or not. This review underlines the need for further sophisticated prospective controlled studies implementing early continuous EEG monitoring in order to contribute to an understanding of the incidence; dynamics; and relevance of this pattern. | 8978624 | [
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Reversible, reproducible reduction of brain water apparent diffusion coefficient by cortical electroshocks. | Rat brains were imaged after cortical electroshock pulse trains (1 ms pulses at 100 Hz) of varying durations (0.1-10 s); with diffusion-weighted echo planar imaging sequences at 2.0 T. The apparent water diffusion coefficient (ADC) decreased after either single or repeat electroshock trains. ADC reductions were observed within 6 s after the first shock. The size of the affected area of the brain increased in subsequent images during the 1st min after a 10-pulse (0.1 s) train; and also increased with the dur | 8978625 | [
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