Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.
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PMID:Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer. 132 13

We have observed three women with partial corneal involvement in the ICE syndrome for over 10 years. During this time, the peripheral anterior synechiae progressed in all three, with glaucoma developing in one patient. In two patients, the abnormal endothelial cells spread to cover the entire posterior corneal surface; in the third, they disappeared entirely (ie, "the ICE melted"). The endothelial permeability to fluorescein remained abnormally low only in the two eyes with diffusely abnormal endothelium, increasing to normal in the third eye as the abnormal endothelium disappeared. The permeability in that eye had been abnormally low only in the superior half of the cornea, where the abnormal endothelium was. As the abnormal endothelium regressed, it was replaced by normal endothelium with a normal cell density similar to that of the opposite, uninvolved eye. Thus, over a 10-year period the partial endothelial involvement associated with the ICE syndrome progressed substantially in two patients and regressed dramatically in a third.
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PMID:Progression and regression of partial corneal involvement in the iridocorneal endothelial syndrome. 149 20

The pancreatic beta-cell-specific expression of the insulin gene is mediated, at least in part, by the interaction of unique trans-acting beta-cell factors with a cis-acting DNA element found within the insulin enhancer (5'-GC CATCTG-3'; referred to as the insulin control element [ICE]) present in the rat insulin II gene between positions -100 and -91. This sequence element contains the consensus binding site for a group of DNA-binding transcription factors called basic helix-loop-helix proteins (B-HLH). As a consequence of the similarity of the ICE with the DNA sequence motif associated with the cis-acting elements of the B-HLH class of binding proteins (CANNTG), the ability of this class of proteins to regulate cell-type-specific expression of the insulin gene was addressed. Cotransfection experiments indicated that overexpression of Id, a negative regulator of B-HLH protein function, inhibits ICE-mediated activity. Antibody to the E12/E47 B-HLH proteins attenuated the formation, in vitro, of a previously described (J. Whelan, S. R. Cordle, E. Henderson, P. A. Weil, and R. Stein, Mol. Cell. Biol. 10:1564-1572, 1990) beta-cell-specific activator factor(s)-ICE DNA complex. Both of these B-HLH proteins (E12 and E47) bound efficiently and specifically to the ICE sequences. The role of B-HLH proteins in mediating pancreatic beta-cell-specific transcription of the insulin gene is discussed.
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PMID:Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated by basic helix-loop-helix DNA-binding proteins. 199 19

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. Transcription from the enhancer is controlled by both positive- and negative-acting cellular factors. Cell-type-specific expression is mediated principally by a single cis-acting enhancer element located between -100 and -91 in the rat insulin II gene (referred to as the insulin control element [ICE]), which is acted upon by both of these cellular activities. Analysis of the effect of 5' deletions within the insulin enhancer has identified a region between nucleotides -217 and -197 that is also a site of negative control. Deletion of these sequences from the 5' end of the enhancer leads to transcription of the enhancer in non-insulin-producing cells, even though the ICE is intact. Derepression of this ICE-mediated effect was shown to be due to the binding of a ubiquitously distributed cellular factor to a sequence element which resides just upstream of the ICE (i.e., between nucleotides -110 and -100). We discuss the possible relationship of these results to cell-type-specific regulation of the insulin gene.
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PMID:Insulin gene expression in nonexpressing cells appears to be regulated by multiple distinct negative-acting control elements. 201 82

The use of cooling garments in conjunction with fully encapsulating suits offers the potential for reducing the heat strain for workers at hazardous waste sites and chemical emergencies. This study examined the use of ice- and Freon-based cooling garments during exercise in the heat while wearing a U.S. Coast Guard chemical response suit (CRS), a fully encapsulating, Teflon-coated, Nomex suit. Responses of nine healthy men (mean age 28.8 yr) were measured during moderate exercise at 30% of their maximal oxygen consumption in an environmental chamber maintained at 33.9 degrees C (93 degrees F) and 82% relative humidity. The four randomly assigned experimental conditions were (1) the CONTROL, consisting of a self-contained breathing apparatus (SCBA) worn in conjunction with shorts, shirt, helmet, and shoes; (2) the CRS, consisting of the Coast Guard CRS worn with shorts, shirt, SCBA, helmet, gloves, and boots; (3) the ICE, which was identical to the CRS ensemble, with the addition of an ice and water cooling system; and (4) the FREON, which was also identical to the CRS ensemble, with the addition of a Freon-based cooling system. To the author's knowledge, this paper is the first to quantify and compare a Freon-based system with a circulating ice water system. The subjects performed repeated rest/work intervals for 45 min, followed by a 10-min recovery period. Measured physiological responses, including heart rate, skin, rectal, and axillary temperatures, were recorded at 1-min intervals during the tests.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effectiveness of ice- and Freon-based personal cooling systems during work in fully encapsulating suits in the heat. 202 17

The insulin gene is expressed almost exclusively in pancreatic beta-cells. Previous work in our laboratory has shown that pancreatic beta-cell-specific expression of the rat insulin II gene is controlled by a number of positive and negative cis-acting DNA elements within the enhancer. We have shown that one element within the enhancer, located between nucleotides -100 and -91 (GCCATCTGCT; referred to as the insulin control element [ICE]) relative to the transcription start site, is controlled by both positive- and negative-acting cellular transcription factors. The positive-acting factor appears to be uniquely active in beta-cells. To identify the nucleotides within the ICE that mediate positive cell-type-specific regulation, point mutations within this element were generated and assayed for their effects on expression. Base pairs -97, -94, -93, and -92 were found to be crucial for the activator function of this region, while mutations at base pairs -100, -96, and -91 had little or no effect on activity. The gel mobility shift assay was used to determine whether specific cellular factors associated directly with the ICE. Several specific protein-DNA complexes were detected in extracts prepared from insulin-producing and non-insulin-producing cells, including a complex unique to beta-cell extracts. The ability of unlabeled wild-type and point mutant versions of the ICE to compete for binding to these cellular factors demonstrated that the beta-cell-specific complex appears to contain the insulin gene activator protein(s). Interestingly, the adenovirus type 2 major late promoter upstream element (USE; GCCACGTGAC) also competed in the gel mobility shift assay for binding of cellular proteins to the ICE. These results suggested that the cellular factor that binds to the USE (i.e., USF) also interacts with the ICE. This was directly demonstrated by showing that ICE and USE sequences completed for the USF required for adenovirus type 2 major late promoter transcription in vitro and by showing that reticulocyte lysate-translated human USF products bound to the ICE. However, the USE sequences were unable to stimulate beta-cell-type-specific activity in vivo. We discuss the possible relationship of these observations to positive and negative control mediated by the ICE.
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PMID:Identification of a pancreatic beta-cell insulin gene transcription factor that binds to and appears to activate cell-type-specific expression: its possible relationship to other cellular factors that bind to a common insulin gene sequence. 218 Dec 78

The diagnosis of pancreatic lesions can be improved with the aid of the diagnostic needle aspiration procedure under computed tomographic guidance. The computer aided diagnostics should be used to distinguish degenerative changed cells of chronic pancreatitis from cells of well differentiated carcinomas. Investigations are performed with a Jenaval microscope (Carl Zeiss Jena), solid state camera C-1000-35 (Hamamatsu Japan) coupled with minicomputer (Typ 1 102 F ICE Rumania). Multivariate discrimination using 35 features of each nucleus (20 fine needle aspirations of pancreatic carcinomas, 20 fine needle aspirations of chronic pancreatitis of histological controlled autopsies with 8,000 nuclei of Feulgen-reaction and 4,000 nuclei hemalum-eosin-stained of the same material) provides a classification result for single cells of 81% of Feulgen-reaction and 77% by hemalum-eosin-staining. Nonessential differences between the Feulgen-reaction and hemalum-eosin-staining are found by the single cases of fine needle aspiration biopsies of pancreatic carcinomas and nontumorous pancreatic lesions.
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PMID:[Computer-assisted diagnosis of fine-needle biopsy of the pancreas using automated microscopic image analysis (comparison of the Feulgen reaction and hemalum-eosin staining in pancreatic cancer and fibrosis]. 247 95

Amphotericin B and some of the imidazole drugs have been shown to suppress certain neutrophil and lymphocyte functions both in vitro and in vivo. We present here the in vitro effects of: amorolfin, a morpholine derivative; the imidazoles clotrimazole and ketoconazole; the N-substituted imidazole bifonazole and a triazole (ICE 195, 739), on neutrophil and lymphocyte function. All of these drugs inhibited neutrophil random migration, chemotaxis and hexose monophosphate shunt activity. The effects of the drugs on neutrophil adherence, deoxyglucose transport and beta-glucuronidase release were variable while lysozyme release was unaffected. Natural Killer cell cytoxicity was depressed by all drugs tested except for amorolfin. Mitogen-induced lymphocyte blastogenesis was suppressed by all the antifungal drugs tested. Similar results were obtained using the mitogens phytohaemagglutinin, concanavalin A and pokeweed mitogen. The mechanism of action of these drugs on these cell functions remains unknown, there may be a correlation between their effects on fungi and their effects on leukocytes. Clearance of systemic fungal infection is heavily dependent on integrity of the cellular immune system and it is clearly undesirable that antifungal drugs have immunosuppressive properties. Further studies are required to determine the in vivo and clinical relevance of our observations.
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PMID:Effects of the newer antifungal agents (bifonazole, ICI 195, 739 and amorolfin) on in vitro phagocytic, lymphocytic and natural-killer cell responses. 259 17

Repetitive intermittent cold exposure (5 degrees C, 6 h/day, 4 weeks) (ICE) resulted in the same cold adaptability as assessed by an enhanced cold tolerance (less drop of colonic temperature at -5 degrees C) and nonshivering thermogenesis (NST) (greater noradrenaline-induced heat production) as that elicited by continuous cold exposure (5 degrees C, 4 weeks) (CA) in rats. Although shorter intermittent (5 degrees C, 2 h/day, 4 weeks) (ICE-2 hr) as well as shorter continuous (5 degrees C, 1 week) (CA-1 wk) cold exposure effected an improved cold adaptability, the magnitude of cold tolerance and NST was smaller as compared with that in CA and ICE. The cold deacclimation process as reflected on the decreased NST did not differ between CA and ICE. Food intake was less in ICE than CA, while increase in body weight during the acclimation period was greater in the former. Increase in adrenal weight was greater in CA than ICE, but plasma corticosterone level did not differ among warm controls (WC), CA, and ICE in resting state (after 18-20 h at warm control temperature of 25 degrees C). Weights of interscapular and dorsocervical brown adipose tissue (BAT) increased to the same degree in CA and ICE. Plasma glucagon level in resting state did not differ among groups, while BAT glucagon levels significantly increased in CA and ICE, but they were higher in dorsocervical site than interscapular site in all acclimated states. Acute cold exposure (-5 degrees C, 15 min) caused increases in plasma corticosterone, glucagon levels, and in BAT glucagon levels in all acclimated groups. The extent of increase was significantly less for plasma glucagon in CA, while plasma corticosterone increased similarly in all groups. These results indicate that repetitive short-term cold exposure could elicit the same cold adaptability as that induced by continuous exposure, but requiring only one-fourth of the time of continuous cold exposure. Moreover, it is suggested that glucagon is involved in both CA and ICE, but the same extent of cold adaptability can be obtained in the less energy-requiring and less stressful state in ICE.
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PMID:Metabolic cold acclimation after repetitive intermittent cold exposure in rat. 276 Nov 20

The inhibition of converting enzyme (CE) activity in target tissues other than blood and lung vascular endothelium may be important for the antihypertensive action of CE inhibitors (ICE) (Unger et al 1983). In order to determine if ICE may have an effect on the transmembrane Na movements implicated in the regulation of vascular tone, we have studied the effects of trandolapril and enalapril on 22Na effluxes from the tail artery of 20 weeks old SHR. In vivo, the chronic oral treatment (14 days) with trandolapril (1.3 mg/kg/day) decreased the ouabain-sensitive 22Na efflux (controls: 0.050 +/- 0.004 min-1 (n = 8); trandolapril (1 mg/kg): 0.030 +/- 0.03 min-1 (n = 10) p less than 0.01), and the ouabain-insensitive 22Na efflux (controls: 0.088 +/- 0.0030 min-1; trandolapril (1 mg/kg): 0.080 +/- 0.003 min-1 (n = 10) p less than 0.05). Enalapril had no effect at the dose of 10 mg/kg/day (14 days). In vitro, trandolapril diacid (RU 44403) decreased the ouabain-sensitive 22Na efflux (controls: 0.045 +/- 0.002 min-1 (n = 6); RU 44403 (10(-9) M): 0.031 +/- 0.002 min-1 (n = 6) p less than 0.01), and the ouabain-insensitive efflux (controls: 0.096 +/- 0.004 min-1 (n = 6); RU 44403 (10(-9) M): 0.084 +/- 0.006 min-1 (n = 6) p less than 0.05). The effects were dose-dependent. Enalapril diacid (MK 422) also dose-dependently decreased 22Na effluxes but it was approximately 10 fold less active.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Ex vivo and in vitro effects of trandolapril on the efflux of 22Na from the caudal artery of the SHR rat. Inhibition of vascular angiotensin II production]. 284 73


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