Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structure of the lipid A component of lipopolysaccharides isolated from two wild-type strains (Fisher 2 and 7) and one rough mutant (PAC 605) of Pseudomonas aeruginosa was investigated using chemical analysis, methylation analysis, combined gas-liquid chromatography/mass spectrometry, laser-desorption mass spectrometry and NMR spectroscopy. The lipid A backbone was found to consist of a pyranosidic beta 1,6-linked D-glucosamine disaccharide [beta-D-GlcpN-(1----6)-D-GlcpN], phosphorylated in positions 4' and 1. Position 6' of the beta-D-GlcpN-(1----6)-D-GlcpN disaccharide was identified as the attachment site of the core oligosaccharide and the hydroxyl group at C-4 was not substituted. Lipid A of the three P. aeruginosa strains expressed heterogeneity with regard to the degree of acylation: a hexaacyl as well as a pentaacyl component were structurally characterized. The hexaacyl lipid A contains two amide-bound 3-O-acylated (R)-3-hydroxydodecanoic acid groups [12:0(3-OH)] at positions 2 and 2' of the GlcN dissacharide and two ester-bound (R)-3-hydroxydecanoic acid groups [10:0(3-OH)] at positions 3 and 3'. The pentaacyl species, which represents the major lipid A component, lacks one 10:0(3-OH) residue, the hydroxyl group in position 3 of the reducing GlcN residue being free. In both hexa- and pentaacyl lipid A the 3-hydroxyl group of the two amide-linked 12:0(3-OH) residues are acylated by either dodecanoic (12:0) or (S)-2-hydroxydodecanoic acid [12:0(2-OH)], the lipid A species with two 12:0(2-OH) residues, however, being absent. The presence of only five acyl residues in the major lipid A fraction may account for the low endotoxic activity observed with P. aeruginosa lipopolysaccharide.
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PMID:Structural characterization of the lipid A component of Pseudomonas aeruginosa wild-type and rough mutant lipopolysaccharides. 190 18

2-deoxyribosylformylamine is a major oxidative DNA damage type which occurs upon the action of ionizing radiation on DNA. The protected 2-deoxyribosylformylamine phosphoramidite was synthesized and used in conjunction with previously reported alkali labile base protected phosphoramidites ('PAC phosphoramidites') for the preparation of oligodeoxyribonucleotides containing this lesion. Final deprotection of the oligonucleotides was performed under mild alkaline conditions to preserve the integrity of the fragile defect. The presence of formylamino deoxyribosyl residue was confirmed by FAB mass spectrometry sequencing. Oligonucleotides bearing deoxyribosyl formylamine were used as templates for studying in vitro replication. They direct the insertion of guanine or induce a deletion opposite the lesion.
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PMID:Incorporation by chemical synthesis and characterization of deoxyribosylformylamine into DNA. 194 71

The binding to human platelets of 3H-para-aminoclonidine (3H-PAC), an alpha2 adrenoceptor partial agonist, appears to be altered in depressed patients. We observed that the parameters of 3H-PAC binding to purified plasma membranes from platelets of normal Red Cross volunteers, compare favorably to those reported for binding to normal human autopsy prefrontal cortical lysates. However, only purified plasma membranes from platelets yielded a close comparison. 3H-PAC binding to intact platelets from healthy volunteers was less than 10% displaceable by an alpha2 adrenoceptor antagonist and was therefore unquantifiable. A low percent of specific binding (approx. 35%) was also observed in washed platelet lysates, and the binding was not of very high affinity (KD greater than 10 nM). In contrast, the binding of 3H-PAC to platelet purified plasma membranes from healthy subjects displayed two high affinity binding sites (KD1 = 10.6 pM and KD2 = 1.2 nM). These results are discussed in relation to our recent finding of elevated 3H-PAC binding to platelet purified plasma membranes from depressed patients as compared to healthy subjects.
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PMID:Comparison of 3H-para-aminoclonidine binding to different platelet preparations. 197 18

Brain alpha-adrenoceptor (alpha-AR) binding was examined as a possible explanation for the persistence of diet-induced obesity (DIO) or resistance (DR) in rats after they were returned to chow from a high-energy, fat and sucrose diet (CM diet). Adult Sprague-Dawley rats (n = 28) were fed the CM diet for 12 weeks. Those that gained more weight than chow-fed controls were classified as DIO and those that gained the same weight as controls were called DR. The 10 heaviest DIO and 8 lightest DR rats were then placed on chow for an additional 14 weeks. After the entire 26-week period, the body weights of DIO rats were still 21 per cent greater and those of the DR rats were 9 per cent less than 7 chow-fed controls. DIO retroperitoneal fat pads were also 62 per cent heavier while DR pads were equal to controls. Plasma insulin and glucose levels were comparable in all 3 groups. Receptor autoradiographic studies of brain alpha 1-AR (3H prazosin; PRZ) and alpha 2-AR (3H-paraminoclonidine; PAC) adrenoceptor binding were carried out using these animals at the end of 26 weeks. Binding to alpha 1-AR was comparable in all groups but alpha 2-AR binding was 47-103 per cent higher in DIO compared to DR and chow-fed controls in 14 of 17 brain areas assessed. These included the dorsomedial, ventromedial and paraventricular hypothalamic n. and all amygdalar areas. Such widespread differences in alpha 2-AR binding in rats fed the same diet but of differing body weights suggest that alpha 2-AR binding is a marker for differences in body weight regulation and may be important in the control of the differences in weight gain.
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PMID:Increased brain 3H-paraminoclonidine (alpha 2-adrenoceptor) binding associated with perpetuation of diet-induced obesity in rats. 197 22

The purpose of this study was to determine whether segment lengths measured from the right ventricular inflow and outflow tract regions of the right ventricle would accurately reflect true volume changes of the right ventricle and to determine the response of the right ventricle to afterload increases induced by both constricting the pulmonary artery (PAC) and embolizing the pulmonary circulation with glass beads (GBE). Three excised hearts were instrumented with segment-length crystals attached to the inflow and outflow tract regions, and saline was instilled into a balloon implanted inside the right ventricular cavity. The experiments showed a high correlation (r greater than or equal to 0.90 in all cases) between static segment lengths and volume instilled. In open chest, open pericardial canine experiments, vena caval occlusion reduced end-diastolic segments lengths and right ventricular systolic pressure consistent with a reduction in right ventricular end-diastolic volume. In a separate group of animals, volume loading with dextran increased inflow and outflow end-diastolic segment lengths and increased cardiac output. In two further groups of animals, one of which was pretreated intravenously with propranolol (Inderal), both forms of pressure overload increased end-diastolic lengths in both regions. However, GBE increased right ventricular stroke work compared with PAC. We conclude that end-diastolic segment lengths reflect true volume changes of the right ventricle. Furthermore, during acute pressure overload, the right ventricle dilates to compensate for the afterload change. However, ventricular function is better maintained after GBE.
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PMID:Pressure segment length analysis of right ventricular function: influence of loading conditions. 201 15

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1-13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.
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PMID:Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide. 201 51

For 10 adult cases of Ebstein's anomaly, tricuspid valve supraannular imposition (TVSI) without excision of native tricuspid valve were performed and its late results (6 mo. to 11.5 y, mean 6.8 years) were investigated. All cases showed the severe low output syndrome after the surgery. But the postoperative recovery of the cardiac function was smooth and there was no early death nor A-V block. Both the A-V conduction and the RV subvalvular structures were preserved in TVSI and it contributed to the postoperative good contractility of RV. In two cases, the serious postoperative ventricular tachycardia or ventricular fibrillation were experienced, one case required open cardiac massage and 6 hours long assist circulation in the other. In late stage, one patient died 9 years after the TVSI from the failure of the bioprosthetic mitral valve which had been implanted simultaneously, and the other 9 survivors returned to the class I of NYHA classification. LVDd and DS obtained by echocardiography showed significant enlargement; 29 +/- 4.5 mm and 19 +/- 4.1 mm before operation to 42 +/- 3.1 mm and 29 +/- 5.8 mm in late stage respectively. EF showed the tendency of slight decrease from the preoperative supernormal value to the normal range. RVD showed significant decrease after the surgery (58 +/- 4.2 mm to 37 +/- 4.1 mm). Bioprosthetic valve failure in tricuspid position was not experienced. PAC or PVC were seen quite often and 8 of 9 cases received medication for arrhythmia even in late stage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Late results of TVSI for Ebstein's anomaly]. 202 14

Twenty-five patients with recurrent or advanced-stage endometrial cancer were treated with cisplatin, doxorubicin, and cyclophosphamide (PAC) from May 1982 to November 1987. A retrospective chart analysis was performed to evaluate the effect of treatment on survival and progression-free interval. Toxicity was moderate. Neutropenia was the most common side effect. Age, performance status, and tumor cytoreduction were statistically significant predictors of survival time (P less than 0.03). In the 17 evaluable patients, the response rate was 47%. PAC is an active regimen in the treatment of endometrial cancer. Larger prospective studies are needed to evaluate whether tumor cytoreduction is important in the treatment of this disease.
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PMID:Treatment of advanced and recurrent endometrial cancer with cisplatin, doxorubicin, and cyclophosphamide. 205 Mar 2

Investigation of the membranous portion of the interventricular septum (MPIS) and its relationship with the aortic valve was performed in 32 human hearts of adult individuals (19 Caucasians and 11 non-Caucasians). With transillumination of the MPIS the specimens were photographed and 35 mm slices obtained. These were digitized into Apple Macintosh II using a Dage Model 68 video camera and a Data Translations DT 2255 frame grabber. The areas and the distances were traced manually, using the NIH Image program (Wayne Rasband, NIH, Research Services Branch, NIHM). The following forms of MPIS were found: oval (31.3%), triangular (28.1%), quadrangular (18.8%), circular (15.6%) and semilunar (6.2%); its surface area varied from 5.65 mm2 to 142.63 mm2 (mean 48.82 +/- 29.17 mm2). The superior border of the MPIS was in close relationship with the aortic valve, and its upper part was usually (41%) in direct continuity with the attachments of both right (RAC) and posterior (PAC) aortic cusps, or with PAC (34%) or RAC (6%) only. Rarely (19%) the MPIS lay below the attachments of both cusps. The distance between the MPIS superior border and the attachment of the RAC was not greater than 5.89 mm (mean 1.69 mm +/- 1.9 mm). The distance between the superior border of the MPIS and the attachment of the PAC was not greater than 5.63 mm (mean 0.77 +/- 1.49 mm). Differences between sex, race and age groups were not statistically significant.
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PMID:The membranous portion of the interventricular septum and its relationship with the aortic valve in humans. 205 41

Surgery was attempted in a case of stage IV ovarian cancer with a hepatic metastatic lesion measuring 119 x 96 mm. However, radical surgery was impossible and the operation ended up as no more than exploratory laparotomy. Before closing, Cisplatin 100 mg and Etoposide 200 mg were instilled into the intraperitoneal cavity. Two courses of systemic chemotherapy with PAC (Cisplatin 50 mg, Pirarubicin 40 mg, Cyclophosphamide 400 mg) were instituted. To examine shrinkage of the hepatic metastasis and the peritoneal tumors, A "Second look" operation was conducted. Abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, omentectomy and partial sigmoidectomy resulted in no residual lesions in the peritoneal cavity with the exception of the hepatic metastatic lesion (69 x 57 mm). Two additional courses of PAC therapy were administered after the "Second look" operation. The hepatic metastatic lesion shrank to 45 x 41 mm; a decrease of 83.8% compared to the pre-therapy in size. Liver function tests and tumor chemical markers (TPA, CA 125, SLX) revealed decreased values that were consistent with a tumor size reduction. Good PR was achieved with only a systemic chemotherapy; i.e., without resorting to local injections of chemotherapeutic agents into the liver.
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PMID:[A case of ovarian cancer with liver metastasis successfully treated by PAC therapy]. 205 78


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