Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We retrospectively evaluated 51 prostate cancer patients found to have pelvic lymph node metastases at the time of pelvic lymphadenectomy and 125I implantation. All of them were followed until death or for a minimum of 70 months. Rabbit polyclonal anti-PSA, anti-PAP, anti-PSP-94, and mouse TURP-27 monoclonal antibodies were used in immunohistochemical evaluation of the metastatic lesions. In addition, Gleason grade and ploidy were assessed and correlated. No tumor with a Gleason grade of less than 7 could be found in the metastatic lymph nodes. Time to progression (P = .003), disease-specific survival (P = .009), and overall survival (P = .003) were significantly shorter in patients whose tumors had a primary Gleason pattern of 5 (grade 9 or 10). In the PSA study, patients whose tumors were reactive in more than 75% of cancer cells experienced significantly longer survival than those with less than 75% of cancer cells expressing PSA (P = .0006 log rank test). The means of overall survival +/- SEM were 71.5 +/- 5.0 and 34.9 +/- 5.4 months, respectively. Similar correlations were found with disease-specific survival and time to progression. Patterns of PAP expression and TURP-27 reactivity were not prognostically useful, whereas PSP-94 expression may add some additional information. These data suggest that evaluation of tissue PSA heterogeneity in lymph node metastases may offer additional prognostic information on prostate cancer patients. Better prediction of individual prognosis may be possible with the combined use of Gleason grade, flow cytometry, and PSA expression.
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PMID:Prognostic significance of antigenic heterogeneity, Gleason grade, and ploidy of lymph node metastases in patients with prostate cancer. 137 12

Reduction of pulmonary vascular resistance by a high inspired oxygen concentration is a common, but not universal phenomenon in patients with pulmonary vascular disease of varying etiology that may determine their response to long-term domiciliary oxygen therapy. We therefore determined changes in PVR during oxygen therapy in two patient populations not previously studied: systemic sclerosis (n = 8, mean age +/- SEM, 44.5 +/- 5.4 years) and primary pulmonary hypertension (n = 7, mean age +/- SEM 38 +/- 7.8 years). All patients were hypoxemic (arterial oxygen tension, on air 9.5 +/- 1.2 kPa for SSc and 8.3 +/- 0.6 kPa for PPH, p greater than 0.05). Right atrial pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, systemic arterial pressure, PaO2 and cardiac output by thermodilution were measured at three, 20-min intervals while inspiring air and again after inspiring 60 percent oxygen for 30 min. The PVR fell significantly with oxygen in patients with SSc from 797.6 +/- 179.2 to 610 +/- 151.6 dynes/s/cm-5 (p less than 0.01), and this fall correlated with baseline PAP and PaO2 prior to oxygen therapy (r = 0.86, p less than 0.025; r = 0.77, p less than 0.05, respectively). In patients with PPH, there was no significant fall in PVR with oxygen (from 969 +/- 80.2 to 851.9 +/- 91.2 dynes/s/cm-5, p greater than 0.05) and no predictor of a vasodilator response in individual patients. In SSc, hypoxic pulmonary vasoconstriction contributes more consistently to elevated PVR than in patients with PPH.
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PMID:Hypoxic pulmonary vasoconstriction in systemic sclerosis and primary pulmonary hypertension. 189 17

While in animal experiments neurogenically initiated pulmonary edema is a well known event and is supposed to be due to centrally initiated hemodynamic disturbances ("neurohemodynamics") in patients with severe cerebral lesions fulminant alveolar edema is reported to occur very rarely. The questions addressed by this study are: 1. whether and to what extent changes in extravascular lung water (EVTVL) can be demonstrated in patients with a severe isolated cerebral lesion; 2. whether a relationship between the severity of the cerebral lesion and accompanying EVTVL changes can be proven; and 3. whether or not EVTVL changes are associated with corresponding changes in intravascular hydrostatic and oncotic Starling parameters; i.e. cardiogenic or noncardiogenic pulmonary edema accompanying the cerebral lesion. This study included 44 patients presenting with a severe isolated cerebral lesion and decerebrate posturing on admission. EVTVL (by thermo-dye double-indicator technique), pulmonary gas exchange (AaDO2/pAO2), colloid oncotic pressure (COP) and mean systemic arterial (SAP), mean pulmonary arterial (PAP), and pulmonary capillary wedge pressures (PCWP) were measured from the day of admission to the 6th day after the acute cerebral lesion maximally; in addition the microvascular pressure in the pulmonary bed and intravascular filtration pressure were calculated from the above mentioned parameters. The neurological status on admission and throughout the observation period was scored using the Innsbruck Coma Scale (ICS) and the neurological outcome by the Glasgow Outcome Scale (GOS). Statistical analysis was performed using the distribution independent Kruskal Wallis test, the correlation coefficient r (Pearsan and Bravais), and the Spearman rank correlation (RSp); values are given as means +/- SEM; the significance has been set at P less than 0.05. Our results reveal an overall increase in EVTVL from 8.8 +/- 0.8 ml/kg on the day of admission up to 11.3 +/- 1.6 ml/kg on the 4th day. While survivors (n = 13) remained within the normal range of EVTVL (less than 9 ml/kg), non-survivors (n = 31) started at an already elevated level (10.05 +/- 1.04 ml/kg) and reached their maximum values (15.4 +/- 2.3 ml/kg) on day 3 to 4. In 3 non-survivors these increased initial EVTVL values were accompanied by pathologically increased intravascular pressures, indicating that hydrostatic mechanisms were involved in the EVTVL rises. While the hydrostatic pressures normalized spontaneously, EVTVL values stayed within the pathological range throughout the remaining observation period.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Cardiovascular and pulmonary changes in patients with an isolated cerebral lesion. II. Extravascular lung water and pulmonary gas exchange ("neurogenic lung edema")]. 277 40

Actin distribution in serially passaged embryonic mouse fibroblasts has been visualized by the anti-actin-PAP method; the organization of the microfilaments has been observed by electron microscopy (SEM and TEM). Four successive actin patterns have been identified: early (few well-organized bundles of microfilaments), middle-aged (many well-organized bundles and patches around the nucleus), late (numerous ill-organized filamentous structures and diffuse perinuclear-actin) and "senescent" (heavy packs of short microfilaments around the nucleus). All the observed actin-positive filaments were disrupted by cytochalasin B treatment. The cytoplasmic actin complex was cell-age and not cell-size-dependent; it behaved differently from the cytoplasmic microtubular complex to serially subcultivated fibroblasts. Measurements of the cell-protein content (Lowry's method) and SDS-polyacrylamide gel electrophoresis (Laemmli's method) have been performed in the successive population doubling levels (PDL) of the primary cultures. Triton-insoluble actin increased in parallel with total protein and reached about 4% of the total proteins in all the PDLs. Triton-soluble actin also increase at the beginning of the middle-aged period (generally 6 PDL) and another in declining cultures (generally 10 PDL). Total actin amounted to about 8% of the total proteins in early fibroblasts, to about 16% at the beginning of the middle-aged period and to about 20% in the declining terminal cultures. Taking into account all the known characteristics of subcultivated primary cultures, we tentatively consider the evolution of the fibroblasts as an in vitro differentiation followed by true in vitro senescence in the declining cultures. Regarding the cytoplasmic actin-complex, senescence would be characterized by a sharp increase in soluble actin, an unbalanced ratio between soluble and insoluble actin and an impairment of the ability of the microfilaments to form well-organized bundles.
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PMID:Actin content and organization of microfilaments in primary cultures of mouse embryonic fibroblasts (in vitro ageing). 293 19

Cyclophosphamide (CYC) is a metabolically activated, DNA-alkylating, antitumor agent that causes pulmonary fibrosis. BALB/cN (B) mice are sensitive and C57Bl/6N (C) mice are resistant to CYC-induced fibrosis. Pulmonary bioactivation may contribute to strain sensitivity. Therefore, we tested the intrinsic susceptibility of murine lung slices to cell injury by direct exposure to CYC for 2-8 hr. Injury was measured by release of lactate dehydrogenase (LDH). DNA damage activates the nuclear enzyme poly(ADP-ribose) polymerase (PAP, EC 2.4.2.30), causing depletion of its substrate, NAD. NAD can also be decreased by phosphorylation to NADP, as seen with oxidative stress. Depletion of NAD can lead to loss of ATP. Thus, we measured LDH release, PAP activation, NAD, NADP and ATP in slices incubated with or without the PAP-inhibitor, 3-aminobenzamide (3-AB). CYC (0.1 to 1.0 mg/mL for 4-8 hr) caused LDH release in slices from both murine strains, but LDH release was significantly greater in B lung slices than in C slices. After an 8-hr incubation 63.9 +/- 3.7% (mean +/- SEM) of total LDH was released from B lung slices with 1.0 mg CYC/mL, whereas only 45.8 +/- 2.6% was released from C lung slices (P < 0.05). 3-AB reduced LDH release to 44.7 +/- 2.4% in B slices and 28.1 +/- 2.0% in C slices (P < 0.05 vs CYC only). PAP activity in nuclei isolated from CYC-treated B lung slices was increased 2- to 4-fold after 2 hr of incubation with 0.5 and 1.0 mg CYC/mL. PAP activation was delayed and reduced with incubation in 3-AB. PAP was activated 2-fold in nuclei from C slices treated with 0.5 mg CYC/mL for 2 hr. NAD was decreased at 2 and 4 hr in B slices treated with 0.5 and 1.0 mg CYC/mL, and at 4 hr with 0.1 mg CYC/mL. NAD depletion occurred only at 4 hr in the resistant C slices treated with 1.0 mg CYC/mL. CYC increased NADP by a similar extent in B and C lung slices. In B slices, NAD losses were approximately 4 times the increases in NADP. CYC did not decrease ATP in B slices and ATP dropped 25% only after 4 hr in the resistant C slices. We conclude that CYC is directly toxic to lung tissue and observe that strain sensitivity in vitro mirrors the sensitivity to fibrosis in vivo. PAP activation and oxidative stress may contribute to this toxicity.
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PMID:Acute pneumocyte injury, poly(ADP-ribose) polymerase activity, and pyridine nucleotide levels after in vitro exposure of murine lung slices to cyclophosphamide. 798 Jun 45

Heparin inhibits smooth-muscle cell (SMC) growth in vitro and inhibits the development of hypoxic pulmonary hypertension and vascular remodeling in vivo. We wondered whether preparations of heparin with different antiproliferative potency in vitro would differ in their ability to inhibit the development of hypoxic pulmonary hypertension in vivo. Two such heparins, a weakly antiproliferative lot of Elkins-Sinn (E-S) (% inhibition of SMC growth at 10 micrograms/ml = 13 +/- 9% [mean +/- SEM, n = 24]) and a more active lot from Upjohn (UJ) (% inhibition = 71 +/- 12% [n = 12, p < 0.05 versus E-S]), were infused subcutaneously (300 U.S.P. units/day; E-S 300 versus UJ 300) via an osmotic pump into guinea pigs exposed to hypoxia (10% O2) for 10 d, after which pulmonary artery pressure (PAP; mm Hg) and cardiac index (CI; ml/min/kg) were measured in room air. Hypoxic controls (HC) received saline. PAP increased from 11 +/- 1 mm Hg in normoxic controls (NC) (n = 5) to 24 +/- 1 mm Hg in HC (n = 8, p < 0.05). The PAP was lower in the E-S 300 (21 +/- 1; n = 7, p < 0.05 versus HC and NC) and even lower in the UJ 300-treated group (18 +/- 0.5; n = 7, p < 0.05 versus HC and NC). Total pulmonary vascular resistance (TPR; mm Hg/ml/min/kg) increased significantly from 0.038 +/- 0.002 in NC to 0.076 +/- 0.003 (p < 0.05) in HC. There was no difference in TPR between the HC and the E-S 300-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of hypoxic pulmonary hypertension by heparins of differing in vitro antiproliferative potency. 800 7