Relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer.

OBJECTIVE--To investigate the relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer as a possible explanation for socioeconomic differences in survival. DESIGN--Retrospective analysis of data from cancer registry and from pathology and biochemistry records. SETTING--Catchment areas of two large teaching hospitals in Glasgow. SUBJECTS--1361 women aged under 75 who had breast cancer diagnosed between 1980 and 1987. MAIN OUTCOME MEASURES--Tumour size, axillary lymph node status, histological grade, and oestrogen receptor concentration in relation to deprivation category of area of residence. RESULTS--There was no significant relation between socioeconomic deprivation and four pathological prognostic factors: 93 (32%) women in the most affluent group presented with tumours less than 20 mm in size compared with 91 (31%) women in the most deprived group; 152 (48%) of the most affluent group presented with negative nodes compared with 129 (46%) of the most deprived group; 23 (22%) of the most affluent group presented with grade I tumours compared with 12 (17%) of the most deprived group; and 142 (51%) of the most affluent group had a low oestrogen receptor concentration at presentation compared with 148 (52%) of the most deprived group. None of these differences was statistically significant. CONCLUSIONS--Differences in survival from breast cancer by socioeconomic deprivation category could not be accounted for by differences in tumour stage or biology. Other possible explanations, such as differences in treatment or in host response, should be investigated.     

Interleukin 2 administered in vivo induces the growth of cultured T cells in vivo

The capacity of exogenous IL 2 to induce the growth of antigen-activated T lymphocytes in vivo was evaluated. The in vivo growth of adoptively transferred T lymphocytes that had been previously cultured long-term with IL 2 was initially examined, because in vitro such T cells are exquisitely dependent upon exogenous IL 2 for proliferation and survival. Daily administration of IL 2 in vivo, beginning on the day of cell transfer, induced these IL 2-dependent long-term cultured T lymphocytes to proliferate in vivo, and the magnitude of in vivo growth was proportional to the dose of IL 2 administered. The capacity of IL 2 to induce the in vivo growth of antigen-activated T cells not previously exposed in vitro to exogenous IL 2 was similarly studied. T lymphocytes from the spleens of immune mice, activated by 5-day culture with tumor antigen before transfer, survived poorly in vivo when injected with antigen alone, but demonstrated marked proliferation in vivo in response to antigen and exogenous IL 2. By contrast, immune spleen cells transferred with antigen, but without prior culture, proliferated without supplementary exogenous IL 2. Moreover, the growth of noncultured donor T cells was not augmented by the administration of exogenous IL 2, implying that noncultured spleen cells immune to tumor antigens can produce sufficient amounts of endogenous IL 2 in vivo to sustain maximal T cell growth over the time period examined. Importantly, the ability of exogenous IL 2 to induce donor T cell growth in vivo correlated with its ability to function in vivo to augment the anti-tumor efficacy of specifically immune donor T cells in models for the adoptive therapy of disseminated antigenic murine leukemia. Thus, the current studies highlight the potential of exogenous IL 2 to induce T cell growth in vivo and suggest that the administration of IL 2 in vivo may be useful for augmenting T cell responses that are relatively deficient in the production of endogenous IL 2.     

Respiratory depression produced by centrally administered taurine in the cat

The effects of taurine (0.8-64.8 mumol) were studied on respiratory activity following intracisternal (cisterna magna) and intracerebroventricular (lateral ventricle) injections in cats anesthetized with alpha-chloralose. Respiratory activity was measured by using a Fleisch pneumotachograph and monitoring tracheal airflow. The flow signal was integrated to obtain tidal volume (VT) and respiratory rate (f) was obtained by counting the number of VT excursions over one minute. Inspiratory (TI), expiratory (TE) and total (TTOT) cycle durations were also determined during this time period. In addition, end-tidal CO2 was continuously monitored. Associated changes in arterial pressure (femoral artery cannula) and heart rate were also determined. After injections into the cisterna magna, taurine caused dose-related decreases in minute ventilation (VE). The maximal decrease in VE was from 495 +/- 59 to 64 +/- 14 ml/min (p less than 0.05), and was due to both decreases in VT (from 27 +/- 3 to 5 +/- 1 ml; p less than 0.05) and f (from 18 +/- 1 to 12 +/- 2 breaths/min; p less than 0.05). TE and TTOT were increased from 2.4 +/- 0.4 to 4.5 +/- 0.6 sec (p less than 0.05) and from 3.7 +/- 0.4 to 6.4 +/- 0.8 sec (p less than 0.05), respectively. Mean inspiratory flow (VT/TI), a measure of inspiratory drive, was decreased from 21 +/- 4 to 4 +/- 2 ml/sec (p less than 0.05). Apnea occurred in 5 of 6 animals after the 64.8 mumol dose. This respiratory depression occurred without any significant change in arterial pressure. After lateral ventricle injections, taurine also caused dose-related, but not as pronounced, decreases in respiratory activity. In addition, taurine caused significant decreases (p less than 0.05) in arterial pressure in doses that decreased VE. Taurine administered intravenously had no significant cardiorespiratory depressant effects. These data indicate that centrally administered taurine produces respiratory depression and, depending on the route of CNS administration, also produces hypotension.     

Enhanced photorelaxation in aorta, pulmonary artery and corpus cavernosum produced by BAY K 8644 or N-nitro-L-arginine.

Segments of endothelium-denuded aorta, pulmonary arterial rings and strips of corpus cavernosum from rabbits were superfused with Krebs medium. Photorelaxation elicited by ultraviolet light (366 nm) was significantly enhanced by either BAY K 8644 (20 nM) or N-nitro-L-arginine (100 and 500 microM) and was associated with increased cyclic GMP. This action of both drugs was greater in pulmonary artery than aorta and corpus cavernosum and persisted in vascular rings for 90 min after drug removal. The effect was significantly attenuated by hemoglobin (10 microM) but was unaltered by superoxide dismutase (30 u/ml). The mechanism of such photosensitization is presently unclear.     

gamma-Carboxyglutamic acids 36 and 40 do not contribute to human factor IX function.

The gamma-carboxyglutamic acid (Gla) domains of the vitamin K-dependent blood coagulation proteins contain 10 highly conserved Gla residues within the first 33 residues, but factor IX is unique in possessing 2 additional Gla residues at positions 36 and 40. To determine their importance, factor IX species lacking these Gla residues were isolated from heterologously expressed human factor IX. Using ion-exchange chromatography, peptide mapping, mass spectrometry, and N-terminal sequencing, we have purified and identified two partially carboxylated recombinant factor IX species; factor IX/gamma 40E is uncarboxylated at residue 40 and factor IX/gamma 36,40E is uncarboxylated at both residues 36 and 40. These species were compared with the fully gamma-carboxylated recombinant factor IX, unfractionated recombinant factor IX, and plasma-derived factor IX. As monitored by anti-factor IX:Ca (II)-specific antibodies and by the quenching of intrinsic fluorescence, all these factor IX species underwent the Ca(II)-induced conformational transition required for phospholipid membrane binding and bound equivalently to phospholipid vesicles composed of phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine. Endothelial cell binding was also similar in all species, with half-maximal inhibition of the binding of 125I-labeled plasma-derived factor IX at concentrations of 2-6 nM. Functionally, factor IX/gamma 36,40E and factor IX/gamma 40E were similar to fully gamma-carboxylated recombinant factor IX and plasma-derived factor IX in their coagulant activity and in their ability to participate in the activation of factor X in the tenase complex both with synthetic phospholipid vesicles and activated platelets. However, Gla 36 and Gla 40 represent part of the epitope targeted by anti-factor IX:Mg(II)-specific antibodies because these antibodies bound factor IX preferentially to factor IX/gamma 36,40E and factor IX/gamma 40E. These results demonstrate that the gamma-carboxylation of glutamic acid residues 36 and 40 in human factor IX is not required for any function of factor IX examined.     

Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance

Lutchen, Kenneth R., and Heather Gillis. Relationshipbetween heterogeneous changes in airway morphometry and lung resistanceand elastance. J. Appl. Physiol.83(4): 1192-1201, 1997.We present a dog lung model to predictthe relation between inhomogeneous changes in airway morphometry andlung resistance (RL) andelastance (EL) for frequenciessurrounding typical breathing rates. TheRL andEL were sensitive in distinctways to two forms of peripheral constriction. First, when there is alarge and homogeneous constriction, theRL increases uniformly over thefrequency range. The EL israther unaffected below 1 Hz but then increases with frequencies up to5 Hz. This increase is caused by central airway wallshunting. Second, the RL andEL are extremely sensitive to mild inhomogeneous constriction in which a few highly constricted ornearly closed airways occur randomly throughout theperiphery. This results in extreme increases in the levelsand frequency dependence of RLand EL but predominantly attypical breathing rates (<1 Hz). Conversely, theRL andEL are insensitive to highly inhomogeneous airway constriction that does not produce any nearly closed airways. Similarly, alterations in theRL andEL due to central airway wallshunting are not likely until the preponderance of the peripheryconstricts substantially. The RLand EL spectra are far moresensitive to these two forms of peripheral constriction than toconstriction conditions known to occur in the central airways. On thebasis of these simulations, we derived a set of qualitative criteria toinfer airway constriction conditions from RL andEL spectra.