Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen

Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance.     

Twenty-four-hour ambulatory blood pressure in community-dwelling elderly men and women,aged 60-102 years

OBJECTIVE: To investigate ambulatory blood pressure in elderly people, including 'old elderly' subjects, aged over 80 years. DESIGN: Cross-sectional study of community-dwelling, elderly subjects. METHODS: Subjects were healthy, self-caring, and living independently. Those who were taking medication affecting blood pressure were excluded. Conventional blood pressure was the mean of two measurements. Ambulatory blood pressure monitoring was performed using the SpaceLabs 90207 device. Daytime and night-time blood pressure were defined by fixed clock intervals. RESULTS: Seventy-five 'young elderly', aged 60-79 years, (39 men, 36 women) and 81 'old elderly' aged 80 years and older (37 men, 44 women) underwent 24-h ambulatory blood pressure monitoring. Systolic blood pressure (SBP) was related to age, correlation coefficients between age and SBP were 0.31, 0.25 and 0.31, respectively, for conventional SBP, daytime SBP and night-time SBP (P < 0.01 for all). There was no correlation between age and diastolic blood pressure. Blood pressure levels were similar in men and women. Mean conventional blood pressure, daytime blood pressure and night-time blood pressure were found to be 149/81, 138/82 and 119/69 mmHg, respectively, in the 'young elderly' and 162/82, 147/83, and 133/71 mmHg, respectively, in the 'old elderly (P < 0.01 for SBP). The night : day SBP ratio was significantly higher in the 'old' elderly compared with the 'young' elderly (0.90 versus 0.86, respectively; P < 0.01). CONCLUSIONS: Ambulatory blood pressure levels in healthy, community-dwelling 'old elderly' are higher than those reported for younger adults and reflect the prominent age-related rise in SBP associated with advanced old age. Advanced old age is associated with a diminished nocturnal dip in blood pressure.     

Membrane-associated inhibitor of DNA synthesis in senescent human diploid fibroblasts: characterization and comparison to quiescent cell inhibitor.

Cell membranes prepared from senescent human diploid fibroblasts (HDF) inhibited entry into S phase by 35% when added to the medium of replicating young HDF. This membrane-associated inhibitory activity was (i) sensitive to trypsin, heat, and periodate, which suggests that the inhibitor is a glycoprotein, and (ii) not able to inhibit DNA synthesis in simian virus 40-transformed HDF, which indicates that not all types of cells are sensitive to this inhibitor. Quiescent young HDF also have a surface membrane-associated inhibitor of DNA synthesis. A comparison of the senescent HDF and quiescent HDF inhibitor activities indicates that they may have the same chemical and physical nature and the same specific activity, but their regulation is different. The inhibitory activity of quiescent young HDF is abolished within 20 hr after refeeding with fresh serum-containing medium, whereas that of senescent HDF remains unchanged. Quiescent old HDF (two or three population doublings remaining) exhibit an intermediate response to serum with approximately two-thirds of the inhibitory activity abolished. The fraction of cells in S phase at 20-24 hr post-stimulation (37% in young HDF, 24% in old HDF, and 0% in senescent HDF) is inversely proportional to inhibitor levels. This suggests that inability to neutralize the inhibitory activity in response to serum stimulation could be involved in the inability of senescent HDF to enter S phase. Disappearance of the inhibitory activity from quiescent young HDF occurs late in G1 phase. Thus, the inhibitor may play a role in determining the length of the G0 to S phase transition in these cells.     

Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology.

Technetium-99m stannous pyrophosphate was utilized for myocardial imaging in 202 patients admitted to the hospital with chest pain of uncertain etiology. One hundred and one patients had clinical and evolved electrocardiographic and enzymatic evidence of acute myocardial infarction. Ninety-six of these 101 patients had increased myocardial uptake of the technetium stannous pyrophosphate and positive myocardial scintigrams; there was nearly precise correlation between the ECG and myocardial imaging localization of the area of infarction for acute transmural myocardial infarctions. In the five patients with negative myocardial images the scintigrams were obtained after seven or more days had elapsed following the myocardial infarction. In the remaining 101 patients no clinical, ECG, or enzymatic evidence of infarction developed; 92 of these patients had negative myocardial scintigrams. Seven of the remaining nine patients were admitted with "unstable angina pectoris", and despite the absence of diagnostic ECG and enzyme evolution each of these patients had faintly and diffusely positive myocardial scintigrams. The remaining two patients had positive myocardial scintigrams but no definite ECG or enzymatic evidence of acute myocardial infarction. Thus the technetium pyrophosphate imaging technique appears safe, inexpensive and to correlate well with ECG and enzyme identification of the presence of infarction and with ECG localization of myocardial infarction. In addition the positive myocardial scintigrams in some patients with "unstable angina" suggest that there may be limited myocardial necrosis that is ordinarily undetected by ECG and enzymes in these patients. The incidence of false positive and false negative scintigrams appears to be small.     

Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity

We have compared multiple assays for the P-glycoprotein (Pgp/MDR1) phenotype in fresh and thawed adult acute leukemia to validate and quantitate measures for the expression and function of Pgp. The results are related to the Pgp-expressing KB8 and KB8-5 call lines. The most sensitive assay was the measurement of modulation of the rhodamine 123 (R123) fluorescence by 2 micromol/L PSC833, followed by the modulation of the probe calcein-AM. We also found a good intralaboratory and interlaboratory correlation between the values of the R123/PSC833 assay for fresh as well as thawed samples. In addition, the affects of PSC833 on 3H-daunorubicin (DNR) accumulation, DNR fluorescence, and 3H- vincristine accumulation were very similar. The correlation between the DNR/PSC833 and R123/PSC833 test was r = .86 (N = 51). The modulation of drug accumulation by 8 micromol/L verapamil was the some as the PSC833 effect for DNR (117%, N = 21), but was higher for vincristine in every single case (161% v 121%, N = 22; P< .001), indicating additional verapamil effects, not related to Pgp. The correlation of the staining of viable cells for Pgp with the monoclonal antibody MRK16 was r = .77 (N = 52) for the R123/PSC833 functional test and r = .84 (N = 50) for the DNR/PSC833 test. From these results it could be calculated that a maximal increase of the mean DNR accumulation of about 50% can be achieved by blocking Pgp pump activity with PSC833 in leukemic blast samples with the highest mean Pgp expression. Subpopulations of blast calls with higher Pgp activity are likely to be present. Their relevance has to be studied further. The methods outlined here allow the reliable, quantitative monitoring of the Pgp/MDR1 phenotype in leukemias in multicentered, clinical Pgp modulation studies.     

Personality differences among black, white, and Hispanic-American male heroin addicts on MMPI content scales

Used MMPI Content Scale scores (Wiggins, 1966) to assess personality differences among black, white, and Hispanic-American heroin addicts. Ss were 423 male veterans who volunteered for the first time for treatment between 1972 and 1979 to an inpatient Drug Dependence Treatment Program (DDTP) of a Veterans Administration Medical Center. Two hypotheses were tested: First, that minority group heroin addicts (blacks and Hispanics) will show better adjustment than majority group (white) heroin addicts; second, that Hispanic-American heroin addicts will evidence personality characteristics unlike those of either whites or blacks. Both hypotheses were confirmed. Results were interpreted as supporting cultural theories of substance abuse and providing implications for diagnosis and treatment of substance abuse disorders among minority ethnic groups.     

Does method of sternal repair influence long-term outcome of postoperative mediastinitis?

Background

Post-sternotomy mediastinitis reduces survival after cardiac surgery, potentially further affected by details of mediastinal vascularized flap reconstruction. The aim of this study was to evaluate survival after different methods for sternal reconstruction in mediastinitis.

Methods

Two hundred twenty-two adult cardiac surgery patients with post-sternotomy mediastinitis were reviewed. After controlling infection, often augmented by negative pressure therapy, muscle flap, omental flap, or secondary closure was performed. Outcomes were reviewed and survival analysis was performed.

Results

Baseline characteristics were similar. In-hospital mortality (15.7%) did not differ between groups. Secondary closure was correlated with negative pressure therapy and reduced length hospital of stay. Recurrent wound complications were more common with muscle flap repair. Survival was unaffected by sternal repair technique. By multivariate analysis, heart failure, sepsis, age, and vascular disease independently predicted mortality, while negative pressure therapy was associated with survival.

Conclusions

Choice of sternal repair was unrelated to survival, but mediastinal treatment with negative pressure therapy promotes favorable early and late outcomes.