Polychlorinated and polybrominated biphenyl congeners and retinoid levels in rat tissues: structure-activity relationships.

The purpose of this study was to examine the structural requirements of polychlorinated and polybrominated biphenyls (PCBs and PBBs) for altering tissue levels of retinoids. Seven congeneric PCBs and PBBs were studied: 3,3',4,4'-tetrachlorobiphenyl (TCB), 2',3,3',4,5- and 3,3',4,4',5-pentachlorobiphenyls (-PeCBs), 3,3',4,4'- and 3,3',5,5'-tetrabromobiphenyls (-TBBs), 2,2',3,3',5,5'-hexachlorobiphenyl (-HCB), and 3,3',4,4',5,5'-hexabromobiphenyl (-HBB). Male Sprague-Dawley rats were fed a vitamin A-adequate diet (1.3 mg/kg) for 30 days before being given a single IP injection of one of seven polyhalogenated biphenyls (150 mumol/kg) in corn oil (10 ml/kg) or vehicle alone. Rats were killed 1 week later. Except for 3,3',4,4',5,5'-HBB, all PCBs and PBBs studied significantly decreased serum retinol levels and, except for 3,3',4,4',5,5'-HBB and 2,2',3,3',5,5'-HCB, all PCBs and PBBs also lowered the serum retinol-binding-protein (RBP) content. The activity of hepatic retinyl ester hydrolase (REH) was reduced by the treatment of 3,3',4,4',5-PeCB, 3,3',4,4'-TBB, and 3,3',4,4',5,5'-HBB. The levels of hepatic retinol were decreased by 2,2',3,3',5,5'-HCB, 2',3,3',4,5-PeCB, and 3,3',4,4',5-PeCB, while levels of hepatic retinyl palmitate were decreased by 2',3,3',4,5-PeCB, 3,3',4,4',5-PeCB, 3,3',4,4'-TCB, 3,3',4,4'-TBB, and 3,3',4,4',5,5'-HBB. The substantial decreases in hepatic retinyl palmitate levels could not be explained solely on the basis of hepatomegaly caused by acutely toxic PCBs and PBBs. All halogenated biphenyls which caused a decrease in hepatic retinyl palmitate also caused an increase in renal retinyl palmitate except 3,3',4,4',5-PeCB. In summary, the acutely toxic (nonortho substituted) congeners had pronounced effects on hepatic, renal, and serum retinoids whereas other biphenyls only decreased serum retinol levels. The effects of these seven compounds on REH activity were not correlated with the effects on serum retinol or RBP levels. Therefore, this study shows that the structure-activity relationships for altering hepatic retinoids differ from those for serum retinol, implying the involvement of multiple mechanisms.     

Prostate cancer after heart transplantation: unicenter case-control study.

BACKGROUND: We have noted an unexpectedly high incidence of prostate cancer in our heart transplant recipients (HTR). METHODS: We conducted a retrospective review of patients after heart transplantation to investigate the prevalence, treatment, and outcome of prostate cancer diagnosed after systematic screening (study group). We compared them with case-matched HTR (control). RESULTS: Among 702 recipients, 15 patients had elevated prostate-specific antigen (PSA) levels. Fourteen cases of prostate cancer were diagnosed and treated. The median time between transplantation and prostate cancer diagnosis was 73 months. No patient was diagnosed in a locally advanced (>T2) or metastatic stage. Eleven patients (78.6%) received curative treatment. During follow-up (median, 44 months), 1 patient died from prostate cancer. The survival rate between the study and control groups did not differ. CONCLUSION: Routine PSA testing is recommended as a screening test for prostate cancer in patients after heart transplantation. We believe this could also result in detection of early stages of prostate cancer, thus allowing curative treatment, and achieving similar survival to other case-matched HTR with no prostate cancer.     

Immunohistochemical localization of heat shock protein-70 in normal-appearing and atherosclerotic specimens of human arteries.

Heat shock proteins (HSPs) are synthesized by cells under metabolic stress and are known to enhance a cell's ability to survive life-threatening stress. The authors have begun to examine HSPs in the context of human atherosclerosis. This study demonstrated immunohistochemically the presence of HSP-70 in human and rabbit arteries, and its distribution in relation to necrosis and lipid accumulation, as well as vascular smooth muscle cells and macrophages, in human atherosclerotic plaques. Advanced lesions from 10 human carotid endarterectomy specimens were compared with 11 human aortic specimens from autopsy and 8 rabbit aortas. The immunostaining procedure used a mouse monoclonal antibody specific for the inducible form of HSP-70. Normal rabbit aortas were tested for changes in HSP-70 up to 24 hours after removal, and were used as controls for the human aortas. Representative plaques were examined for lipid content by osmium staining, and for smooth muscle cell and macrophage components using cell-specific monoclonal antibodies followed by immunostaining. The results indicated that HSP-70 was present in human and rabbit arteries and remained unchanged in distribution or concentration up to 15 hours after death. HSP-70 was present weakly throughout the media of normal-appearing arterial specimens. In contrast, HSP-70 was concentrated in the central portions of more thickened atheromas around sites of necrosis and lipid accumulation. Macrophages were coincident with these areas and were observed to be lipid-loaded. In contrast, patches of smooth muscle cells were observed in very complicated plaques, but without consistent association with necrosis or increased HSP-70; plaque smooth muscle cells also were observed to contain lipid. Large, relatively avascular and collagenous areas of plaque also were occasionally positive for HSP-70 staining. The results support the hypothesis that elevated HSPs indicate which plaque cells, particularly macrophages, are more stressed in the depth of atheroma, especially in association with necrosis, and should prompt further investigation of the significance of HSP accumulation to the evolution of atherosclerotic plaques.     

Long-term survival of heart transplant recipients with lung cancer: the role of chest computed tomography screening

OBJECTIVE: We sought to evaluate the screening modality and outcome of lung cancer occurring in heart transplant recipients (HTR) during a 21-year period. METHODS: We conducted a retrospective review to investigate the incidence, risk factors, screening modality, treatment, and outcomes in HTR with lung cancer. We compared them with a case-matched HTR control group. RESULTS: Out of 829 recipients of heart transplants, 19 cases of bronchogenic carcinoma were found either by routine chest X-ray (n = 10), chest computed tomographic (CT) scanning (n = 4), or by assessment of clinical symptoms (n = 5). The mean time from transplantation to bronchogenic carcinoma diagnosis was 68.8 +/- 42.4 months. A history of smoking was the only risk factor in HTR with bronchogenic carcinoma compared to their case-matched HTR control group ( P < 0.05). Of 18 patients with non-small cell lung cancer (NSCLC), 13 underwent surgery and 5 with advanced cancer underwent chemotherapy and/or radiotherapy. NSCLC was diagnosed by chest X-ray (n = 10), and 6 of these patients died after an average of 43.7 +/- 62.2 months following cancer detection. NSCLC was also diagnosed on the basis of clinical symptoms (n = 4), and 2 of these patients died after a mean follow-up of 9 +/- 4.2 months after cancer diagnosis. All 4 patients in whom cancer was detected by CT scan were alive at an average of 53.5 +/- 36.7 months following cancer detection. The survival rates did not differ between the study and control groups ( P = 0.5). CONCLUSIONS: Optimal outcomes of treatment for primary lung cancer after heart transplantation seem to be related to early detection. A high proportion of deaths from NSCLC may be prevented by chest CT scan screening.     

Antibodies to delta antigen in asymptomatic hepatitis B surface antigen-reactive blood donors in the United States and their association with other markers of hepatitis B virus

A total of 1,915 sera collected in 1979 from asymptomatic hepatitis B surface antigen (HBsAg) carriers were tested for delta antigen, antibody to delta antigen (anti-delta), hepatitis B e antigen (HBeAg) and antibody to hepatitis B e antigen (anti-HBe) in addition to HBsAg and its subtypes. These sera represented blood donated by volunteers to 49 of 57 regions of the American Red Cross located in nine geographic regions of the United States and Puerto Rico. A total of 72 (3.8%) sera had anti-delta activity while none had a detectable level of delta antigen. A significantly higher (p less than 0.01) prevalence of anti-delta (12.1%) was found in San Jose, California (Pacific Region); on the other hand, the East South Central region covering Alabama, Kentucky, Mississippi and Tennessee had a significantly lower (p less than 0.05) prevalence (1.4%) of anti-delta when compared with all other regions combined. Anti-delta was, however, detected in all regions of the United States and in Puerto Rico. The cause of significant differences in the prevalence of anti-delta was not clear. The distribution of anti-delta was not associated with age, sex or blood type of the donor. Sixty-nine of 70 samples with anti-delta were found among the 1,527 samples that had either HBeAg or anti-HBe. And among 149 that lacked both HBeAg and anti-HBe, only one sample had anti-delta. The difference is statistically significant (p less than 0.05). The presence of anti-delta was not associated with HBsAg/ad (2.7%) or HBsAg/ay (4.6%).     

Arterial prostaglandins and lysosomal function during atherogenesis. II. Isolated cells of diet-induced atherosclerotic aortas of rabbit

This report validates and expands further the interpretation of our findings on prostaglandins and lysosomes in rabbit aortic homogenates (see paper I of this series) to enzymatically isolated and separated aortic cell populations during atherogenesis. Evidence is provided by which isolated arterial cells may be considered representative of in situ increases of diseased aortic tissue prostaglandin I2 and E2 levels, as well as lysosomal acid hydrolase activities and total cholesterol content based on DNA. Increasing latency of aortic lysosomal N-acetyl-beta-glucosaminidase activity was confirmed and correlated with increasing severity of atherosclerosis, in parallel to increasing levels of prostaglandin I2 but not increasing levels of prostaglandin E2. Ultrastructural observations also confirmed aortic intracellular lipid accumulation within lysosomes and as lipid droplets. Consistent with these relationships, separated low density, lipid-filled aortic cells were especially increased in total (197%) and latent (15%) lysosomal acid hydrolase activities, catalase activity (274%), total cholesterol (151%), and in both prostaglandin I2 (67%) and E2 (325%) levels based on DNA, as compared to control aortic cells or more normal-appearing high-density diseased aortic smooth muscle cells; high-density diseased aortic cells were increased in prostaglandin E2 but similar in latent acid hydrolase activity compared to control aortic cells. Since the total cholesterol content of rabbit atherosclerotic aortas was evidenced more intracellularly (75%) than extracellularly (25%) in this study, the association of increased prostaglandin I2 and E2 levels with low-density lipid-filled cells suggest the participation of these prostaglandins in the genesis of aortic foam cells during arterial lipid accumulation in rabbit atherosclerosis. The association of increasing prostaglandin I2 levels and increasing latent lysosomal N-acetyl-beta-glucosaminidase activities also implicates a possible relationship between this prostaglandin and lysosomal membranes of aortic cells, either primary or secondary to intralysosomal lipid accumulation.     

Left ventricular pacing site-timing optimization during biventricular pacing using a multi-electrode patch

A 71-year-old man with class IV congestive heart failure and an infected pacemaker/implantable cardioverter defibrillator (ICD) underwent median sternotomy for removal of endocardial leads with a 15-mm vegetation. Cardiac output during biventricular pacing was optimized with an aortic flow probe, a multi-electrode left ventricular patch, and a randomized protocol assessing 54 combinations of pacing site and right ventricle-left ventricle delay. Results that were assessed with response surface methodology determined permanent epicardial lead position and timing. The difference between the best and worst site-timing combinations altered cardiac index by nearly 70%. This experience demonstrates potential importance of the epicardial approach to site-timing optimization for biventricular pacing.