Sustained reduction of neointima with c-myc antisense oligonucleotides in saphenous vein grafts

BACKGROUND: Treatment of saphenous veins with c-myc antisense oligomers during preparation for grafting reduces medial cellular proliferation and macrophage infiltration, and preserves medial smooth muscle content at 3 days. Accordingly, the purpose of this study was to examine whether c-myc antisense oligomers have an impact on late vein graft remodeling. METHODS: Sixty-two pigs underwent unilateral saphenous vein-carotid artery interposition grafting. Harvested veins were incubated either in saline (control group) or 20-micromol/L or 200-micromol/L concentrations of c-myc antisense oligomers (treated groups) for 30 minutes intraoperatively. Three months after surgery, vein graft histology was assessed. RESULTS: Forty-five of 62 randomized animals survived the experiment; no differences in animal survival or graft patency among the groups were observed (p = NS, chi2). C-myc antisense oligomers significantly decreased neointimal and wall thickness, as well as increased lumenal index, in treated groups (p<0.04, p<0.03, and p<0.001, respectively, analysis of variance). In contrast, there was no difference in medial thickness or perivascular wound healing. CONCLUSION: Intraoperative treatment of saphenous veins with c-myc antisense oligomers decreased neointimal formation at 3 months after grafting. In conjunction with our previous reports, these findings suggest that early inhibition of cellular proliferation and inflammatory infiltration results in a sustained reduction in neointimal formation and favorable graft remodeling.     

Cytochrome P450 induction, uroporphyrinogen decarboxylase depression, porphyrin accumulation and excretion, and gender influence in a 3-week rat model of porphyria cutanea tarda

An experimental model of porphyria cutanea tarda, consisting of depressed hepatic uroporphyrinogen decarboxylase (URO-D) activity and accumulation of highly carboxylated porphyrins in the liver, was produced in 3 weeks in Fischer 344 rats. A single administration of a polychlorinated biphenyl mixture (Aroclor 1254) to iron-loaded female rats maintained continuously on delta-aminolevulinic acid supplemented drinking water produced the porphyric state. Without iron loading, URO-D activity appeared slightly less inhibited (33% of normal vs 23% of normal) but porphyrin accumulation was dramatically less (70 vs 605 micrograms porphyrin/g liver). Similar treatment in male rats produced URO-D activities of 54 and 70% of normal with and without iron loading, respectively, and porphyrin concentrations of 76 and 17 micrograms/g. When hexachlorobenzene was substituted for Aroclor 1254 treatment in female rats, URO-D activity was 61 and 69% of normal (with and without iron loading, respectively) and liver porphyrin concentrations were 96 and 25 micrograms/g, respectively. Hexachlorobenzene did not produce significant porphyric effects in male rats. Aroclor 1254 induced CYP1A to a greater extent in females than in males and to a greater extent than hexachlorobenzene, which showed a greater propensity to induce CYP2B. Overall correlation between URO-D activity depression and porphyrin accumulation was highest when fitted to an exponential curve, indicating the importance of the extreme of the depression URO-D activity in evoking experimental porphyria cutanea tarda.     

Washington State's late night retail worker crime protection regulation. Relationships with employer practices

Washington's late night retail worker crime protection regulation, enforced by the state Occupational Safety and Health Administration (OSHA) program, was intended to prevent injuries by deterring violent crimes. We investigated whether the regulation was associated with businesses' violence prevention activities. We surveyed 1,516 employers at high risk of robbery, including gas stations, groceries, hotels, restaurants, and taverns, in 1995 to determine whether they had violence prevention training programs for their employees (a requirement of the standard). Awareness of the regulation was low (4.4%). Employers covered by the regulation were more likely to have programs (Odds Ratio [OR] = 1.4), as were those aware of a regulation (OR = 3.4). State OSHA plan contact (an inspection or consultation) was also associated with having a program (OR = 1.9). Despite low awareness of the standard, results suggested that regulatory efforts to protect high-risk employees were associated with employers' robbery and crime prevention activities.     

Synthesis and characterization of aflatoxin B1 mercapturic acids and their identification in rat urine

Biologic effects of the hepatocarcinogenic mycotoxin aflatoxin B1 are principally induced by one of its metabolites, the exo-aflatoxin B1 epoxide which produces both DNA and protein adducts in vivo. Detoxication of the exo-aflatoxin B1 epoxide can be mediated in part by glutathione S-transferases whose induction could be important in chemoprotection interventions. Thus, biomarkers of the enzymatic conjugation of exo-aflatoxin B1 epoxide with glutathione may be important indices of protection against the toxic effects of this agent. Since glutathione conjugates undergo further metabolic processing in vivo to yield mercapturic acids, increased urinary excretion of exo-aflatoxin B1 mercapturate could be expected during chemoprotection intervention. To determine if this mercapturic acid could be used as a biomarker, techniques for its specific measurement were developed using monoclonal antibody immunoaffinity chromatography and reverse phase high-performance liquid chromatography with ultraviolet absorbance and mass spectral detection. First, a synthetic exo-aflatoxin B1 mercapturate was characterized using mass spectrometry, ultraviolet absorbance, circular dichroism spectrometry, and chemical derivatization. In vivo metabolite characterization was then facilitated by comparison with the synthetically prepared exo-aflatoxin B1 mercapturate and both aflatoxin B1-glutathione conjugate diastereoisomers. In rats, 1% of the aflatoxin dose was excreted as exo-aflatoxin B1 mercapturate within 24 h. The finding that exo-aflatoxin B1 mercapturate was excreted in urine in a dose-dependent manner provides the basis for investigating its applicability as a biomarker of glutathione S-transferase status in aflatoxin chemoprotection studies.     

Why go see the doctor? Care goes from office to home as technology divorces function from geography

Two functions of home care, assistance to improve disabled and aged patients' mobility and function, and self-care that includes treatment, screening-monitoring, exercise assistance, and information exchange, are described, as are the technologies used for these functions. Social and economic pressures as well as professional rationales that expand the use of technologies at home are noted, as is their impact on the site of care and on the patient-doctor relationship.     

An investigation of the explanatory model of venous disease: a pilot study

Overall seventy patients with chronic hypertensive encephalopathy and acute cerebral circulatory disorders were examined, their age ranging between 35 to 75 years, by ACT, MRT, USG. MRT was found out to be the most objective method for identifying structural changes in the brain in cerebrovascular disorders. The main signs of MR-tomography are vascular changes presenting as lacunar infarctions with or without perifocal area of edema, hydrocephalus, brain swelling, intracranial hypertension, poor differentiation of gray and white substances of the brain, with hygromas being readily identifiable. Lacunar infarctions, periventricular edema, dilatation of the ventricular system are regarded as equivalent of clinical signs of chronic hypertensive encephalopathy.     

Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls

PURPOSE: To assess the computed tomographic (CT) and histologic findings of intrathoracic lymphoproliferative disease (LPD) associated with the Epstein-Barr virus (EBV). MATERIALS AND METHODS: The authors retrospectively reviewed the CT scans of the chest and the pathologic specimens obtained in 24 patients with histologically proved intrathoracic LPD and with positive serologic findings or immunohistochemical staining for EBV. Five patients had acquired immunodeficiency syndrome (AIDS); one had common variable immune deficiency; and 18 were receiving immunosuppressive therapy for heart, lung, or heart-lung (n =15) or bone marrow (n = 2) transplantation and vasculitis (n = 1). RESULTS: Final diagnoses included malignant lymphoma (n = 15), polyclonal LPD (n = 8), and hyperplasia of bronchus-associated lymphoid tissue (n = 1). CT findings included multiple nodules (n = 21), lymphadenopathy (n = 9), areas of groundglass opacification (n = 8), septal thickening (n = 7), consolidation (n = 5), pleural effusion (n = 4), and solitary endobronchial lesion (n = 2). The nodules were 2-4 cm in diameter, involved mainly the middle and lower lung zones, and frequently had a predominantly peribronchovascular (n = 15) or subpleural (n = 14) distribution. CONCLUSION: EBV-associated LPD may range from benign lymphoid hyperplasia to high-grade lymphoma. The most common CT manifestation consists of multiple nodules, frequently in a predominantly peribronchovascular or subpleural distribution.     

Tyrosine phosphorylation of annexin II tetramer is stimulated by membrane binding

In the present article we have examined if the interaction of the Ca2+-binding protein, annexin II tetramer (AIIt) with the plasma membrane phospholipids or with the submembranous cytoskeleton, effects the accessibility of the tyrosine phosphorylation site of AIIt. In the presence of Ca2+, pp60(c-src) catalyzed the incorporation of 0.22 +/- 0.05 mol of phosphate/mol of AIIt (mean +/- S.D., n = 5). The Ca2+-dependent binding of AIIt to purified adrenal medulla plasma membrane or phosphatidylserine vesicles stimulated the pp60(c-src)-dependent phosphorylation of AIIt to 0.62 +/- 0.04 mol of phosphate/mol of AIIt (mean +/- S.D., n = 5) or 0.93 +/- 0.07 mol of phosphate/mol of AIIt (mean +/- S.D., n = 5), respectively. Phosphatidylserine- or phosphatidylinositol-containing vesicles but not vesicles composed of phosphatidylcholine or phosphatidylethanolamine, stimulated the phosphorylation of AIIt. In contrast, the binding of AIIt to F-actin resulted in the incorporation of only 0.04 +/- 0.04 mol of phosphate/mol of AIIt (mean +/- S.D., n = 5). These results suggest that the interaction of AIIt with plasma membrane and not the submembranous cytoskeleton, activates the tyrosine phosphorylation of AIIt by inducing a conformational change in the protein resulting in the enhanced exposure or accessibility of the tyrosine-phosphorylation site.