Nitrosation of amines by stimulated macrophages

Rats and mice treated in vivo with Escherichia coli lipopolysaccharide (LPS) synthesize and excrete large quantities of nitrate. Murine peritoneal macrophages, elicited in vivo with thioglycolate and stimulated in vitro with LPS and/or gamma-interferon (IFN), produce copious amounts of nitrate and nitrite. We report here experiments showing N-nitrosamine formation by macrophages immunostimulated in vitro. Macrophage cell lines J774.1, PU5-1.8, WEHI-3 and RAW 264 and freshly isolated macrophages from C3H/He mice were used. Macrophages were cultured in Dulbecco's modified Eagle's medium (pH 7.5) supplemented with calf serum (10%). Supernatant NO2- and NO3- were measured. N-Nitrosamines were extracted with dichloromethane and the extracts analyzed by a gas chromatography--thermal energy analyzer. Cells (1.5 X 10(6)/ml) were incubated with LPS (10 micrograms/ml) and morpholine (15 mM) for 72 h at 37 degrees C. Under these conditions, all of the cell types listed above produced nitrite (40-70 microM) and N-nitrosomorpholine (NMOR; 114-940 nM). LPS was required for both processes, and this effect was enhanced by IFN. Nitrite (150 microM) incubated with morpholine in cell-free medium did not form NMOR nor did cells plus morpholine and NO2-. The rate of NMOR formation in the J774.1 cell line was highest in the middle incubation period (24-36 h) although [NO2-] was highest in the final incubation period (48-72 h). Thus, the cells do not catalyze nitrosamine formation per se, rather the amine traps out a reactive nitrosating species prior to the formation of NO2- and NO3-. These results suggest that immunostimulated macrophages may be capable of nitrosamine formation under physiological conditions.     

Male breast carcinoma. I. A study of the total material reported to the Swedish Cancer Registry 1958-1967 with respect to clinical and histopathologic parameters

During the time period 1958-1967 190 cases of male breast cancer were reported to the Swedish Cancer Registry. The reported cases were thoroughly re-evaluated from the evidence of the clinical records and histopathologic specimens. The material contained 166 cases of histologically verified invasive breast carcinoma which were analyzed with respect to different clinical and histopathologic parameters. In contrast to the rate in females, the breast cancer incidence rate in males did not increase significantly during the period under review, and the age-specific incidence rate did not show a Clemmesen's hook but increased relatively more rapidly at high ages than for female breast carcinoma. The mean age at diagnosis was 4 to 5 years higher in male breast cancer patients than in females. Larger tumours were more frequent among older patients and there was a 5-year shift between the age-distribution curves for small (less than 2 cm) and larger (2-5 cm) tumours. A similar difference was found between pN0 and pN1 tumours. This difference might reflect the progression rate of male breast cancer. The histopathology pattern and distribution of histologic malignancy grades were similar to those in female breast carcinoma with the exception that lobular carcinoma and medullary carcinoma with lymphoid infiltration were lacking in the male material.     

Serum protein electrophoresis patterns in chronic lymphocytic leukemia. Clinical and epidemiologic correlations

Serum protein electrophoresis (SPEP) data obtained at diagnosis were available for 98 of 342 patients with chronic lymphocytic leukemia (CLL) identified in a population-based case-control epidemiologic study. Patients tested with SPEP at diagnosis were significantly younger, more likely to have lymphadenopathy, and more likely to have had their conditions diagnosed at a university hospital than those not tested. Four categories of electrophoretic patterns were identified: normal (N = 56), hypogammaglobulinemia (N = 28), hypergammaglobulinemia (N = 11), and monoclonal gammopathy (N = 3). A higher proportion of those with hypergammaglobulinemia were black, and patients with hypergammaglobulinemia and monoclonal gammopathy were more likely to die within the first year following diagnosis than patients in the other SPEP groups. No association was found, however, between SPEP pattern and a clinical staging classification for CLL. These findings suggest that SPEP may be a useful adjunct in categorizing possible subtypes of CLL and developing future clinical staging classifications.     

Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma

The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricle in Noonan's syndrome. Electro-vecto-echo and angiocardiographic aspects

The electrocardiographic features of Noonan's syndrome have been known for several years, but the discordance between these electrical findings and the underlying haemodynamic disorders remains unexplained. In an attempt to elucidate the genesis of electrical abnormalities, we present here a retrospective study of 14 children with Noonan's disease, aged from a few days to 16 years and evaluated by electrocardiography, vectography, one- or two-dimensional echocardiography, angiography and His bundle electrophysiology. The electrocardiographic abnormalities observed concerned ventricular depolarization and intracardiac electric conduction with, notably, a QRS axis directed towards the right upper part of the electric field and a first degree infra-hisian atrioventricular block (His bundle potentials). Vectography showed in some cases an image of inferior pseudo-necrosis due to the absence of initial inferior forces; this image is highly characteristic. In other cases the QRS loop showed an image of left segmental block which is unusual in this type or cardiac pathology (pulmonary stenosis with or without atrial septal defect of the ostium secundum type).     

The effects of caffeine on various body systems: a review

Caffeine is the most widely consumed drug in Western society. The intake of caffeine-containing beverages in many adults and children often reaches levels that can induce pharmacological effects. Ninety-nine percent of ingested caffeine is absorbed and distributed to all tissues and organs. The effects of caffeine intake differ greatly according to acute or chronic intake, level of intake, and the development of tolerance. Caffeine administered acutely to non-users or recent abstainers can induce hypertension, arrhythmias, altered myocardial function, increased plasma catecholamine levels, plasma renin activity, serum cholesterol levels, increased production of urine, gastric acid secretion, and alterations in mood and sleep patterns. Tolerance to chronic caffeine intake develops in most individuals, with the cessation of its effects on the renal system, the cardiovascular system, the gastrointestinal system and, to some extent, the central nervous system. Moderate caffeine consumers probably need to have little concern for the effect of caffeine intake on their health if their other life-style habits are also moderate.     

Smoking behavior among participants in the nurses' health study.

We analyzed smoking behavior of 91,651 married female nurses, aged 30-55 years in 1976. The prevalence of smoking was similar among all birth cohorts. The largest percentage increase in starting to smoke occurred between ages 15 and 25 years; by age 25, 50 per cent had started smoking. The cessation rate was lowest in earlier birth cohorts and among nurses starting to smoke at earlier ages. The cessation rate increased substantially between 1963-73 compared with the period 1948-58.