Industrial work and lung cancer

In a hospital-based case-control study, 316 lung cancer cases and 536 controls were interviewed for their occupational, smoking, passive smoking, cancer in the family and residential histories as well as social economic status, by trained interviewers, using a standardized questionnaire. Cases and controls were matched by hospital, sex and age. The study was carried out between 1st July 1990 and 31st January 1991 in 14 hospitals in the Metropolitan Region of S. Paulo, the most highly industrialized and urbanized region in Brazil. Score criteria were developed for the ordering of the individuals of the study by occupational exposure to know carcinogens to the lung, in order to evaluate this exposure during the occupational life of each person. The criteria accumulated information on exposure to carcinogens as regards type, sector of work and time in each employment. The unconditional logistic regression analysis showed an odds ratio of 1.97 (95% IC: 1.52 to 2.55) for the highest exposure group. This result showed that workers linked to the production sectors of several industries have about twice the risk of developing lung cancer as workers involved in non-industrial activities.     

Immunological and functional characterization of Mycobacterium leprae protein antigens: an overview

A major focus of leprosy research in the last 10 years has been the identification and characterization of antigens of Mycobacterium leprae that interact with antibodies and T cells of the host's immune response. Through the combined efforts of many different laboratories, a substantial number of protein antigens have been identified and characterized. In this MicroReview we present an updated list of M. leprae protein antigens, and, with emphasis on recent developments, summarize what is known regarding their functional and immunological features.     

Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase

1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.     

The kinetics of ACTH expression in rat leukocyte subpopulations

The peripherin gene has three potential ATG translation initiation sites at positions 38, 56, and 290. The second ATG has been proposed to be the initiation codon used for translation of the protein, but there is no experimental evidence for this conjecture. We have isolated a full-length peripherin cDNA (designated as p61-11) from a rat brain cDNA library. Upon sequencing, we found that this cDNA contains a point mutation at the second potential translation initiation codon, which changes this ATG to ACG. When expressed in SW13 cl.2 vim- cells, a cell line without any detectable cytoplasmic intermediate filaments, the protein product of p61-11 cannot form a filamentous network and the major product is 45 kDa in size, which is most likely initiated from the third ATG. The protein product from the first ATG (57 kDa in size) of p61-11 is also detected albeit in smaller amounts. We introduced a frame-shift mutation upstream of the third ATG in p61-11 to create p61-11FS and showed that the third ATG is able to initiate translation efficiently even in the presence of the first ATG, and the 45 kDa protein leads to a diffuse nonfilamentous staining pattern in vim- cells confirming that the first ATG may not be the preferred translation initiation codon, since it cannot suppress a downstream ATG. We increased the translation efficiency from the first ATG of p61-11 by mutating the three nucleotides preceding this first ATG and thereby placing it in a better Kozak consensus sequence for translation initiation. The resulting 57 kDa protein is able to form a filamentous network in vim- cells. We corrected the mutation in the original p61-11 by polymerase chain reaction and generated two peripherin constructs: perM1M2 (which contains all three translation initiation codons) and per delta 1M2 (the first ATG is deleted, but the other two are present). When transfected, their protein products, about 57 kDa in size, form filamentous networks in the absence of other cytoplasmic intermediate filaments. Since there is no 45 kDa protein detected for these latter two constructs, it is reasonable to conclude that in the presence of the second ATG, little or no translation is initiated from the third ATG. Taken together, these results strongly suggest that the second ATG is the preferred translation initiation codon for the peripherin gene.     

The role of angiotensin AT1 receptors in the diuretic, natriuretic, kaliuretic and blood pressure responses induced by angiotensin II activation of the median preoptic nucleus in conscious rats

We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar1, Ala8]-ANG II and [Sar1, Thr8]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was collected in rats submitted to a water load (5% body weight) 1 h later. The volume of the drug solutions injected was 0.5 microliters over 10-15 s. Pre-treatment with [Sar1, Ala8]-ANG II (12 rats) and [Sar1, Thr8]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/0 1.0 and 10.7 +/0 1.2, respectively), whereas losartan (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs 7.6 +/- 1.5) the urine excretion induced by injection o 12 ng of ANG II (14 rats). [Sar1, Ala8]-ANG II impaired Na+ excretion (193 +/- 16 vs 120 +/- 19), whereas [Sar1, Thr8]-ANG II and losartan block Na+ excretion (193 +/- 16 vs 77 +/- 15 and 100 +/- 12, respectively) induced by ANG II. Similar effects induced by ANG II on K+ excretion were observed with [Sar1, Ala8]-ANG II, [Sar1, Thr8]- ANG II, and losartan pretreatment (133 +/- 18 vs 108 +/- 11, 80 +/- 12, and 82 +/- 15, respectively). The same doses as above of [Sar1, Ala8]-ANG II (8 rats), [Sar1, Thr8]-ANG II (8 rats), and losartan (9 rats) blocked the increase in the arterial blood pressure induced by 12 ng of ANG II (12 rats) (32 +/- 4 vs 4 +/- 2, 3.5 +/- 1, and 2 +/- 1, respectively. The results indicate that the AT1 receptor subtype participates in the increases of diuresis, natriuresis, kaliuresis and arterial blood pressure induced by the administration of ANG II into the MnPO.     

Studies on the hypodermosis affecting red deer in central and southern Spain

From November 1992 to February 1993, 455 red deer (Cervus elaphus) were surveyed in order to estimate the prevalence of warble fly (Hypoderma actaeon) larvae under the skin of this ungulate species. Material came from Montes de Toledo, Sierra Morena, Sierra de Alcaraz, and Sierras de Cazorla, Segura y Las Villas Natural Park (central and southern Spain). We observed a prevalence of 92%, with a mean +/- SD intensity of 35.7 +/- 41.3 grubs per parasitized host; there was a maximum of 317 larvae per host. No significant differences in prevalence by host sex were found, although significant differences were observed in prevalences among different host age classes. The main location of feeding larvae in deer was in the back tissues.     

The anabolic effects of parathyroid hormone on cortical bone mass, dimensions and strength--assessed in a sexually mature, ovariectomized rat model

We examined the effect of the pineal neurohormone melatonin (MLT) on protection from viral encephalitis. The antiviral activity of MLT was evaluated in normal mice inoculated with Semliki Forest virus (SFV) and in stressed mice injected with the attenuated non-invasive West Nile virus (WN-25). Administration of MLT (s.c.) daily from 3 days before through 10 days after virus inoculation reduced viremia and significantly postponed the onset of disease and death by 7 to 10 days. Moreover, MLT injection reduced mortality of SFV (10 PFU) inoculated mice from 100% to 44%. In mice inoculated with high dose of SFV (100 PFU), MLT postponed death and reduced mortality by 20%. In all of the surviving mice anti-SFV antibodies were detected 22 days after virus inoculation. Infection of mice stressed by either isolation or dexamethasone injection with WN-25 induced mortality of 75% and 50% respectively, which was reduced by MLT administration to 31% and 25%, respectively. The efficiency of MLT in protecting from lethal viral infections warrants further investigations on its mechanisms of action.