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PubMed1983

A unique and essential role for insulin in the phenotypic expression of rat mammary epithelial cells unrelated to its function in cell maintenance.

Mammary explants from pregnant rats can be induced in regard to casein synthesis and alpha-lactalbumin activity when cultured in the presence of hydrocortisone, prolactin and levels of insulin approaching physiological concentrations. No detectable induction occurs in the absence of insulin. Although epidermal growth factor and multiplication stimulating activity, in the presence of hydrocortisone, can maintain the initial level of NADH-cytochrome c reductase as well as insulin, neither can substitute effectively for insulin in the induction of the milk proteins. Proinsulin, nerve growth factor, platelet-derived growth factor and fibroblast growth factor are also ineffective substitutes for insulin in this regard. Whereas prolonged tissue exposure to multiplication stimulating activity, hydrocortisone and prolactin does not result in induction of alpha-lactalbumin activity, subsequent addition of insulin leads to prompt response. The results suggest that the ability of insulin to function as a unique, essential factor in the induction of rat milk proteins is independent of its cell-maintenance activity. Thus, in addition to its well established functions in metabolic processes, insulin appears to play a vital role in certain developmental processes.

Animals↗
PubMed1995

delta 9-Tetrahydrocannabinol modulates antigen processing by macrophages.

delta 9-Tetrahydrocannabinol (THC) exposure suppresses multiple immunological functions of macrophages. The ability of macrophages exposed to THC to process and present soluble protein antigens was investigated by the stimulation of antigen-specific helper T cell hybridomas to secrete interleukin-2. The T cell response to hen egg lysozyme was dramatically reduced after a 24-hr pretreatment of a macrophage hybridoma with THC. In contrast, THC exposure did not alter the capacity of the macrophage hybridoma to process chicken ovalbumin and augmented their presenting cell function for a pigeon cytochrome c response. These findings could not be attributed to differential effects of THC on either cell viability or expression of the antigen receptor-associated CD3 complex by the T cells. The level of T cell activation with peptides of lysozyme and cytochrome c, which do not require processing, was inhibited only at the highest concentrations of THC, suggesting that THC mainly affects antigen processing. Peritoneal macrophages exposed to THC during an antigen pulse and fixed with paraformaldehyde showed similar effects on the subsequent T cell responses to lysozyme and cytochrome c in the absence of THC, arguing against a possible influence of THC on the T cells. Therefore, THC differentially modulates the capacity of macrophages to process antigens that is necessary for the activation of CD4+ T cells.

Animals↗
PubMed2001

Biological monitoring of n-hexane exposure in Portuguese shoe manufacturing workers.

Occupational risk of exposure to organic solvents concerned many shoe manufacturing workers. The most common organic solvents found in workplace environments were n-hexane and others hexane isomers. The aim of this study was to evaluate the exposure of shoe manufacturing workers to n-hexane, with 2,5 hexanedione in urine (2,5HD) as a biomarker and to investigate effect in 2,5 HD excretion of the co-exposure to other organic solvents. Post-shift urine samples from workers who performed gluing tasks (n = 45) in five shoe manufacturers were collected, as well as urine samples from a similar number of unexposed controls (n = 51) in the same factories. 2,5 HD was measured by capillary gas chromatography. Air monitoring of organic solvents in the workplaces was performed and the compounds were analyzed by gas chromatography. Significant more 2,5 HD was found in the urine of personnel who performed gluing tasks than in the unexposed workers. A significant correlation was observed between n-hexane exposure and urinary 2,5 HD, with a high correlation coefficient. Multiple regression analysis indicated that n-hexane exposure and co-exposure to others solvents were significant predictors of the concentration of 2,5 HD. Co-exposure led to higher urinary 2,5 HD concentrations. The significant effect of co-exposure reinforces the interest of biological monitoring for n-hexane exposure evaluation. In case of multiple exposures, biological monitoring can be a better predictive measurement for early detection of n-hexane neurotoxic lesions than air monitoring data.

Adhesives↗
PubMed2006

The contamination levels of organochlorines and the pattern of gene expressions in human umbilical cords from intra-pairs of twins at delivery.

In this study, we examined the contamination levels of organochlorines and the patterns of gene expressions using umbilical cords of twins. The contamination levels of total PCBs, HCB and HCHs of intra-pair of twins were close to each other, but that of DDTs were not so as the others. It shows that the placental or fetal factor may influence the transfer or the accumulation of DDTs. The patterns of gene expressions of intra-pair of twins were similar to each other. It may because the environmental factor (sharing same mother), genetic factor or the both of twins are similar. This study gave us some information to understand the fetal exposure to organochlorines. Moreover, it showed the possibility that the pattern of gene expression in umbilical cord reflected the intra-uterine environment. However, the information from general pattern of the gene expression is limited. Therefore, further investigation is necessary to find new markers not only mRNA but also protein to estimate the effects of fetal exposure of multiple organochlorines.

Adult↗
PubMed1981

Plasma angiotensin II changes with noise exposure at three levels of ambient temperature.

Significant plasma elevations of the powerful vasoconstrictor angiotensin II (AII) were measured in rats following exposure to either 100-dB or 20-dB SPL white noise in three environmental temperatures (5 degrees 21 degrees, and 38 degrees C). Loud noise exposure in the normal temperature condition (21 degrees C) and both temperature extremes with soft noise exposure resulted in plasma AII elevations. The two extreme temperatures combined with loud noise exposure resulted in plasma AII concentrations not different from the levels observed following 20-dB noise at normal temperature. These results indicate that separately administered noise and temperature extremes stimulate the production of AII and thus vasoconstriction. Simultaneous exposure to multiple stressors including noise and temperature extremes may result in severely elevated plasma catecholamines and reduce renal responsiveness to beta-adrenergic stimulation thus reducing plasma AII levels.

Angiotensin II↗
PubMed1989

Determination by western blot (immunoblot) of seroconversions to toxic shock syndrome (TSS) toxin 1 and enterotoxin A, B, or C during infection with TSS- and non-TSS-associated Staphylococcus aureus.

Serum antibody responses to toxic shock syndrome (TSS) toxin 1 (TSST-1) and staphylococcal enterotoxins A, B, and C were determined by western blot (immunoblot) analysis of acute- and convalescent-phase paired sera from 18 TSS- and 31 non-TSS-associated Staphylococcus aureus infections. Compared with non-TSS cases, seroconversion to TSST-1 was significantly more frequent among both menstrual (5 of 8 versus 1 of 31; P less than 0.001) and nonmenstrual (3 of 10; P less than 0.05) patients. Seroconversion to staphylococcal enterotoxin A was also more frequent among both menstrual (2 of 8 versus 0 of 31; P less than 0.05) and nonmenstrual (2 of 9; P less than 0.05) TSS patients. In general, patients with TSS associated with TSST-1-positive S. aureus were more likely to seroconvert exclusively to TSST-1 (4 of 12 versus 0 of 6; P = 0.16), whereas those associated with TSST-1-negative S. aureus were more likely to seroconvert exclusively to enterotoxins (3 of 6 versus 0 of 11; P less than 0.05). Concurrent seroconversions to multiple exoproteins were more frequent among both menstrual (3 of 8; P less than 0.05) and nonmenstrual (2 of 9; P less than 0.05) TSS patients compared with persons without TSS (0 of 31). These data suggest but do not prove that enterotoxins (especially staphylococcal enterotoxin A) in addition to TSST-1 may be involved in both menstrual and nonmenstrual TSS. Furthermore, since exposure to multiple exoproteins is more likely to occur during TSS-associated than non-TSS-associated S. aureus infections, the possibility of additive or synergistic effects of these putative toxins in the pathogenesis of TSS should be further explored.

Acute Disease↗
PubMedDate not supplied

Pesticide exposure: human cancers on the horizon.

Dichlorodiphenyltrichlorethane, a halogenated hydrocarbon, was introduced as an insecticide in the 1940s. In her book "Silent Spring", Rachel Carson expressed her concern for the environment, plants, animals, and human health about the potential harmful effects of such chemicals. In 1972, the Environmental Protection Agency banned the chemical in the USA. DDT and its metabolite DDE are lipid soluble compounds that persist in the environment and bioaccumulate in the body in adipose tissue at levels far higher than those in blood and breast milk. This paper evaluates the possibility of cancer occurring in humans from DDT exposure. Some risk of lymphoma, leukemia, pancreatic cancer, and breast cancer was found in humans exposed to DDT. Animal studies showed a significant association between DDT administration and lymphoma, respiratory cancer, liver cancer, and estrogenic effects on mammary tissue. On the basis of on epidemiological principles, human studies were deficient in adequate sample sizes and were not exempt from such confounding factors as multiple chemical exposure, lifestyle factors, genetic, and other environmental influences. Extrapolation of data on DDT toxicity from animals to humans has limitations. With the persistence of DDT and DDE in the environment, the potential risk to the health of man, animals, and the environment remains.

Animals↗
PubMed1999

[Endoscopic diagnosis of mesothelioma].

Mesothelioma is a rare disease but its incidence is rising. Diagnosis is still difficult but has been improved by immunohistochemical techniques and panels of pathologists. At the present time thoracoscopy is the most sensitive method for diagnosis of mesothelioma and a good alternative to thoracotomy. The main indication for thoracoscopy is unexplained pleurisy that cannot be diagnosed by needle biopsy. Thoracoscopy allows diagnosis in 95% of cases. Pleural ultrasound can be useful for diagnosis of limited pleurisy without multiple radiation exposure. Thoracoscopy is usually performed under light general anesthesia using a rigid endoscopic system. If possible, pneumothorax should be induced the day before the procedure to allow better assessment of the entry route and prevent adherences or symphysis. Tolerance of thoracoscopy is excellent. Thoracoscopy allows not only complete visualization of the pleural cavity including the diaphragmatic visceral pleura and the lung but also multiple biopsies. In early stage disease, thoracoscopy permits distinction of patients with stage Ia (involvement confined either the parietal or diaphragmatic pleura and purely inflammatory aspect in 50% of cases) from patients with stage Ib (involvement of the visceral pleura). Median survival is 28.3 months for stage Ia versus 10 months for stage Ib. Endoscopic observation enables accurate staging of tumor involvement which is an important prognostic finding and is an essential technique for early diagnosis of mesothelioma.

Humans↗
PubMed2004

Memory for how one learned of multiple deaths from AIDS: repeated exposure and distinctiveness.

Studies of memories for the circumstances in which an emotional event was learned of have generally explored isolated, single-occurrence events--for example, the Kennedy assassination. Such factors as the event's distinctiveness, its personal importance, its surprise, the elicited emotional change, and overt rehearsal have been posited as predictors of the memory's vividness and elaborateness. We examined whether these predictor variables would apply to a repeated trauma, using the repeated nature of the trauma to test, in particular, the contribution of distinctiveness. Focusing on the multiple deaths of loved ones from AIDS that many gay men have experienced, we contrasted the vividness and elaborateness of the circumstantial memory of the first death encountered with that of the most recent death, treating distinctiveness as the number of intervening deaths. In an analysis of responses by 80 gay men to a survey, no support was found for the claim that distinctiveness predicts a circumstantial memory's vividness or elaborateness. Only emotional change predicted these characteristics of the memories.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Impact of internal parasites on beef cattle.

Internal parasitism is a pervasive constant that reduces returns in beef cattle production. Parasitism may influence production sufficiently so that data derived investigating performance response will be erroneous. The interaction of internal parasites of cattle with other facets of their lives makes it imperative that more parasite research be done on cattle to consider their impact. Results of trials designed to determine forage production at various stocking densities may not reflect the nutritive value of the forage, but instead the severity of parasite exposure. Relative resistance or susceptibility to certain parasites vary with the breed of livestock and the species of parasite. Extensive work to evaluate the ability of various breeds and sires to influence parasitic numbers has been conducted in sheep but not in cattle. Some parasite trials have ignored the effects of nutrition on the establishment and retention of parasites. This becomes especially important where multiple parasite exposure may occur. Susceptible cattle, even on an optimal diet, will become parasitized, but if reexposed to the same species of parasite, cattle on an optimal diet may be able to resist reinfection, whereas those on deficient diets will not.

Animals↗
PubMed2006

Postnatal lung development: immediate-early gene responses post ozone and LPS exposure.

Exposure to environmental pollutants may severely affect lung growth and development. The present study was designed to test the hypothesis that lung damage caused either by ozone or lipopolysaccharide (LPS) occurs through distinct early responses, which are age dependent in the postnatal lung. C57Bl/6 mice ages 4, 10, and 56 days were exposed to inhalation of LPS with an estimated deposited dose of 26 EU and examined 0.5, 1, or 4 h post inhalation exposure; or to 1 or 2.5 ppm ozone for 4 h or sequential exposures of LPS followed by ozone. Abundance of c-fos, c-jun, interleukin (IL)-1beta, Toll-like receptor (TLR) 2, TLR 4, and tumor necrosis factor (TNF) alpha message levels were measured by RNase protection assay. Exposure to ozone for 4 h induced a c-fos and c-jun response in 4-; 10-; and 56-day-old mice in a dose-dependent manner, was localized to conducting and terminal airways, and also induced TLR 4 message abundance in 10- and 56-day-old mice. Exposure to LPS induced c-fos and c-jun 30 and 60 min postinhalation in 10- and 56-day-old mice only. TLR 2 and 4 message abundance was increased at 10 and 56 days, but was undetectable at 4 days of age, and correlated with proinflamatory message induction. Exposure to LPS followed by ozone increased message abundance of IL-1beta, TNFalpha, TLR 2, TLR 4, and c-jun/c-fos at 10 and 56 days, suggesting that combined exposures that induce cellular stresses can regulate gene expression by activating signaling pathways that operate through both transcription factors activator protein (AP)-1 and nuclear factor (NF)-kappaB. However, only c-jun/c-fos and TNFalpha were elevated in 4-day-old mice after sequential exposures, suggesting that the early activation of the inflammatory response after sequential exposures may occur through a TLR-independent pathway. These results suggest that sequential exposures induce multiple signaling pathways that are age dependent.

Air Pollutants↗
PubMed1996

Neurotoxicity resulting from coexposure to pyridostigmine bromide, deet, and permethrin: implications of Gulf War chemical exposures.

Of the three-quarters of a million service personnel involved in the Persian Gulf War, approximately 30,000 have complained of neurological symptoms of unknown etiology. One contributing factor to the emergence of such symptoms may be the simultaneous exposure to multiple agents used to protect the health of service personnel, in particular, the anti-nerve agent pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methylpyridinium bromide), the insect repellent DEET (N,N-diethyl-m-toluamide), and the insecticide permethrin (3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester). This study investigated neurotoxicity produced in hens by individual or simultaneous exposure to these agents (5 d/wk for 2 months to 5 mg/kg/d PB in water, po; 500 mg/kg/d DEET, neat, sc; and 500 mg/kg/d permethrin in corn oil, sc). At these dosages, exposure to single compounds resulted in minimal toxicity. Combinations of two agents produced greater neurotoxicity than that caused by individual agents. Neurotoxicity was further enhanced following concurrent administration of all three agents. We hypothesize that competition for liver and plasma esterases by these compounds leads to their decreased breakdown and increased transport of the parent compound to nervous tissues. Thus, carbamylation of peripheral esterases by PB reduces the hydrolysis of DEET and permethrin and increases their availability to the nervous system. In effect, PB "pumps" more DEET and permethrin into the central nervous system. Consistent with this hypothesis, hens exposed to the combination of the three agents exhibited neuropathological lesions with several characteristics similar to those previously reported in studies of near-lethal doses of DEET and permethrin. If this hypothesis is correct, then blood and liver esterases play an important "buffering" role in protecting against neurotoxicity in the population at large. It also suggests that individuals with low plasma esterase activity may be predisposed to neurologic deficits produced by exposure to certain chemical mixtures.

Administration, Oral↗
PubMed1977

Toxic neuropathy--an overview.

The involvement of the nervous system in systemic intoxication offers diagnostic and investigative challenges to the occupational health team. Often early evidence of neurotoxicity is vague, of a highly subjective nature and may be complicated by the presence of neuropathies due to other causes such as diabetes mellitus or exposure to multiple neurotoxins such as lead and solvents. The variety of agents producing neurotoxicity is wide, including heavy metals, organophosphates, acrylamide and its analogs, industrial solvents, therapeutic agents and plant alkaloids. The identification of neurotoxic substances requires well controlled epidemiologic studies of humans, including electrodiagnostic testing and well planned experimental animal studies. The latter include consideration of choice of animal species, routes of administration, duration of exposure, clinical evaluation, electrodiagnostic testing, morphologic description of the damage produced and its distribution, and the recognition of the potential for intercurrent naturally occurring neuropathologic processes. The aim of this discussion is to give an overview of these and other factors involved in the assessment of a neurotoxic potential.

Animals↗
PubMed1991

Performance recovery following +Gz-induced loss of consciousness.

Seven male baboons (average weight, 20.6 kg) were trained in a simple shock-avoidance performance task on the USAFSAM centrifuge. A red light was presented to the baboon at approximate 2-s intervals. The animal was allowed 1 s to turn off the light or receive a 1-s shock. The shock could be abbreviated by a late trigger pull. Thus, the animal could avoid, escape, or accept the full shock. EEG was monitored from three transcranial stainless steel electrodes. Loss of consciousness (LOC) was induced by a rapid onset (4 or 6/s) exposure to 8 +Gz and sustained until LOC was identified by a near isoelectric EEG signal. Performance recovery time was measured from the return of EEG activity to the time when the animal resumed the performance task. These data were compared with previously obtained human data and found to be very similar. Also, it was found that time of performance recovery became significantly shorter after multiple LOC exposures and the performance recovery time significantly increased with increased time of unconsciousness. This study demonstrates the utility of the baboon as an animal model for G-induced LOC (G-LOC) research.

Aerospace Medicine↗
PubMed1990

The relationship between foliar injury, nitrogen metabolism, and growth parameters in ozonated soybeans.

A single 12 h ozone exposure peaking at 0.20 ppm proved phytotoxic to greenhouse-grown 'Cutler 71' soybeans at each growth stage tested from V5 to R6. Visible injury occurred within 40 h on the unifoliodate leaves and middle-aged and older trifoliolates while the younger leaves were free from toxicity symptoms. In some instances visible injury was accompanied by a decrease in chlorophyll and an increase in leaf diffusive resistance. Although nitrogen fixation was not significantly altered except at early pod formation (R3), and nitrate reductase activity was significantly reduced only if the ozone exposure occurred at the time of maximal enzyme activity (V5), nitrogen content of the leaves was reduced by ozone treatment. Shoot dry weight was not affected 40 h after ozone treatment, but root dry weight was significantly reduced. Plants grown with supplemental NO(3)(-) were more sensitive to ozone than those dependent on fixed nitrogen. At plant maturity, there was no evidence of an ozone effect on shoot, root, or seed dry weight, NO(3)(-) -grown plants showed a significant increase in growth and yield over N(2)(-) plants; but no ozone effect was observed, despite the increased foliar sensitivity. Multiple ozone exposures at growth stages V3, R1 and R3 exacerbated the effects noted with a single episode and also reduced nitrogenase activity (reflected in specific and total nodule activity) and shoot and root dry weight. At plant maturity, there was again no evidence of a significant effect of multiple ozone treatment on shoot dry weight or seed yield although root weight remained low. The results would tend to support the hypothesis that older leaves of soybean do not make a significant contribution to seed yield. Although they may be injured by ozone during the reproductive phases of growth, seed yield may not be affected if the younger O(3)-tolerant leaves remain functional.

Journal Article↗
PubMed1991

The clinical and biochemical study of pesticide sprayers.

Clinical, haematological and biochemical studies of 34 subjects, occupationally exposed to different types of pesticides, were conducted. The findings have been compared with those observed in 14 control subjects. Inhibition of cholinesterase activity was observed in the exposed group. Serum alkaline phosphatase was also found to be raised. Radiological examination revealed pneumonitic patches in the chest skiagrams of three exposed subjects. Paraesthesia with hyporeflexia was also found in 8.8% of exposed subjects. The findings suggest that exposure to multiple pesticides over many years affects the normal functioning of different organ systems and may produce characteristic clinical effects.

Acetylcholinesterase↗
PubMed2000

Exposure of the anterior spine: technique and experience with 66 patients.

PURPOSE: Anterior spinal fusion has become an increasingly popular technique used by orthopedic surgeons for a variety of lower spine pathology. At our institution urologists have assisted as retroperitoneal surgeons in achieving exposure of the appropriate spinal disk space. We report our experience with anterior spinal fusion in 66 patients. MATERIALS AND METHODS: Since 1991 we have performed 66 exposures using the flank, modified Gibson, thoracoabdominal, paramedian and midline transperitoneal approaches. Exposure of each level has subtle technical issues which are reviewed. RESULTS: During the study 34 men and 32 women 24 to 74 years old (mean age 43.8) underwent discectomy and anterior fusion of the spine. Access from T12 through L5-S1 interspace was required, and exposure of multiple spinal levels was necessary in 27. There was 1 death from massive pulmonary embolism in a patient with widely metastatic lung cancer. Retrograde ejaculation was reported by 2 men. There have been no episodes of deep or superficial wound infection and no ureteral or major vascular injuries. CONCLUSIONS: As surgeons of the retroperitoneum urologists have an important role in providing our orthopedic colleagues with safe, adequate exposure to the anterior surface of the spine during discectomy and anterior fusion.

Adult↗
PubMedDate not supplied

[Effect of extremely high frequency electromagnetic radiation of low intensity on parameters of humoral immunity in healthy mice].

The modification of indices of the humoral immune response to thymus-dependent antigen (sheep erythrocytes) after a whole-body exposure of healthy mice to low-intensity extremely-high-frequency electromagnetic radiation was studied. Male NMRI mice were exposed in the far-field zone of horn antenna at a frequency of 42.0 GHz and energy flux density of 0.15 mW/cm2 under different regimes: once for 20 min, for 20 min daily during 5 and 20 successive days before immunization, and for 20 min daily during 5 successive days after immunization throughout the development of the humoral immune response. The intensity of the humoral immune response was estimated on day 5 after immunization by the number of antibody-forming cells of the spleen and antibody titers. Changes in cellularity of the spleen, thymus and red bone marrow were also assessed. The indices of humoral immunity and cellularity of lymphoid organs changed insignificantly after acute exposure and series of 5 exposures before and after immunization of the animals. However, after repeated exposures for 20 days before immunization, a statistically significant reduction of thymic cellularity by 17.5% (p < 0.05) and a decrease in cellularity of the spleen by 14.5% (p < 0.05) were revealed. The results show that low-intensity extremely-high-frequency electromagnetic radiation with the frequency and energy flux density used does not influence the humoral immune response intensity in healthy mice but influences immunogenesis under multiple repeated exposures.

Animals↗