Polychlorinated biphenyl dechlorination in aquatic sediments.

The polychlorinated biphenyl (PCB) residues in the aquatic sediments from six PCB spill sites showed changes in PCB isomer and homolog (congener) distribution that indicated the occurrence of reductive dechlorination. The PCB dechlorinations exhibited several distinct congener selection patterns that indicated mediation by several different localized populations of anaerobic microorganisms. The higher (more heavily chlorinated) PCB congeners that were preferentially attacked by the observed dechlorination processes included all those that are either pharmacologically active or persistent in higher animals. All the lower (less heavily chlorinated) PCB congeners formed by the dechlorinations were species that are known to be oxidatively biodegradable by the bacteria of aerobic environments.

C-CAM1 expression: differential effects on morphology, differentiation state and suppression of human PC-3 prostate carcinoma cells.

Studies in rat prostate and liver have suggested that C-CAM1 is involved in the formation and maintenance of histotypic associations in tissues and possibly tumors. Most recently, C-CAM1 has been shown to suppress tumorigenicity of prostate and colon carcinoma cells. However, the mechanisms whereby C-CAM1 suppresses growth and the relationship of this activity to its proposed role in histotypic interactions remain largely unknown. In the present study, we have analysed the growth, phenotypic, morphological and ultrastructural characteristics of four human PC-3 prostate carcinoma cell lines transduced with C-CAM1 retrovirus. We report that three of four lines regained their tumorigenic phenotype in vivo while maintaining high levels of C-CAM1 expression and a growth retarded phenotype in vitro. These findings suggested that high levels of C-CAM1 expression were negatively influencing recovery during reconstitution after freezing or during the latency period after subcutaneous injection and that loss of suppression resulted from changes in expression of other molecules required for full disclosure of C-CAM1 mediated growth inhibition. Results from Northern blot and immunofluorescence analyses of tumor nodules demonstrated that C-CAM1 decreased rather than enhanced phenotypic differentiation and induced ultrastructural and morphological changes that occurred independently of tumor suppression.

Nitric oxide synthase and arginase in cells isolated from the rat gastric mucosa.

Nitric oxide (NO) synthase activity, which converts arginine to citrulline and NO, is present in homogenates of rat gastric mucosal cells. The aims of this study were to identify the form of NO synthase expressed in gastric cells isolated from fed rats, and to investigate the metabolism of arginine by suspensions of intact mucosal cells. Antibodies directed against the neuronal form of NO synthase recognised a protein of 160 kDa on immunoblots of extracts of gastric cells, and stained isolated cells of approx. 8 microm in diameter. NO synthase was enriched in a cell fraction which banded at high-density in a Percoll gradient, and was inhibited (IC50) by N(G)-nitro-L-arginine (0.8 microM), N(G)-monomethyl-L-arginine (12.6 microM), L-canavanine (147 microM), trifluoperazine (140 microM) and by phosphorylation involving protein kinase C. Intact gastric cells converted exogenous arginine to ornithine and citrulline. Arginase was present in the cells, and was predominantly responsible for arginine metabolism because formation of ornithine and citrulline was reduced by the arginase inhibitors, N(G)-hydroxy-L-arginine and L-ornithine, but not by NO synthase inhibitors such as N(G)-nitro-L-arginine. In conclusion, NO synthase that resembles the neuronal isoform is present in gastric mucosal cells, but a pathway involving arginase seems to be largely responsible for citrulline formation from exogenous arginine in intact mucosal cells.

Pulmonary and rhinocerebral mucormycosis. Successful outcome with amphotericin B and griseofulvin therapy.

An ominous prognosis is associated with combined pulmonary and rhinocerebral mucormycosis (phycomycosis). We report the case of a diabetic patient with ketoacidosis who had extensive pulmonary and rhinocerebral mucormycosis that responded satisfactorily to amphotericin B and griseofulvin therapy. The affected lung is completely atelectatic and has remained so for 12 months without evidence of necrosis or abscess formation.

Role of mast cells, neutrophils and nitric oxide in endotoxin-induced damage to the neonatal rat colon.

1. The mechanisms involved in mediating bacterial endotoxin lipopolysaccharide (LPS)-induced injury in the colon of neonatal rat pups aged 10-12 days was examined. 2. Administration of LPS (3 mg kg(-1), i.p.) caused a time-related increase in the plasma concentration of rat mast cell protease-II (RMCP-II) which was attenuated dose-dependently, by the non-selective mast cell stabilizer doxantrazole (0.05-5 mg kg(-1), i.p.). The selective connective tissue mast cell stabilizer ketotifen (5-25 mg kg(-1), i.p.) was without effect at the lower dose and had only a limited inhibitory effect at the higher dose. 3. In addition, doxantrazole (5 mg kg(-1), i.p.) inhibited mast cell degranulation in response to LPS in sections of neonatal rat colon, but ketotifen (5 mg kg(-1), i.p.) was without effect. 4. The increase in plasma RMCP-II concentration in response to LPS treatment preceded increases in tissue myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) activity and tissue lipid peroxidation. These events were all attenuated by pretreatment with doxantrazole (5 mg kg(-1), i.p.), antineutrophil serum (100 microl kg(-1), i.p.), dexamethasone (2 mg kg(-1), i.p.) and the selective iNOS inhibitor, aminoguanidine (25 mg kg(-1), i.p.). 5. In addition, lipid peroxidation was inhibited by pre-administration of the antioxidant enzymes superoxide dismutase (2000 u kg(-1), i.p.) and catalase (2000 u kg(-1), i.p.), the xanthine oxidase inhibitor allopurinol (100 mg kg(-1), i.p.) and the peroxyl scavenger deferoxamine (10 mg kg(-1), i.p.), suggesting the involvement of reactive oxygen metabolites in the colonic injury. 6. These findings suggest that the sequence of events resulting in colonic damage in the neonatal rat following administration of LPS include mast cell degranulation, neutrophil infiltration, elevation in iNOS activity and subsequent lipid peroxidation.

Effects of PCB exposure on biochemical and hematological findings in capacitor workers.

Certain former operations in capacitor manufacturing resulted in extensive direct contact of the workers with electrical grade polychlorinated biphenyls (PCBs). A study group of 194 such individuals, all exposed to Aroclor 1016 and many previously exposed to Aroclors 1242 and/or 1254, was examined before (1976) and after (1979) discontinuance of PCB use in the operations (1977). At the two examinations, the approximate geometric mean serum levels (in ppb) and 5 to 95% ranges were for lower PCBs (LPCB), 363 (57-2270) and 68 (12-392); and for higher PCBs (HPCB), 30 (6-142) and 19 (4-108), respectively. The statistical associations among 42 measured clinical chemical and hematological parameters, five different measures of PCB exposure, and seven confounding variables observed in the two examinations were determined by three regression procedures. Similar regressions were performed with DDE, which was present at background levels. The principal statistical findings were a depression in serum bilirubin and elevations in serum GGTP and lymphocyte levels at the time of the first examination, and only an elevation in monocytes at the second. Appraisal of the results suggested an induction of microsomal enzymes which appeared to be subsiding after the cessation of direct exposure to PCBs. The statistical association between serum levels of PCBs and lipids reported by others was confirmed, but shown to be explained by the partitioning behavior of PCB in the body, rather than to changes in liver function. No evidence for health impairment related to PCBs was found, despite the high serum levels of PCBs in the study population.

Comparative carcinogenicity in Sprague-Dawley rats of the polychlorinated biphenyl mixtures Aroclors 1016, 1242, 1254, and 1260.

A comprehensive chronic toxicity and carcinogenicity study was conducted on a series of Aroclors (1016, 1242, 1254, and 1260). Each Aroclor was assessed at multiple dietary concentrations, ranging from 25 to 200 ppm, for 24 months in male and female Sprague-Dawley rats. Liver toxicity was indicated by elevated serum enzyme activity (AST, ALT, and GGT), elevated serum cholesterol concentration, decreases in hematologic parameters (RBC, Hb, and Hct), hepatocellular hypertrophy, an increased incidence of altered hepatocellular foci, and an increased incidence of hepatocellular neoplasms (primarily adenomas). Liver toxicity was distinctly more severe in females than in males. The incidence of hepatocellular neoplasms was highly sex-dependent (females >> males), differed between Aroclor mixtures and, for females, increased with dose and followed the general incidence pattern of Aroclor 1254 > Aroclor 1260 approximately Aroclor 1242 > Aroclor 1016. A significant response (p < 0.05) in males was seen only for the high dose of Aroclor 1260. A small increase in the incidence of thyroid gland follicular cell adenomas was noted in males for Aroclors 1242, 1254, and 1260, with the incidence being uniform across dose groups and Aroclor mixtures. For females, increased survival relative to controls was observed for all Aroclor treatment groups. A significantly decreased trend in the incidence of mammary gland neoplasms compared to control was also noted for females receiving Aroclors 1242, 1254, and 1260.

Nitric oxide donors increase mucus gel thickness in rat stomach.

Instillation of the nitric oxide (NO) generator isosorbide dinitrate (0.1-1 mM) into the rat gastric lumen in vivo produced a dose-related increase in mucus gel thickness that was prevented by coadministration of oxyhaemoglobin (10 microM). Isosorbide dinitrate did not induce epithelial cell damage. S-Nitroso-N-acetyl-penicillamine (0.3 mM) and dibutyryl cyclic GMP (1 mM) also increased mucus thickness. These findings, along with the presence of NO synthase in the gastric mucosa, imply a role for NO in vivo in mediation of gastric mucus release.

The effect of protein kinase C activation on colonic epithelial cellular integrity.

We have investigated whether activation of protein kinase C has a direct cytotoxic effect on colonic mucosal epithelial cells and whether oxidant-induced damage to colonocytes is mediated by activation of cellular protein kinase C. Incubation of freshly harvested cells from rat colon with the protein kinase C activator, phorbol 12-myristate, resulted in a concentration-dependent increase in the extent of cell injury. Phorbol 12-myristate acetate (0.1-10 microM) also increased cellular protein kinase C activity and this was reduced significantly by treating cells with the antagonists staurosporine or 2-[1-(3-dimethylaminopropyl)-indol-3-yl]3-(-indol-3-yl)maleimide (GF 109203X; 10 microM). Phorbol 12-myristate acetate treatment also resulted in increased translocation of proteins for protein kinase C isoforms alpha, delta and epsilon from cytosol to membrane particulate fractions. The antagonists reduced the extent of cell damage in response to phorbol 12-myristate acetate. Furthermore, cell injury in response to the phorbol acetate was also inhibited by the addition of the oxidant scavengers, superoxide dismutase or catalase to the cell suspension. Addition of H(2)O(2) to the incubation medium (0.1-100 microM) resulted in an increase in cellular protein kinase C activity, an increase in the expression of the alpha, beta and zeta isoforms and a reduction in cell integrity. The cellular damaging actions of H(2)O(2) were significantly reduced by the protein kinase C antagonists, staurosporine or 2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(-indol-3-yl)maleimide (GF 109203X). These findings suggest that protein kinase C activation results in colonic cellular injury and this damage is mediated, at least in part, by release of reactive oxidants. Furthermore, oxidant-mediated damage to these cells also involves protein kinase C activation.

Lipopolysaccharide induces Ca(2+)-independent nitric oxide synthase activity in rat gastric mucosal cells.

Ca(2+)-independent nitric oxide synthase was detected in gastric mucosal cells isolated from rats injected 4 h previously with Escherichia coli lipopolysaccharide (3 mg/kg i.v.). Induced nitric oxide synthase was located in an elutriated cell fraction of intermediate size which contained epithelial cells, but was absent from the parietal cell fraction. Administration of dexamethasone (2 mg/kg i.p.) 1 h before lipopolysaccharide inhibited the appearance of Ca(2+)-independent nitric oxide synthase, and prevented the observed reduction in cell viability (trypan blue exclusion). Ca(2+)-independent nitric oxide synthase activity can thus be induced in certain cells of the gastric mucosa, and may contribute to gastric pathologies where there is activation of the immune system.

Clinical, computed tomographic, and histopathologic characteristics of juvenile ossifying fibroma with orbital involvement.

A 9-year-old boy who had had painless progressive proptosis of the right eye for 18 months, initially diagnosed as fibrous dysplasia, was found to have a circumscribed mass involving the frontal bone in the roof of the orbit. Biopsy of the mass led to the diagnosis of juvenile ossifying fibroma and the tumor was removed by a craniotomy approach. One year after surgery, the child appeared to be healthy. Ossifying fibroma can sometimes be differentiated from fibrous dysplasia both clinically and by computed tomography. Ossifying fibroma usually appears between the ages of 7 and 28 years and produces slowly progressive proptosis and displacement of the globe in a direction that depends on the original site of the tumor. Fibrous dysplasia usually develops during the first decade of life and produces facial asymmetry, proptosis, and displacement of the globe. An ossifying fibroma characteristically has well-defined margins, is round or ovoid, is usually monostotic, and produces expansion of the involved bone. Fibrous dysplasia is usually sclerotic and expands the bone throughout its length rather than in a localized fashion. Its borders are poorly defined and the lesion is often polyostotic.

New clinical roles for pharmacists: a study of role expansion.

This study assessed the legitimacy of expanded roles for pharmacists with different status audiences. Pharmacy is a profession in transition and is characterized by considerable ambiguity and uncertainty concerning its status as a health care profession. Significant changes have occurred within the profession of pharmacy in the past few decades which have led to loss of function, social power and status. The response of the profession has been a movement toward a patient-oriented, clinical role for pharmacists. Hypotheses concerning level of support for expanded roles were derived from two conflict-based models of professionalization: a power model which focuses on conflict between professions and the central role of power in defining occupational territory; and a process model which focuses on conflict of interest and diversity within a profession and the development of 'segments' which struggle for control of a profession's direction. Data were collected by self-administered questionnaires sent to California pharmacists, physicians and nurses. Respondents were asked to indicate level of support for 20 role activities for pharmacists working in two practice settings (community and hospital). Pharmacy faculty were the most supportive of the clinical role activities, followed by practicing pharmacists, nurses and physicians. Physicians and nurses were more antagonistic toward clinical activities in the community than hospital practice setting, and were most antagonistic toward role activities which require independent judgement or autonomous action relevant to patient care on the part of the pharmacist. Differences were also noted in support for clinical role activities within the pharmacists' group. The effect of experience in working with a clinical pharmacist on support for clinical role activities is also discussed.

Isolation and characterization of phenoloxidase from egg masses of the gastropod mollusc, Biomphalaria glabrata.

Previous studies have shown that phenoloxidase activity is present in the albumen gland and egg masses of Biomphalaria glabrata, and its potential role in egg formation in this snail has been proposed. In the present study, a phenoloxidase enzyme has been isolated from the supernatant of egg mass homogenates using a combination of hydrophobic interaction chromatography and gel filtration high-performance liquid chromatography (GF-HPLC). The isolated phenoloxidase eluted as a single peak of activity upon GF-HPLC (representing a 132-fold purification) and subsequently was detected as a single band with an estimated molecular mass of 35 kDa by SDS-PAGE analysis. Phenylthiourea-inhibitable mono- and diphenoloxidase activities were demonstrated for the isolated enzyme suggesting that both enzyme activities are associated with a single, tyrosinase-type molecule.

Maternal hypothyroxinemia: psychoneurological deficits of progeny.

Maternal thyroid function was evaluated clinically, by reproductive history, and by serial measurements of serum butanol-extractable iodine (thyroxine-like iodine), two before and two after 24 gestational weeks during 1,349 pregnancies. Three percent of the women were hypothyroxinemic. Developmental, intellectual, and motor abilities of progeny born to (Group I) 210 euthyroxinemic, (Group II) 15 hypothyroxinemic given adequate thyroid replacement therapy, and (Group III) 21 inadequately treated hypothyroxinemic women were compared. The groups of mothers exhibited no significant differences in intelligence, years of education, or chronological age. Mean developmental and intellectual scores at eight months, four and seven years of Group II progeny evidenced remarkably consistent similarity to scores of siblings and controls. At each age, mean developmental and intellectual scores were lower for Group III progeny, and motor scores of the latter were lowest. Some progeny of Group II mothers, treated only after 12 or 29 weeks, failed the ball catch and line walk tests; some had strabismus and other ocular disturbances. Could these deficits have originated with maternal hypothyroxinemia during first semester weeks before the thyroid-pituitary axis matures? Now in 1990-1991, early findings fit into the modern concepts of significant maternal gestational transfer of thyroxine to the fetus. The authors encourage prenatal and/or early gestational screening for maternal hypothyroxinemia and urge prescription of adequate thyroid replacement therapy for hypothyroxinemic women.

PCB metabolism, persistence, and health effects after occupational exposure: implications for risk assessment.

Analysis of the kinetics and congener selectivities for PCB metabolism in occupationally exposed workers shows that the lipid PCB concentrations required for the induction of P4502B cytochromes must be > 20 mg/kg; for inducing P4501A and the associated toxic effects, > 600 mg/kg. The observed kinetic behavior indicates that the reported statistical associations between serum PCB levels and certain disease states in the general population (lipid PCBs generally 0-2 mg/kg) probably arise from correlations with the factors that control steady-state xenobiotic levels in human serum (notably, P450 activity and serum lipids) rather than from novel toxic activities of the PCBs.

Diseases and parasites of red foxes, gray foxes, and coyotes from commercial sources selling to fox-chasing enclosures.

Fifty-six red foxes (Vulpes vulpes), 18 gray foxes (Urocyon cinereoargenteus), and 13 coyotes (Canis latrans) obtained by the South Carolina Wildlife and Marine Resources Department during an investigation of suspected illegal wildlife translocation were examined for diseases and parasites. Red foxes and coyotes were confiscated from an animal dealer based in Ohio (USA), and gray foxes were purchased from an animal dealer in Indiana (USA). Emphasis was placed on detection of pathogens representing potential health risks to native wildlife, domestic animals, or humans. All animals were negative for rabies; however, 15 gray foxes were incubating canine distemper at necropsy. Serologic tests disclosed antibodies to canine parvovirus, canine distemper virus, canine adenovirus, canine coronavirus, canine herpesvirus, and canine parainfluenza virus in one or more host species. Twenty-three species of parasites (two protozoans, three trematodes, four cestodes, eleven nematodes, and three arthropods) were found, including species with substantial pathogenic capabilities. Echinococcus multilocularis, a recognized human pathogen not enzootic in the southeastern United States, was found in red foxes. Based on this information, we conclude that the increasingly common practice of wild canid translocation for stocking fox-chasing enclosures poses potential health risks to indigenous wildlife, domestic animals, and humans and, therefore, is biologically hazardous.

Comparability and precision of serum PCB measurements.

The 95% prediction interval for single measurements of serum "Aroclor" reported by a reputable commercial analyst was found to be approximately +/- 42%. The geometric mean serum PCB levels in a population of capacitor workers who had formerly had direct exposure to the commercial PCBs--Aroclors 1016, 1242, and 1254-were found to be alternatively reportable as 1905 ppb minimum initial PCBs (as calculated from most persistent peaks present); 1093 ppb non-overlapping analytical "Aroclor" levels (as calculated by the conventional sum-of-the-peak-heights method); 303 ppb total PCBs actually present; or 19 ppb "human PCB" (as calculated by the NHMP procedure). The broad spread in reportable values was relatable to the PCB isomer distribution and clearance patterns in the occupationally exposed population.

Behavioral and neurological effects of symptomatic and asymptomatic lead exposure in children.

Forty-five children 4 to 8 yr of age who had been exposed to environmental lead were studied, consisting of an acute encephalopathy group and groups with short- and long-term exposure but without encephalopathy. Control children were matched for age, sex, race, and socioeconomic status with lead-exposed subjects, but lived in post-1945 housing and had negative neurological history and blood tests. The encephalopathy group had a significantly higher incidence of neurological deficits, retarded mental development, and higher hyperactivity than control subjects. Children with short- and long-term exposure short of encephalopathy were somewhat inferior to matched control subjects, but not to a statistically significant extent.

Epistemological differences within psychological science: a philosophical perspective on the validity of psychiatric diagnoses.

The debate over the validity of psychiatric diagnoses remains a central, unresolved issue in psychological science. Although it is often taken to be an ontological matter, this paper argues that, in fact, the dispute stems from differences in epistemology. Two epistemological themes, the objective of science and the nature of causality, are discussed to provide examples of how commitments made at this level inevitably lead to differing ontological conclusions about whether diagnoses constitute valid clinical terms. Discussions that fail to address the deeper epistemological disagreements that underpin the opposing arguments will never fully capture the complexity of the dispute and hence are unlikely to lead to its resolution.