Suppression of splenic T lymphocyte proliferation by acute cocaine administration

We have recently demonstrated that cocaine administration has a limited effect on mitogen-stimulated T lymphocyte proliferation. The present study investigated the effect of cocaine on splenic T cell response to alloantigens. Rats received intraperitoneal injections of cocaine HCI, and splenocytes were isolated either thirty minutes or three hours post-administration. In the thirty minute exposure group, cocaine at 10.0 and 25.0 mg/Kg/B.Wt. suppressed (p<0.05) T cell proliferation in mixed lymphocyte cultures. Compared to control data, proliferation was decreased by 46.6% and 56.4%, respectively. However, this effect was not as pronounced in cells isolated three hours post-administration, indicating a transient inhibition of T cell function by cocaine. The decrease in splenic T cell proliferation in response to alloantigens in the thirty minute exposure group did not reflect alterations in calcium influx or IL-2 production. Although this study did not ascertain the exact mechanism of inhibition, these results demonstrate that short-term cocaine exposure can alter T cell reactivity to alloantigens, suggesting a reduction in the functional status of these cells.     

The phosphopeptide-binding specificity of Src family SH2 domains

BACKGROUND: Epidemiologic evidence suggests that exposure to UV radiation plays a significant role in the development of melanoma skin cancers. As early surgical removal of the melanoma is the only effective therapy, current strategies for reducing mortality from melanoma focus on prevention of the disease. Chemical sunscreens protect mice from development of skin cancers that resemble sunlight-induced human squamous cell cancers, but there appears to be a complex relationship between UV radiation exposure and development of melanoma. PURPOSE: We asked whether common sunscreens would protect mice against UV radiation-induced enhancement of melanoma incidence. METHODS: C3H mice were exposed to 4.8 kJ/m2 UVB from FS40 sunlamps twice a week for 3 weeks. Sunscreens containing 7.5% 2-ethylhexyl-p-methoxycinnamate, 8% octyl-N-dimethyl-p-aminobenzoate, 6% benzophenone-3, or the oil-in-water vehicle alone were applied to the ears and tails of the mice 20 minutes before irradiation. At various times during and after exposure, we determined UV radiation-induced inflammation by measuring ear swelling. We also examined the ears histologically for UV radiation-induced alterations. One day after the final irradiation, 2.5 x 10(4) syngeneic K1735 melanoma cells were injected into the external ears. Mice were examined weekly for tumor growth for 5-8 weeks after tumor cell injection. Control mice were treated in the identical way except for exposure to UV radiation. RESULTS: The incidence of melanomas was significantly higher in the UV-irradiated mice. All three sunscreens protected against UV radiation-induced ear swelling and clearly diminished histopathologic alterations, including sunburn cell formation, epidermal hyperplasia, and mononuclear cell infiltrate in the dermis. However, the sunscreens failed to protect against UV radiation-induced increase in melanoma incidence. The sunscreens or vehicle alone did not significantly alter tumor growth. CONCLUSIONS: Protection against sunburn does not necessarily imply protection against other possible UV radiation effects, such as enhanced melanoma growth. IMPLICATIONS: Sunscreen protection against UV radiation-induced inflammation may encourage prolonged exposure to UV radiation and thus may actually increase the risk of melanoma development. These findings suggest that further research on the ability of sunscreens to prevent melanoma is urgently needed.     

UVB radiation preferentially induces recruitment of memory CD4+ T cells in normal human skin: long-term effect after a single exposure

Acute, low-doses of ultraviolet (UV)-B radiation affect the immune competent cells of the skin immune system. In this study, we examined the time-dependent changes of the cutaneous T cell population in normal human volunteers following a single local exposure to UV. Solar-simulated UV radiation caused an initial decrease in intraepidermal T cell numbers, even leading to T cell depletion at day 4, whereupon a considerable infiltration of T cells in the epidermis occurred that peaked at day 14. In the dermis the number of T cells was markedly increased at days 2 (peak) and 4 after irradiation, and subsequently declined to the nonirradiated control values at day 10. Double-staining with several T cell markers showed that the T cells, infiltrating the (epi)dermis upon UV exposure, were almost exclusively CD4+ CD45RO+ T cells, expressing an alpha/beta type T cell receptor, but lacking the activation markers HLA-DR, VLA-1, and IL-2R. Application of UVB radiation resulted in similar dynamics of T cells, indicating that the UVB wavelengths within the solar-simulated UV radiation were responsible for the selective influx of CD4+ T cells. In conjunction with UVB-induced alterations in the type and function of antigen-presenting cells (i.e., Langerhans cells and macrophages), the changes of the cutaneous T cell population may also contribute to UVB-induced immunosuppression at skin level in man.     

Age-dependent intestinal lymphoproliferative disorder due to stem cell factor receptor deficiency: parameters in small and large intestine

Signaling through c-Kit/stem cell factor (SCF) is crucial for normal development of erythroid and myeloid hematopoietic precursors and of melanocytes and germ cells. While peripheral lymphoid populations of W/Wv and SI/SId mice appear normal, we demonstrated that the intraepithelial lymphocyte (IEL) populations of small (SI) and large (LI) intestine were significantly affected. IEL populations of young W/Wv animals were indistinguishable from those of their control littermates, but an age-dependent decrease in SI and LI TCRgamma delta IEL occurred in c-Kit mutant mice. In SI, but not in LI, this diminution was accompanied by gross expansion of TCRalpha beta IEL that resulted in significantly increased IEL:epithelial cell ratios in c-Kit mutant mice. Bromodeoxyuridine labeling studies revealed that the increase in cell numbers was due to lymphoproliferation that occurred in situ. Interestingly, TCRgamma delta IEL expressed cell surface c-Kit, while the expanding population of TCRalpha beta IEL did not. Analysis of radiation bone marrow chimeras demonstrated that the dysregulation required either disruption of stromal cell SCF or IEL c-Kit and showed that the effect on IEL or their precursors was not due to other changes in the intestinal microenvironment. Lamina propria T cell populations in these mice were unaffected, reinforcing the idea that the developmental requirements of these gut-resident lymphocyte populations are distinct. Overall, the results demonstrated that the development of intestinal TCRgamma delta IEL, regardless of location, shares common requirements for SCF, while SI and LI TCRalpha beta IEL may develop along distinct pathways. Possible mechanisms for the loss of proliferative regulation in gut T cells in c-Kit/SCF deficiency are discussed.     

Effect of simian virus large T antigen expression on cell cycle control and apoptosis in rat pleural mesothelial cells exposed to DNA damaging agents

Cell cycle progression and apoptosis are controlled by regulatory proteins, including p53, of which functional alterations are linked to carcinogenesis. Recently, malignant mesothelioma (MM), a primary tumour related to asbestos exposure, alternatively to post therapeutic radiations, has proven to be an important problem in oncogenesis. The p53 protein does not seem mutated or deleted in MM but a possible inactivation by binding to other proteins [mdm2; SV40 large T antigen (Tag)] has been suggested. The present work investigated cell cycle regulation in normal rat pleural mesothelial cells (RPMC) and in RPMC expressing Tag (RPMC-TSV40), under exposure to asbestos and radiations. In RPMC, these agents induced activation of cell cycle checkpoints located at G1/S and G2/M and/or mitosis but a lack of control at G1/S was found in RPMC-TSV40. A loss of G2/M control may account for the formation of micronuclei observed after exposure of RPMC-TSV40 to radiations. In RPMC-TSV40 the enhancement of abnormal mitoses and apoptosis after asbestos exposure, in comparison with RPMC, suggests a loss of mitotic control and a p53-independent mechanism of apoptosis. Thus Tag expression in mesothelial cells might have both adverse and beneficial effects by impairing the control of DNA integrity and enhancing apoptosis respectively.     

Sensitivity of human prostatic carcinoma cell lines to low dose rate radiation exposure

PURPOSE: Low dose rate radioemitters, such as 125I, 103Pd, and 89Sr, have been used both for local and systemic treatment of prostate cancer. Most normal cells exposed to ionizing radiation characteristically activate cell cycle checkpoints, resulting in cell cycle arrest at the G1/S and G2/M transition points. Cancer cells are typically quite sensitive to radiation killing late in the G2 phase of the replicative cell cycle. Furthermore, most cancer cells accumulating at the G2/M transition point as a result of low dose rate radiation exposure appear to become sensitive to further low dose rate irradiation. For this reason, protracted exposure of cancer cells to low dose rate radiation has been proposed to result in increased cancer cell killing as compared with brief exposures of cancer cells to high dose rate radiation. Since many human prostatic carcinomas contain somatic genome alterations targeting genes which affect the cell cycle and radiation-associated cell cycle checkpoints, we evaluated the effects of low dose rate radiation exposure on the cell cycle and on clonogenic survival for various human prostatic carcinoma cell lines. MATERIALS AND METHODS: Human prostatic carcinoma cells from the LNCaP, DU 145, PC-3, PPC-1, and TSU-Pr1 cell lines were exposed to low dose rate (0.25 Gy/hour) or high dose rate (60 Gy/hour) radiation in vitro and then assessed for radiation cytotoxicity by clonogenic survival assay. Cell cycle perturbations following protracted exposure to low dose rate radiation were evaluated using flow cytometry. RESULTS: For LNCaP cells, low dose rate radiation exposure resulted in an accumulation of cells at both the G1/S and the G2/M cell cycle transition points. For DU 145, PC-3, PPC-1, and TSU-Pr1 cells, treatment with low dose rate radiation triggered G2/M cell cycle arrest, but not G1/S arrest. Unexpectedly, the cell cycle redistribution pattern phenotypes observed, G1/S and G2/M cell cycle arrest versus G2/M arrest alone, appeared to have little effect on low dose rate radiation survival. Furthermore, while PC-3, PPC-1, and TSU-Pr1 cells exhibited increased cytotoxic sensitivity to low dose rate versus fractionated high dose rate radiation treatment, DU 145 and LNCaP cells did not. CONCLUSIONS: Radiation-associated pertubations in replicative cell cycle progression were not dominant determinants of low dose rate radiation killing efficacy in human prostate cancer cell lines in vitro.     

Diagnostic delay and related factors in women with breast cancer

Experiments were undertaken in order to verify whether or not a strong magnetic field would have any biological effects on the cell growth, viability and radiation response of mammalian cells. Magnetic field exposures were conducted using a superconducting magnet with freshly-isolated human peripheral blood T-lymphocytes maintained at their normal growing temperature of 37 degrees C. The static magnetic fields with intensities up to 6.3-tesla (T) exerted little influence on the cell growth and viability of actively-growing T-lymphocytes under normal cell-culture conditions. On the other hand, the T cells exposed to the magnetic fields (4 T-6.3 T) during PHA stimulation were inhibited in their cell growth when compared to controls. The effects of the magnetic fields with intensities up to 2 T on cell growth properties, however, were minimal in this system. Also, the radiosensitivity of T-lymphocytes previously exposed to the strong magnetic fields was more sensitive than that of control cells. These results suggest that exposure to a static magnetic field of 4 T or stronger might lead to physiological and growth abnormalities at the cellular level.     

Identification and characterization of new elements involved in checkpoint and feedback controls in fission yeast

To investigate the mechanisms that ensure the dependency relationships between cell cycle events and to investigate the checkpoints that prevent progression through the cell cycle after DNA damage, we have isolated mutants defective in the checkpoint and feedback control pathways. We report the isolation and characterization of 11 new loci that define distinct classes of mutants defective in one or more of the checkpoint and feedback control pathways. Two mutants, rad26.T12 and rad27.T15, were selected for molecular analysis. The null allele of the rad26 gene (rad26.d) shares the phenotype reported for the "checkpoint rad" mutants rad1, rad3, rad9, rad17, and hus1, which are defective in the radiation checkpoint and in the feedback controls that ensure the order of cell cycle events. The null allele of the rad27 gene (rad27.d) defines a new class of Schizosaccharomyces pombe mutant. The rad27 complementing gene codes for a putative protein kinase that is required for cell cycle arrest after DNA damage but not for the feedback control that links mitosis to the completion of prior DNA synthesis (the same gene has recently been described by Walworth et al. (1993) as chk1). These properties are similar to those of the rad9 gene of Saccharomyces cerevisiae. A comparative analysis of the radiation responses in rad26.d, rad26.T12, and rad27.d cells has revealed the existence of two separable responses to DNA damage controlled by the "checkpoint rad" genes. The first, G2 arrest, is defective in rad27.d and rad26.d but is unaffected in rad26.T12 cells. The second response is not associated with G2 arrest after DNA damage and is defective in rad26.d and rad26.T12 but not rad27.d cells. A study of the radiation sensitivity of these mutants through the cell cycle suggests that this second response is associated with S phase and that the checkpoint rad mutants, in addition to an inability to arrest mitosis after radiation, are defective in an S phase radiation checkpoint.     

Changes in serum levels of sialoglycoproteins in mice exposed to UV-B radiation

In the acute phase reaction, hepatocytes in the liver are activated and increase the plasma levels of acute phase reactants. Our previous study has shown that plasma sialic acid, an acute phase reactant, was increased following exposure of mice to UV-B radiation. Plasma sialic acid is derived from many plasma components. To clarify the type of plasma sialic acid that is increased by exposure to UV-B radiation, we performed two-dimensional electrophoresis and staining for sialic acid. Consequently, the increases in haptoglobin and hemopexin were marked and 90% or more of the increased sialic acid was derived from these two glycoproteins after exposure to UV radiation. The increase in alpha1-acid glycoprotein levels was slight and did not contribute to the total increase in plasma sialic acid after exposure to UV radiation. Plasma levels of several proteins including antichymotrypsin (ACT), were reduced following exposure to UV radiation. The discrepancy between our results and published ones regarding ACT levels are discussed in terms of the type of cytokine.     

Long recovery times improve the detection of cellular resistance in vitro

In vitro cytotoxicity testing is used increasingly during the development of clinical treatment protocols. These tests are influenced by many variables, not all of which have been assessed systematically yet. We analyzed the influence of the recovery time between the end of treatments and measurements on the detection of cellular resistance. The development of resistance to cisplatin and radiation was chosen as a model since the schedule of these treatments is the objective of several ongoing clinical trials. C6 rat glioma, T98G, 86HG-39, A172 human glioma and TE671 human rhabdomyo-sarcoma cells were pretreated with radiation or cisplatin. The cellular resistance was then compared in pretreated and wild-type cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. In all cell lines, apparent drug concentrations killing 50% of the cells were dependent on the recovery time. In A172 cells this concentration was 10.3+/-02.1 microM after 48 h but decreased to 3.56+/-0.44 microM after 120 h recovery time (P < 0.001). After recovery times of more than 168 h, 53% of all pretreated cell lines were resistant to cisplatin or radiation, 25% were unchanged and 22% were more sensitive. However, only half the resistant cells could be identified when the MTT test was done with only 48 h recovery time. The sensitivity of detection increased from 0.46 to 0.83 when the recovery time of the test system was extended from 48 h to 168 h. The specificity was not dependent on the recovery time. Experiments showing resistance after short recovery times are reliable, but lack of resistance can only be shown in experiments with long recovery times. Cisplatin treatment can result in resistance to radiation in glioma cells.     

Effects of ionizing radiation on proliferation and differentiation of osteoblast-like cells

Diagnostic radiation for immediate post-surgical assessment of osseointegrated dental implants has been discouraged, due to the possibility of detrimental effects of ionizing radiation on healing and remodeling of bone. To assess this possibility, we investigated the effects of ionizing radiation on proliferation and differentiation of osteoblasts using osteoblast-like cells isolated from the calvariae of newborn rats (ROB) and a clonal osteoblastic cell line (MC3T3-E1). The cells were exposed on day 3 to a single dose of x-rays at either 40, 100, 400, or 4000 mGy, respectively, from a linear accelerator radiotherapeutic machine (Linac) or a 40-mGy dose from a diagnostic chest x-ray machine. The effects of radiation on cell growth and alkaline-phosphatase-specific (ALP) activity were evaluated at three-day intervals after irradiation up to day 12 in ROB cells, and evaluated at day 12 in MC3T3-E1 cells. At the culture end-point, the effects on formation of bone-like nodules were also evaluated in both ROB and MC3T3-E1 cells. Exposure of 4000 mGy differentially affected the two cell types. It inhibited cell growth and alkaline phosphatase activity, and inhibited DNA content in MC3T3-E1 cells. This irradiation also strongly inhibited the formation of bone-like nodules in ROB cells. On the other hand, exposure of 40-, 100-, and 400-mGy (Linac) and 40-mGy (diagnostic quality) irradiation induced no significant changes in cell growth, alkaline phosphatase activity, and formation of bone-like nodules in ROB cells. These doses also induced no significant changes in DNA content and ALP activity in MC3T3-E1 cells. These results indicate that ionizing radiation at a single dose of up to 400 mGy induces no significant changes in cell growth and differentiation of osteoblast-like cells, at least in vitro. Higher radiation doses (4000 mGy) may exert different effects on cell proliferation and cell differentiation of osteoblasts, depending on the cell types affected. Thus, diagnostic radiation seems to have less effect on proliferation and differentiation of osteoblasts.     

Natural killer cell development is blocked in the context of aberrant T lymphocyte ontogeny

Over-expression of human or mouse CD3-epsilon transgenes profoundly disturbs T lymphocyte and natural killer (NK) cell development. One of these transgenic strains, termed tgepsilon26, displays a very early block in T lymphocyte and NK cell development. We showed previously that the absence of early thymocyte progenitors results in an abnormal thymic microenvironment. Due to this thymic defect, T cell development could not be restored by bone marrow (BM) transplantation in adult tgepsilon26 mice but could in fetal tgepsilon26 mice. Here we examine the effect of this abnormal thymic environment on NK cell development. We demonstrate that NK cell maturation in tgepsilon26 mice was reconstituted by BM derived from completely T cell-deficient mice, i.e. RAG-2(-/-) and TCRbeta x delta-/-, but not from wild-type mice. Moreover, tgepsilon26 mice transplanted with BM from partially T cell-deficient mice, i.e. TCRalpha-/-, TCRbeta-/- and TCRdelta-/- mice, did not reconstitute their NK cell compartment. We conclude from these studies that the thymic environment is not required for NK cell development, but that aberrantly educated alphabeta or gammadelta T lymphocytes can influence NK cell ontogeny. Furthermore, high serum levels of tumor necrosis factor (TNF) were detected in the vast majority of tgepsilon26 mice transplanted with BM cells derived from partially T cell-deficient mice, but never from tgepsilon26 mice transplanted with BM cells derived from completely T cell-deficient mice. The high levels of TNF may play an important role in the observed inhibition of NK cell development, since in vivo treatment with an anti-TNF antibody restored NK cell development.     

Environmental exposure, social class, and cancer risk

Exposure to a variety of environmental factors associated with cancer occurrence varies by social class. These factors include air pollutants (SO2, NO2, total suspended particulates, etc.), toxic waste hazards, and ionizing and other radiation. Heavy environmental pollution has been associated with an increased risk of some cancers and in particular lung cancer. There is limited evidence suggesting that individuals from lower social classes are exposed to higher levels of environmental pollutants than are individuals from higher social classes. This may be due to the placement of new sources of pollution or of toxic processes in disadvantaged areas, or to the selective migration of the poorer sectors of society to these areas. The available data do not allow any conclusion on the possible contribution of exposure to environmental pollution to social class differences in cancer occurrence. Exposure to ultraviolet (UV) radiation, principally from sunlight, is modified strongly by personal behaviours such as choice of recreation and use of protective clothing. Those in outdoor occupations are likely to receive the highest cumulative exposure to UV radiation. There is no clear evidence from recent survey research in Australia and North America that socioeconomic factors are strongly related to non-occupational exposure to UV radiation. Information is lacking on the influence of socioeconomic status on sun exposure in other parts of the world. There is little information on the social distribution of exposure to ionizing radiation.     

Corneal manifestations of metabolic diseases

The extent to which sex differences in the behavioral effects of frontal injury in the adult rat can be attributed to differential exposure to testosterone (T) during development was investigated. The effects of these factors on brain weight and relative brain size were also examined. At birth, males were gonadectomized (GDX) or not and females were given T or oil injections. In adulthood, all animals were GDX or sham-operated and received either bilateral aspiration lesions of the medial frontal cortex or a sham operation. Rats were tested on the Morris water maze task, the radial arm maze (RAM), and the landmark water task. The effects of frontal injury on performance of the Morris water maze task were greater in rats not exposed to T at birth, there was no effect of neonatal T exposure on performance on the RAM, and on the landmark water task there was a complicated interaction of sex and neonatal T exposure in rats with frontal injury.     

Transplacental and transgenerational carcinogenesis

Effects of exposure to carcinogens at early stages of ontogenesis are considered. An increased cancer risk due to prenatal exposure may be related to: 1) exposure of the fetus during pregnancy to chemicals able to cross the placental barrier or to radiation; 2) exposure to a chemical or radiation of the parents or one parent prior to conception. In transplacental carcinogenesis, the effects observed after birth are a consequence of a direct interaction of the carcinogen with somatic cells of the fetus. DES and radiation were shown to increase cancer risk in humans following exposure during pregnancy, while in experimental animals a large variety of chemicals of quite different structure (including the widely used therapeutic agent cisplatin) were demonstrated to induce tumors in the progeny after administration during pregnancy. The experimental multigeneration effect of carcinogens is manifested in an increased incidence of tumors in several generations of untreated descendants of: a) females exposed to carcinogen during pregnancy; b) males exposed to carcinogen prior to mating with untreated females. The inherited change may be an initiating event revealed by the exposure during post-natal life to a promoting agent. In humans deleterious information inherited through the germ cells (occurring either following a spontaneous error in DNA replication and repair or as a consequence of a chemical or physical agent) can increase the risk of developing cancer in certain individuals by several orders of magnitude (retinoblastoma, familial polyposis of the colon and some others). The multigeneration transmission of carcinogenic risk is also demonstrated by cancer prone families that are probably more frequent than originally thought, with a risk that is one order of magnitude higher than in general population. Familial clusterings of cancer may also indicate germline mutations in one or more genes. Thus the inherited predisposition to cancer that is observed today may, at least in part, be explained by the exposure to environmental noxious agents in previous generation(s). Since humans are exposed throughout life to many environmental agents, either carcinogenic or capable to enhance the progression of cancer, an understanding of the contribution of prenatal exposure to carcinogens could improve the efficacy of prevention.     

Radiation-induced genomic instability

Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.     

Health of tree swallows (Tachycineta bicolor) nesting in pesticide-sprayed apple orchards in Ontario, Canada. II. Sex and thyroid hormone concentrations and testes development

To investigate the effects of pesticides on wild birds, sex (17beta-estradiol; testosterone) and thyroid (triiodothyronine (T3) hormone concentrations, body mass, and testes mass were measured and the development of testes was evaluated in wild tree swallows (Tachycineta bicolor) nesting in four sprayed apple orchards and three nonsprayed sites in southern Ontario, Canada, in 1995-1996. In orchards, birds were exposed to asmany as 11 individual spray events and five sprays of mixtures of chemicals. Residues of organochlorine pesticides, PCBs, lead, and arsenic concentrations were low and not variable among sites except p,p'-DDE concentrations, which ranged from 0.36 to 2.23 microg/g wet weight in eggs. These persistent compounds were not correlated with any endocrine response measured in tree swallows. In 16-d-old male tree swallow chicks, body mass and concentrations of 17beta-estradiol (estradiol), testosterone, and T3 in plasma showed no significant differences between sprayed and nonsprayed groups and among sites within those groups. However, T3 concentrations were slightly elevated in the sprayed group compared to the nonsprayed group, and there was a significant and positive correlation between T3 and the number of mixtures of sprays applied during egg incubation through chick rearing. In 16-d-old female chicks, there were no significant differences among spray treatments or sites and no correlations with spray exposure for testosterone, estradiol, or T3 in plasma. Body mass was correlated positively with T3 and negatively with estradiol but showed no differences among spray exposure groups or sites. Histology of testes of 16-d-old male chicks indicated there were no significant differences among sprayed and nonsprayed birds in testes mass, area, or diameter, or the presence of Leydig cells in the interstitium, the distribution of the Sertoli cells, or the occurrence of heterophils in the testicular interstitium. For the percentage of spermatogonia present on the basement membrane, there were significant differences among sites, but these differences were not specifically associated with spray exposure. However, there was a marginally significant trend between increasing occurrence of a disrupted Sertoli cell population on the seminiferous tubular basement membranes as the number of mixtures of pesticides sprayed during chick rearing increased. In adult male and female parent tree swallows, there were no differences in hormone concentrations between birds from sprayed and nonsprayed sites. Nor were there any significant correlations between the concentration of any hormone and collection date, body mass, or any type of spray exposure for adults. The correlations between increasing pesticide exposure and abnormal thyroid hormone and testes development in male chicks indicate that further reductions of pesticide use in orchards may benefit the health of birds that nest there. However, it is unclear which of these pesticides or spray mixtures are responsible for these effects, and this needs to be examined in future studies.     

Gamma delta T cells in the peripheral blood of individuals from an area of holoendemic Plasmodium falciparum transmission

gamma delta T cells bearing V gamma 9 T cell receptors from unexposed Caucasian donors make large responses to Plasmodium falciparum in vitro. This finding, together with observations of others showing high levels of V gamma 9+ T cells in the blood of infected non-immune individuals, led us to hypothesize that the response of these cells might contribute to the pathology of P. falciparum malaria. Acquisition of immunity to disease in people naturally exposed to infection may therefore be due in part to down-regulation or alteration of the function of gamma delta T cells. Supporting this view, and in contrast to infection in non-immune individuals, V gamma 9+ T cells are not elevated in peripheral blood of children or adults living in an endemic area despite constant exposure to P. falciparum. After in vitro stimulation with P. falciparum, however, the expansion of V gamma 9+ cells from the African donors is of similar magnitude to that observed for non-exposed Europeans. Thus, although these cells are not elevated in peripheral blood, they are still able to respond to P. falciparum antigens. In adult European donors the major gamma delta T cell population in peripheral blood is V gamma 9+ (approximately 70% of all gamma delta cells), whereas in the majority of adult Africans V delta 1+ V gamma 9- T cells predominated (approximately 70% of total gamma delta cells).     

Pneumatic retinopexy as supplemental therapy for persistent retinal detachment after scleral buckling operation

BACKGROUND: Factors associated with the development of basal cell carcinomas (BCCs) are radiation exposure, sunlight, trauma, and burns. OBJECTIVE: We wish to further document the relationship between the development of BCCs and previous diathermic exposure for therapeutical purposes. Moreover, we compared the histological subtypes of BCCs developed in patients with or without previous therapy. METHODS: A retrospective study of 1053 patients with BCCs seen at our dermatologic clinic was performed. RESULTS: Twenty-three patients had histories of diathermic therapy for different osteoarticular problems. The interval of time between the treatments and the appearance of the tumor was 12-31 years. The histologic subtypes involved were the same of other BCCs on the same areas. CONCLUSIONS: Our study supports the association of BCCs and diathermic therapy in the development of the tumor of the previously treated areas. Histological subtypes do not seem to be affected by environmental factors but are a characteristic of the site location of the tumor.     

Pharmacokinetic aspects of measurement of glomerular filtration rate in the dog: a review

Oxidative insults, whether over-excitation, excessive release of glutamate or ATP caused by stroke, ischemia or inflammation, exposure to ionizing radiation, heavy-metal ions or oxidized lipoproteins may initiate various signaling cascades leading to apoptotic cell death and neurodegenerative disorders. Among the various reactive oxygen species (ROS) generated in the living organism, hydroxyl and peroxynitrite are the most potent and can damage proteins, lipids and nucleic acids. It appears that some natural antioxidants (tocopherol, ascorbic acid and glutathione) and defense enzyme systems (superoxide dismutase, catalase and glutathione peroxidase) may provide some protection against oxidative damage. Recent findings indicate several polyphenols and antioxidant drugs (probucol, seligilline) are effective in protecting the cells from ROS attack. Further development of these antioxidant molecules may be of value in preventing the development of neurodegenerative diseases.