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Biomedical subjects

A N Taylor

Publications and source records attributed to A N Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1996

Increased susceptibility to metastasis during pro-oestrus/oestrus in rats: possible role of oestradiol and natural killer cells.

It has been suggested that tumour development and immunocompetence are affected by the menstrual and the oestrous cycle, and sex hormones have been shown to modulate lymphokine production, neuroendocrine activity and immunity. In this study, we assessed natural killer cell activity and host susceptibility to metastasis during the oestrous cycle in the Fischer 344 inbred rat strain. Females were inoculated intravenously with MADB106 tumour cells, a syngeneic mammary adenocarcinoma cell line that metastasises only to the lungs. The susceptibility to metastatic development of this tumour was found to be significantly higher during pro-oestrus and oestrus than during metoestrus and dioestrus. Two days of exposure to oestradiol benzoate caused similar effects in ovariectomised females, and a single administration of progesterone reduced this effect of oestradiol to a statistically non-significant level. The tumour was found to be negative for oestradiol receptors, and its in vitro proliferation rate was not affected by oestradiol or progesterone, suggesting that the effects of sex hormones on the metastatic process are not attributable to a direct effect on tumour cells. Because the metastatic process of MADB106 tumour cells is known, and confirmed here, to be highly controlled by large granular lymphocyte/natural killer (LGL/NK) cell activity, we assessed their role in mediating the effects of the oestrous cycle. The number and activity levels of circulating blood LG/NK cells (NKR-PI+ bright) were studied. Findings indicated oestrous-dependent alterations in the number of LGL/NK cells and suggested a diminished NK activity per LGL/NK cell during pro-oestrus/ oestrus, the same phases that were characterised by higher susceptibility to metastatic development. These findings provide the first empirical evidence for a causal relationship between a short-term exposure to elevated oestradiol/low progesterone levels and decreased resistance to tumour metastasis, and it is hypothesised that an alteration in LGL/NK cell activity underlies these effects. Homologies and relevance to clinical phenomena are discussed.

Adenocarcinoma↗
PubMed1996

Acute alcohol intoxication suppresses natural killer cell activity and promotes tumor metastasis.

Alcohol consumption is associated with increased morbidity and mortality related to infectious diseases and malignancy (1-5), although immune mediation of these relationships is controversial. Specifically, the activity of natural killer (NK) cells, which are involved in the resistance to infections and metastasis, can be suppressed in the presence of ethanol in vitro. However, acute consumption or infusion of ethanol in vivo exerts no effects on NK activity assessed in vitro thereafter. Therefore, we have developed and used a method to study the effects of ethanol on NK activity in living rats by using an NK-sensitive metastatic process and selective depletion of NK cells in vivo. Acute ethanol intoxication caused a marked suppression of NK activity in vivo and a tenfold increase in the number of MADB106 tumor metastases. Ethanol had no effect in rats selectively depleted of NK cells or when an NK-insensitive tumor (C4047) was used. These findings suggest that even acute ethanol intoxication markedly suppresses NK activity in the living organism. This suppression may underlie some aspects of the association between alcoholism, infectious disease and malignancies.

Alcohol Drinking↗
PubMed1996

Fetal ethanol exposure: hypothalamic-pituitary-adrenal and beta-endorphin responses to repeated stress.

Previous studies provide evidence that fetal ethanol exposure induces hypothalamic-pituitary-adrenal (HPA) and pituitary beta-endorphin (beta-EP) hyperresponsiveness to acute stressors. The present study demonstrates significant effects of in utero ethanol exposure on the parallel response patterns of the HPA axis and the pituitary beta-EP system to repeated exposures to a stressor, restraint stress, and indicates sex differences in response. Together, data from the two experiments indicate that, after repeated restraint exposures, fetal ethanol-exposed (E) males and females both show significantly increased plasma levels of adrenocorticotropin (ACTH), and E males also show significantly increased plasma levels of beta-endorphin-like immunoreactivity (beta-EPLIR), compared with their respective pair-fed and control counterparts. Marginal increases in the corticosterone response of E males and the beta-EPLIR response of E females, compared with their controls, were also observed. In addition, delayed or deficient habituation to restraint stress was observed in the beta-EPLIR response of E males and the ACTH response of E females. These data demonstrate that fetal E-exposed males and females both exhibit hormonal hyperresponsiveness and/or deficits in recovery after repeated exposures to restraint stress, but that the patterns of response may differ depending on the number and duration of restraint exposures, the time course measured, and whether the endpoint measured is corticosterone, ACTH, or beta-EPLIR. In addition, the finding that E and pair-fed animals both differed from their respective controls in certain developmental and hormonal measures suggests that prenatal nutritional factors may play a role in mediating some of the changes that are observed.

Adrenocorticotropic Hormone↗
PubMed1995

Is lung cancer associated with asbestos exposure when there are no small opacities on the chest radiograph?

This study was designed to test the hypothesis that the risk of lung cancer from asbestos exposure is confined to persons with radiographic evidence of pulmonary fibrosis. Occupational and smoking histories were obtained from 271 patients with a confirmed diagnosis of primary lung cancer and 678 referents (279 with other respiratory disease and 399 with cardiac disease). Histories were reviewed blind to assess the timing, duration, and probability of exposure to asbestos. To allow for a lag between asbestos exposure and the development of lung cancer, subjects were classified by the time they had spent in an occupation entailing definite or probable exposure more than 15 years before diagnosis. The presence and extent of fibrosis was assessed blindly from chest radiographs by three readers and scored for small opacities with the ILO 1989 International Classification of Radiographs of the Pneumoconioses. 93 (34.3%) cases had worked in an occupation with definite or probable asbestos exposure compared with 176 (25.8%) referents (crude odds ratio for lung cancer 1.49, 95% CI 1.09-2.04). After adjustment for age, sex, smoking history, and area of referral, the odds ratio (95% CI) was 2.03 (1.00-4.13) in the subgroup of 211 with a median ILO score for small parenchymal opacities of 1/0 or more, and 1.56 (1.02-2.39) in the 738 with a score of 0/1 or less (ie, those without radiological evidence of pulmonary fibrosis). These results suggest that asbestos is associated with lung cancer even in the absence of radiologically apparent pulmonary fibrosis.

Aged↗
PubMed1995

The development of sexual dimorphism in natural killer cell activity and resistance to tumor metastasis in the Fischer 344 rat.

The development of sexual dimorphism in the number and activity level of natural killer (NK) cells was studied in the inbred Fischer 344 rat from prepubescence to maturity. Additionally, in view of the biological significance of NK cells in controlling cancer, especially the metastatic process, we used a syngeneic mammary tumor (MADB106) to assess the host anti-metastatic activity. This tumor model was used because NK cells control the lung clearance of i.v.-injected MADB106 tumor cells, a process that critically affects the metastatic colonization of these tumor cells in the lungs. The results indicated that although prepubescent (36 days of age) males and females exhibited greater NK cytotoxicity (assessed in vitro) and higher anti-metastatic activity, evidenced by fewer tumor cells retained in the lungs. On the other hand, the mature males (140-170 days of age) displayed greater LGL/NK number and activity per ml blood, retained fewer tumor cells, and developed fewer lung tumor colonies compared to the females. During early postpubescence (63 days of age), a transitional stage between prepubescence and maturity, females and males exhibited equivalent numbers of circulating LGL/NK cells, and females displayed slightly greater NK cytotoxicity per ml blood yet retained somewhat greater numbers of tumor cells compared to the males. Overall, whereas the males exhibited increasing levels of NK number and activity throughout the age span tested, the females, despite displaying greater NK function compared to the males at prepubescence and slight improvement at postpubescence, fell behind the males in these indices of NK function at maturity.

Animals↗
PubMed1995

Fetal alcohol and thymocyte phenotypes in offspring: response to food deprivation.

Restriction of food availability is a reliable stimulus that leads to significant hypothalamo-pituitary-adrenal (HPA) activation to which rats do not habituate. Based on our previous data that indicated that the HPA response to some, but not all, stressful stimuli is significantly greater in adult offspring of Sprague-Dawley dams exposed to 35% alcohol during the last 2 weeks of gestation than that of control rats and on the mounting neuroendocrine-immune literature that describes the role of pituitary-adrenal products in modulating cellular immunity, we hypothesized that the outcomes of food restriction would be significantly more marked in fetal alcohol-exposed (FAE) offspring, compared with control rats. Data we report herein show that--whereas food restriction at 30-35 days of age produced significant changes in body weight, thymus weight-to-body weight ratio, adrenal weight-to-body weight ratio, plasma corticosterone levels, and in thymocyte number, as well as in the percentage and absolute number of CD4+ and CD8+ thymocytes that express CD45RC-FAE and control rats were equally affected. We conclude that food restriction is another example of a stressful stimulus that fails to distinguish satisfactorily between FAE and control rats of prepubertal age.

Animals↗
PubMed1995

Prenatal alcohol exposure and pineal response to isoproterenol, vasoactive intestinal polypeptide, and desmethylimipramine.

Pineals from neonatal rats born to alcohol-fed mothers had lower unstimulated serotonin-N-acetyltransferase activity (NAT) and responded less to isoproterenol, vasoactive intestinal polypeptide, or desmethylimipramine challenge than did pineals from pups born to normal or pair-fed mothers. Group differences disappeared after the first week of life. Reduced NAT activity is coincident with elevated glucocorticoids in these pups. In contrast to these effects of chronic in utero ethanol exposure, acute ethanol addition to normal adult pineals in organ culture enhanced ISO but not VIP stimulation of NAT activity. The results suggest that the neonatal pineal is more affected by ethanol-induced activation of the adrenocortical axis during gestation than by the direct effect of ethanol on membrane fluidity.

Animals↗
PubMed1994

Mechanism of the impaired T-cell proliferation in adult rats exposed to alcohol in utero.

Although attempts have been made to assess the effect of ethanol on the immune responses in individuals with fetal alcohol syndrome, there is no consensus as to the effect of ethanol on the immune system. Evidence that fetal alcohol-exposed (FAE) humans and animals have diminished proliferative response of T-cells to mitogenic lectins is well established. However, little is known about the mechanism of a toxic effect of ethanol on T-cell growth. Thus, a rat model was used to delineate the mode of ethanol action on T-cell proliferation. We found that the diminished T-cell proliferation in young adult FAE rats was due to a decreased responsiveness to interleukin 2 (IL2), but not to an impaired production of IL2 and expression of IL2 receptors (IL2R). Furthermore, the decreased proliferative response did not result from the presence of an excessive suppressor T-cell activity. Measurements of [Ca+2]i and T-cell proliferation were concurrently performed in batches of cells from the same animals. It was demonstrated that an increase in [Ca+2]i induced by Concanavalin A (Con A) in T-cells from FAE rats was not impaired, although the T-cell proliferation induced by Con A was significantly diminished. The results of the IL2-binding study showed that the Kd values and the number of both high- and low-affinity IL2R binding sites on the T-cells of FAE rats were comparable to those of pair-, or chow-fed rats. Finally, the results of the kinetics and rate of the internalization of IL2 showed that (1) the amount of the internalized IL2 was significantly reduced in T-cells from FAE rats, and (2) the half-time (t1/2) for dissociation of IL2 from the receptors in the T-cells from FAE rats was also greater than that of the control rats. These results taken together indicate that ethanol suppresses T-cell proliferation by interfering with events following the IL2-IL2R interaction.

Animals↗
PubMed1994

Administrative support team. A structural innovation.

In response to societal, organization, and leadership changes, an innovative nursing structure was implemented and evaluated. An administrative support team was developed to provide specialized internal consultation and support to a flattened and decentralized nursing division. The four administrative support team roles provided an organization perspective that ensured constancy of purpose throughout the division. This structural innovation proved to be congruent with nursing shared governance and total quality management initiatives occurring in the organization. Evaluation studies indicated that the model has effectively supported 5 years of continuing organizational change.

Hospital Bed Capacity, 300 to 499↗
PubMed1994

Corticotropin-releasing factor reduces lipopolysaccharide-induced pulmonary vascular leak.

Previous studies have suggested that corticotropin-releasing factor (CRF) has immunoregulatory effects in addition to its neuroendocrine role. We examined the ability of CRF to inhibit lipopolysaccharide (LPS)-induced pulmonary vascular leak in vivo. Female BALB/C mice were treated with either normal saline (NS) or CRF prior to injection with LPS. Pulmonary vascular leak was inhibited by CRF as assessed by measurement of lung wet-to-dry ratios. The stress-induced increase in serum corticosterone levels in mice injected with LPS alone was not further increased by treatment with CRF. This indicates that the effect of CRF was not mediated centrally by stimulation of endogenous steroid release. Histologic examination of the lungs revealed that leukocyte infiltration was significantly depressed in CRF-treated mice thus confirming the protective effect of CRF. In addition, a modest prolongation of survival was demonstrated in CRF-treated mice following challenge with LPS (p = .08). These data indicate the potential utility of CRF as a modulator of pulmonary vascular leak.

Animals↗
PubMed1993

Antagonism of the non-opioid component of ethanol-induced analgesia by the NMDA receptor antagonist MK-801.

Recent evidence from our laboratory suggests that the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) selectively antagonizes non-opioid (i.e. naloxone-insensitive) mechanisms of stress-induced analgesia in mice. For example, we have recently demonstrated that a low dose of MK-801 (0.075 mg/kg, i.p.) antagonizes the non-opioid component of a mixed opioid/non-opioid swim stress-induced analgesia (SSIA) resulting from forced swimming for 3 min in 20 degrees C water. Since ethanol-induced analgesia (EIA) has been found to be only partially attenuated by naloxone, we hypothesized that MK-801 would similarly block the non-opioid component of EIA. The effects of MK-801 and of the opioid receptor antagonist naloxone (10 mg/kg, i.p.) on analgesia produced by ethanol (2.5 g/kg in 20% vol/vol, i.p.) were studied in control mice and in mice selectively bred for high (HA) or low (LA) SSIA. HA mice showed significantly more, and LA mice significantly less, EIA than controls. Naloxone and MK-801 significantly attenuated EIA in control and HA mice, and in these lines the combined administration of both antagonists blocked EIA completely. In LA mice, which displayed very little EIA, naloxone but not MK-801 reversed EIA completely. These findings provide additional evidence for the role of the NMDA receptor in non-opioid mechanisms of analgesia. The finding that mice selectively bred for high and low SSIA, also display high and low EIA suggests common mediation of the effects of stress and ethanol on antinociceptive processes.

Analgesia↗
PubMed1993

Fetal alcohol exposure attenuates lipopolysaccharide-induced fever in rats.

Exposure to alcohol in utero can lead to long-lasting impairments of immune functions and to decreased resistance to infectious agents. We studied the effects of fetal alcohol exposure (FAE) in rats on the core body temperature response to an exogenous challenge of the immune system with lipopolysaccharide (LPS). We report that FAE rats show markedly decreased LPS-induced fever [i.e., they require a higher dose than control rats to show any LPS-induced hyperthermia (50 micrograms/kg vs. 10 micrograms/kg)], and even with the higher LPS dose they manifest a weaker hyperthermia, which declines faster than in control animals. These results suggest that FAE produces an impairment in the release of endogenous pyrogens and/or in the neural substrate for body temperature regulation. This impairment may account for at least some of the decreased resistance to infections observed in FAE animals and humans.

Animals↗
PubMed1993

Adrenalectomy but not adrenal demedullation during pregnancy prevents the growth-retarding effects of fetal alcohol exposure.

Growth retardation, both in the prenatal and the early neonatal period, is a consistent feature of fetal alcohol exposure, but the mechanism by which alcohol affects growth has not been elucidated. Because other stressors--such as maternal restraint and neonatal glucocorticoid treatment--can also affect growth, we examined the effect of ethanol on pup birthweight under two experimental conditions that altered maternal adrenal function. In the first study when dams were adrenalectomized and given low replacement doses of dexamethasone, the ethanol-exposed offspring of the adrenalectomized dams had birthweights similar to those of dams maintained on regular lab chow diets. In a second study, we found that maternal adrenal demedullation did not alter the reduction in birthweight produced by fetal ethanol exposure. The results suggest that the effects of ethanol on fetal growth may be mediated in part through ethanol-induced changes in the function of the maternal adrenal cortex.

Adrenal Cortex↗
PubMed1993

Immunocytochemical localization of sodium-calcium exchanger in canine nephron.

The sodium-calcium exchanger was localized in tissue sections of canine kidneys with two different polyclonal antisera raised against purified sodium-calcium exchanger protein derived from dog cardiac sarcolemma. The sodium-calcium exchanger was prominent in the basolateral plasmalemma of the majority of cells in all connecting tubules. In contrast, it was observed rarely and inconspicuously over the basolateral aspects of proximal tubular cells. The sodium-calcium exchanger was undetectable in all other portions of the nephron.

Animals↗
PubMed1993

Actions of alcohol on immunity and neoplasia in fetal alcohol exposed and adult rats.

Alterations of immune function can result not only from alcohol consumption by the adult human or animal, but also from fetal alcohol exposure (FAE). We have demonstrated long-lasting effects of FAE on T cell function and effects of adult ethanol (EtOH) consumption on tumorigenesis. Here, we present recent data that demonstrate that 1) FAE alters the biphasic pattern of thymocyte activation during peripubertal development probably due to effects other than the CD3 pathway; and 2) the long-lasting impaired proliferative response of splenocytes from FAE rats is not due to loss of their ability to express interleukin-2 receptors (IL2R), thus reflecting interference with events following the IL2-IL2R interaction. We also provide direct evidence that acute in vivo administration of EtOH to adult Fisher 344 rats can suppress blood natural killer (NK) cytotoxicity and that such suppression mediates the observed enhanced metastatic growth of a syngeneic mammary tumor.

Animals↗