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Biomedical subjects

T Reynolds

Publications and source records attributed to T Reynolds.

At least 145 records · Page 8Linked to original sources
PubMed1995

A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic.

Sewage, a complex mixture of organic and inorganic chemicals, is considered to be a major source of environmental pollution. A random screen of 20 organic man-made chemicals present in liquid effluents revealed that half appeared able to interact with the estradiol receptor. This was demonstrated by their ability to inhibit binding of 17 beta-estradiol to the fish estrogen receptor. Further studies, using mammalian estrogen screens in vitro, revealed that the two phthalate esters butylbenzyl phthalate (BBP) and di-n-butylphthalate (DBP) and a food antioxidant, butylated hydroxyanisole (BHA) were estrogenic; however, they were all less estrogenic than the environmental estrogen octylphenol. Phthalate esters, used in the production of various plastics (including PVC), are among the most common industrial chemicals. Their ubiquity in the environment and tendency to bioconcentrate in animal fat are well known. Neither BBP nor DBP were able to act as antagonists, indicating that, in the presence of endogenous estrogens, their overall effect would be cumulative. Recently, it has been suggested that environmental estrogens may be etiological agents in several human diseases, including disorders of the male reproductive tract and breast and testicular cancers. The current finding that some phthalate compounds and some food additives are weakly estrogenic in vitro, needs to be supported by further studies on their effects in vivo before any conclusions can be made regarding their possible role in the development of these conditions.

Animals↗
PubMed1994

Different types of bombesin receptors on neurons in the dorsal raphe nucleus and the rostral hypothalamus in rat brain slices in vitro.

The actions of the peptides bombesin (BN), gastrin releasing peptide (GRP), neuromedin C (NMC), litorin and neuromedin B (NMB) were studied on neurons in slices of rat brain maintained in vitro to determine the BN receptor type present in different brain areas. Intracellular and extracellular recordings were made from hypothalamic neurons on the border of the periventricular nucleus (PVN) and suprachiasmatic nucleus (SCN) and from mesencephalic 5-HT sensitive neurons in the dorsal raphe nucleus. In the region of the brain containing the SCN and PVN, BN and the BN-related peptides excited 31 out of 77 neurons on which they were tested. There was little difference in the potency of the BN-related peptides as excitants of neurons, the EC50 being about 10 nM. The response to the peptides usually lasted between 5 and 15 min with little sign of desensitization. Using NMC, GRP and NMB as agonists, the equilibrium constant for the GRP receptor antagonist [D-Phe6]-BN-(6-13)-ethylamide was approximately 10 nM. The response to the peptides fully recovered on washout of the antagonist. The CCKB/gastrin receptor antagonist CI-988 (1 microM) had no effect on either GRP- or NMC-mediated excitation. In the dorsal nucleus 40 of 75 neurons were sensitive to the BN-related peptides. BN, [Tyr4]-BN, NMB and litorin, were 10-20 times more potent than GRP and NMC. The responses to the BN-related peptides were not blocked by the selective GRP receptor antagonists [D-Phe6]-BN-(6-13)-methylester, [DF5Phe6][D-Ala11]-BN-(6-13)-methylester and [D-Phe6]-BN-(6-13)- ethylamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

2-Chloroadenosine inhibits the MHC-unrestricted cytolytic activity of anti-CD3-activated killer cells: evidence for the involvement of a non-A1/A2 cell-surface adenosine receptor.

Adenosine is likely to be a frequent constituent of the tumor microenvironment since this purine nucleoside is produced in quantity by hypoxic cells such as those found in the interior of poorly vascularized solid tumors. In this study we show that 2-chloroadenosine (2CA), a stable analogue of adenosine, inhibits, in a dose-dependent fashion, MHC-unrestricted killing of P815 tumor target cells by anti-CD3-activated killer (AK) lymphocytes. 2CA mediates this effect by interfering with the recognition/adhesion phase of cytolysis. Blocking cellular uptake of 2CA with dipyridamole, rather than attenuating the inhibitory effect, potentiated the inhibition of cytolysis, indicating the involvement of a cell-surface receptor. However, neither the A1 receptor antagonist DPCPX, nor the A2 receptor antagonist DMPX were able to block the inhibitory effect of 2CA on AK lymphocyte function. Similarly, the nonselective A1 and A2 receptor antagonists, theophylline and 8-phenyltheophylline, had no effect on 2CA-mediated inhibition of AK cell activity. Taken together, these data provide evidence that 2CA inhibits the cytolytic activity of AK lymphocytes by interacting with a novel non-A1/A2 cell-surface receptor. A similar effect mediated in vivo by tumor-elaborated adenosine may be involved in tumor-associated immunosuppression.

2-Chloroadenosine↗
PubMed1994

Colon adenocarcinoma cells inhibit anti-CD3-activated killer cell induction.

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells has shown some promise in the treatment of certain cancers that are unresponsive to conventional treatment approaches. However, colon adenocarcinomas tend to respond poorly to LAK therapy, possibly as a result of tumor-induced immunosuppression. Recently, in vivo administration of anti-CD3 antibody has been shown to induce mouse T lymphocytes to mediate major-histocompatibility-complex(MHC)-unrestricted tumoricidal activity which is distinct from natural-killer-cell-derived LAK activity. It has therefore been suggested that anti-CD3 therapy may find application in tumor immunotherapy in humans. However, the effectiveness of anti-CD3-activated killer cell induction within the environment found in the vicinity of colon adenocarcinoma cells has not been evaluated. The present report demonstrates that colon cancer cells of human (HT-29) and mouse (MCA-38) origin markedly inhibit the generation of activated killer cells in murine spleen cell cultures. DNA synthesis and interleukin-2 production by spleen cells following stimulation with anti-CD3 antibody are also profoundly depressed in the presence of MCA-38 and HT-29 adenocarcinoma cells. MCA-38- and HT-29-mediated inhibition of activated killer cell development is exerted through the production of a tumor-associated soluble factor that is distinct from transforming growth factor beta or prostaglandins. Local immunosuppression associated with sites of tumor growth may therefore represent a major obstacle to successful anti-CD3 immunotherapy of certain colon adenocarcinomas.

Adenocarcinoma↗