Acquired immunodeficiency syndrome: a perspective

Infection by the Human T-Lymphotropic Virus Type III (HTLV-III) may lead to the devastating and ultimately fatal disease, acquired immunodeficiency syndrome (AIDS). As the virus is transmitted in similar ways to the hepatitis B virus, concern has developed within the dental profession regarding the possibility of clinicians acquiring AIDS through treatment of infected patients. This paper aims to place the significance of HTLV-III infection to dental practice in perspective.     

Discriminative stimulus properties of the serotonin agonist MK 212

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT₁/5-HT₂ antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT₂ antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT₁/5-HT₂ but not by selective 5-HT₂, antagonists suggests the possibility that 5-HT₁ receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.Portions of this research were presented at the Meeting of the Committee on Problems of Drug Dependence Satellite Session (International Study Group Interested in Drugs as Reinforcers and the Society for the Stimulus Properties of Drugs) in Baltimore, MD (1985)     

The effects of betamethasone on maternal cellular resistance to infection

Antenatal administration of glucocorticoids is often used to facilitate fetal lung maturation in cases of prematurity; however, the effects of betamethasone on maternal immune function have not been established. Therefore maternal immune function was assessed with the use of in vitro techniques. Transient and incomplete suppression of the proliferative response to the T-cell mitogen phytohemagglutinin was demonstrated as early as 24 hours after administration of betamethasone. The magnitude and duration of suppression showed a corresponding increase with advancing gestational age, but these effects were not cumulative and were always short-lived (less than 72 hours). No such suppression of the B-cell mitogen lipopolysaccharide was detected. The nonspecific cellular resistance to infection of maternal monocytes was determined through coincubation with the facultative intracellular pathogen Listeria monocytogenes. Increased phagocytic activity with a normal bactericidal effect was measured in the cell preparations obtained from recipients versus nonrecipients of betamethasone. Taken together, these findings clearly show that both specific and nonspecific immune function are intact in the preterm gravid woman after administration of betamethasone and should allay concerns over its use for reasons of infection control alone.     

A human amphotropic retrovirus receptor is a second member of the gibbon ape leukemia virus receptor family.

Retrovirus infection is initiated by binding of the viral envelope glycoprotein to a cell-surface receptor. The envelope proteins of type C retroviruses of mammals demonstrate similarities in structural organization and protein sequence. These similarities suggest the possibility that retroviruses from different interference groups might use related proteins as receptors, despite the absence of any relationship between retrovirus receptors isolated to date. To investigate this possibility, we have identified a human cDNA clone encoding a protein closely related to the receptor for gibbon ape leukemia virus and have found that it functions as the receptor for the amphotropic group of murine retroviruses. Expression of this protein (GLVR-2) is likely to be a requirement for infection of human cells by amphotropic retroviral vectors for purposes of gene therapy.     

2'-Chlorodeoxyadenosine: evaluation of a novel predominantly lymphocyte selective agent in lymphoid malignancies.

2''-Chlorodeoxyadenosine (2CDA) is a purine analogue selectively active against both resting and dividing lymphoid cells. Twenty-one patients with a variety of previously treated lymphoid malignancies received a total of 41 courses of 2CDA (0.1-0.15 mg/kg/day over 7 days continuous intravenous infusion) on compassionate grounds. The profile of the patient population was as follows: low grade non-Hodgkin''s lymphoma (NHL) = 8, intermediate grade NHL = 2, transformed (intermediate grade NHL) = 6, Hodgkin''s disease = 1, lymphoplasmacytoid NHL = 3 and lymphoblastic NHL = 1. The overall response rate was 53%, with three patients attaining complete remission (CR) and eight partial remission (PR). Three of 16 patients with primary resistant or resistant recurrent disease entered either CR (1) or PR (2). Ten patients had no response or progressive disease. The latter group was comprised of patients who had extensively pre-treated lymphoplasmacytoid tumours and/or poor performance status (WHO grades 2-4). The median duration of response is 6 months (range 1 to 12 months). Treatment was well tolerated and the chief toxicities were leucopenia and thrombocytopenia which were most pronounced when there was bone marrow involvement. As a result of dose limiting myelotoxicity, a dose escalation to 0.15 mg/kg/day was possible on just three occasions. These data confirm other reports of the activity of 2CDA in low grade NHL and indicate it may have activity in Hodgkin''s disease. There was no demonstrable activity in poor performance status patients or those with extensively pre-treated lymphoplasmacytoid tumours.