Analysis of contractile properties of muscles from rats immunized with purified acetylcholine receptor

Experimental autoimmune myasthenia gravis (EAMG) was induced in rats by injection of purified acetylcholine receptor (AChR). In addition to detecting elevated serum titers of anti-AChR antibodies, we observed decreased twitch-tension at submaximal stimulation voltages and increased curare sensitivity by muscles obtained from immunized rats when compared to muscles obtained from nonimmune control rats. Furthermore, antibody-induced neuromuscular impairment was expressed to differing extents dependent on whether the diaphragm, soleus, or extensor digitorum longus muscle was examined. Thus, we conclude that potential antibody perturbation of AChR function will depend not only on the nature of the antibody, but also on the complex structure-function relationships that exist in individual muscles. This may partially explain the variable impairment of different muscle groups in patients with myasthenia.     

Cognition and life events in major depression: A test of the mediation and interaction hypotheses

This study tested two hypotheses derived from Beck's cognitive model of depression. The mediation hypothesis states that the relations of depression to dysfunctional attitudes and negative life events are mediated by the individual's perceptions of those events. The interaction hypothesis states that the relation of depression to negative events is greater in the context of disfunctional attitudes and/or event perceptions, and, analogously, the relations of depression to dysfunctional attitudes and event perceptions are greater in the context of negative events. We compared 65 unipolar major depression patients with 28 nondepressed schizophrenic patients on measures of dysfunctional attitudes, negative event frequency, and event perceptions. We found that (1) depressed patients reported more dysfunctional attitudes and a greater number of recent negative events, and differed from nondepressed schizophrenic patients on a number of event perceptions; (2) the data supported the mediation hypothesis but not the interaction hypothesis.We would like to thank the staff and patients at the Manhattan Veterans Administration Hospital, Beth Israel Medical Center, and the Foundation for Depression and Manic Depression for their cooperation in facilitating the study, and Deborah Long for secretarial assistance. The first author gratefully acknowledges support from National Institute of Mental Health Research Grant MH-40917 during the period in which this paper was written. The data were collected while the first two authors were at New York University.     

Recombinant ricin toxin A chain cytotoxicity against carcinoembryonic antigen expressing tumour cells mediated by a bispecific monoclonal antibody and its potentiation by ricin toxin B chain

A bispecific monoclonal antibody recognising both carcinoembryonic antigen (CEA) and ricin toxin A chain (RTA) was tested for its ability to target recombinant RTA (r-RTA) to CEA-expressing tumour cells, alone and in combination with ricin B chain (RTB). The antibody, 636 (Robins et al., 1990), induced significant RTA cytotoxicity against MKN45 gastric carcinoma cells which express high levels of CEA, using the r-RTA at a concentration below that known to be intrinsically cytotoxic. The addition of ricin toxin B chain (RTB) also potentiated cytotoxicity of r-RTA, and there was an additive increase in potentiation against CEA-positive cells when both RTB and 636 were included. The bispecific antibody restored potentiation by RTB after blocking of its binding site with excess galactose, and also the cytotoxic activity of whole ricin which had been blocked with galactose. It was concluded that the 636 bispecific antibody was highly effective in targeting the toxic moiety of the molecule to CEA-expressing cells, and allowed exploitation of the additional ability of the B chain to facilitate cellular incorporation. The facilitating function of the B chain was equally effective whether or not its lectin site was active.     

Hope and Spiritual Well-Being: Essentials for Living With AIDS

Without a cure on the horizon there is a need to identify ways to sustain hope and spiritual well-being in patients with AIDS. This article examines the impact of AIDS on the emotional and spiritual health of its victims and summarizes current research findings on spiritual well-being in the ill. It also summarizes the authors' study on hope and existential and spiritual well-being in a group of 65 adult male patients who were either serum positive for the human immunodeficient virus or who had been diagnosed with AIDS Related Complex or AIDS.     

Beta-blockade during whole-body hyperthermia: a toxicity study in the dog.

A radiant heat device (RHD) for whole-body hyperthermia (WBH) has been safely and effectively used with a dog model. The cardiovascular changes which occur in the dog during WBH--including heart rate, blood pressure, cardiac output, stroke volume and ejection fraction--agree qualitatively and quantitatively with changes observed in previous WBH-RHD studies done in pigs and humans. We elected to study the effect of propanolol in dogs during WBH in order to evaluate this drug's potential use in human cancer patients who are ineligible for WBH because of coronary artery disease. This report details cardiovascular changes which occur with beta-blockade during 42 degrees C WBH in the dog. Our results show that the level of beta-blockade needed to control heart rate during WBH produces acute cardiovascular decompensation.     

Gold thioglucose selectively damages dorsal vagal nuclei

To characterize the lesion produced in the medulla oblongata by gold thioglucose (GTG), the present experiment quantified the medullary damage in C57B1 mice that had become obese after treatment with 800 mg/kg of GTG at 30 days of age. At the rostrocaudal level of the area postrema, the neurotoxin destroyed up to 75% of the neurons in the medial cell column of the dorsal motor nucleus of the vagus (DMX), while sparing the lateral pole of the nucleus. GTG also produced significant tissue loss in the central and commissural subnuclei of the nucleus of the solitary tract (NST). In contrast, the GTG lesion did not affect cell number in the hypoglossal nucleus or reduce the volume of the area postrema. Additional observations indicated that at 48-72 h after GTG administration the affected regions of the medulla already show advanced necrosis including cell loss and gliosis; and when the relative contributions of hypothalamic, DMX, and NST damage to the obesity that develops are evaluated statistically with partial correlational analysis, it appears the the obesity primarily correlates with the hypothalamic lesion produced by GTG.