Analysis of antigen specific T cell helper function in first degree relatives of patients with systemic lupus erythematosus (SLE).

Fourteen families with first degree relatives of patients with systemic lupus erythematosus (SLE) were studied for the ability of their members to respond to the synthetic polypeptide antigen (T,G)-A-L. The family members were also tested for their HLA determinants. All SLE patients tested responded to (T,G)-A-L as measured by the production of (T,G)-A-L specific T cell helper factors by their antigen activated T cells, confirming our previous findings that 100% of SLE donors responded to (T,G)-A-L in contrast to 50% responders in a control population of healthy donors. The general defect in the regulation of immune responses in SLE patients was further indicated by the demonstration that an SLE patient who is a daughter of non-responder parents to (T,G)-A-L, responded to this genetically regulated antigen. In contrast to our observations with SLE patients, the genetic regulation of the ability to respond to (T,G)-A-L was shown not to be impaired in healthy first degree family members of SLE patients and the segregation of the immune response potential in these families was as expected from an inherited dominant trait.     

Evolutionary conservation of brain Thy-1 glycoprotein in vertebrates and invertebrates

The evolutionary conservation of brain Thy-1 glycoprotein in 24 vertebrate and invertebrate species has been investigated by means of a soluble phase radioimmunoassay (RIA) and by the "Western blot" technique. The brain glycoproteins from virtually all the vertebrate species inhibited the precipitation of mouse Thy-1.1 by a rabbit anti-rat Thy-1 antiserum. Most reagents also inhibited the binding of a mouse anti-rat Thy-1 monoclonal antibody to rat Thy-1. Whole tissue glycoproteins from earthworm, snail and oyster and ganglia glycoproteins of a locust species were also found to be inhibitory. Western blotting analysis on NaDod SO4 polyacrylamide gel electrophoresis under reducing conditions revealed a Thy-1 homologous molecule (22-25 KD) in mammals, birds, fish, reptiles and invertebrate species. The snail Thy-1-like molecule was eluted from the gel and was shown to specifically inhibit the serological reaction. The rabbit anti-rat Thy-1 antiserum also detected a doublet molecule of approximately 85,000 KD, which is conserved in all species, including yeast and bacteria. The origin and nature of the presumed glycoproteins is unknown. Our results suggest that the Thy-1 molecule has been conserved throughout metazoan evolution and that the Thy-1 gene is the most conserved among the immune related genes (immunoglobulins, beta 2-microglobulin and major histocompatibility) which share extensive amino acid homology.     

A cognitive-interpersonal case study of a self

This article presents an integrated conception of the self based on cognitive and interpersonal theories. Implications for clinical practice are outlined, which include understanding the therapeutic relationship as a laboratory and change as involving self-expansion. Implications for clinical research are also presented and exemplified by two strategies, which are demonstrated in a single case study of a patient who successfully underwent a brief-term treatment. The first involves the use of Interpersonal Scenarios, which are structured idiographic vignettes scaled on several parameters, to measure change between psychotherapy sessions. The second involves the use of the Structural Analysis of Social Behavior, a measure of interpersonal process, and the Experiencing Scale, a measure of emotional involvement, to measure change within a session.     

Regulation of interleukin 1 generation in immune-activated fibroblasts

In the present study we have demonstrated that fibroblasts can generate the inflammatory cytokine interleukin 1 (IL 1) under conditions similar to those abundant in cellular immune responses. Thus, induction of IL 1 requires a sequential two-step protocol which consists of preactivation of mouse embryo fibroblasts (MEF) with crude preparations of T cell or macrophage-derived conditioned media (CM; 72 h), followed by a challenge with lipopolysaccharide (LPS; 24 h). Unstimulated fibroblasts or such cells activated by either CM or LPS produced only low levels of IL 1, while a synergism between both signals was observed for obtaining maximal IL 1-like activity in MEF. Each of a series of individual recombinant lymphokines and cytokines (IL 2, granulocyte/macrophage-colony-stimulating factor, tumor necrosis factor, IL 1 beta and interferons-alpha, beta and gamma) was shown to serve as an efficient priming signal for the induction of IL 1. IL 1-like activity in fibroblasts was detected in cell lysates or associated with the producing-cell membrane but not in culture fluids. Immune-stimulated fibroblasts, activated under such experimental conditions, were shown to actively transcribe mRNA of both IL 1 genes (alpha and beta). For the expression of IL 1-specific mRNA in fibroblasts a single stimulus, provided by either LPS or a lymphokine/cytokine, was sufficient; however, a more intense signal was observed when both stimuli were applied. The IL 1-like biological activity of fibroblast origin was significantly reduced by anti-IL 1 alpha antibodies. Thus, fibroblasts, when activated by immune and bacterial products, generate IL 1 which in turn possibly amplifies cellular immune responses or inflammatory processes in connective tissues.     

Role of ligand exchange processes in the reaction kinetics of the antitumor drug cis-diamminedichloroplatinum(II) with its targets

The kinetics of a model reaction between the antitumor drug cis-diamminedichloroplatinum(II)(cis-DDP) and the signal nucleotide diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) has been investigated by spectrophotometry. The formation of the reactive platinum aquated species was first analyzed by potentiometry using a chloride-specific electrode. Both equilibrium and rate constants were measured. The rate constants for the release of the first and second chloride were found 1.1 +/- 0.5 (S.D.) X 10(-4) and 4.2 +/- 0.2 X 10(-5) sec-1, respectively, at 37 degrees. It was shown that anions such as acetate, phosphate, and pyrophosphate were able, in some conditions, to exchange with chloride to form acetato, phosphato, or pyrophosphato complexes. The reaction of cis-DDP with Ap4A or other targets involves at least four steps, which have been analyzed separately. The values of rate constants deduced from the analysis of the overall reaction are in agreement with those determined independently from the separated steps. The second-order rate constants for the reaction of acetato, phosphato, and pyrophosphato complexes with Ap4A (0.2 +/- 0.02, 0.20 +/- 0.02, and 0.16 +/- 0.03 M-1 sec-1, respectively) are close to that of monoaqua-monochloro (0.16 +/- 0.1 M-1 sec-1) and lower than that of the diaqua species (0.94 +/- 0.06 M-1 sec-1). At a high concentration of Ap4A, the reaction kinetics is slowed down. The formation of a complex of cis-platinum with the Ap4A phosphate groups is suggested. The intracellular concentration of phosphates, pyrophosphates, and carboxylates is large enough to displace chloride from cis-DDP. Inside cells, therefore, ligand exchange processes have to be taken into account to analyze the in vivo reactivity of cis-DDP with its potential targets.     

Effects of amphetamine,methylphenidate, and apomorphine on regional brain serotonin and 5-hydroxyindole acetic acid

Electrophysiological and cytofluorometric data suggest that doses of amphetamine which enhance locomotor activity and promote focused stereotypies produce pronounced effects on serotonin pathways in the CNS. However, the biochemical evidence regarding changes in serotonergic function produced by moderate doses of this drug is inconsistent. Therefore, the present study was designed to further examine the effects of amphetamine (1–5 mg/kg) on regional brain serotonin and its metabolite and to compare these effects to behaviorally comparable doses of methylphenidate and apomorphine. At doses which produce a multiphasic behavioral response pattern, including a stereotypy phase consisting primarily of repetitive head movements and occasional oral stereotypies, amphetamine (3 mg/kg) and methylphenidate (30 mg/kg) increased levels of 5HIAA in striatum and frontal cortex, two brain regions which receive serotonergic projections from the dorsal raphe nucleus. In contrast, these drugs decreased or had no effect on 5HIAA levels in hippocampus, a brain region which receives its serotonergic innervation from the median raphe nucleus. A moderate dose of apomorphine (0.5 mg/kg) produced a comparable pattern of neurochemical effects. These data are consistent with electrophysiological and cytofluorometric data suggesting enhanced dorsal raphe serotonergic function following amphetamine-like stimulants. Pretreatment of animals with -methyltyrosine at a dose sufficient to prevent the locomotor stimulation and stereotypy promoted by amphetamine, or by haloperidol, failed to prevent the amphetamine-induced increase in 5HIAA, indicating that these serotonergic effects are not secondary to the amphetamine facilitation of dopaminergic transmission. The results of this study suggest that serotonin may play a modulatory role in the behavioral effects of amphetamine-like stimulants which is dependent for its expression on an intact dopamine system.Abbreviations DA dopamine - AMPH S(+)amphetamine - 5HT serotonin - MP methylphenidate - APO apomorphine - 5HIAA 5-hydroxyindoleacetic acid - MT -methyltyrosine - DOPAC 3,4-dihydroxyphenylacetic acid - HVA homovanillic acid - HAL haloperidol     

Synovial cysts of unusual localization. 2 cases and review of the literature

Two patients with true synovial cysts in atypical sites (internal compartment of knee and inguinal hollow) were investigated by radioarthrography, ultrasound and computed tomography imaging. The cyst in the hip region originated from a dilated serous bursa of the iliopsoas muscle that did not communicate or was no longer in communication with the joint. In contrast, the cyst of the knee appeared to be a lateral synovial capsule hernia. Positive diagnosis in both cases was dependent on combined ultrasound-CT scan imaging, this eliminating a tumor (sarcoma) of soft tissues. However, affirmation of the synovial origin (mesothelial covering of the wall) of the lesion was obtained by histology only, this allowing differentiation from a "capsular" (fibrous wall) cyst, which probably provokes similar ultrasound and CT scan images.     

Playing doctor, seriously: graduation follies at an American medical school

In American medical schools, the period of time between the announcement of internships and graduation is known as FYBIGMI, for "Fuck You Brother I Got My Internship." At University Medical School (pseudonym), as at most American medical schools, this period culminates in an elaborate musical comedy (attended by faculty and relatives) in which faculty are abused, patients are represented in terms of stigmatized stereotypes, and the students demonstrate a profane familiarity with cultural taboos. Using the analytic methods of cultural anthropology, this examination of the FYBIGMI performance at U.M.S. focuses primarily on the seniors' presentation of their newly acquired professional identity, which is constituted in the skits by recurring oppositions to socially stigmatized, medically self-destructive patients. In this oppositional logic, racial stereotypes play a particularly large role. In addition, the seniors establish their new social status by inverting their relationship to their (former) supervisors on a personal basis, and by confronting the audience with their professional ability to treat cultural taboos with profane familiarity. The FYBIGMI theatrical, and its representation of professional identity, is analyzed in relation to a proposed model of the underlying structure of the process of medical education, that is, an escalating dialectic of intimidation and self-congratulation.