The glycosyl phosphatidylinositol-linked Fc gamma RIIIPMN mediates transmembrane signaling events distinct from Fc gamma RII.

To investigate the ability of FcgammaRIII(PMN), the GPI-anchored isoform of FcgammaRIII (CD16) in polymorphonuclear leukocytes (PMN), to mediate transmembrane signaling events, we measured changes in membrane potential with DiOC(5) and in intracellular calcium with indo-1. FcgammaR were ligated by anti-FcgammaRIII mAb 3G8 (IgG and Fab), anti-FcgammaRII mAb IV.3 (IgG and Fab), and human IgG aggregates. Cell bound mAbs were also crosslinked by goat F(ab')(2) anti-mouse IgG. 3G8 IgG elicited a rapid change in [Ca(2+)](i), which was unaffected by EGTA, Vibrio cholerae toxin (CT), or Bordetella pertussis toxin (PT), and was abolished by BAPTA . Univalent receptor binding with 3G8 Fab gave no response but crosslinking with F(aV)2 GAM gave a rapid [Ca2,](i) response. Neither IV.3 Fab, IV.3 IgG, nor crosslinking of IV.3 Fab elicited a calcium signal. PI-PLC-treated PMN with the density of FcgammaRIII(PMN) reduced to that of FcgammaRII showed an unattenuated change in [Ca(2+)](i), with a 3G8 stimulus. The effects of IgG aggregates paralleled those of 3G8 mAb. These data indicate that multivalent ligation of FcgammaRIII(PMN) initiates an increase in [Ca(2+)];, derived from intracellular stores, that is distinct from both the FMLP- and FcgammaRII-induced responses. Ligand-dependent interaction with FcgammaRII is not required. Since FcgammaRIII(PMN) can internalize the FcgammaRIII-specific probe Con A-opsonized E and lyse anti-FcgammaRIII heteroantibody-opsonized chick E, this GPI-anchored molecule mediates both signal transduction and integrated cell responses.

Monoamine oxidase inhibitors in the treatment of atypical depression.

In a 6-week, double-blind study outpatients diagnosed as suffering from atypical depression were treated with either isocarboxazid or placebo. Selection criteria were purposely broad so as to capture the entire range of patients so diagnosed. Patients were then subclassified along several symptomatic, syndromal, phenomenological, and diagnostic categories in order to identify clinical characteristics specifically responsive to isocarboxazid. Although isocarboxazid was clearly superior to placebo for the overall group of atypical depressives, the authors were by and large unable to identify subgroups specifically responsive to the monoamine oxidase inhibitor. A few factors correlated with better response to both isocarboxazid and placebo: no family history of alcoholism or sociopathy, lack of self-pity, and not meeting Research Diagnostic Criteria for major depressive disorder. The single item that was associated with a statistically significant advantage of isocarboxazid over placebo was loss of anticipatory pleasure. Clinical implications and suggestions for further research are discussed.

Screening for borderline personality disorders with the MMPI-168.

Investigated the possible use of the MMPI-168 as a screening instrument for identifying individuals (N = 27) with DSM III diagnosed borderline personality disorder. Using previously reported percentile norms for bright young college graduates as a reference, borderline patients as a group fell above the 98th percentile on the F, Hypochondriasis, Depression, Hysteria, Psychopathic Deviate, Psychasthenia and Schizophrenia scales, as well as the general psychopathology scale (PSY). Additionally, the borderline sample's mean score on the Paranoia scale was above the 95th percentile, and the mean Social Introversion scale was above the 90th percentile. Almost equally distinguishing was the finding that the mean K scale score for the borderline sample fell as low as the 8th percentile for the normative college sample. These results demonstrate that the MMPI-168 response pattern of borderline patients was clearly distinguishable from the great majority of college graduates.

Measuring symptoms of grief and bereavement.

As part of an effort to develop an instrument to measure grief, a 58-item questionnaire was completed by 211 subjects who had lost a loved one because of death. The results demonstrated wide individual variations in specific symptoms and in their intensity and duration. Long after the immediate grief period, most bereaved individuals continued to feel upset, empty, or tearful; many experienced anniversary reactions and/or physical symptoms; and some had persistent identification phenomena. Although the acute dysphoria peaked between 1 and 2 years, several grief-related feelings, symptoms, and behaviors continued indefinitely. The relevance of present work and directions for future studies are discussed.

Amoxapine and amitriptyline: serum levels and clinical response in patients with primary unipolar depression.

Amoxapine, a new antidepressant of the dibenzoxazepine class, was compared with amitriptyline in 80 patients with primary unipolar depressive disorders. In a four-week double-blind trial, the two medications were equally effective and had similar onsets of therapeutic action. The range of side effects was similar, although there was a trend for fewer side effects in the amoxapine group. Serum levels were not related to therapeutic response for either medication.

Treatment validity of different diagnostic concepts of depression.

This study evaluated the comparative treatment validity of four different but overlapping sets of criteria for the diagnosis of depression: the St. Louis, New York, Texas Actuarial, and Composite criteria. Results revealed that none of the criteria offered predictive strength or demonstrated particular advantages over the others. Patients excluded by each of the various criteria tended to do as well as those included; a small percentage of patients included by each of the criteria were nonresponders to drug therapy. Once a clinical and psychometric diagnosis was established, then no additional (short-term) prognostic information was gained by further scrutiny with the various research diagnostic criteria examined.

Life events and response to antidepressants.

The present study examined the relationship of life events and response to tricyclic antidepressants among 80 outpatients with unipolar, primary depressions. Participants were randomly assigned to receive either amitriptyline or amoxapine. Events occurring in either the two or 12 months prior to starting treatment (antecedent events) were unrelated to antidepressant response. However, events occurring during the treatment period itself (concurrent events) were significantly related to tricyclic response. Patients evidencing the poorer response reported almost three times as many concurrent events as the more improved patients. A poorer tricyclic response was associated in particular with concurrent events which were undesirable, health related, and perceived as being outside of the patient's own control. It was suggested that the continuing occurrence of stressor events probably interferes with treatment efforts and, therefore, it may be important for the therapist to pay careful attention to the ongoing life stresses of the depressed patient.

Research criteria for the diagnosis of depression.

Four sets of research criteria for depression are compared: the Feighner, Spitzer, Texas Actuarial, and Composite methods. Of 80 carefully selected depressed patients, 68% satisfied Feighner's criteria, 71% Spitzer's, 75% the Texas Actuarial, and 94% the Composite criteria. Not only did the criteria sets select different proportions of the total, but they also selected substantially different patients, suggesting that results obtained from studies using one set of criteria for diagnosis or selection might not be generalizable to other groups of "depressed" patients. The authors recommend further studies, comparing relative validity as well as reliability, of alternative research diagnostic criteria.

Evaluations of loxapine succinate in the ambulatory treatment of acute schizophrenic episodes.

138 acutely ill schizophrenic patients were treated with oral loxapine succinate for up to 4 weeks in nine studies, all of which shared an identical protocol. These nine, open-label studies were conducted primarily in outpatient settings. For most patients, loxapine, at daily dosages of 30-80 mg, was observed to provide safe, effective, and relatively immediate symptomatic relief and, in most cases, helped to keep acutely ill schizophrenic patients out of the hospital. Side effects, which occurred in 95 patients, were mostly mild and controllable and consisted mainly of extrapyramidal effects.