Biomedical subjects
J Clancy
Publications and source records attributed to J Clancy.
Tritiated imipramine binding to platelets is decreased in patients with agoraphobia.
Controversy exists regarding the relationship between anxiety states and major depression. We studied the binding of tritiated imipramine to platelet membranes in order to determine if patients with agoraphobia and panic attacks differed from depressed subjects or healthy volunteers on this biological parameter. Mean (+/- SD) Bmax and Kd values were significantly lower in patients with agoraphobia and panic attacks (787 +/- 276 fmole/mg protein and 0.35 +/- 0.14 nM, respectively) than in healthy volunteers (1237 +/- 201 fmole/mg protein and 0.71 +/- 0.37 nM, respectively). In addition, patients with agoraphobia and panic attacks had binding parameters that were similar to those of patients with bipolar or familial pure depressive disorder, but significantly lower than those of patients with depressive spectrum or sporadic depressive disorder. These findings have implications for both the nosology and pathophysiology of anxiety disorders.
Abnormal escape from dexamethasone suppression in agoraphobia with panic attacks.
Patients who met DSM-III criteria for agoraphobia with panic attacks underwent dexamethasone suppression tests (DSTs) before, during, and after treatment with alprazolam or placebo. Similarly, outpatients with major depression were given multiple DSTs as they participated in a study of desmethylimipramine efficacy. The likelihood of an abnormal escape from dexamethasone was similar in the two diagnostic groups; nonsuppression was somewhat more likely among patients with primary depression, but comparisons with agoraphobic groups remained statistically insignificant. These results apparently did not reflect misclassification of primary depression patients as agoraphobics since a history of major depression was not related to the likelihood of nonsuppression within that group. Moreover, change in DST results during treatment reflected clinical change among agoraphobics. After a review of relevant followup and family studies, we conclude that panic disorder and primary depression are separate illnesses and that hypothalamic-pituitary-adrenal axis hyperactivity is an epiphenomenon of both.
Sublethal fractionated total-body irradiation and donor bone marrow infusion for induction of allograft tolerance.
Tolerance to skin allografts across the strong histocompatibility barrier H-2b to H-2d was achieved with sublethal fractionated total-body irradiation, FTBI, delivered to H-2d mice in 3 doses of 250 rads within 24 hr, followed by transfusion of 3 X 10(7) H-2b donor bone marrow (BM) cells. H-2b skin allografts were applied within 48 hr after the initial radiation. 70% of the mice became long-term (greater than 180-day) survivors with fur-bearing grafts. Marked interexperiment variability in survival rates suggested that infection was the major cause of death in this model and lower weight gain and survival rates for allogenic BM vs. media-treated controls suggested that graft-versus-host disease (GVHD) was also a factor. The observation, however, that long-term survivors (70% of all mice) gained weight and appeared healthy suggested that the GVHD might be self-limiting. Chimeric analysis revealed that approximately 25% of spleen cells were of donor origin, both at short-term (6 weeks) and long-term (greater than 1 year) intervals after tolerance induction. In spite of hematopoietic chimerism, a low incidence of spontaneous tumors, less than 1%, occurred in the long-term survivors.
A withdrawal syndrome after abrupt discontinuation of alprazolam.
A patient who received therapeutic doses of alprazolam for 8 weeks experienced a withdrawal syndrome beginning 18 hours after its abrupt discontinuation. Short-acting and minimally sedating benzodiazepines may have increased potential for withdrawal reactions.
Diazepam and propranolol in panic disorder and agoraphobia.
The response to diazepam and propranolol hydrochloride was compared in 21 patients who (with one exception) met DSM-III criteria for panic disorder and agoraphobia. Each drug was administered for two weeks in double-blind fashion according to a crossover design. The response to diazepam was significantly superior on all measures. By observer rating, 18 patients showed at least moderate improvement with diazepam compared with seven receiving propranolol. Panic attacks and phobic symptoms responded to diazepam, but not to propranolol. The results suggest that benzodiazepines constitute effective short-term treatment for these newly defined disorders.
Cellular basis of graft-versus-host reactions.
The biologic basis of Graft-Versus-Host Disease (GVHD) is presented as an extremely complex immunopathologic syndrome that involves interaction between many different donor and host cell types. A model of acute lethal GVHD was employed where adult unirradiated (DA X LEW)F1 rats were injected with LEW spleen and lymph node cells. Controls received the same dose of syngeneic cells. At intervals from 2 to 21 days after cell injection, GVHD and control animals were killed and nonadherent cell suspensions prepared from their lymph nodes, spleen and peripheral blood. Cell suspensions were treated with LEW-anti-DA-alloantiserum or normal LEW serum and then analyzed for sIgM+ (B cells), W 3/13+ (T cells), and IgG-Fc receptors (FcR). Evidence is discussed for the selective removal of host cells with the alloantiserum. In addition, the level of naturally cytolytic (NK/NC) cells was assessed by adding GVHD and control nonadherent lymphoid cells to heterologous lymphoma and sarcoma target cells. Evidence is presented that during acute GVHD, in this parental----F1 combination, there is an early increase within most compartments of donor as well as host W 3/13+ and W 3/13+FcR+ cells. NK/NC cells are increased as well at day 7. During middle stages of acute GVHD, host sIgM+ cells predominate. Late-stage acute GVHD rats contain few donor and host W 3/13+, W 3/13+FcR+, and NK/NC cells but many null cells most of which are FcR-. The importance of unraveling the nature of donor- and host-cell interactions occurring during acute GVHD, which result in rats whose lymphoid tissues are severely depleted of all nonadherent lymphoid cells but FcR- null cells, is discussed.
Acute lethal graft-versus-host disease stimulates cellular proliferation in Peyer's Patches and follicle associated ileal epithelium of adult rats.
In this study cell proliferation in Peyer's Patches (PP) and the crypts of Lieberkuhn of the follicle-associated ileal epithelium was analyzed during the development of acute lethal graft-versus-host disease (GVHD) in adult rats. In addition, the effect of thymectomy on GVHD-induced lymphoproliferation was determined by analyzing the 3H-thymidine labeling index in neonatally thymectomized-control and thymectomized-GVHD rats. A significant increase in the 3H-thymidine-labeling index was found in interfollicular (days 2-7), dome (days 5-10), and follicular (days 5-12) regions of PP as well as in associated ileal crypts (days 5-12) of GVHD rats as compared with controls. Thymectomy altered the proliferative response in PP of GVHD rats in that incorporation of 3H-thymidine by follicular and interfollicular cells was significantly lower than in sham-thymectomized GVHD controls during the later stages of the disease. The results suggest a possible role for host thymus-dependent cells in stimulation of or participation in cell proliferation within follicular and interfollicular areas of PP.
Autoradiographic analysis of cell proliferation and protein synthesis in the pulmonary trunk of rats during the early development of hypoxia-induced pulmonary hypertension.
The results of this study indicate that both cell proliferation and increased synthesis of extracellular matrix protein contribute to hypertrophy of the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension. As determined by autoradiography after 3H-thymidine injection, pulmonary hypertension results in increased labelling in all cell compartments of the pulmonary trunk wall, the most dramatic response occurring in the adventitia following 3 days' hypoxic exposure. Autoradiography also demonstrated differences in the degree of incorporation of 3H-proline into extracellular protein between hypoxic (3 and 21 days) and control rats. The major focus of 3H-proline incorporation shifted from the adventitia at 3 days to the tunica media at 21 days, although incorporation was significantly higher at 3 compared to 21 days in all wall compartments. The patterns of hyperplasia and matrix protein synthesis in the extrapulmonary arteries of the rat, as reported here, are distinctly different from those seen in many large elastic arteries during development of systemic hypertension. For example, the hyperplastic response of arterial vessels follows a similar temporal sequence in pulmonary and systemic hypertension. However, the adventitia is the region of the pulmonary trunk with highest cell proliferation in pulmonary hypertension while the media is most affected by systemic hypertension. The relevance of the changing patterns of cell proliferation and protein synthesis in the wall of the pulmonary trunk of chronically hypoxic rats to the structural and biochemical properties of this vessel during the early development of pulmonary hypertension is discussed.
Spontaneous blastogenesis and protein synthesis as monitors of renal allograft rejection.
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Level and temporal pattern of naturally cytolytic cells during acute Graft-versus-Host Disease (GVHD) in the rat.
The purpose of the present study was to determine the level of nonadherent lymphoid cells from Graft-verus-Host Disease (GVHD) rats able to naturally kill (NK/NC cells) various solid tumor or lymphoma cells in vitro. Acute lethal GVHD was produced in either newborn or adult (DA x LEW)F1 rats by iv injection of LEW spleen and lymph node (LN) cells. Controls received the same dose of syngeneic cells. At 7, 14, and 21 days after cell injection, the ability of non-adherent mononuclear cells from the LN, spleen, peripheral blood lymphocytes (PBL), marrow, and thymus to kill 51Cr-labeled dog (DT-5) lymphoma, and undifferentiated sarcoma (11031) or human (HUS-2) sarcoma cells in vitro was determined. Only spleen and marrow of controls caused significant 51Cr release from the target cell lines. However, LN, spleen, marrow, PBL, and thymus from neonates and adults with GVHD of 7 days duration caused greater release from all targets than controls (P less than 0.05-0.001). By Day 14 the level of 51Cr released was significantly less than controls except for the values from LNs and thymus which remained elevated. By Day 21 all lymphoid compartments exhibited a decrease in NK/NC cells. Thus, early during acute GVHD, there is an activation and/or expansion of NK/NC cells while later-stage GVHD rats have depressed NK/NC levels.
Psychiatric diagnosis and risk for tardive dyskinesia.
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Panic disorder and primary unipolar depression. A comparison of background and outcome.
Outcome at discharge and during a follow-up averaging 5 years clearly distinguished 116 panic disorder inpatients from 123 age- and sex-matched inpatient controls with primary unipolar depression - 60.2% of the primary depression patients recovered at some time during follow-up compared to only 15.5% of the panic disorder patients. Differences in recovery rates grew larger with increasing follow-up length and were undiminished by the exclusion of patients who received antidepressants or convulsive therapy. Furthermore, these two groups had no predictors of outcome in common. These findings accord with other family and follow-up studies in support of a clear separation between panic disorder and primary depression.
Functional visual loss: I. A true psychiatric disorder?
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Functional visual loss: II. Psychiatric aspects in 42 patients followed for 4 years.
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Excess mortality in panic disorder. A comparison with primary unipolar depression.
We located 113 former inpatients with panic disorder 35 years after index admission. According to age- and sex-specific Iowa population figures, patients with panic disorder had significant excess mortality due to death by unnatural causes. Other studies suggest that secondary depression and alcoholism may have had a role in these deaths. Men with panic disorder also exhibited excess mortality due to circulatory system disease. In an age- and sex-matched patient group with primary unipolar depression, both men and women showed excess mortality. Suicide accounted for 20.0% and 16.2% of deaths in the panic disorder and primary depression groups, respectively. We conclude that panic disorder accounted for much of the excess mortality formerly noted in the "neuroses."
Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.
The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate.
A rapid technique for detecting IgGFc and complement receptors on T and B cells in the neonatally thymectomized and normal adult rat.
Numerous studies have demonstrated the presence of IgGFc and C3 receptors on mammalian lymphoid cells. However, the further characterization of these cells as T, B, or null has been cumbersome and time consuming. A simple method is described for surface fluorescent labeling of (DA X L)F1 rat cell suspensions indirectly with either anti-rat IgM (sIg+) or monoclonal anti-rat thymocyte (sT+) antibody and then rosetting with EA or EAC. Staphylococcus protein A had no significant effect on the level of sIg+ or sT+ attained. From 58-78% of IgGFc+ cells were SIg+ with 14-18% sT+ in the spleen, lymph nodes, and peripheral blood. Almost 100% of C3+ cells were sIg+. Neonatally thymectomized adults exhibited a 254-413% decrease in sT+ cells but a 154-329% increase in sIg+ and a 177-330% increase in null cells. They also exhibited a 140-400% increase in IgGFc+ and C3+ cells in all lymphoid compartments. Fifty-two to 65% of IgGFc+ cells and again almost 100% of C3+ were sIG+. The methods and results are discussed as a basis for studies of B and T lymphocyte maturation and function within various rat lymphoid compartments.