Psychometric properties of the Suicidal Behaviors Questionnaire.

In order to assess the reliability and validity of Cole's (1988) four-item version of the Suicidal Behaviors Questionnaire (SBQ), 57 clinical outpatients completed it and the Reasons for Living Inventory (RFL), and 86 undergraduates completed it and the Scale for Suicide Ideation (SSI). Two weeks later, 30 undergraduates completed the SBQ again. Cronbach alphas were moderate (clinical sample = .75; nonclinical sample = .80). Test--retest correlations were also significant (r = .95). The SBQ and SSI were significantly correlated (r = .69). The SBQ and RFL were also significantly correlated (r = -.34), although modestly. In view of its moderate to strong reliability, its construct and fact validity, its ease of administration and scoring, and its brevity, the SBQ is recommended as a brief screening instrument for suicidality for researchers and clinicians.

Childhood sexual abuse and current suicidality in college women and men.

In previous research, adults who reported childhood sexual abuse have been more suicidal than nonabused adults, but no research has examined their cognitive deterrents to suicide. Strict definitions of sexual abuse in these studies have excluded (a) unwanted sexual experiences with peers, and (b) exploitive experiences not involving genital contact (i.e., unwanted sexual invitations or suggestions, unwanted exposure to others' genitals via exhibitionism, unwanted kissing or hugging in a sexual way). The present study compared suicidal behavior and cognitive deterrents to suicide in 266 college students using both a strict and a liberal definition of sexual abuse. Both women and men abused by adults or peers were more suicidal as adult college students than were women and men with no such history. Women reported similar degrees of suicidality as men, but greater survival and coping beliefs and more fear of suicide. Those whose sexual abuse involved touching were more suicidal, and felt less able to cope, and less responsibility for their families, than nonabused adults. Implications are that adults who experienced childhood sexual abuse that involved touching are more suicidal and have less cognitive deterrents to suicide than adults who have not, regardless of whether they are men or women or whether they were abused by adults or by peers.

The pharmacokinetics and absolute bioavailability of selegiline in the dog.

Selegiline is beneficial to Parkinsonian patients as an adjunct to levodopa therapy. Currently no pharmacokinetic data are available for selegiline in the literature, mainly due to lack of analytical methods that can measure concentrations below 10 ng mL-1 in plasma. A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase-B (MAO-B) in vitro has been developed to measure selegiline in plasma as low as 0.25 ng mL-1. The pharmacokinetics of selegiline were investigated following intravenous and oral administration to four female mongrel dogs. Each dog received 1 mg kg-1 selegiline in solution via gavage or by an intravenous route separated by one week. The mean terminal half-life, volume of distribution of the central compartment, and systemic clearance of selegiline were 60.24 +/- 9.56 min, 6.56 +/- 0.56 L kg-1, and 159.91 +/- 19.28 mL min-1 kg-1, respectively. After oral administration selegiline appeared to be absorbed rapidly with a tmax and Cmax of 25 +/- 5.8 min and 5.2 +/- 1.36 ng mL-1, respectively. The absolute bioavailability of selegiline in the dog was 8.51 +/- 3.31%.

Complement-mediated adipocyte lysis by nephritic factor sera.

Recent data indicate a previously unsuspected link between the complement system and adipocyte biology. Murine adipocytes produce key components of the alternative pathway of complement and are able to activate this pathway. This suggested to us an explanation for adipose tissue loss in partial lipodystrophy, a rare human condition usually associated with the immunoglobulin G(IgG) autoantibody nephritic factor (NeF) which leads to enhanced alternative pathway activation in vivo. We hypothesized that in the presence of NeF, there is dysregulated complement activation at the membrane of the adipocyte, leading to adipocyte lysis. Here we show that adipocytes explanted from rat epididymal fat pads are lysed by NeF-containing sera but not by control sera. A similar pattern is seen with IgG fractions of these sera. Adipocyte lysis in the presence of NeF is associated with the generation of fluid-phase terminal complement complexes, the level of which correlates closely with the level of lactate dehydrogenase, a marker of cell lysis. Lysis is abolished by ethylenediaminetetraacetic acid, which chelates divalent cations and prevents complement activation, and reduced by an antibody to factor D, a key component of the alternative pathway. These data provide an explanation for the previously obscure link between NeF and fat cell damage.

Effects of ancrod and rtPA on fibrin accumulation, glomerular inflammation and renal function in nephrotoxic nephritis.

We have compared the effects of ancrod and recombinant tissue plasminogen activator (rtPA) on nephrotoxic nephritis induced in pre-immunized rabbits by the administration of nephrotoxic globulin (NTG; sheep anti-rabbit glomerular basement membrane). We used three different doses of NTG: in each experiment three groups of six rabbits were preimmunized with normal sheep globulin and given NTG: group A received no further treatment; group B received rtPA, 2 mg/kg 12 hourly; group C received ancrod 2 U/kg 12 hourly. Animals were bled daily for estimation of plasma fibrinogen and serum creatinine, then killed on day 5 and kidneys removed for histology. 1 ml/kg of NTG caused massive glomerular necrosis, all three groups having severe renal failure. With 0.5 ml/kg of NTG, ancrod and rtPA both effectively prevented fibrin deposition in Bowman's space, but all animals had severe proliferative glomerulonephritis and marked renal failure. With 0.25 ml/kg of NTG, control animals developed severe proliferative nephritis and advanced renal failure, ancrod provided almost complete protection, and the rtPA group had renal injury and functional impairment intermediate between the other two groups. We conclude that renal failure in severe nephrotoxic nephritis is fibrin-independent, but in less fulminant nephritis renal function can be protected by defibrination with ancrod. rtPA is capable of reducing glomerular fibrin accumulation as effectively as ancrod, but provides inferior protection of renal function.

Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies.

To determine whether plasma exchange was of additional benefit in patients treated with oral immunosuppressive drugs for focal necrotizing glomerulonephritis (without anti-GBM antibodies), we performed a randomized controlled trial with stratification for renal function on entry. Forty-eight cases were analyzed, 25 in the treatment group (plasma exchange, prednisolone, cyclophosphamide and azathioprine) and 23 in the control group (drug therapy only). There was no difference in outcome in patients presenting with serum creatinine less than 500 mumol/liter (N = 17), or greater than 500 mumol/liter but not on dialysis (N = 12), all but one of whom had improved by four weeks. However, patients who were initially dialysis-dependent (N = 19) were more likely to have recovered renal function (P = 0.041) if treated with plasma exchange as well as drugs (10 of 11) rather than with drugs alone (3 of 8). Long-term follow-up showed that improvement in renal function was generally maintained. The results of this trial confirm that focal necrotizing glomerulonephritis related to systemic vasculitis responds well to immunosuppressive drugs when treatment is started early, and suggest that plasma exchange is of additional benefit in dialysis-dependent cases.

Factors distinguishing samples of lesbian and heterosexual women.

This study utilized non-clinical samples of women and examined historical, familial, sexual, and attitudinal variables to assess differences between groups endorsing heterosexual or homosexual orientations. Drawing from social learning theory, researchers expected the lesbian group to report more negative childhood sexual experiences with males, more positive childhood sexual experiences with females, more accepting parental attitudes toward sexuality and sexual experimentation, and more distant relationships with parents. Results indicate that, rather than childhood sexual experiences distinguishing groups, respondents' current attitudes are significant between-group discriminators. These findings are consistent with the recent body of literature that suggests that sexual orientation cannot be explained in terms of early sexual trauma or negative heterosexual experiences.

Binding and internalization of biotinylated interleukin-2 in human lymphocytes.

The binding, internalization, and fate of interleukin-2 (IL-2) were studied in phytohemagglutinin (PHA)-activated human lymphocytes using biotinylated recombinant IL-2 (rIL-2). Streptavidin adsorbed to 18-nm colloidal gold beads (Au18-streptavidin) and streptavidin covalently bound to horseradish peroxidase (HRP-streptavidin) were used to follow the movement of biotinylated rIL-2 within cells over a 4-hour period. Results obtained from either probe were similar. Biotinylated rIL-2 was taken up in coated pits, transferred to a series of small uncoated vesicles and tubules in the peripheral cytoplasm of the cell, then concentrated and sequestered in uncoated vesicles, multivesicular bodies (MVB), and dense bodies (DB) in the peripheral and juxtanuclear cytoplasm of the cell. Occasionally, MVB containing Au18-streptavidin, or HRP-streptavidin, appear to have fused with the plasma membrane of the cell. No labeling of the Golgi cisternae, nuclear envelope, or nucleus was observed. Results from a competitive receptor binding assay and a cell proliferation assay indicate that both the affinity of rIL-2 for high affinity rIL-2 receptors and the proliferative activity of rIL-2 were negligibly affected by the biotinylation procedure. These studies suggest that in activated lymphocytes, IL-2 is bound to receptors on the cell surface, gathered in coated pits, internalized by receptor-mediated endocytosis, concentrated in the endosomal compartments, and delivered to lysosomes for degradation.

Autoimmunity and the pathogenesis of glomerulonephritis.

Self-tolerance is maintained by: thymic influences on developing T cells; peripheral mechanisms that can tolerise post-thymic T cells; and to a variable extent the tolerisation of potentially autoreactive B cells. The presence of autoreactive T cells in normal individuals suggests that mechanisms to control the activity of such cells may be important. Failure of any of these processes may lead to autoimmunity. The relationship between glomerulonephritis and the mechanisms leading to breakdown of self-tolerance remains elusive. An important observation is that autoimmune diseases are strongly associated with particular products of the major histocompatibility complex (MHC). This association may reflect the intimate involvement of the MHC in thymic T cell education. Another explanation is that T cells only recognise antigens presented in the context of MHC molecules. Although there has been progress in identifying the targets recognised by autoantibodies in vasculitis and anti-GBM disease, nothing is known about the T cells involved. Despite our ignorance, therapy aimed specifically at the T cell can be effective. This approach is being supplemented by attempts to engage immunoregulatory mechanisms, such as idiotype-antiidiotype interactions. The hope is that such treatments, or combinations thereof, will allow a more focused suppression of the autoimmune response, in contrast to the non-specific (and therefore potentially dangerous) methods of immunosuppression available at present.

Monoclonal rheumatoid factor-IgG immune complexes. Poor fixation of opsonic C4 and C3 despite efficient complement activation.

Monoclonal IgM rheumatoid factor forms complexes with IgG in essential mixed cryoglobulinemia. We demonstrate that such complexes fix C3 and C4 poorly, although efficient fluid-phase C3 conversion can occur. Fixation of small amounts of C4 may be sufficient to generate a C3 convertase, but may prevent subsequent fixation of C3 by competing for binding sites on the complex. These complexes bind inefficiently to normal erythrocyte complement receptor type 1 (CR1) in vitro, and are undetectable on erythrocytes of patients with essential mixed cryoglobulinemia in vivo. Clearance of such phlogistic complexes from tissues by CR1-bearing cells may be inefficient.

A lysine-binding protein in SLE sera inhibits the binding of immune complexes to normal erythrocyte CR1 (complement receptor type 1).

The binding of 125I-labelled immune complexes (IC) to normal human erythrocyte CR1 (complement receptor type 1) by sera from patients with SLE was found to be significantly decreased compared to normal sera. In 13/29 patients, there was an inhibitor which decreased the binding of opsonized IC in normal sera to normal erythrocytes. It was found in each of the nine patients who had clinically active disease. The inhibitor was shown to be a globulin that was labile at 56 degrees C and bound to lysine; low concentrations of tranexamic acid and of lysine abolished the effects of the inhibitor which suggests that it possesses lysine-binding sites: these may block the CR1-binding site on IC opsonized with complement. This inhibitor may decrease the efficiency of IC carriage by erythrocyte CR1.