A specific stimulator of granulocyte colony-stimulating factor accelerates recovery from cyclophosphamide-induced neutropenia in the mouse

We have identified a small molecular weight compound, SCH 14988, which specifically stimulates in vitro granulocyte-colony stimulating factor (G-CSF) production from activated human peripheral blood mononuclear cells and monocytes but not other cytokines or CSFs with hematoregulatory activity. In vivo administration of SCH 14988 to mice rendered neutropenic by cyclophosphamide treatment resulted in the accelerated recovery of the peripheral neutrophil compartment. This activity correlated with increased in vivo G-CSF levels and stimulation of marrow granulopoiesis, and was comparable to that of exogenously administered recombinant human G-CSF. No alterations to other leukocyte populations in peripheral blood, spleen, or the peritoneal cavity were observed. These findings suggest that SCH 14988 may be clinically useful to enhance neutrophil granulopoiesis, as well as to study the mechanisms involved in G-CSF gene regulation.     

Membrane and synaptic properties of mitral cells in slices of rat olfactory bulb

We are able to recognize very many different faces of individuals we know, apparently using a complex and ill-understood set of identifying features; it seems natural to assume that faces are perceived as spanning the equivalent of a high-dimensional vector space. I explore ways to probe the structure of perceptual face space without making a priori hypotheses about either the space itself or the mechanisms of perception and recognition, and using solely neuronal responses recorded in the monkey, and metrics derived from their mutual similarities. Within this approach, the dimensionality of face space remains an elusive concept, but the metric content and ultrametric content of the face sets used can be quantified and compared with those of other perceptual sets.     

Substituted 3-phenylpiperidines: new centrally acting dopamine autoreceptor antagonists

The (+)-and (-)-enantiomer of compounds 4 and 5 were synthesized and tested for central dopamine (DA) receptor stimulating activity, using biochemical and behavioral tests in rats. Based on the available data the (-)-enantiomers of 4 and 5 are characterized as centrally acting DA autoreceptor antagonists with oral activity. They display a similar pharmacological profile as the prototype DA autoreceptor antagonists (+)-1 and (+)-2 and show a certain preference for the D3 DA receptor antagonist binding site.     

Developmental and symptom specificity of hopelessness, cognitive errors, and attributional bias among clinic-referred youth

The present study examined the unique and interactive relationships between age and indices of psychopathology (i.e., anxiety, aggression, and depression), with three types of maladaptive cognitions: hopelessness, negative cognitive errors, and attributional bias. Some negative cognitions were not unique to depression and were associated with broader psychopathology. Developmental considerations also influenced some negative cognitions or qualified the association between negative cognitions and depression.     

Anismus: fact or fiction?

PURPOSE: Although anismus has been considered to be the principal cause of anorectal outlet obstruction, it is doubtful whether contraction of the puborectalis muscle during straining is paradoxical. The present study was conducted to answer this question. METHODS: During the first part of the study, we retrospectively reviewed 121 patients with constipation and/or obstructed defecation (male:female, 10/111; median age, 51 years). All of these patients underwent electromyography (EMG) of the pelvic floor and the balloon expulsion test (BET) in the left lateral position. Evacuation proctography was performed in all of these patients in the sitting position. Both the posterior anorectal angle and the central anorectal angle were measured. EMG and BET were also performed in ten controls (male:female, 4/6; median age, 47). In 147 patients with fecal incontinence (male:female, 24/123; median age, 58) only EMG activity was recorded. Criteria for anismus during straining were increase or insufficient (<20 percent) decrease of EMG activity, failure to expel an air-filled balloon on BET, and decrease or insufficient (<5 percent) increase of anorectal angle on evacuation proctography. Between June 1994 and March 1995, we conducted a second prospective study in a consecutive series of 49 patients with constipation and/or obstructed defecation and 28 patients with fecal incontinence. Both groups were compared with 19 control subjects. In this study, all three tests were performed. EMG and BET were performed both in the left lateral position and in the sitting position. RESULTS: The retrospective study was undertaken by comparing the constipated patients with the incontinent patients and the controls, and the anismus detected by EMG was found in, respectively, 60, 46, and 60 percent. Failure to expel the air-filled balloon was observed in 80 constipated patients (66 percent) and in 9 control subjects (90 percent). Based on posterior anorectal angle and central anorectal angle measurements, anismus was diagnosed in, respectively, 21 and 35 percent of constipated patients. In the prospective study, none of the tests showed significant differences regarding the prevalence of anismus between the two subgroups of patients and the control subjects. The prevalence of anismus only differed between constipated and incontinent patients when the diagnosis was based on BET in the sitting position (67 vs. 32 percent; P < 0.005). Our study shows that contraction of the puborectalis muscle during straining is not exclusively found in patients with constipation and/or obstructed defecation. The three tests most commonly used for the diagnosis of anismus showed an extremely poor agreement. CONCLUSION: Based on these findings, we doubt the clinical significance of anismus.