Functional and biophysical analyses of the class XIV Toxoplasma gondii Myosin D

Summary The obligate intracellular parasite Toxoplasma gondii uses gliding motility to migrate across the biological barriers of the host and to invade cells. This unique form of locomotion requires an intact actin cytoskeleton and involves at least one motor protein (TgMyoA) that belongs to the class XIV of the myosin superfamily. TgMyoA is anchored in the inner membrane complex and is essential for the gliding motion, host cell invasion and egress of T. gondii tachyzoites. TgMyoD is the smallest T. gondii myosin and is structurally very closely related to TgMyoA. We show here that TgMyoD exhibits similar transient kinetic properties as the fast single-headed TgMyoA. To determine if TgMyoD also contributes to parasite gliding motility, the TgMyoD gene was disrupted by double homologous recombination. In contrast to TgMyoA, TgMyoD gene is dispensable for tachyzoite propagation and motility. Parasites lacking TgMyoD glide normally and their virulence is not compromised in mice. The fact that TgMyoD is predominantly expressed in bradyzoites explains the absence of a phenotype observed with myodko in tachyzoites and does not exclude a role of this motor in gliding that would be restricted to the cyst forming but nevertheless motile stage of the parasite.Both authors contributed equally to the work.     

Bone marrow transplantation for refractory acute leukemia in 34 patients with identical twins

Thirty-four patients aged 4-67 yr (median 17) with acute lymphocytic leukemia (ALL) (18 patients) or acute nonlymphocytic leukemia (ANL) (16 patients) who failed to enter complete remission (CR) or relapsed on conventional chemotherapy were treated with cyclophosphamide (CY), 60 mg/kg/day for 2 days, 1000 rad total body irradiation, and a marrow transplant from a genotypically identical normal twin. Sixteen of the patients received additional chemotherapy within the week before CY. After the transplant, 23 patients received immunotherapy consisting of killed autologous leukemic cells and/or normal twin peripheral blood lymphocytes, 16 as part of a prospectively randomized study. One moribund patient died before engraftment. Nine patients (6 ALL, 3 ANL) continued to have detectable leukemic cells. Twenty-four patients (70%) achieved CR. One of them died of viral hepatitis at 1 mo and another of viral interstitial pneumonitis at 4 mo in CR. Fourteen patients (7 ALL, 7 ANL) relapsed 2-16 mo (median 4) after transplantation. However, 8 patients (24%) (3 ALL, 5 ANL) remain in CR without any maintenance chemotherapy at 29-103 mo (median 80) after the transplant. The end results were not signficantly influenced by the type of leukemia, the immediated pre-CY chemotherapy, or the immunotherapy. The results show that this approach, even when applied to endstage patients with acute leukemia in relapse, causes tolerable morbidity, rare nonleukemic deaths, and frequent remissions, some of which represent cures.     

Cognitive-behavioral group therapy versus phenelzine in social phobia: long-term outcome

To evaluate the effects of maintenance treatment and durability of gains after treatment discontinuation, responders to either phenelzine (PZ) or cognitive-behavioral group therapy (CBGT) from an acute trial comparing these two treatments as well as pill placebo and a psychotherapy control (educational supportive group therapy) were enrolled into maintenance and treatment-free follow-up phases. EXPERIMENTAL DESIGN: Responders to an acute trial contrasting PZ and CBGT entered a six-month maintenance phase. Patients who continued to respond through the maintenance phase entered a six-month treatment free phase. Patients receiving pill placebo or educational supportive group therapy in the acute trial did not enter the long term study. PRINCIPAL OBSERVATIONS: PZ patients entered maintenance more improved than CBGT patients, and nonrelapsing PZ patients maintained their superior gains throughout the study. Relapse during maintenance did not differ between treatments. However, PZ patients showed a trend toward greater relapse during treatment-free follow-up. There was a greater relapse among patients with generalized social phobia with phenelzine. CONCLUSIONS: PZ and cognitive-behavioral group therapy may differ in their long term effects. The superiority seen with PZ on some measures in the acute study persisted in patients who maintained their gains over the course of maintenance and treatment-free follow-up. However, CBGT may lead to a greater likelihood of maintaining response after treatment has terminated. Replication with larger samples is needed, as is a study of the acute and long-term efficacy of combined PZ and CBGT.     

Childhood trauma and dissociative symptoms in panic disorder

OBJECTIVE: Childhood trauma has been associated with increased risk for both panic disorder and dissociative symptoms in adulthood. The authors hypothesized that among individuals with a primary diagnosis of panic disorder, those experiencing depersonalization/derealization during panic attacks would be more likely to have a history of childhood trauma. METHOD: Rates of traumatic events were compared between panic disorder patients with (N=34) and without (N=40) prominent depersonalization/derealization during panic attacks. Symptom severity in the two groups was also examined. RESULTS: Contrary to the authors' hypothesis, no evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma. Minimal differences in severity of illness were found between patients with dissociative symptoms and those without such symptoms. CONCLUSIONS: This finding is consistent with a multifactorial model of dissociation. Factors other than childhood trauma and general psychopathology may underlie vulnerability to dissociative symptoms in panic disorder.     

Neonatal cholestasis and hypopituitarism

The diagnosis of optic nerve hypoplasia and hypopituitarism must be entertained in infants who present for evaluation of cholestatic jaundice, particularly if there is associated hypoglycaemia and wandering nystagmus. Although the hepatic dysfunction seems to resolve, the long term prognosis of liver disease in optic nerve hypoplasia remains unknown.     

Evaluation of the clinical global impression scale among individuals with social anxiety disorder

BACKGROUND: The clinical Global Impression Scale (CGI) is commonly used as a primary outcome measure in studies evaluating the efficacy of treatments for anxiety disorders. The current study evaluated the psychometric properties and predictors of clinicians' ratings on an adapted version of the CGI among individuals with social anxiety disorders. METHOD: An independent assessor administered the CGI Severity of Illness and Improvement ratings to 123 patients at baseline and the subset of treated patients again mid- and post-treatment. RESULTS: Improvement ratings were strongly related to both concurrent Severity of Illness and changes in Severity of Illness ratings from baseline. Additionally, both CGI ratings were positively correlated with both self-report and clinician-administered measures of social anxiety, depression, impairment and quality of life. Measures of social anxiety symptoms accounted for a large portion of the variance in Severity of Illness ratings, with significant additional variance accounted for by measures of impairment and depression. Changes in social anxiety symptoms from baseline accounted for significant variance in Improvement ratings, but no significant additional variance was accounted for by changes in impairment and depressive symptoms. CONCLUSIONS: Our findings support the utility of the CGI as an index of global severity and symptom-specific improvement among individuals with social anxiety disorder.