Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host

The temporal synthesis of the P21 protein of Borrelia burgdorferi and the development of the humoral response to this antigen was assessed in infected mice. p21 is a member of the ospE-F gene family and its protein, P21, has been shown to be expressed by B. burgdorferi within infected mice but not by spirochetes cultured in vitro. P21 was not detected on B. burgdorferi in unfed or engorged Ixodes dammini (also known as I. scapularis) ticks, further supporting the postulate that P21 synthesis is specific for the mammalian host. In B. burgdorferi-infected mice, ospE mRNA and OspE antibodies were observed at 7 d, whereas p21 mRNA and P21-specific antibodies were detected at 21-28 d, suggesting that p21 is expressed later than ospE. Moreover, ospA mRNA was not discernible until day 14, indicating that ospA, like p21, is not expressed in the early stages of tick-transmitted murine Lyme borreliosis. Because p21 is expressed during infection in mice, we assessed the human humoral response to P21. 28% (34 of 122) of the patients with either early- or late-stage Lyme disease, and 33% (11 of 33) of the individuals with Lyme arthritis had P21 antibodies, suggesting that a P21 response may serve, at least partially, as a marker of infection. Active immunization with recombinant P21 did not protect C3H mice from tick-borne B. burgdorferi infection, and passive transfer of P21 antiserum to infected mice did not alter the course of disease. These data suggest that the antigenic structure of B. burgdorferi changes during the early stages of murine infection.     

Antigen specificity of dual reactive T hybridomas determines the requirement for CD40 ligand-CD40 interactions

CD40 ligand (CD40L) expression on T cells is known to play a crucial role in B cell responses. Some evidence also supports a role for CD40L-CD40 interactions in T cell responses, at least in vivo. Whether the T cell requirement for these interactions is an invariable finding, however, is less clear. Here, we provide evidence that the Ag specificity of T cells influences the requirement for CD40L. T cell hybridomas with dual reactivity for two different Ags, allo-H2-Ap and Mls(a) superantigens, display a differential requirement for CD40L expression. Whereas the response to splenic APC expressing Mls(a) Ags requires CD40L expression, the response to alloantigen-bearing APC does not. The requirement for CD40L expression for the Mls(a) response appears to reflect a strong dependence of this response on ICAM-1 (intercellular adhesion molecule-1) and the ability of CD40-mediated signals to regulate ICAM-1 expression. These findings demonstrate that CD40L-CD40-mediated cross-talk is important for some but not all T cell responses and is influenced by both the type of Ag recognized and the type of APC.     

Does risperidone improve verbal working memory in treatment-resistant schizophrenia?

OBJECTIVE: Treatment efficacy in schizophrenia is typically defined in terms of symptom reduction. However, new antipsychotic medications could potentially have an impact on aspects of disability, such as neurocognitive deficits. The authors evaluated the effects of risperidone on verbal working memory, a memory component of theoretical interest because of its link to prefrontal activity and of practical interest because of its link to psychosocial rehabilitation. METHOD: Verbal working memory of 59 treatment-resistant schizophrenic patients was assessed as part of a randomized, double-blind comparison of treatment with risperidone and haloperidol. Verbal working memory was measured under both distracting and nondistracting conditions at baseline and after 4 weeks of both fixed- and flexible-dose pharmacotherapy. RESULTS: Risperidone treatment had a greater beneficial effect on verbal working memory than haloperidol treatment across testing conditions (with and without distraction) and study phases (fixed and flexible dose). The treatment effect remained significant after the effects of benztropine cotreatment, change in psychotic symptoms, and change in negative symptoms were controlled. Neither benztropine status nor symptom changes were significantly related to memory performance. CONCLUSIONS: Treatment with risperidone appears to exert a more favorable effect on verbal working memory than treatment with a conventional neuroleptic. The beneficial effect appears to be due, at least partially, to a direct effect of the drug, possibly through antagonism of the 5-HT2A receptor. Results from this study suggest that pharmacotherapeutic efficacy in schizophrenia treatment could be broadened to include impact on neurocognitive abilities.     

The offensive subtype of Taijin-kyofu-sho in New York City: the phenomenology and treatment of a social anxiety disorder

The action of two isomers of thioctic acid was tested in-vitro by using the hippocampal slice technique. Various models to induce hyperexcitability of the pyramidal cells were used in order to characterize the drug action. Increases of the applied glucose above the usual concentration of 10 mM lead to a concentration dependent enhancement of the population spike amplitude peaking in a 200% increase at a concentration of 30 mM, whereas lower glucose concentrations result in diminished amplitudes. Both isomers of thioctic acid antagonize the hyperexcitability to a different degree with IC50's of 43 microM and 281 microM for the l- and the d-isomer, respectively. As thioctic acid passes the blood brain barrier very well, these results might suggest a protective action of thioctic acid on the brain during hyperglycemic episodes in diabetic patients. Regarding the mechanism of action, thioctic acid firstly reverses the effect of 6 mM calcium in the superfusion fluid and secondly reverses the effect of apamin, an highly selective neurotoxin of bee venom, acting as the most specific blocker of the small conductance calcium dependent potassium channel. As this channel has been described to occur also in liver, an interaction with it may underly the central and peripheral action of thioctic acid. Together with the already available evidence, these experiments support the hypothesis that thioctic acid can be regarded as a stereoselective neuroprotective agent preventing cells from being damaged by excess of calcium or hyperexcitability induced by blockade of a specific class of potassium channels.     

Evanescent wave fibre optic sensor for detection of L. donovani specific antibodies in sera of kala azar patients

An easy-to-use technique for detection of antibodies specific for the parasite L. donovani in human serum sample has been developed. The method is based on an evanescent wave generated from a tapered configuration of decladded optical fibre and does not require any volumetric measurement. Tapered fibres are immobilized with the purified cell surface protein of L. donovani by covalent bonding. Treated fibres are incubated with the patient serum for 10 min followed by incubation with goat anti human IgG tagged FITC. Fluorescent intensity from the fibre has been shown to be proportional to L. donovani specific antibodies present in the test sera. Direct readings can be obtained after signal enhancement through a photomultiplier tube within 5 min. The system, when tested on 12 positive sera, did not show any false negative result. Also, no false positive result was obtained with serum samples of patients infected with leprosy, tuberculosis, typhoid and malaria, showing the specificity of the sensor and efficacy of the technique.