Epitopes of the Plasmodium falciparum clustered-asparagine-rich protein (CARP) recognized by human T-cells and antibodies

Linear B- and T-cell epitopes have been identified in the Plasmodium falciparum clustered-asparagine-rich-protein (CARP). Twenty-six synthetic peptides, 15-25 amino acids in length, were assayed for their ability to stimulate purified, human T-cells primed to P.falciparum by natural infection to proliferate and/or secrete gamma-interferon (IFN gamma). The plasma of malaria exposed individuals were tested for antibody reactivity with peptides coupled to bovine serum albumin in a semiquantitative ELISA. Two of the peptides (NNFMNRNMKNKNMN/NAKNVNDMYRDGEMS) induced T-cells from many malaria exposed donors to proliferate and/or secrete-IFN gamma. Six peptides bound antibodies from a large number of the plasma samples, the amounts ranging from ten to more than 200 micrograms specific antibody/ml. T-cell activation was most pronounced when the T-cells were from highly immune donors. In contrast, high anti-peptide specific antibody levels were usually detected in the plasma of less immune donors, recently exposed to infection. One short sequence (NAKNVNDMYRDGEMS) was found to contain both T- and B-cell epitopes. Thus, CARP includes both T- and B-cell reactive elements recognized by the human immune system following exposure to the parasite by natural infection.     

The effects of co-dependence on physicians and nurses

To evaluate the effect on physicians and nurses of being closely involved with one or more chemical dependent persons, a sample of 67 physicians and 133 nurses with chemical dependent significant others was surveyed. The majority reported that the quality of their work was adversely affected by this association. Reduced ability to concentrate, absenteeism, errors, poor judgment, and patient neglect were reported. Most reported their professional education had not prepared them to recognize and assist people with chemical dependence and half thought their professional education negatively influenced their ability to help. About half had attempted to treat the chemical dependent person (s) themselves, sometimes giving medication and occasionally diverting drugs for this purpose. Most said their self-esteem and self-confidence were damaged by these relationships. Over one-third reported being diagnosed as depressed and 12% had attempted suicide. There were few differences between physicians and nurses on the effects of being in a co-dependent relationship (s), although nurses and women were more likely to have chemically dependent parents. Implications for professional education are identified.     

Human immune recognition of recombinant proteins representing discrete domains of the Plasmodium falciparum gamete surface protein, Pfs230

The 230 kD gamelocyte/gamete-specific surface protein of Plasmodium falciparum, Pfs230, is a target of antibodies which inhibit the development of the parasite inside the mosquito vector. A transmission blocking vaccine based on Pfs230 may be a powerful tool for malaria control. As a first step, Pfs230 has been expressed in E. coli as a series of recombinant proteins, fused to maltose binding protein. We have used the fusion proteins to assess cellular and humoral immune responses to Pfs230 in malaria-immune adult Gambian blood donors; responses to the fusion proteins have been compared with responses to native Pfs230. The tetrapeptide repeat region of the molecule appears to be immunodominant for both antibody-producing cells and peripheral blood T cells. We postulate that this may represent a mechanism for immune evasion since the N-terminal repeat region of the molecule is cleaved from the mature protein and shed into the plasma. Responses to fusion proteins representing the seven-cysteine motifs were correlated within individual donors, suggesting that cross-reactive epitopes occur within the motifs. Antibody responses to recombinant proteins were poorly correlated with responses to native Pfs230 suggesting that dominant epitopes of the native protein are not adequately represented in the recombinant proteins. Although prokaryotic expression products may be suitable for induction of cellular immune responses to Pfs230, alternative expression systems may be needed for creation of appropriate B cell epitopes.     

The effects of diuretics on nasal transmucosal potential difference

The effects of application of frusemide, amiloride and bumetanide on nasal transmucosal potential difference (NTPD), at rest and during exercise, were studied in 8 normal subjects. In a double-blind placebo controlled study, 8 volunteers had NTPD recorded at 4-min intervals during 12-min periods of rest, before and after treatment, during 12min of exercise, and recovery. Application of placebo, frusemide and bumetanide did not significantly alter NTPD at rest. Amiloride caused a significant reduction (P < 0.025). During exercise there was a significant rise in NTPD with placebo (P < 0.05), frusemide (P < 0.05) and amiloride (P < 0.05). There was no increase in NTPD during exercise with bumetanide.     

Tenascin expression in hyperproliferative skin diseases

The expression of tenascin, a recently discovered extracellular matrix glycoprotein, was studied by immunohistochemistry in normal human skin and in a number of skin diseases with epidermal hyperproliferation such as psoriasis, basal cell carcinoma, Bowen's disease and solar keratosis. Tenascin expression in the upper dermis of normal skin was found to vary from almost absent to patchy along the basal membrane. Staining was continuous and intense around blood vessels, hair follicles and eccrine sweat ducts. In basal cell carcinoma a marked expression of tenascin was found in the tumour stroma, especially adjacent to the basal membrane surrounding the tumour cell nests. In Bowen's disease and solar keratosis, tenascin expression was found in the dermis next to the keratinocytes. In psoriasis the dermal papillae of clinically involved skin were intensely stained and a continuous band of tenascin was present in the upper dermis along the basal membrane. The distribution of tenascin differed from other known extracellular matrix components.     

Screening, Detection and Management of Depression in Elderly Primary Care Attenders. I: The Acceptability and Performance of the 15 Item Geriatric Depression Scale (GDS15) and the Development of Short Versions

One-hundred and ninety-eight elderly subjects attending theirgeneral practitioners (GPs) were asked to complete the 15 itemGeriatric Depression Scale (GDS15). Analysable results wereobtained from 194 (98%). Of these, 67 (34%) scored above theGDS15 cut-off (4/5) for significant depressive symptomatology.87.6% found the questionnaire to be acceptable and only 3.6%found it very difficult or very stressful. The GDS15 had a highlevel of internal consistency (Cronbach's alpha = 0.80). Allthe individual items of the GDS15 associated significantly (P<0.01) with total score and ‘caseness’. A singlequestion "do you feel that your life is empty?" identified 84%of ‘cases’. In an attempt to devise short scalesto screen elderly primary care patients for depression, thedata were subjected to logistic regression analysis. Ten (GDS10),four (GDS4) and one (GDS1) item versions were generated. Agreementbetween these short scales and the GDS15 in the original samplewas 95, 91 and 79% respectively. Cronbach's alpha was 0.72 forthe GDS10 and 0.55 for the GDS4. The short scales were thenvalidated in an independent sample of 120 patients in whom bothGDS data and the results of a detailed psychiatric interview(the Geriatric Mental Status Schedule, GMS) were available.The sensitivity and specificity of the GDS10 against GMS casenesswere 87 and 77% (cut-off 3/4); those of the GDS4 were 89 and65% (cut-off 0/1) and 61 and 81% (cut-off 1/2). Sensitivityand specificity for the GDS1 were 59 and 75%. It is concludedthat these short scales may be useful in helping GPs and practicestaff to identify elderly patients with significant depressivesymptoms.     

Assessing the Efficacy of Azaprophen and Physostigmine as a Pretreatment for Soman-Induced Incapacitation in Guinea Pigs by Response-Surface Modeling

Assessing the Efficacy of Azaprophen and Physostigmine as aPretreatment for Soman-lnduced Incapacitation in Guinea Pigsby Response-Surface Modeling. GENNINGS, C, CARTER, W. H., JR.,HARRIS, L. W., CARCHMAN, R. A., CAMPBELL, E. D., BOYLE, R. M.,TALBOT, B. G., AND SOLANA, R. P. (1990). Fundam. Appl. Toxicol.14, 235–242. Physostigmine (PHY) has the advantage overpyridostigmine of minimizing OP-induced incapacitation becauseit penetrates into the CNS. However, physostigmine is behaviorallytoxic at relatively low concentrations. It is anticipated thatthis could be offset by a cholinolytic to prevent behavioraldeficit due to the carbamate pretreatment alone. The therapeuticefficacy of physostigmine/azaprophen pretreatment therapy wasevaluated in soman-challenged guinea pigs. Response surfacemethodology was employed to describe the relationship of thepretreatment combination with duration of incapacitation. Thesignificance of the combination relative to PHY alone was evaluatedin addition to dose combinations that yield optimal time torecovery. Analysis of the fitted response surface indicatedthat combination pretreatment with these compounds significantlyreduces the time to recovery after soman challenge versus pretreatmentwith PHY alone.