Convulsions due to increased permeability of the blood-brain barrier in experimental cerebral malaria can be prevented by splenectomy or anti-T cell treatment

Experimental cerebral malaria (ECM) can be induced in C57B1 mice by infection with Plasmodium berghei K173 parasites. Behavioral changes shortly before they die of ECM may reflect disturbance of the integrity of the blood-brain barrier (BBB). Folic acid elicits strong convulsive activity if the permeability of the BBB is increased. Administration of folic acid to mice during development of ECM induced convulsions. Interventions known to prevent fatal outcome from ECM, such as splenectomy or treatment with anti-CD4 or anti-CD8 monoclonal antibodies, also prevented sensitivity to folic acid-induced convulsions. In addition, infected mice with ECM and sensitive to folic acid-induced convulsions, recovered from this sensitivity after treatment with anti-T cell antibodies within 4 h. These data suggest that disturbance of the permeability of the BBB can be reversed and depends on the involvement of T cells.     

Dynamic contrast perception assessed by pattern masking

The perceived contrast of a pulsed grating varies markedly with the exposure duration and spatial frequency of the grating. We studied dynamic changes in perceived grating contrast with a pattern-masking paradigm. We measured masking of a brief, localized test pattern (a D6 stimulus, 30 ms in duration) by fixed-contrast cosine grating patterns of varying duration (50-500 ms). The cosine mask pattern had spatial frequency of either 1 or 6 cycles per degree (cpd) at a contrast of 0.3. The D6 test pattern was centered on a light bar of the mask and was either positive peak contrast (same-polarity test and mask) or negative peak contrast (opposite-polarity test and mask). In Experiment 1, the test and mask had simultaneous onset. With a 6-cpd mask, the same-polarity test-threshold elevation versus mask-duration function increases monotonically. For a 1-cpd mask, the same-polarity threshold-mask-duration function is nonmonotonic, with peak masking effect produced by a grating pulse of 80-100 ms. These masking effects are closely congruent with known dynamic contrast effects. With negative tests, masking-duration functions are elevated from same-polarity functions and are essentially similar in shape for 1- and 6-cpd masks. The elevated thresholds suggest inhibitory interaction between ON and OFF pathways, with a similar time course across spatial frequency. In Experiment 2, the D6 test was delayed from mask onset by 33 ms. Positive contrasts only were employed. For 1-cpd stimuli, the delay of test greatly reduced masking at all mask durations and eliminated the nonmonotonic function. This suggests that for low-spatial-frequency patterns, perceived contrast is determined by an early peak component of the neural response. But for 6-cpd stimuli, masking of the delayed test was somewhat greater at all mask durations, consistent with a gradually increasing underlying neural response to the grating. Finally, in Experiment 3, same-polarity masking effects at both spatial frequencies were replicated with negative-contrast test and mask (OFF pathway mediation). This indicates that the ON and OFF pathways have similar response dynamics.     

Increased incidence of congenital malformations in children with transient thyroid-stimulating hormone elevation on neonatal screening

Huntington's disease is an autosomal-dominant inherited progressive neurodegenerative disease associated with an expanded trinucleotide repeat (CAG) sequence on the short arm of chromosome 4. The disease is considered rare in Africans. We report five black South African families of different ethnic origin with proven expansions typical of Huntington's disease and discuss the possible origins of the disease in Africa.     

Response of retinal ganglion cell axons to striped linear gradients of repellent guidance molecules

The application of molecular biology in the study of the pathogenesis of herpes simplex virus type 1 (HSV-1) has led to significant advances in our understanding of mechanisms that regulate virus behavior in sensory neurons and epithelial tissue. Such study has provided insight into the relationship of host and viral factors that regulate latency, reactivation, and recurrent disease. This review attempts to distill decades of information involving human, animal, and cell culture studies of HSV-1 with the goal of correlating molecular events with the clinical and laboratory behavior of the virus during latency, reactivation, and recurrent disease. The purpose of such an attempt is to acquaint the clinician/scientist with the current thinking in the field, and to provide key references upon which current opinions rest.     

The effect of adrenergic agonists on the systemic response to hemorrhage

An in vivo antitumor screening of extracts of Gomphrena martiana indicated positive activity in the petroleum ether extract, and its further bioactivity-directed fractionation resulted in a lipophilic flavonoid fraction. Upon inoculation of various doses of 5,6,7-trisubstituted flavones on two murine tumor lines, Sarcoma 180 and Ehrlich's carcinoma, a decrease of tumor growth was observed. An in vitro KB cultured cell screen indicated cytotoxicity.     

Pollen identification

LEARNING OBJECTIVES: The purpose of this review is to introduce the reader to a systematic approach to categorizing pollen types. This will enable the reader to recognize pollen characteristics of the most common botanical sources and determine the relevant contributors to the local aeroallergen burden. DATA SOURCES: Allergenic plant and pollen atlases for pollen characteristics, allergy texts for procedures and overviews, and relevant reviews from the English medical literature (1985 to present). RESULTS: By applying a visual gestalt utilizing grain number, size, shape, surface structures, and internal detail, one is able to identify pollen source to the appropriate botanical taxonomic level. Identification may be possible only to the family or order, but most frequently to the genus, and occasionally to the species. CONCLUSIONS: Outdoor sampling allows the identification of aeroallergen burden in a locale. In conjunction with field work, the relevant sources can be identified as well as time of pollination. This allows the physician to correlate symptoms with exposure and relevant sensitization.     

Balance retraining in a hemiparetic patient using center of gravity biofeedback: a single-case study

A single-subject experimental design was used to evaluate the effects of center of gravity biofeedback on retraining balance control in a 72-yr.-old male hemiparetic patient. For both assessment and training the subject stood on dual force-plates enclosed on three sides by a visual surround. A 4-wk. training period consisted of subject-initiated shifts in body weight to control movement of a real-time computer display of the subject's center of gravity. A Sensory Organization Test and evaluation of weight distribution indicated that biofeedback retraining positively affected balance control during dynamic conditions and when the ground support moved forward.     

Subclinical surface alterations of human pleura. A scanning electron microscopic study

Pleuritis or pleural effusion frequently develops in patients with pneumonia or heart failure. Most of these pleural changes regress without intrapleural intervention. The detailed mechanisms of the regression of the pleural changes in humans are not well documented. We studied the parietal pleura of nine patients with lung cancer and two patients with coronary artery disease by scanning electron microscopy (SEM). All patients had neither radiographic nor gross evidence of pleural disease but all had mixed surface alterations by SEM. Focal denudation of mesothelial cells was common. Deeper injuries exposed thick and thin interweaving collagen bundles. Patchy depositions of amorphous or crystallized fibrin covered normal and damaged pleural surfaces, frequently admixed with macrophages, red blood cells, and tissue debris. Reactive mesothelial cells appeared to proliferate over the fibrin. Our findings suggest that subclinical pleural alterations occur often in patients with pulmonary or cardiac diseases and that an intact pleural surface in those patients is restored mainly by the proliferation of reactive mesothelial cells.     

Antithrombins Wibble and Wobble (T85M/K): archetypal conformational diseases with in vivo latent-transition, thrombosis, and heparin activation

The inherent variability of conformational diseases is demonstrated by two families with different mutations of the same conserved aminoacid in antithrombin. Threonine 85 underlies the opening of the main beta-sheet of the molecule and its replacement, by the polar lysine, in antithrombin Wobble, resulted in a plasma deficiency of antithrombin with an uncharacteristically severe onset of thrombosis at 10 years of age, whereas the replacement of the same residue by a nonpolar methionine, antithrombin Wibble, gave near-normal levels of plasma antithrombin and more typical adult thromboembolic disease. Isolated antithrombin Wibble had a decreased thermal stability (Tm 56.2, normal 57.6 degreesC) but was fully stabilized by the heparin pentasaccharide (Tm 71.8, normal 71.0 degreesC), indicating that the prime abnormality is a laxity in the transition of the main sheet of the molecule from the 5- to 6-stranded form, as was confirmed by the ready conversion of antithrombin Wibble to the 6-stranded latent form on incubation. That this transition can occur in vivo was shown by the finding of nearly 10% of the proband's plasma antithrombin in the latent form and also, surprisingly, of small but definitive amounts of latent antithrombin in normal plasma. The latent transition will be predictably accelerated not only by gross mutations, as with antithrombin Wobble, to give severe episodic thrombosis, but also by milder mutations, as with antithrombin Wibble, to trigger thrombosis in the presence of other predisposing factors, including the conformational stress imposed by the raised body temperatures of fevers. Both antithrombin variants had an exceptional (25-fold) increase in heparin affinity and this, together with an increased inhibitory activity against factor Xa, provides evidence of the direct linkage of A-sheet opening to the conformational basis of heparin binding and activation.     

Evaluation of nefazodone as a serotonin uptake inhibitor and a serotonin antagonist in vivo

Nefazodone (2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl- 2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one) has been reported to be effective in the treatment of depression. Antagonism of serotonin type 2A (5HT2A) receptors, as well as inhibition of the serotonin (5HT) uptake carrier, has been suggested to contribute to the antidepressant action of nefazodone in vivo (Eison et al., 1990). Nefazodone weakly antagonized the quipazine-induced rise in rat serum corticosterone levels and the quipazine-induced increase in rat hypothalamic 3-methoxy-4-hydroxy-phenylglycol sulfate, suggesting blockade of 5HT2A receptors in vivo. Nefazodone, however, failed to antagonize the p-chloroamphetamine-induced depletion of mouse or rat brain 5HT, displaying a lack of effect on the 5HT uptake carrier. These data extend previous in vitro and in vivo data (Eison, et al. 1990) reporting nefazodone to be an antagonist at 5HT2A receptors, but fail to show inhibition of the 5HT uptake carrier in the same dose range.