Substantia nigra stimulation evoked antidromic responses in rat neostriatum

Summary Electrical stimulation of the substantia nigra of rats elicits a burst of small amplitude waves with a latency of 4–6 ms that may last for 10–15 ms throughout much of the neostriatum. Frontal cortex stimulation also elicits a burst response, which can occlude the substantia nigra response. The substantia nigra evoked burst response was still present after chronic neocortical ablation or thalamic transection or both treatments combined. The response corresponds to the first sharp negative wave of the substantia nigra evoked neostriatal field potential. Single substantia nigra evoked action potentials were recorded in neostriatum with a mean latency of 9.8 ms, ranging from 4–22 ms. These action potentials were considered to be antidromic because 1) they were occluded during appropriate collision intervals by orthodromic action potentials elicited by frontal cortex stimulation. Subthreshold frontal cortex conditioning stimulation did not alter the threshold for activation from substantia nigra. The refractory period for the axon was at least as long as that for the soma and ranged between 0.8–2.0 ms. The antidromic responses failed to follow low frequency stimulation (< 40 Hz for 3000 ms). This failure occurred in the axon between substantia nigra and globus pallidus. The burst response and first sharp negative wave of the field potential probably represent the antidromic activation of the ubiquitous and densely packed medium spiny neostriatal projection neurons. These responses 1) occur at the same latency, 2) respond in the same manner to twin pulse and repetitive stimulation and 3) are occluded by frontal cortex stimulation in the same manner as antidromic action potentials.     

Murine peritoneal macrophage gangliosides inhibit lymphocyte proliferation

Gangliosides have been shown to act as immunoregulatory agents by altering proliferative responses of lymphocytes to both antigens and mitogens. Most early studies have utilized brain gangliosides and have required high concentrations. The role of endogenous gangliosides from macrophages has remained unexplored. In this study, thioglycolate-elicited murine peritoneal macrophage gangliosides were purified and added to cultures of murine lymphocytes. Nanogram amounts caused a profound inhibition of LPS-induced DNA synthesis of splenocytes and of purified B lymphocytes, without demonstrable cellular toxicity. No effect was seen using asialo-GM1. This effect was present across a wide range of lipopolysaccharide (LPS) doses. Nanogram amounts of macrophage gangliosides also inhibited concanavalin A (ConA)-mediated lymphocyte proliferation. Inhibition of LPS-induced mitogenesis was present even if gangliosides were removed from the extracellular environment after 15-60 min of incubation prior to the addition of LPS. This inhibition was reversible with incubation of ganglioside pre-treated lymphocytes in medium containing serum. These inhibitory properties of macrophage gangliosides are distinct from those found in studies using brain gangliosides, and support a potential role for macrophage gangliosides as negative modulators of lymphocyte proliferation.     

Pulmonary endothelial cell killing by human neutrophils. Possible involvement of hydroxyl radical

Human blood neutrophils stimulated by a variety of agents were shown to have cytotoxic effects on bovine pulmonary artery endothelial cells. Effective agonists included immune complexes, opsonized zymosan and 12-O-tetradecanoyl phorbol acetate. Unstimulated human neutrophils and neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine or with platelet-activating factor failed to induce significant killing even though secretory release of lysosomal enzymes occurred. In comparing the effects of the different agonists, endothelial cell killing showed a better correlation with the production of H2O2 than with the generation of O2-. Endothelial cell killing by stimulated human neutrophils was inhibited by catalase but not by soybean trypsin inhibitor or superoxide dismutase. Killing was also inhibited by two scavengers (N, N-dimethylthiourea and D-mannitol) of hydroxyl radical and by deferoxamine mesylate, an iron-chelator. Iron-saturated deferoxamine mesylate was significantly less effective in protecting the endothelial cells against killing. Agents that were protective against endothelial cell killing did not interfere with the generation of O2- in stimulated neutrophils. These results suggest that leukocyte-induced endothelial cell killing in vitro can be induced by some but not all agonists for neutrophils and that the killing is oxygen-dependent and may be directly due to hydroxyl radical production.     

Meningococcal infections in the Province of Québec, Canada, during the period 1991 to 1992.

A total of 234 strains of Neisseria meningitidis obtained from hospitalized patients living in the province of Québec during the period 1991 to 1992 were characterized according to their serogroup, serotype, subtype, electrophoretic type, and antimicrobial susceptibility. All these strains were recovered from sterile body fluids, except for one strain that was isolated postmortem from a cutaneous lesion. For both years, serogroup C was the most prevalent (69.7%), followed by serogroup B (27.4%). Serotype 2a represented 80.3% of serogroup C isolates, and P1.2 was the most common subtype associated with this serotype. Clone ET 15 accounted for 76.5% of serogroup C isolates and 90.0% of serotype 2a strains. Although meningococcal disease occurred mostly in children under the age of 5 (9.7 cases per 100,000 children), with a peak incidence for children under 1 (20.3 cases per 100,000 children), most fatalities occurred among teenagers (12 to 19 years old). The total fatality rate was 11.5%, and serogroup C strains were responsible for 88.9% of these fatalities. Thirteen strains had a reduced susceptibility to penicillin G, and 28 strains were resistant to sulfadiazine. One strain was resistant to both rifampin and sulfadiazine and showed a reduced susceptibility to penicillin G.     

Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the Guinea pig cochlea

Large-conductance calcium-activated potassium (BK) channels are known to play a prominent role in the hair cell function of lower vertebrates where these channels determine electrical tuning and regulation of neurotransmitter release. Very little is known, by contrast, about the role of BK channels in the mammalian cochlea. In the current study, we perfused specific toxins in the guinea pig cochlea to characterize the role of BK channels in cochlear neurotransmission. Intracochlear perfusion of charybdotoxin (ChTX) or iberiotoxin (IbTX) reversibly reduced the compound action potential (CAP) of the auditory nerve within minutes. The cochlear microphonics (CM at f1 = 8 kHz and f2 = 9.68 kHz) and their distortion product (DPCM at 2f1-f2) were essentially not affected, suggesting that the BK specific toxins do not alter the active cochlear amplification at the outer hair cells (OHCs). We also tested the effects of these toxins on the whole cell voltage-dependent membrane current of isolated guinea pig inner hair cells (IHCs). ChTX and IbTX reversibly reduced a fast outward current (activating above -40 mV, peaking at 0 mV with a mean activation time constant tau ranging between 0.5 and 1 ms). A similar block of a fast outward current was also observed with the extracellular application of barium ions, which we believe permeate through Ca2+ channels and block BK channels. In situ hybridization of Slo antisense riboprobes and immunocytochemistry demonstrated a strong expression of BK channels in IHCs and spiral ganglion and to a lesser extent in OHCs. Overall, our results clearly revealed the importance of BK channels in mammalian cochlear neurotransmission and demonstrated that at the presynaptic level, fast BK channels are a significant component of the repolarizing current of IHCs.     

Vaccinated mice remain more susceptible to Mycobacterium tuberculosis infection initiated via the respiratory route than via the intravenous route

Mice given Mycobacterium tuberculosis bacilli via the respiratory route succumbed much sooner to infection than mice given 1,000 times more bacilli via the intravenous route. Vaccination provided increased protection to an M. tuberculosis challenge infection; however, mice infected via the respiratory route remained much more susceptible.     

Effect of target size on anomalous sensory responses in the Bagolini striated lens test

Different results obtained by different methods of retinal correspondence testing are generally accepted to be a sign of the depth of the anomalous sensory adaptation. The Bagolini striated lens test is considered a standard "natural" test to which others are compared. In this study, the Bagolini striated lens test was performed on 25 strabismic subjects using three target sizes in order to determine if target size might be a factor in response variability. Kappa Measure of Agreement, used to analyze the results statistically, showed a moderately high to high level of agreement among the three targets. This indicates that practitioners can feel confident of consistent test results on the striated lens test using any of the three readily available target sizes selected. A brief literature review has been provided as a guide to the theories of strabismus and correspondence and to emphasize the purpose of this research.     

Breast feeding and smoking hygiene: major influences on cotinine in urine of smokers'' infants.

The determinants of urine cotinine levels were studied in a group of 101 infants aged 3 months, including 79 infants whose mothers were current smokers. At a pre-arranged home visit the infants' mothers completed an interviewer-administered questionnaire, and samples of maternal urine and breast milk and infants' urine were collected. Cotinine and nicotine levels were determined by gas-liquid chromatography. Infant urine cotinine levels ranged from 0 to 140 micrograms/l (0-1120 ng cotinine/mg creatinine). A linear dose response relation between mother's smoking rate and infant urine cotinine level was observed among breast-fed infants (r = 0.79, p less than 0.001). The relation was weaker among infants fed by both breast and bottle (r = 0.56, p = 0.01) and was not apparent among bottle-fed infants (r = 0.15, p = 0.16). In addition to mode of feeding and mother's smoking rate, mother's smoking "hygiene" (assessed by the reported frequency of smoking while feeding and with infant in same room) was independently associated with infant urine cotinine level. Father's smoking pattern and exposure to smoke outside the household did not relate significantly to infant cotinine levels. We conclude that when mothers smoke, breast feeding is the principal determinant of cotinine in infants' urine. It is likely that most of this cotinine comes from cotinine in mothers' breast milk, but further research is needed to establish how much nicotine is ingested by breast-fed infants of mothers who smoke, and to investigate possible health effects.