What is your diagnosis? Right maxillary sinusitis or sinus cyst in a cow.
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Biomedical subjects
Publications and source records attributed to J E Alexander.
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Pneumolysin, the major Streptococcus pneumoniae cytotoxin, contributes to the early pathogenesis of invasive pneumococcal pneumonia by facilitating intrapulmonary bacterial growth and invasion into the blood. Pneumolysin is a multifunctional toxin, with distinct cytolytic ("hemolytic") and complement-activation ("complement") activities that have been mapped to several regions of the molecule. To characterize the specific contributions of pneumolysin's hemolytic and complement properties to the pathogenesis of pneumococcal pneumonia, we compared the in vivo effects of type 2 S. pneumoniae mutant strains, which produce pneumolysins deficient in these activities. The absence of either pneumolysin's hemolytic or complement activities rendered mutant strains less virulent than the wild-type strain during pulmonary infection. Pneumolysin's hemolytic activity correlated with acute lung injury and bacterial growth at 3 and 6 h after endotracheal instillation. In contrast, pneumolysin's complement activity correlated with bacterial growth and bacteremia at 24 h after pulmonary infection. Pneumolysin's complement activity was not associated with the degree of alveolar-capillary injury or recruitment of leukocytes during initial pulmonary infection. However, pneumolysin's complement activity inhibited killing of mutant bacteria in an in vitro complement-dependent neutrophil killing assay. Thus, both pneumolysin's hemolytic and complement activities made specific contributions to the early pathogenesis of pneumococcal pneumonia at different stages of infection and by different mechanisms.
The P3(00) event-related potential (ERP) was elicited in 20 left- and 20 normal right-handed young adult male subjects using a simple visual stimulus discrimination task. For left-compared to right-handed subjects, P3 amplitude was larger at anterior electrode sites for the target stimuli and larger overall for the novel visual stimuli; P3 latency was shorter for left-compared to right-handers for the target stimuli. The N1, P2, and N2 components demonstrated similar handedness effects. The relationships of ERP amplitude and handedness to anatomical variables and cognitive factors are discussed.
The P3(00) event-related potential (ERP) was elicited in 80 normal, right-handed male subjects using a simple visual discrimination task, with electroencephalographic (EEG) activity recorded at 19 electrodes. P3 amplitude was larger over the right than over the left hemisphere electrode sites primarily at anteromedial locations (F3/4, C3/4) for target, novel, and standard stimuli. The N1, P2, and N2 components also demonstrated hemispheric asymmetries. The strongest P3 hemispheric asymmetries for all stimuli were observed at anterior locations, suggesting a frontal right hemisphere localization for initial stimulus processing, although target stimuli produced larger P3 amplitudes at parietal locations that did novel stimuli. The relationships of hemispheric asymmetries to anatomical variables, background EEG activity, and neurocognitive factors are discussed.
The thiol-activated toxin pneumolysin is a known pneumococcal virulence factor, with both cytotoxic (hemolytic) and complement activation properties. Copies of the pneumolysin gene carrying defined point mutations affecting either or both of these properties were introduced into the chromosome of Streptococcus pneumoniae D39 by insertion-duplication mutagenesis. The virulences of these otherwise isogenic strains were then compared. There was no significant difference in either the median survival time or overall survival rate between mice challenged with D39 derivatives producing the wild-type toxin and those expressing a pneumolysin gene with an Asp-385-->Asn mutation, which abolishes the complement activation property. However, mice challenged with strains carrying either His-367-->Arg or Trp-433-->Phe plus Cys-428-->Gly mutations, which reduce hemolytic activity to approximately 0.02 and 0.0001% of the wild-type level, respectively, had significantly greater median survival times and overall survival rates than mice challenged with D39 derivatives expressing a wild-type pneumolysin gene. No additional reduction in virulence was observed when mice were challenged with a D39 derivative carrying Trp-433-->Phe, Cys-428-->Gly, and Asp-385-->Asn, rather than Trp-433-->Phe and Cys-428-->Gly, mutations in the pneumolysin gene. Thus, it appears that in the intraperitoneal challenge model, the contribution of pneumolysin to virulence is largely attributable to its hemolytic (cytotoxic) properties rather than to its capacity to activate complement. Interestingly, however, the amount of pneumolysin required for full virulence may be very small, as D39 derivatives carrying the Trp-433-->Phe mutation (which reduces hemolytic activity to 0.1% of the wild-type level) had intermediate virulence.
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Event-related potentials (ERPs) were recorded from normal subjects for the purpose of evaluating measurement consistency among six laboratories located in different cities within the United States. At each laboratory location 15 male subjects were tested using a simple auditory stimulus discrimination task and identical electrophysiological equipment and recording methods. Assessment of the N1, P2, N2, and P3(00) potentials from both the target and standard stimuli resulted in no reliable differences among laboratories for component amplitudes, latencies, and scalp distributions. Quantitative evaluation of overall waveform and specific component morphology yielded good to excellent agreement across laboratories. The findings suggest that large-scale inter-laboratory human electrophysiological studies are feasible and may prove of value when using ERPs to evaluate cognitive function in humans.
O'Boyle and Benbow (1990) have suggested that enhanced involvement of the right hemisphere (RH) during basic information processing is a neuropsychologic characteristic of the gifted brain. To provide converging evidence for this hypothesis, the present study was conducted using a concurrent finger-tapping paradigm. Specifically, 24 mathematically precocious and 16 average ability adolescent males were required to tap a key as quickly as possible while sitting silently (baseline condition), concurrently reading a paragraph aloud (verbal load), or encoding a random form into memory (spatial load). For average ability subjects, the concurrent verbal load reduced tapping rate for the right but not the left hand, reflecting a division of LH resources between linguistic processing of the paragraph and motor control of the contralateral hand. In contrast, for gifted subjects, both their left- and right-hand tapping rates were significantly reduced, suggesting that both hemispheres were engaged during verbal processing. The concurrent spatial task produced a small but reliable reduction in finger-tapping rate for both the left and right hand in each group. These findings provide additional support for the notion that enhanced reliance on RH functioning is a physiological correlate of mathematical precocity in gifted males.
Pneumolysin is the thiol-activated cytolysin produced by Streptococcus pneumoniae. Mice were immunized with a genetically engineered toxoid version of pneumolysin, which was derived from a serotype 2 pneumococcus. The toxoid carried the mutation Trp-433-->Phe. Alum was used as the adjuvant. Immunized mice had significantly increased levels of anti-pneumolysin antibodies, principally immunoglobulin G1. Mice were challenged intraperitoneally or intranasally with 12 strains covering capsular serotypes 1 to 6, 7F, 8, and 18C. Following challenge, the survival rate and/or the time of death of nonsurvivors (survival time) was significantly greater than that of sham-immunized mice for all nine serotypes. However, differences in the degree of protection were noted between different strains. The route of challenge also appeared to influence the degree of protection. Nevertheless, the significant, albeit in some cases partial, protection provided against all nine pneumococcal serotypes supports the conclusion that pneumolysin toxoids warrant consideration for inclusion in a human vaccine.
A preliminary investigation was conducted to determine whether hemispheric patterns of electrophysiological activation in male homosexuals differ from that of male and female heterosexuals. Electroencephalographic (EEG) activity was recorded over left and right cerebral hemispheric locations while subjects performed verbal and spatial cognitive tasks. Male homosexuals demonstrated different patterns of alpha power compared to heterosexual males and females during baseline recording. Different hemispheric patterns of alpha activity also were observed between homosexual and heterosexual males during affective judgments of both verbal and spatial stimuli, but not between homosexual males and heterosexual females. These results provide further evidence of biologically-mediated functional differences between homosexuals and heterosexuals.
A transposon insertion mutant of Listeria monocytogenes was shown to be deficient in prephenate dehydratase, an enzyme acting late in the pathway for biosynthesis of phenylalanine. This mutant had reduced virulence in mice. The mutant and parent strains persisted to the same extent in the tissues of infected mice and elicited similar degrees of splenomegaly. Mice vaccinated with the mutant were protected significantly from subsequent challenge with virulent L. monocytogenes.
Class III beta-tubulin, isolated from adult bovine brain, is resolved into at least seven charge variants on isoelectric focusing gels. To identify the posttranslational modifications responsible for this heterogeneity, a mixture of brain tubulins was treated with cyanogen bromide and the C-terminal fragments from the class III beta-tubulin isoforms were then isolated by binding them to the monoclonal antibody TuJ1. Combined use of tandem mass spectrometry and both subtractive and automated Edman degradation chemistry on the isolated peptides indicates that many of the isoforms differ by phosphorylation at Ser-444 plus attachment of one to six glutamic acid molecules to the side chain of the first glutamate residue, Glu-438, in the C-terminal sequence Tyr-Glu-Asp-Asp-Glu-Glu-Glu-Ser-glu-Ala-Gln-Gly-Pro-Lys.
A preliminary electroencephalographic (EEG) investigation was conducted to determine if the pattern of hemispheric activation in mathematically precocious youth differs from that of average math ability subjects. Alpha activity at four brain sites (frontal, temporal, parietal, and occipital lobes) over the left and right cerebral hemispheres (LH/RH) was monitored while 12- to 14-year-old, right-handed males: (a) looked at a blank slide (baseline condition), (b) judged which of two chimeric faces was "happier," and (c) determined if a word was a noun or a verb. At baseline, the LH of the precocious group was found to be more active at all four brain sites relative to that of the average ability group. During chimeric face processing, the gifted subjects exhibited a significant reduction in alpha power over the RH, primarily at the temporal lobe, while no such alpha suppression was observed in the average ability subjects. For noun/verb determinations, no significant alpha power reductions were obtained for either group. These electrophysiological data generally corroborate the behavioral findings of O'Boyle and Benbow (1990a) and support their contention that enhanced RH involvement during cognitive processing may be a correlate of mathematical precocity. Moreover, the pattern of activation observed across tasks suggests that the ability to effectively coordinate LH and RH processing resources at an early age may be linked to intellectual giftedness.
Fourteen adult beavers (Castor canadensis) weighing 16.5 +/- 4.14 kg (mean +/- SD) were anesthetized for surgical implantation of radio telemetry devices. Beavers were anesthetized with diazepam (0.1 mg/kg) and ketamine (25 mg/kg) administered IM, which provided smooth anesthetic induction and facilitated tracheal intubation. Anesthesia was maintained with halothane in oxygen via a semiclosed circle anesthetic circuit. Values for heart rate, respiratory rate, esophageal temperature, direct arterial blood pressure, end-tidal halothane concentration, and end-tidal CO2 tension were recorded every 15 minutes during the surgical procedure. Arterial blood samples were collected every 30 minutes to determine pH, PaO2, and PaCO2. Values for plasma bicarbonate, total CO2, and base excess were calculated. Ventilation was spontaneous in 7 beavers and controlled to maintain normocapnia (PaCO2 approx 40 mm of Hg) in 7 others. Vaporizer settings were adjusted to maintain a light surgical plane of anesthesia. Throughout the surgical procedure, all beavers had mean arterial pressure less than 60 mm of Hg and esophageal temperature less than 35 C. Mean values for arterial pH, end-tidal CO2, PaO2, and PaCO2 were significantly (P less than 0.05) different in spontaneously ventilating beavers, compared with those in which ventilation was controlled. Respiratory acidosis during halothane anesthesia was observed in spontaneously ventilating beavers, but not in beavers maintained with controlled ventilation. All beavers recovered unremarkably from anesthesia.
Serum haloperidol levels were measured in patients who received haloperidol alone and, subsequently, haloperidol in combination with carbamazepine or lithium carbonate. Haloperidol levels and the level- dose ratios dropped about 50% in patients receiving carbamazepine. They remained the same in most patients receiving lithium carbonate. One patient receiving added carbamazepine experienced worsening of symptoms; this was associated with a drop in serum haloperidol level. Two other patients receiving added carbamazepine showed significant symptom reduction, although they also sustained drops in serum haloperidol levels. It is not clear whether these two individuals benefited from a primary antipsychotic effect of carbamazepine or from reduction of "toxic" haloperidol levels. Serum levels of antipsychotic medication should be monitored carefully when these medications are prescribed in combination with carbamazepine.
Electroporation was used to facilitate transformation of Listeria species with plasmid DNA. Optimal conditions for transformation of L. monocytogenes were a field strength of 8.5 kV/cm, 200 Ohms resistance, 25 microF capacitor with a time constant of 5 ms. With these conditions, 3.9 x 10(6) transformants/micrograms DNA were obtained. Under the same conditions, L. innocua and L. ivanovii exhibited a frequency of transformation similar to that of L. monocytogenes but a somewhat lower level was obtained with L. seeligeri.
Hip ultrasound was performed on 44 children (114 exams) presenting with a painful hip or a limp thought to be due to hip disease. Effusions were found in 20 patients (21 hips). Hip ultrasound in combination with aspiration of the joint was found to be useful in diagnosis of osteomyelitis and septic joints, transient synovitis, trauma, and traumatic synovitis. We had no false positives or false negatives for hip effusions by ultrasound. In previous reports, absolute measurements have been relied upon for determination of hip effusions. We present a characteristic appearance of a capsule with and without abnormal joints fluid. The results of these 44 patients are summarized.