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Biomedical subjects

P C Fox

Publications and source records attributed to P C Fox.

142 records · Page 8Linked to original sources

The role of frontal cortex-reticular interactions in performance and extinction of the classically conditioned nictitating membrane response in the rabbit.

In order to investigate the behavioral role of interactions between frontal cortex and reticular nuclei, we examined the effects of single and combined lesions of these structures on the classically conditioned nictitating membrane response (NMR) of rabbits. Lesions of frontal cortex decreased latencies of the conditioned NMRs in reacquisition and retarded extinction of the conditioned response. Lesions of nucleus reticularis pontis oralis (NRPO) produced similar effects. In contrast, lesions of nucleus reticularis tegmenti (NRT) increased NMR latencies during reacquisition. The opposite effects of frontal cortex and NRT lesions were abolished when the two lesions were combined, indicating that the two lesion effects summed. In contrast, the deficits due to frontal and NRPO lesions did not sum; combined frontal-NRPO lesions produced deficits very similar in magnitude and time course to those of the NRPO lesions alone. These findings suggest that frontal cortex may exert its inhibitory effects on behavior not by directly interacting with NRT, but by facilitating NRPO, which in turn may inhibit the nucleus of the VIth nerve, the final common pathway to the NMR. NRT may facilitate the motor pathway by modulating the inhibitory effect of NRPO on the VIth nerve nucleus.

Animals↗

Mouse mast cell activation and desensitization for immune aggregate-induced histamine release.

Immune aggregate-induced histamine release and desensitization were studied in mouse mast cells. Maximal histamine release was rapid, occurred at 37 degrees C, and required the addition of alpha-L-phosphatidyl-L-serine and Ca2+. The amount of histamine released varied with the composition of the immune aggregates and was dependent on the antibody concentration. Saturation of mast cell Fc epsilon receptors with rat or mouse IgE had no effect on subsequent immune aggregate-induced release. The incubation of mouse mast cells with immune aggregates in the absence of cations of alpha-L-phosphatidyl-L-serine did not stimulate the release of histamine but resulted in desensitization of the cells for release with the addition of the same or unrelated immune aggregates. Such cells are capable, however, of IgE-mediated histamine release. Mast cells desensitized for IgE-mediated histamine release by incubation with anti-IgE were capable of immune aggregate-induced release. These data suggest that IgE-mediated and immune aggregate-induced triggering of mouse mast cells occurs through separate receptors.

Animals↗

Enhancing the frequency of antigen-specific hybridomas.

Techniques were developed to enhance the frequency of antigen-specific hybridomas by enriching for antibody precursor or-producing lymphocytes prior to cell fusion. Spleen cells of immunized animals were either (a) cultured in vitro for 3-4 days in the presence of the immunizing antigen or (b) adoptively transferred into X-irradiated syngeneic recipients followed immediately by an in vivo antigen boost 4 days prior to use in cell fusion. There was a 10-fold increase in the percentage of wells which develop antigen-specific, antibody-secreting hybridomas following these treatments. These techniques allow an increased yield of hybridomas with a greatly decreased technical effort.

Animals↗

IgE antibody suppression following aerosol exposure to antigens.

Exposure of mice to aerosolized antigens induced a low level IgG1 response but not detectable IgE antibodies. Subsequent intraperitoneal immunization of these mice demonstrated immunoglobulin class-specific IgE suppression. Low concentrations of nebulized antigen induced IgE suppression which was antigen specific and persisted on subsequent secondary and tertiary injections. Although a single aerosolized antigen exposure significantly decreased the IgE response, maximal suppression was observed when the mice were exposed to nebulized antigen once weekly for at least 6 weeks. The suppression was not observed until 3 weeks following nebulizer exposure. Mice exposed once weekly to nebulized antigen for 6 weeks and then rested for 2 months before intraperitoneal immunization still demonstrated suppression. However, animals first immunized intraperitoneally and then exposed to nebulized antigen produced normal secondary IgE and IgG1 responses. These results suggest that antigen exposure by aerosol may profoundly alter the IgE response.

Aerosols↗

The effects of LSD and some analogues on the responses of single cortical neurons of the cat to optical stimulation.

The effects of lysergic acid diethylamide (LSD) and its analogues, 2-bromo-LSD (BOL) and methysergide, have been investigated on the responses to photic stimulation of single neurons in the striate cortex of the paralyzed, anesthetized cat. Systemic LSD (0.1--50 micrograms/kg, i.v.) produced: (a) enhancement or depression of evoked activity, the former being common with low, the latter with high doses; (b) changes in directional selectivity; and (c) changes in unstimulated background discharges. The effectiveness of the drug was reduced by repeated administration. Both BOL (10--75 micrograms/kg) and methysergide (100-700 micrograms/kg) produced effects qualitatively similar to LSD, but were considerably less potent. Microelectrophoretic administrations of LSD to single cortical neurons had actions similar to those caused by intravenous administration. BOL and methysergide required much larger currents to produce any effect and sometimes no effect could be induced by iontophoresis. It was concluded that these drugs influence visually evoked neuronal responses mainly by acting directly on cortical cells or synapses; and that the interference with visual cortical function could account for the distortion of visual perception caused by lysergic acid analogues; but that the hallucinogenic and psychotomimetic actions of LSD probably require additional subcortical effects.

Animals↗

Effects of monocular lid closure on development of receptive-field characteristics of neurons in rabbit superior colliculus.

1. The receptive-field characteristics of superior colliculus neurons were studied in rabbit pups that had one eyelid sutured prior to eye opening. Units recorded from the superior colliculus (SC) receiving input from the unsutured eye provided normal developmental data, and those from the colliculus receiving input from the sutured eye were used to study the effect of visual deprivation. 2. A total of 1,054 cells recorded from 89 animals ranging in age from 7 to 35 days were obtained, 514 cells in the normal colliculus and 540 cells in the deprived colliculus. During normal development, three nonoriented cell types (concentric, uniform, motion) showed a progressive increase in relative frequency of occurrence, starting at about 7 days and reaching the adult level at about 15 days. Directionally selective cells developed slightly later, reaching an adult level at 3 wk. Oriented directional cells were the slowest to mature, requiring about 4 wk to reach the final level. 3. Eyelid suturing significantly affected the oriented directional cell development; these cells developed at a normal rate for about 3 wk, then rather abruptly began to decrease in number; a stable relative frequency of about one-fourth the normal value was reached at about 4 wk. A corresponding increase in the relative number of indefinite cells to above the normal level also occurred. In contrast, the development of nonoriented cells and directionally selective cells was not affected by the deprivation. 4. The development of rabbit superior colliculus receptive fields was found to be, in general, similar to development of kitten SC receptive fields. It also correlates well with developmental changes seen in rabbit ganglion cell receptive fields and with anatomical changes in developing rabbit SC. Indirect support is given for the hypothesis that changes seen in SC with deprivation are secondary to changes in the visual cortex.

Animals↗

Thrombotic thrombocytopenic purpura: report of case.

TTP is an acute, usually fatal disease of unknown etiology. Diagnostic confirmation of the disease requires histologic demonstration of the deposition of hyaline thrombi within the lumens of arterioles and capillaries in the absence of vasculitis. The clinical, laboratory, and histological manifestations of TTP were reviewed and a case was reported in which a gingival biopsy specimen was used to confirm the diagnosis. Emphasis is placed on the rapidity and ease of gingival biopsy and the possibility of earlier institution of therapy.

Adult↗

Development of receptive fields in rabbit visual cortex: changes in time course due to delayed eye-opening.

Rabbit pups had one eye sutured closed before the time at which the eyes normally open. At 20-27 days of age, single-unit recordings were made both from the striate cortex contralateral to the sutured eye (deprived cortex) and from that contralateral to the eye which had opened normally (control cortex). The percentages of units encountered which fell into various receptive field categories differed on the two sides. The deprived cortices had a lower percentage of visually responsive cells, a higher percentage of indefinite cells, and totally lacked cells sensitive to orientation of a stimulus bar. In these respects they closely resembled previous observations on rabbit pups just before normal eye-opening. By contrast, the control cortices of the same animals were comparable to normally reared rabbits of the same age. We conclude, therefore, that developmental events which normally follow eye-opening can be affected in their time course by delaying eye-opening.

Aging↗

Safety and efficacy of adenovirus-mediated transfer of the human aquaporin-1 cDNA to irradiated parotid glands of non-human primates.

This study evaluated the safety and efficacy of a single administration of a recombinant adenovirus encoding human aquaporin-1 (AdhAQP1) to the parotid glands of adult rhesus monkeys. In anticipation of possible clinical use of this virus to correct irradiation damage to salivary glands, AdhAQP1 was administered (at either 2 x 10(9) or 1 x 10(8) plaque-forming units/gland) intraductally to irradiated glands and to their contralateral nonirradiated glands. Radiation (single dose, 10 Gy) significantly reduced salivary flow in exposed glands. Virus administration resulted in gene transfer to irradiated and nonirradiated glands and was without untoward local (salivary) or systemic (sera chemistry, complete blood count) effects in all animals. However, the effect of AdhAQP1 administration varied and did not result in a consistent positive effect on salivary flow rates for all animals under these experimental conditions. We conclude that a single adenoviral-mediated gene transfer to primate salivary glands is well-tolerated, although its functional utility in enhancing fluid secretion from irradiated parotid glands is inconsistent.

Adenoviridae↗

Focal sialadenitis in patients with early synovitis.

OBJECTIVE: To investigate the frequency of sialadenitis on lip biopsy in patients with synovitis of recent onset (ES), and see how sialadenitis relates to clinical and laborator findings of ES. METHODS: Joint involvement, laboratory measures and biopsies of the minor salivary glands were evaluated in 10 ES patients. Diagnosis at a one-year follow-up exam was noted. RESULTS: Six ES patients (60%) had a positive lip biopsy (mononuclear cell focus score greater than 1). ES patients with a positive lip biopsy presented with oligoarthritis, while ES patients with a negative lip biopsy had a more polyarticular presentation. No differences in laboratory measures between patients with a positive and negative lip biopsy were present. Seven ES patients had a diagnosis of rheumatoid arthritis and three had undifferentiated arthritis at the end of one year. CONCLUSION: ES patients had a higher than expected frequency offocal sialadenitis.

Adult↗

Oral and sialochemical findings in patients with autoimmune rheumatic disease.

Forty-two patients with autoimmune rheumatic diseases were evaluated for oral-dental findings and a biopsy of labial minor salivary glands was obtained. Stimulated parotid salivary gland function was assessed and levels of total protein, chloride and albumin in these secretions measured. The patients were stratified into three groups according to the severity of labial gland histopathology (normal histology, 1+ and 2+). Individuals with chronic inflammatory disease of the minor salivary glands had no decrease in stimulated parotid salivary flow but were found to have a greater incidence of oral soft tissue changes commonly associated with salivary dysfunction. However, there were no statistically significant differences in total protein or chloride levels between the groups and no albumin was detected in any samples. These data suggest that stimulated parotid function may be a poor indicator of the extent of salivary involvement in individuals with autoimmune-mediated salivary gland disease.

Arthritis, Rheumatoid↗

Comparison of conorphone, a mixed agonist-antagonist analgesic, to codeine for postoperative dental pain.

The analgesic efficacy of two doses of conorphone (20 and 40 mg), a mixed agonist-antagonist analgesic, were compared to two doses of codeine for postoperative pain in the oral surgery model. Each subject received 2 of the 4 possible treatment at two separate sessions in an incomplete block, single crossover design. Both doses of conorphone and the 60 mg dose of codeine were superior to 30 mg of codeine for the various indices of analgesic activity. The 40 mg dose of conorphone resulted in a high incidence of side effects (25/30 subjects) such as drowsiness, dizziness, nausea and vomiting. The low dose of conorphone resulted in side effects similar to 60 mg of codeine with the exception of a greater incidence of drowsiness. These data suggest that while 40 mg of conorphone may not be well tolerated clinically, 20 mg of conorphone may be an alternative to 60 mg of codeine for postoperative pain.

Adolescent↗

Prednisone and piroxicam for treatment of primary Sjögren's syndrome.

Primary Sjögren's syndrome is a systemic autoimmune exocrinopathy characterized by a lymphoplasmacytic infiltrate and destruction of salivary and lacrimal glandular tissues. There is no widely accepted or effective systemic therapy for this disorder. The purpose of this 6-month randomized, double-blinded, placebo-controlled study was to examine the effects of prednisone (30 mg, alternate days), piroxicam (20 mg, daily), or placebo on the salivary, lacrimal and immunologic alterations of primary Sjögren's syndrome. Eight patients were enrolled in each group. Salivary and lacrimal function were assessed at entry and at the completion of treatment. Labial minor salivary gland tissue was obtained at these times and examined for intensity of infiltration (focus scores) and for the relative proportion of glandular elements. Serologic and subjective evaluations were done as well, and patients were monitored for therapy-related side effects. Neither active treatment led to significant improvement in salivary or lacrimal function, although prednisone improved salivary flow in selected patients and was associated with positive subjective responses. Prednisone also significantly decreased the serum total protein, IgG, IgA, and sedimentation rate and increased the white cell count. There were no significant alterations in either focus scores or the percentage of glandular component tissues of minor glands with either active treatment. This study demonstrated that 6 months of prednisone or piroxicam at the doses utilized failed to improve the histological or functional parameters of salivary and lacrimal glands in primary Sjögren's syndrome.

Adult↗