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Biomedical subjects

J R Kennedy

Publications and source records attributed to J R Kennedy.

At least 19 recordsLinked to original sources
PubMed1996

The effects of the organophosphorous insecticides Dursban and Lorsban on the ciliated epithelium of the frog palate in vitro.

The ciliotoxic potential of the organophosphorous insecticides Dursban and Lorsban, their active ingredient, chlorpyrifos, and their carrier ingredients (Blanks) were assessed. Since chlorpyrifos inhibits acetylcholinesterase, the acetylcholine-innervated ciliated epithelial cultures of frog palate were used as the model. All compounds caused a decrease in frequency of ciliary beat overtime. EC50 values followed the same order as the time to inhibition. The orders were Lorsban > Dursban > chlorpyrifos, and Lorsban > Dursban approximately Lorsban Blank > Dursban Blank. Stimulation of ciliary beating occurred immediately after exposure to all compounds, followed by inhibition. Dursban, Lorsban, and both Blanks elicited stimulatory effects in the presence of atropine. Atropine only blocked the initial stimulatory response with chlorpyrifos. In addition to chlorpyrifos, some component(s) of the inert ingredients were initially stimulatory but ultimately inhibitory to ciliary beating in the frog palate model. All compounds caused mitochondrial damage, including swelling, disruption of cristae, and loss of matrix.

Animals↗
PubMed1995

Reflections on an interface.

This discusses an immune recognition model of autoimmunity and tolerance which is based on an idiotypic and an anti-idiotypic immune network response at a virus receptor interface.

Antibodies, Anti-Idiotypic↗
PubMed1995

The effects of benomyl and its breakdown products carbendazim and butyl isocyanate on the structure and function of tracheal ciliated cells.

The effects of the fungicide benomyl and its breakdown products, carbendazim and butyl isocyanate, were examined on canine tracheal epithelial tissue in primary culture. Changes in ciliary frequencies were monitored with an optical spectrum analysis system. Serial dilutions of the test compounds were prepared in 100% corn oil and applied to the cell cultures for intervals up to 6 hours and frequencies measured at intervals of 15 minutes to 1 hour. Benomyl and butyl isocyanate caused concentration-dependent decreases in ciliary beat frequency. Benomyl at 300 micrograms/ml (3 mM) caused ciliostasis within 75 minutes of exposure. Butyl isocyanate at a molar concentration three times lower than benomyl (1 mM) caused a similar response, although within 30 minutes. The IBC50 for benomyl was 0.75 mM, while for butyl isocyanate it was 0.52 mM. Carbendazim caused a moderate decrease in frequency over a 6 hour exposure period. Benomyl caused moderate to severe swelling of the mitochondria of ciliated epithelial cells with other cell organelles appearing normal. Butyl isocyanate did not cause any noticeable effect on cell ultrastructure and the apparently low rate of penetration of carbendazim into cells made it impossible to obtain an effect which justified ultrastructural analysis. It appears, at least for benomyl and butyl isocyanate, that while the physiological effect of these two compounds (inhibition of ciliary beat) is the same, the sites of action in the cell may be different.

Animals↗
PubMed1994

Intra-epithelial palatine nerve endings and their regulation of ciliary activity of frog palate epithelium.

1. Direct contact between intra-epithelial nerve endings and ciliated cells was observed in frog (Rana pipiens) palate epithelium. 2. Electrical stimulation of the palatine nerve to the explant or the explant culture induced an increase in ciliary beat frequency in explant and outgrowth cells. 3. Atropine inhibited electrically stimulated ciliary beat frequency increase in the explant and outgrowth cells. 4. Gap junctional intercellular communication appears to be involved in the propagation of stimulated ciliary beat frequency increase from innervated to non-innervated ciliated cells.

Animals↗
PubMed1993

Does HIV disrupt a naturally occurring immune modulation system?

An immune modulation complex is proposed which recognizes and is driven by an MHC presented epitope of the CD4 molecule present on the surface of up regulated CD4+ lymphocytes. Immune modulation is affected by both CD4 lymphocyte destruction and impairment of their potential for immune recognition. These two processes are carefully controlled by an idiotypic, anti-idiotypic feedback mechanism. The CD4 tropic area of HIV impersonates some components of that feedback loop resulting in increased CD4 lymphocyte destruction.

Animals↗
PubMed1992

AIDS--an autoimmune model.

In AIDS a complementary interface between the HIV virus and the CD4 molecule of the T4 lymphocyte suggest a possible cause of immune self-recognition. Because of this complementarity, an anti-idiotypic immune response to the CD4 attachment area of HIV should result in an autoimmune reaction to CD4 positive lymphocytes. Experimental demonstration of such an immune recognition model by autoreactive lymphocytes is presented and a hypothetical immune response unit is suggested.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Primary ciliary dyskinesia in the dog.

A disorder caused by congenital ciliary dysfunction occurs in dogs. Most of the clinical signs are directly or indirectly attributable to immotile or dyskinetic cilia and spermflagella. Due to severely impaired mucociliary clearance, a continuous mucoid nasal discharge and intermittent sneezing and coughing are typically observed during the neonatal period. Recurrent bacterial rhinosinusitis and bronchopneumonia usually start within a few weeks of birth. Hypoplastic nasal sinuses and atresia of the frontal sinuses are variable features of the disease that may be caused by neonatal colonization of these structures by specific bacteria. Bronchiectasis is an acquired lesion resulting from chronic inflammation and obstruction of airways. A secretory otitis media is caused by dysfunction of the cilia in the middle ear, and is manifested in some dogs by sclerotic tympanic bullae. Male infertility is caused by live, but immotile to hypomotile spermatozoa; however, unexplained oligospermia and azoospermia have been reported. Hydrocephalus and situs inversus are common but variable features of the disease; the genesis of these lesions has not yet been determined. The probable mode of inheritance is autosomal recessive, but dominant mutations cannot be excluded. The diagnosis can be confirmed by demonstrating the absence or near absence of nasal or tracheal mucociliary clearance and the presence of a specific ultrastructural lesion in a large percentage of cilia from multiple sites (airways, middle ear, or oviduct). The ultrastructure of sperm flagella should mirror that of the cilia. Not all dogs have ultrastructural ciliary lesions, and in these cases, results of in vitro analysis of ciliary activity may be highly suggestive, if not diagnostic. In dogs without mucociliary clearance in which structural and functional analysis of cilia are not diagnostic, confirmation of congenital ciliary dysfunction can be established only by ruling out other diseases with similar signs (e.g., congenital immunodeficiency syndromes). The clinical course in an longevity of affected dogs are highly variable. Appropriate antibiotic treatment and pulmonary physical therapy may result in prolonged survival, although cor pulmonale and reactive systemic amyloidosis are potential sequelae of chronic hypoxia and chronic bacterial infection of the airways, respectively.

Animals↗
PubMed1991

The immediate effects of silicon carbide whiskers upon ciliated tracheal epithelium.

Considering the relationship between toxicity of dust and particle geometry, as exhibited by asbestos, we have examined short-term biological effects of SiC whiskers (SiCW) in vitro and in vivo. Cultured explants of tracheal epithelium were exposed to a range of SiCW concentrations. There were no dramatic effects on ciliary function as measured by an optical spectrum analysis system that provided discrete ciliary frequencies. Particles were swept by ciliary activity into nonciliated regions where foci of extensive cell damage and death were observed with whiskers penetrating epithelial layers into the underlying tissues. Similar necrotic foci were observed in tracheae from rats exposed by intratracheal instillation to SiC whiskers in vivo.

Animals↗
PubMed1990

An immune model defined by AIDS.

An immune control system is proposed which is made up of a pair of idiotypic T4 and T8 cells which recognize self-antigen, and a pair of anti-idiotypic T4 and T8 cells which recognize those idiotypic receptors. The protective and destructive elements of the control cells and their induced immunoglobulins are in equilibrium, allowing self-recognition and tolerance. One of the self-antigens monitored by the system is CD4, the T4 surface marker and also the HIV attachment site. In AIDS the HIV attachment antigen is immunologically identical to one of the CD4 control cell receptors. This disrupts the equilibrium of the system causing chronic T4 cell destruction.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Familial immotile-cilia syndrome in English springer spaniel dogs.

A laboratory-maintained colony of English springer spaniel dogs heterozygous for a putative autosomal recessive immotile-cilia syndrome (ICS) has been studied. Matings between dogs thought to be heterozygous for ICS resulted in 22 pups, five (three males and two females) of which were homozygous for ICS. Four of the five ICS-affected dogs had chronic rhinitis and bronchopneumonia. The other dog had a serious nasal discharge and died at 10 days. Four dogs had situs inversus totalis (kartagener syndrome), and the two males of reproductive age were azoospermic. In the two ICS dogs studied for ciliary function, in vivo mucociliary clearance was absent, and in vitro ciliary beat was rarely observed and of low frequency. Scanning and transmission electron microscopy disclosed the same lesions in respiratory cilia from all dogs with ICS, including random orientation and partial outer dynein arm deficiency. Four of five dogs with ICS had dilated lateral ventricles. One female pup with neonatal rhinitis and bronchopneumonia, situs solitus, and dilated lateral ventricles was presumed to be homozygous for ICS, but died without functional or structural confirmation of defective respiratory cilia. An autosomal recessive mode of inheritance for the ciliary defects and respiratory signs of ICS in these dogs is proposed.

Animals↗
PubMed1989

Use of Peldri II (a fluorocarbon solid at room temperature) as an alternative to critical point drying for biological tissues.

A new chemical, Peldri II, is evaluated as a compound for drying soft biological tissues for scanning electron microscopy. Peldri II, a fluorocarbon, is a solid at room temperature and is a liquid above 25 degrees C. Cells or tissues are embedded in Peldri II by immersing them in the liquid form and allowing it to solidify. Once solidified, Peldri II will sublime with or without vacuum to dry tissues, probably without introducing surface tension. Several types of cells and tissues have been examined to compare preservation with Peldri II and critical point drying techniques. No differences were detected between the two techniques when normal surface structures were examined. Peldri II appears to be a significant improvement over hexamethyldisilazane as a drying agent for scanning electron microscopy. It is also very convenient for drying large numbers of samples.

Animals↗
PubMed1988

Utilization of digital image processing to study dynein arms (ATPase) in normal and immotile cilia.

Tracheal ciliary cross sections were examined with scanning transmission electron microscopy and the resultant images were digitized for image enhancement. A gray-scale histogram of each ciliary image was produced and manipulated to enhance the image for dynein arms. Tracheal epithelial tissue from the pig, rabbit, and dog, including dogs with immotile cilia syndrome, was examined by using this technique. Tissue from each animal was fixed with each of three different fixatives and sections were evaluated for preservation of dynein arms. The same fixative did not consistently provide optimal fixation for ciliary dynein arms in all three species examined. Each species, therefore, must be evaluated to determine the optimal fixative for preservation of normal ciliary ultrastructure. Digital image processing provides a mechanism for enhancing dynein arms in situ without the need for addition of special stains or the use of techniques such as image summation. With this technique it has been shown that about two-thirds of outer dynein arms are partially or completely missing on cilia from dogs with immotile cilia syndrome.

Adenosine Triphosphatases↗
PubMed1986

Calcium regulation of ciliary activity in rabbit tracheal epithelial explants and outgrowth.

Ciliated epithelial cells from rabbit trachea were employed to examine the role of Ca2+ in the regulation of ciliary motility. Tracheal explants and outgrowths were maintained in culture, and ciliary frequency was determined using a photomultiplier interfaced with a spectrum analyzer capable of Fast Fourier transform analysis. Relative cellular Ca2+ levels were determined by measuring 45Ca2+ uptake and efflux. Elevated cellular Ca2+, from exposure to 10(-5) M calcium ionophore A23187, led to an increase in ciliary frequency followed by inhibition of motility after prolonged treatment. A decrease in ciliary frequency was observed upon lowering intracellular Ca2+ by exposing the epithelium to 1 mM EGTA. Exposure of ciliated cells to 10(-4) M trifluoperazine resulted in inhibition of ciliary motility, a result suggesting a possible role for calmodulin- or phospholipid-sensitive Ca2+-dependent protein kinases in ciliary function. These results support the hypothesis that intracellular Ca2+ is actively involved in modulating the frequency of ciliary beat.

Animals↗