Search PubMed⌕ Search

Biomedical subjects

J Tomlinson

Publications and source records attributed to J Tomlinson.

At least 19 recordsLinked to original sources
PubMed1992

Involvement of nitric oxide in nerve-mediated inhibition and action of vasoactive intestinal peptide in colonic smooth muscle.

Neurally mediated relaxation of canine colonic smooth muscle is associated with an increase in the resting membrane potential and is blocked by inhibition of nitric oxide synthesis. N omega-nitro-L-arginine completely prevented nerve-mediated relaxation, an effect that was reversed by L-arginine but not D-arginine. Vasoactive intestinal peptide (VIP) also relaxed canine colonic smooth muscle. Part of this relaxation was due to activation of inhibitory nerves and this effect was mediated by nitric oxide. In addition to the neurally mediated effect, VIP affected smooth muscle directly. This relaxation was associated with a reduction of the plateau phase of the slow-wave type action potential, without an effect on the resting membrane potential. This action of VIP was similar to that of forskolin which suggests that VIP increases intracellular cyclic AMP. In summary, nitric oxide mediates inhibitory innervation to smooth muscle as well as activation of inhibitory nerves by VIP. The electrophysiological mechanism by which VIP directly affects smooth muscle is described, an effect not mediated by nitric oxide.

Animals↗
PubMed1991

Analysis of rat lens 45Ca2+ fluxes: evidence for Na(+)-Ca2+ exchange.

The influx and efflux kinetics of 45Ca2+ were studied in the rat lens in vitro. Both data sets could be fitted by a multi-compartment mathematical model and were interpreted in terms of extracellular, cytosolic and slowly-exchanging (bound) components. At the end of a 16-hr influx period, when uptake into the extracellular and cytosolic compartments is complete, the 45Ca2+ exchanged fraction is less than 20% of the total calcium determined by atomic absorption. The bound compartment is therefore by far the largest in the lens. The efflux rate constant determined from the model for the cytosolic compartment was approximately 8 x 10(-3) min-1 and its origin was confirmed by its sensitivity to temperature, absence of external sodium and presence of the amiloride-analogue, dichlorobenzamil. A 55% reduction in efflux was obtained in sodium-free solution, indicating that Na(+)-Ca2+ exchange is responsible for a large proportion of calcium movement from the lens against its electrochemical gradient. This was confirmed in influx studies where, reduction of the lens sodium gradient by either exposure to sodium-free medium or 0.1 mM ouabain significantly elevated the 45Ca2+ content of the lens relative to the control level. Exposure to sodium-free conditions also rendered the lens opaque, which did not occur in the absence of external calcium. These experiments suggest a critical role for Na(+)-Ca2+ exchange in maintaining a low internal Ca2+ and hence transparency.

Amiloride↗
PubMed1991

Complications of fractures repaired with casts and splints.

Complications of external coaptation of fractures include delayed and nonunion healing from lack of adequate fracture stability, pressure and rub sores, leg swelling, dermatitis, joint laxity or stiffness, cast or splint breakage, and refracture. Most of the complications are a result of improper application of the coaptation device or poor management of the patient. Early recognition and treatment of complications are needed to minimize their effect. The number of complications resulting from external coaptation can be minimized by proper application of the cast or splint.

Animals↗
PubMed1990

Ferritin is a translationally regulated heat shock protein of avian reticulocytes.

Heat-shock avian reticulocytes exhibit enhanced synthesis of a greater than 450-kDa protein. Biochemical, immunochemical, and visual criteria were used to identify this protein as the iron storage protein ferritin. The 21-kDa ferritin subunits synthesized during heat shock are similar in size and pI to the subunits that are constitutively synthesized. The 2-6-fold heat shock-induced increase in ferritin synthesis appears to be regulated at the translational level as it is insensitive to actinomycin D. Northern and dot-blot hybridization analyses of cytoplasmic RNAs with avian H-ferritin cDNA fragments support the contention that the heat shock stimulation of ferritin synthesis is translationally regulated. These latter studies demonstrate that the heat shock-induced synthesis of ferritin does not involve a change in the amount of total cytoplasmic ferritin mRNAs, but rather appears to entail a translocation of cytoplasmic H-ferritin mRNAs from a polyribosome-free, translationally repressed state to a polyribosome-associated, translationally active state. These results suggest that thermally stressed avian reticulocytes have a critical and functional need for the synthesis of additional ferritin and that its enhanced synthesis, unlike the new and/or enhanced synthesis of the well-established avian heat shock proteins, is regulated wholly at the translational level.

Animals↗
PubMed1990

Mammalian lens inter-fiber resistance is modulated by calcium and calmodulin.

The relationship between Ca2+ and lens fiber cell communication was investigated in the isolated intact rat lens by using radiotracer and electrophysiological techniques. The lens internal calcium was increased by adding the SH oxidant diamide (1 mM), by incubating in a sodium-free (n-methylglucamine) solution or by increasing external calcium from 1 to 10 mM. A 12 hours incubation in diamide produced a ten-fold increase in 45Ca uptake into the lens which was accompanied by a ten-fold increase in internal resistance. Incubation in Na-free solution or in 10 mM Ca2+ both produced a 5-fold increase in 45Ca content, while the increase in internal resistance was five and six fold respectively. This uncoupling was prevented in the diamide and Na-free treated lenses by omitting Ca2+ from the incubation medium. Fiber cell uncoupling was noticed in each of these experimental conditions after approximately 5 hours incubation, and good recovery was obtained in the high calcium solution if the stress was removed. The calmodulin antagonists calmidazolium (3 microM) and W7 (100 microM) both prevented uncoupling in the high calcium solution, provided there was a 2 hours preincubation period in calcium-free solution containing antagonist before the stress was applied. These data indicate that lens fiber cell communication is required by Ca2+ and calmodulin.

Animals↗
PubMed1990

Calcium-induced opacification and proteolysis in the intact rat lens.

When intact rat lenses were incubated in artificial aqueous humor in the presence of 1 mM calcium and a sulfhydryl reagent p-chloromercuriphenyl sulfonate (pCMPS) a visible annular opacity developed within 4 hours. Combined photographic and ion-sensitive microelectrode investigations of the lenses demonstrated that the subsequent linear increase in opacification was accompanied by an increase in internal free calcium. Opacities were not observed in lenses incubated in the absence of either pCMPS or calcium. Gel electrophoresis of the soluble and urea-soluble fractions from lenses exposed to 1 mM calcium for periods of up to 14 hours showed no evidence for crystallin degradation and only minor proteolysis of cytoskeletal proteins. When lenses were incubated under identical conditions, but with 5 mM calcium, the degree of opacification increased up to approximately 8 hours and then remained constant. A progressive loss in cytoskeletal proteins was observed which correlated with a further increase in free calcium such that by 14 hours of incubation, when the internal calcium approached 1 mM, most of the spectrin and vimentin present in the cortex of the lens had disappeared. An unidentified 110-kilodalton protein also disappeared from lenses incubated in 5 mM calcium. These results indicate that proteolysis by calcium-dependent enzymes such as calpain may play a significant role in cytoskeletal regulation and metabolism in the lens. A role for cytoskeleton/membrane/crystallin interaction in calcium-induced opacification is discussed.

4-Chloromercuribenzenesulfonate↗
PubMed1989

Calcium-induced cleavage and breakdown of spectrin in the rat lens.

Incubation of intact rat lenses under conditions that stimulated a net influx of calcium resulted in a pronounced loss of transparency and a major decrease in the levels of spectrin. The progressive loss of this cytoskeletal component coincided with the appearance of polypeptides of approximately 150 kDa which showed immunoreactivity with an antibody raised to spectrin. These bands disappeared on further incubation. It is, therefore, suggested that a calcium-activated protease is present in the lens which is capable of degrading spectrin by the initial removal of approximately 90 kDa fragments. This process calcium-induced proteolysis may be the basis for the cytoskeletal reorganisation observed during the differentiation of lens fibre cells and may be involved in cataract development.

Animals↗
PubMed1989

Classification of primary lung tumors in dogs: 210 cases (1975-1985).

Two hundred ten dogs that had primary lung tumors diagnosed between 1975 and 1985 were evaluated. The majority of the tumors were classified as adenocarcinoma (74.8%) and alveolar carcinoma (20%). The most common clinical signs of disease were cough (52%), dyspnea (23.8%), lethargy (18.1%), weight loss (12.4%), and tachypnea (4.8%). The clinical methods that were most successful in directly or indirectly leading to a diagnosis of primary lung tumor were thoracic radiography (77.1%) and cytologic examination of fine-needle aspirate specimens (24.8%).

Adenocarcinoma↗
PubMed1989

Prognostic factors for tumor remission and survival in dogs after surgery for primary lung tumor: 76 cases (1975-1985).

The association of various prognostic factors with remission and survival after the excision of lung tumors was evaluated in 76 dogs. Overall, the median survival time of treated dogs was 120 days; 72% had tumor that underwent remission (median duration of remission, 120 days). Dogs with tumors that underwent remission had significantly (P = 0.001) increased survival time (median, 330 days vs 28 days for dogs with tumors that did not undergo remission). The finding of normal-sized lymph nodes at the time of therapeutic thoracotomy was significantly (P = 0.001) correlated with increased remission probability (85.4% remission rate vs 43.6% in dogs with large lymph nodes). Use of various diagnostic methods to find normal regional lymph nodes before surgery indicated that such finding was significantly (P less than or equal to 0.01) correlated with increased remission duration (median remission duration, 365 days, vs 60 days for tumors in dogs with large lymph nodes), and the finding of normal lymph nodes at the time of surgery was significantly (P less than or equal to 0.01) correlated with increased survival time (median, 345 days, vs 60 days for dogs with large lymph nodes).

Adenocarcinoma↗
PubMed1989

Rapid purification of ferritin from lysates of red blood cells using proteinase-K.

A simple, rapid, and novel procedure for purifying ferritin from the postnuclear supernatant of red blood cell lysates is described. This report establishes the resistance of commercially available holo- and apo-ferritins to proteinase-K digestion, and documents how the use of this enzyme, in conjunction with the well-documented resistance of ferritins to heat denaturation (75-80 degrees C for 10 min), makes it possible to obtain high yields (greater than 90%) of pure, undegraded ferritin from the postnuclear supernatant of hypotonically or Triton X-100 lysed red blood cells. The resultant purified ferritin contains the same amount of iron as ferritin not treated with proteinase-K and, as judged by one- and two-dimensional gel electrophoresis and electron microscopy, consists of intact ferritin with a subunit isoform composition identical in molecular mass and isoelectric points to that obtained from ferritin prepared in the absence of this enzyme.

Animals↗
PubMed1989

Human lens membrane cation permeability increases with age.

Parallel studies of the ionic balance and membrane permeability characteristics of normal human lenses were carried out in three countries (USA, England and Italy). Similar age-related changes were found in each laboratory. The lens membrane potential and resistance declined markedly with age while internal Na+ and free Ca2+ increased. There was a concomitant stimulation of Na+ and K+ transmembrane fluxes. These data indicate that in the ageing process there is an increasing contribution to membrane ion traffic from a channel, or channels, that permit Na+, K+ and Ca2+ to pass. The increase in permeability coincides exactly with the increase in optical density that occurs in the ageing human lens.

Adult↗
PubMed1988

Intraspinal epidermoid cyst in a dog.

A 2-year-old female Rottweiler was examined because of progressive gait deficits consistent with transverse myelopathy between the T2 and L3 spinal cord segments. Myelography confirmed an intramedullary spinal cord lesion between T13 and L1, so the dog was euthanatized. At necropsy, an intramedullary epidermoid cyst was confirmed in the T13 and L1 spinal cord segments. The epidermoid cyst probably resulted from a congenital cause.

Animals↗
PubMed1986

Relative bioavailability of a new transdermal nitroglycerin delivery system.

The purpose of this study was to measure the bioavailability of nitroglycerin from a new transdermal delivery system, Nitro-Dur II, relative to that of Nitro-Dur. Twenty-four healthy male volunteers completed a two-way crossover study. Each subject randomly received Nitro-Dur (I) and Nitro-Dur II (II) for a 24-h period. Both transdermal systems had an active surface area of 20 cm2. Blood samples were collected immediately before treatment, at 0.5, 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after topical application of the units, and 30 min after the units were removed. Nitroglycerin was determined with an analytical sensitivity of 50 pg/mL using gas chromatography with electron capture detection (GC-EC). Mean steady-state concentrations of nitroglycerin were 182 and 224 pg/mL for I and II, respectively. There were no statistical differences between I and II in the pharmacokinetic parameters measured (Css, AUC, Cmax, % fluctuation). Residual nitroglycerin content was measured in each transdermal unit after application to each of the 24 volunteers. The amounts of nitroglycerin delivered by I and II were 9.78 +/- 4.11 and 10.67 +/- 4.78 mg, respectively, or approximately 10 mg in 24 h. Statistical analysis of these data using an analysis of variance indicated no significant difference between these treatments (p = 0.27). Since there were also no differences in the plasma concentrations and pharmacokinetic parameters calculated after treatment with I and II, the bioequivalence of the two delivery systems was established.

Administration, Cutaneous↗
PubMed1985

Myotonia in a chow chow.

Congenital myotonia was diagnosed in an inbred Chow Chow pup with severe muscle stiffness that regressed with exercise. Voluntary movement, percussion, or needle insertion caused sustained contraction of the muscles involved. Electromyographic recordings from several muscles contained myotonic discharges. Creatine kinase activity was mildly increased. Slight myofiber hypertrophy and a few atrophic fibers were seen in muscle biopsy specimens. Treatment of the pup with procainamide caused a marked decrease in clinical signs. Myotonia congenita in the Chow Chow appears to be inherited as an autosomal recessive trait. This condition can be diagnosed on the basis of clinical signs. Satisfactory clinical management of myotonia congenita can be achieved with procainamide.

Animals↗
PubMed1985

Tetraparesis following cervical disk fenestration in two dogs.

Two dogs were nonambulatory and tetraparetic following cervical disk fenestration used as the treatment for cervical disk disease. Severe pain and cervical muscle fasiculation also were evident. The site of disk extrusion was localized radiographically, and cervical ventral decompression was used to remove the disk material. Recovery in both cases was complete.

Animals↗