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Biomedical subjects

W C Hulbert

Publications and source records attributed to W C Hulbert.

50 records · Page 3Linked to original sources

Histamine dose-response curves in guinea pigs.

Histamine dose-response curves were performed on anesthetized tracheostomized guinea pigs that were paralyzed and mechanically ventilated at a constant tidal volume and breathing frequency. The dose was calculated by generating an aerosol of known concentration and measuring the volume delivered to the lung. Increasing the dose was accomplished by increasing the number of breaths of aerosol delivered. The response to each dose was determined by measuring the change in airway resistance (RL) and dynamic compliance (Cdyn) using the method of Von Neergaard and Wirz (Z. Klin. Med. 105: 51-82, 1927). With increasing doses of histamine, RL increased and reached a plateau at approximately five times the base-line value and Cdyn fell to approximately 20% of its initial value. The variability in the base-line and maximum response as well as the calculated sensitivity and reactivity was less than that previously reported. Propranolol pretreatment increased resting RL and shifted the dose-response curve for RL to the left of the controls, increasing reactivity but not sensitivity. Atropine shifted the dose-response curve to the right of the control, decreasing sensitivity but without changing reactivity. The data for Cdyn showed that atropine pretreatment caused a higher resting value and propranolol pretreatment a lower value at the highest histamine dose but no differences in either sensitivity or reactivity.

Aerosols↗

A re-assessment of the tricellular region of epithelial cell tight junctions in trachea of guinea pig.

The tricellular region of epithelial tight junctions was previously dismissed as a possible avenue of permeability. One reason was that the two parallel vertical fibers, which penetrate the depth of the tight junction, were apparently cross-linked. Another reason was that the tricellular region of the tight junction is deeper than the adjacent bicellular regions. In the course of several freeze-fracture studies of epithelial tight junctions we have made observations which led us to re-assess the tricellular region as an avenue of permeability. We believe that information from ectoplasmic fracture faces is less subject to artifacts and, in ectoplasmic fracture faces of tricellular regions, cross-linking of the vertical furrows has not been observed. In guinea pig tracheal epithelium the tricellular junction is only about 1 micron deep. Following exposure to cigarette smoke, lanthanum ion staining has been observed in some tricellular junctions. It seems that earlier reasons for dismissing tricellular regions of the tight junction as permeability sites may be insufficient and that there is some evidence to support a role in permeability.

Animals↗

The structure of tight junctions in the tracheal epithelium may not correlate with permeability.

To test the hypothesis that cigarette smoke produces changes in the morphology of tight junctions guinea pigs were exposed to cigarette smoke or air in a previously standardized fashion (Simani et al. 1974). Permeability is greatest one half hour following exposure to cigarette smoke (Hulbert et al. 1981). The animals were sacrificed at that time. The tracheal epithelium was studied using both thin-section and freeze-fracture techniques. A quantitative analysis of the organization and integrity of junctional complexes was performed for each animal. Organization was assessed by measuring and comparing areas delimited by PF fibers and EF furrows. PF fiber integrity was assessed by measuring uninterrupted lengths of fibers and furrows from freeze-fracture replicas. This assessment did not demonstrate a change in tight-junction morphology following exposure to cigarette smoke.

Animals↗

Intussusception following resection of Wilms tumor.

Postoperative intussusception is a documented complication of pediatric surgical and pediatric urologic abdominal operations. In contrast to "primary" intussusception's triad of crampy abdominal pain, palpable abdominal mass, and "currant jelly" stools, postoperative intussusception is generally characterized by abdominal pain and vomiting. An abdominal mass is not usually palpable, and few children have bloody stools. Proper diagnosis and treatment may be delayed because of similar abdominal symptoms in children who may be receiving radiation and chemotherapy, or with prolonged ileus. Two children operated on for Wilms tumor demonstrate the need for awareness of this potential problem in the postoperative patient.

Child↗

Urinary incontinence.

Accurate diagnosis and successful management depend on knowledge of the anatomy and regulatory physiology of micturition. Incontinence is classified according to its mechanisms--passive incontinence, active incontinence with or without complete emptying, and overflow incontinence. Approaches to management include pharmacotherapy, surgical procedures and important steps in supportive care. This is a problem of any age. Educating the patient is essential.

Female↗

An improved method for fixation of the respiratory epithelial surface with the mucous and surfactant layers.

A new technique for the stabilization of the mucous layers in the upper respiratory tree is described. The methodology combines perfusion of the thoracic vasculature through the carotid, thyroid, and bronchial arteries, with aerosolization of fixative onto the airway surface through a tracheostomy. The biphasic nature of the mucous layer in healthy animals is confirmed and is compared with the nature of the mucus in animals exposed to cigarette smoke. The fundamental advantage of the technique is that, because airway surface phenomena are stabilized, more thorough correlates of physiology and morphology can be accomplished. The intrapulmonary airways and parenchyma are also fixed by using this technique, and the results are discussed. A preliminary communication using this technique to document leukocyte transit across the respiratory mucosa has been published.

Aerosols↗

Airway permeability to horseradish peroxidase in guinea pigs: the repair phase after injury by cigarette smoke.

Airway permeability was examined in the 24-h period immediately after injury by cigarette smoke in 30 guinea pigs studied in groups of five at 30 min and 1, 6, 12, and 24 h after smoke exposure, and in 1 control group. The animals were anesthetized, tracheostomized, a carotid cannula inserted, and purified horseradish peroxidase was instilled on the airway surface via the tracheostomy tube. Blood samples (0.8 ml) were drawn and replaced with heparinized saline before and at 10, 15, 20, 30, and 40 min after horseradish peroxidase instillation. The animals were then killed, and samples of trachea and lung tissue taken for wet/dry wt determinations and for light and electron microscopic examination. The HRP concentrations in the blood were determined using an Elisa plate assay. We found the acute exposure to 100 puffs cigarette smoke resulted in a transient increase in airway epithelial permeability of HRP with a maximum at 30 min and a return to control values by 12 h after insult. These changes in mucosal permeability occurred in relation to a well-defined inflammatory reaction where increased permeability occurred during the exudative phase, which was monitored by measuring airway wet wt/dry wt ratios and the infiltration of polymorphonuclear cells. The return to the control value of permeability was associated with the repair phase of the inflammatory reaction, which was measured by monitoring basal cell mitoses.

Animals↗

The site of leukocyte migration through the tracheal mucosa in the guinea pig.

The tracheal mucosa of the guinea pig was examined using light microscopy, thin section, and freeze-fracture replicas with transmission electron microscopy and scanning electron microscopy. These studies demonstrated that inflammatory cells en route to the mucosal surface migrate through the epithelium in file through solitary openings rather than randomly between epithelial cells. The fact that leukocytes migrate through these openings rather than randomly between epithelial cells has important implications. First, it provides a pathway for circulating cells to gain access to the surface of the airway where they can function as the first line of defense against inhaled material. Second, the movement of leukocytes through specified pathways rather than randomly between cells minimizes the number of openings required for cell transit so that fluid and solute movement can be more tightly controlled. Third, the prevention of random migration may also be important in minimizing the contact between the migratory cells and the epithelial sensory nerve net.

Animals↗

Metabolic sources of heat and power in tuna muscles. I. Muscle fine structure.

As part of an investigation into the generation of muscle heat in the tuna, the histochemistry and ultrastructure of the myotomal muscles were studied. Both red and white fibres are differentiated into two forms. The two forms of red muscle are very similar except for differential electron absorbance and different kinds of glycogen granules stored. In both forms, capillarity, mitochondrial numbers, and intracellular lipid droplets are abundant, implying the potential for a vigorous aerobic metabolism. During bursts of swimming, glycogen granules and intracellular lipid droplets are both largely depleted. The two types of white fibre differ in electron absorbance, pinocyotic activity, glycogen abundance, and insertion pattern, all of which are more pronounced in the 'dense' fibre form. Several features of tuna white muscle are unique or unusually developed. Thus, tuna muscle contains more glycogen than does red muscle. Glycogen granules may be randomly dispersed in myofibrillar or peripheral regions or may be sequestered in membrane-bound structures termed glycogen bodies. During short bursts of swimming, glycogen granules from all storage sites are mobilized. The white muscle has an ample capillary supply, small, but significant, amounts of intracellular lipid, and unusual numbers of mitochondria.

Animals↗

Metabolic sources of heat and power in tuna muscles. II. Enzyme and metabolite profiles.

Tuna appear able to maintain their muscles at 5-10 degrees C above ambient by balancing heat produced in situ and conserved by a counter-current heat exchanger with heat lost to the sea. Metabolite profiles under three different activity states (rest, burst swimming, and steady state swimming during feeding frenzies at sea) were used to identify which metabolic processes in white and red muscles could account for observed excess temperatures. During burst swimming, transient changes in metabolite levels indicate that the metabolism of both red and white muscle contributes to powering burst swimming; red muscle work is sustained mainly by oxidative metabolism while white muscle work depends upon an intense anaerobic glycolysis. The rate of metabolism in red muscle is easily high enough to account for the measured (10 degrees C) increase in temperature at this time. However, in white muscle, anaerobic glycolysis can account for only about a 2 degrees C maximum rise in temperature. The highest sustained swimming speeds and the highest muscle temperatures in skipjack are found during feeding frenzies at sea. As in burst swimming, during steady-state swimming red muscle temperatures can be accounted for by oxidative metabolism. In the case of white muscle, the lactate measurements indicate that anaerobic glycolysis could only lead to a 0.3 degree C temperature rise. However, if the fraction of utilized glycogen that is not fermented (about 60%) is assumed to be fully oxidized, enough heat is generated to raise white muscle temperatures by over 10 degrees C. The observed excess temperature at this time is about 8-10 degrees C, showing that anarerobic carbohydrate metabolism in white muscle is probably the major heat source during feeding frenzies. These interpretations are fully consistent with enzyme profiles of red and white muscles in tuna. They do not, however, explain why tuna have warm muscles. The latter problem is briefly discussed.

Aerobiosis↗

The phosphoenol-pyruvate branchpoint in adult Hymenolepis diminuta (Cestoda): a study of pyruvate kinase and phosphoenol-pyruvate carboxykinase.

The properties of pyruvate kinase (PK) and phosphoenol pyruvate carboxykinase (PEP CK), two enzymes that determine the preferrential accumulation of either succinate or lactate as endproducts of carbohydrate metabolism, are described in adult Hymenolepis diminuta. PK activity at Vmax and Km levels of PEP was unaffected by ATP, alanine, FDP4, OR H+ ions, but was inhibited by 50% at 6.3 mM L-lactate and 30 mM HCO3. The addition of 30 mM HCO3 increased the Km(PEP) by 6-fold but did not alter the Vmax. The inhibition of PK by HCO3 cannot be explained entirely by an effect of ionic strength, but probably represents a specific modulator-enzyme interaction. Under similar conditions PEP CK was maximally activated. Although L-lactate inhibited PEP CK (Ki(lac) = 1.8 mM), this effector may play a minor role in regulation of PEP flux. These results implicate the poise of the HCO3-:CO2 system as a major determiner of endproduct accumulation in H. diminuta.

Animals↗