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Biomedical subjects

T Bell

Publications and source records attributed to T Bell.

At least 55 records · Page 3Linked to original sources

Predesquamin inhibits desquamation.

Predesquamin is a Con A binding glycoprotein from human epidermis, with a molecular weight of 650 kDa. Its isolation and characterization are detailed, as well as the preparation of a polyclonal antibody to it. The antibody labels primarily the lower stratum corneum in fluorescent and ultrastructural immunolocalization, both in normal skin and plantar callus. A desquamation model system, in which plantar callus is incubated with the chelating agent ethylenediaminetetraacetic acid (EDTA) is refined by substituting for EDTA the Ca(2+)-specific ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Moreover, the shedding activity can be suppressed by raising the Ca2+ concentration. Within this model, it is demonstrated that predesquamin at nanomolar concentrations inhibits squame shedding in a dose-dependent manner. We conclude that predesquamin plays an important role in blocking premature desquamation of the lower stratum corneum.

Bony Callus↗

Assessing what high risk young children know about drugs: verbal versus pictorial methods.

Very young children are generally not targeted for drug education efforts for two basic reasons. First, it is generally assumed that young children are not cognitively ready to learn about specific drugs through systematic drug prevention efforts. And second, it is difficult to measure pre- and posttest changes on the part of young children if drug education intervention is instituted. This study involved measuring what children three to eight years old learned from systematic drug education over the course of eight months. Two assessment methods were compared: pictorial and verbal interviews. The posttest results revealed that the children who received the intervention knew significantly more about several drugs than a matched comparison group. Both methods were useful in providing a comprehensive view of what the children knew about alcohol and other drugs.

Audiovisual Aids↗

Culture of basal cell carcinoma.

Studies of basal cell carcinoma have been hindered by a lack of a suitable and reproducible tissue-culture model system. We have succeeded in growing this tumor in primary culture from eight different patients. We can separate and grow the tumor cells and the stromal cell component. We also culture normal keratinocytes and fibroblasts from the same patient for comparative studies. All the cell types have been subcultured four to five times and cryopreserved. The normal keratinocytes were indistinguishable from the tumor cells in ploidy, in rate of growth, and in the failure to express ICAM-1. Both cell types also fail to synthesize the matrix proteins: types I and IV collagens. Differences were noted in the expression of fibronectin and the bullous pemphigoid antigen, with the normal cells expressing the antigens although the tumor cells did not. Interferons exogenously added to the culture media preferentially killed the basal cell carcinoma cells, as compared to normal keratinocytes from the same patients. We believe that our culture system opens possibilities for biochemical and molecular studies of this disease, and for in vitro testing of antitumor agents for clinical therapy.

Basal Cell Carcinoma↗

Interferon-gamma modulates terminal differentiation and the expression of desquamin in cultured keratinocytes.

Interferon (IFN)-gamma has been shown to modulate cell differentiation and the expression of cell surface molecules of cultured human keratinocytes; it also induces cell shedding. We have previously described the properties of desquamin, a cell surface adhesion molecule from the stratum corneum. We report here on the impact of IFN-gamma on the expression of desquamin. We document the related morphological changes in terminal differentiation. We cultured human keratinocytes in three different culture systems: in serum-free medium at low Ca2+ (0.1 mM), at high Ca2+ (1.5 mM), and at high Ca2+ with 10% serum. IFN-gamma (100 U/ml) was added to each culture system after overnight incubation. In all cases, IFN-gamma induced an altered phenotype, as shown by phase contrast and electron microscopy. We exposed cultured cells to antibodies to the desquamins (glycoproteins from the stratum corneum). Immunoflurescent localization and Western blotting showed that the desquamins were expressed only under culture conditions where both serum and IFN-gamma were present. The induction of desquamin expression by IFN-gamma coupled with an increase in cell shedding, suggests that we have developed a suitable culture system for the study of desquamation in vitro.

Antibodies, Monoclonal↗

Grafting of leg ulcers with undifferentiated keratinocytes.

A procedure for transplanting cultured human keratinocytes has been developed and used successfully to treat patients with persistent leg ulcers. Shave excisions of donor skin of 1 cm2 or less were expanded in culture in 1 week to cover wounds as large as 90 cm2. The uniqueness of this system is the use of a biochemically modified surgical dressing that permits the transplantation of undifferentiated cells. Several hours after inoculation, trypsinized single cells become attached to the dressing and are ready for grafting. Seven of eight persistent stasis ulcers completely reepithelialized after application of the modified surgical dressing with undifferentiated keratinocytes.

Bandages↗

Sensitivity of desquamin to proteolytic degradation.

The stratum corneum is both a desquamating and degradative tissue; cell contacts become weaker in the outer lamellae and a variety of proteolytic and glycolytic enzymes cleave many macromolecules into free amino acids and saccharides. We have reported on a 40-kilodalton glycoprotein from human stratum corneum; because of its unique lectin-like properties, we believe that it plays a major role in desquamation and have named it desquamin. If desquamin is to function as a lectin during desquamation, it must survive enzymatic degradation in the outer stratum corneum. Accordingly, we treated this glycoprotein with a number of proteinases and found that desquamin is resistant in vitro to most of the types of proteinases that have been reported in the stratum corneum as well as several others that have not been identified as present in the tissue. In the stratum corneum, the lipids of the intercorneal mortar shield the glycoproteins; hence, desquamin is even less likely to be susceptible to endogenous proteolysis in vivo than in vitro.

Blotting, Western↗

Regional blood flow of the canine vocal cord: the microsphere surface technique.

The vocal fold's microcirculation has been well described, but there are few reports regarding the blood flow to this region. A number of methods have been used to evaluate the blood flow to an organ system. Among the most sensitive is the microsphere surface technique, which has been used to measure blood flow in many organ systems, including the cochlea. In this study, the blood flow to the canine vocal fold was assessed using the microsphere surface technique. Overall flow was measured, as well as flow to the lamina propria and muscularis layers. The technique and the results are reported.

Animals↗

Cohesive properties of terminally differentiated keratinocytes.

The stratum corneum can be dissociated into single squames by several extraction methods: mechanically, with organic solvents, and with detergents. We have performed studied of reaggregation from single squames prepared by these methods. Mechanically dispersed corneocytes recombined into a lamellar-like structure closely resembling intact stratum corneum. Squames obtained by dissociation in ether formed a multilayered structure which differed from the intact tissue in the collapse of the bilayered lamellar structure into a single lucent band with osmiophilic deposits. Squames obtained after extraction with detergent failed to reaggregate.

Cell Adhesion↗

Procaterol metered-dose inhaler: a multiclinic study evaluating the efficacy and safety in patients with asthma.

Procaterol hydrochloride aerosol, a potent beta 2-adrenergic bronchodilator, was evaluated in a double-blind, placebo-controlled study for efficacy and safety in 210 patients with documented mild to moderate reversible airway obstruction. Patients were randomized to receive procaterol in two inhalations (high dose) or one inhalation (low dose), 0.01 mg/inhalation, three times daily, or placebo. Pulmonary function tests were recorded at five and 30 minutes and hourly for eight hours after the first dose and following 1 and 2 weeks of treatment. Both doses of procaterol produced significantly greater improvement in PFTs at one hour and for up to seven hours after dosing compared with placebo (p less than 0.05). Mean percent increases in FEV1 were 35% in the high-dose group and 29% in the low-dose group at week 2. The high-dose group showed no loss of duration of bronchodilation with continued dosing. Improvement in PFTs and peak flow rates was significantly greater in the high-dose than in the low-dose group (p less than 0.05). Tremor was the most frequent side effect. Procaterol had no effect on electrocardiograms, heart rate, blood pressure, or clinical laboratory tests. The high dose of procaterol aerosol was shown to be an effective and well-tolerated bronchodilator with a rapid onset and long duration of action.

Adolescent↗

Purification of proteins from polyacrylamide gels, free of detergent or dye.

A two step procedure recovers proteins from sodium dodecyl sulfate polyacrylamide gels. The proteins are eluted by electrophoretic dialysis. The eluent is then passed through an Amberlite CG-400 anion-exchange resin. The recovery of protein is nearly total. The recovered proteins have no detectable sodium dodecyl sulfate contamination. With gels that have been stained with Coomassie Brilliant Blue R, the procedure recovers the proteins free of the dye. We have used this procedure successfully during the purification of epidermal glycoproteins.

Chromatography, Ion Exchange↗

Primary hypertension in a colony of dogs.

A 5-year-old female Siberian husky that was diagnosed as an essential hypertensive was bred several times over a 5-year period, producing a colony of 39 offspring. Thirty of the 39 animals were subjected to biweekly systemic arterial blood pressure determinations with femoral arterial puncture and were placed into two hypertensive and two normotensive groups based on mean blood pressure: Group 1 (mean blood pressure, 128 +/- 12 mm Hg), Group 2 (mean blood pressure, 121 +/- 3 mm Hg), Group 3 (mean blood pressure, 114 +/- 8 mm Hg), and Group 4 (mean blood pressure, 101 +/- 9 mm Hg). Groups 1, 2, and 3 had mean blood pressures significantly higher than that of Group 4 (p less than 0.05). Ten dogs (representatives from Groups 1, 2, and 3) were subjected to more detailed clinical testing including angiography, echocardiography, ophthalmic examination, plasma catecholamine and renin activity measurements, plasma lead and cadmium determinations, cerebrospinal fluid examination, renal profile, and serum chemistry and hematological analysis. Five unrelated normotensive Siberian huskies were compared with colony dogs by using echocardiography. Groups 1 and 2 showed a clear but statistically insignificant upward trend in left ventricular wall thickness indexed against body weights when compared with that in Group 3 and in the unrelated five normal Siberian dogs. Thus, the only specific difference from group to group in the colony at the termination of this study was the difference in mean blood pressure. Based on these data, it is possible and likely that aging will reveal changes secondary to chronic primary hypertension. The pathogenesis of this hereditary disorder remains unknown.

Animals↗

Regeneration of the eighth cranial nerve. II. Physiologic verification in the bullfrog.

Two experiments were performed to document the functional capacity of the regenerated eighth cranial nerve. In experiment 1, the eighth cranial nerve was sectioned preganglionically and allowed to regenerate in a group of bullfrogs with normal contralateral eighth nerve and labyrinth. Posture and reflex to lateral tilt were measured preoperatively and postoperatively for a minimum of 3 months. Similar measures were performed in a second group of bullfrogs in which the eighth nerve had been destroyed by ganglionectomy and in a third with peripheral labyrinthectomies. In experiment 2, the eighth nerve was sectioned and allowed to regenerate in bullfrogs in which the contralateral nerve had previously been destroyed. Posture and reflex to lateral tilt were measured as in experiment 1. Similar measures were performed in a group of bullfrogs that had undergone bilateral nerve destruction. Regeneration of the eighth cranial nerve in bullfrogs in both experiments was documented histologically by labeling the regenerated fibers with horseradish peroxidase (HRP). In both experiments, posture recovered completely only in the bullfrogs in which the eighth cranial nerve was allowed to regenerate. Reflex to lateral tilt recovered more rapidly in the bullfrogs with regenerated nerves than in any of the other bullfrogs.

Animals↗

Localization of Chlamydia trachomatis infection by direct immunofluorescence and culture in pelvic inflammatory disease.

Fifty-five women with suspected pelvic inflammatory disease underwent diagnostic laparoscopy and endometrial and tubal biopsy, with specimens for isolation of Chlamydia trachomatis and for staining with a species-specific monoclonal fluorescein-conjugated antibody to C. trachomatis were obtained from the urethra, rectum, endocervix, endometrium, tubes, and cul-de-sac. C. trachomatis was isolated from 21 patients (38%), including 10 (18%) who had positive endometrial or tubal cultures. The fluorescein-conjugated antibody stain was positive for 43 (86%) of 50 culture-positive specimens, for 14 (18%) of 78 culture-negative specimens from 21 patients who had positive cultures from other sites, and for one (0.5%) of 192 specimens from 34 patients who had negative cultures at all sites. Thus the sensitivity of direct fluorescein-conjugated antibody for culture-positive specimens was 86% and the specificity for specimens from culture-negative patients was 99%. Twelve upper genital tract specimens were positive by fluorescein-conjugated antibody only. Fluorescein-conjugated antibody staining of 50 paraffin-embedded endometrial aspirates showed extracellular or intracellular elementary bodies and or cytoplasmic inclusions in all of seven culture-positive specimens, in four of six culture-negative specimens from patients who had positive cultures at other sites, and in none of 34 specimens from patients with negative cultures. Thus fluorescein-conjugated antibody staining is useful for confirming the role of C. trachomatis in endometritis and salpingitis. It is more sensitive than culture for detection of chlamydia in endometrial or tubal specimens and is able to confirm that the organism is actually present in endometrial tissue (rather than simply reflecting contamination from the cervix) in women with clinical evidence of pelvic inflammatory disease.

Antibodies, Bacterial↗

Penetrating injuries of the Iliac vessels. Early recognition and management.

Exsanguination due to hemorrhage caused death in 18 percent of patients with penetrating iliac vessel trauma. Improved survival demands earlier recognition and expedient operative control. One hundred fourteen patients were treated at a single institution during an 11 year period. Gunshot wounds were the predominant cause of injury and combined arteriovenous injury was present in 40 percent of the patients. Twenty-one of the 28 deaths were directly related to vascular injury. All deaths occurred in patients who were initially hypotensive. Seventy-six percent of patients presented with entry wounds below the umbilicus, positive abdominal examination, and hypotension. Earlier recognition is based on this triad. Failure to respond to volume repletion portends a grave prognosis, but it is often reversed by rapid operative intervention. All hypotensive patients with entry wounds below the umbilicus and positive abdominal examination should be taken immediately to the operating room for resuscitation and operation.

Humans↗

Theophylline pharmacokinetics: variations between two similar study populations using oral oxtriphylline syrup.

The pharmacokinetics of two unmatched populations of asthmatic children, one from an asthmatic convalescent center in Denver and the other from an urban outpatient clinic, are compared after single and repeated dosing of a new asthma formulation, oxtriphylline syrup. Significant differences (p less than 0.05) in populations' theophylline total body clearance, apparent volume of distribution and absorption rates suggest future studies of multiple center design representing patterns of asthma more typical to the population at large would be more appropriate for selection of theophylline dosage guidelines.

Administration, Oral↗

Sustained-release theophylline therapy for chronic childhood asthma.

The efficacy of continuous, around-the-clock sustained-release (S-R) theophylline therapy, adjusted to approximate serum or plasma steady state theophylline concentrations (Tc) of 15 microgram/ml three hours following the last dose, was assessed in 18 children suffering from moderately severe chronic asthma. Two of the three formulations studied, Slo-Phyllin Gyrocaps and Theo-Dur, had excellent bioavailability and produced stable therapeutic Tc throughout an eight-hour dosing interval, using average doses of 8.7 +/- 0.5 and 8.4 +/- 0.6 (SE) mg/kg/dose, respectively. Pulmonary function responses paralleled Tc and were also stable throughout the dosing interval. Aerolate provided comparatively less stability, and higher doses (11.3 +/- 0.7 mg/kg) were necessary to produce therapeutic Tc. Toxicity was not evident when dosage was adjusted to avoid Tc exceeding 20 microgram/ml. S-R theophylline therapy, with the use of formulations of acceptable bioavailability, provides excellent control of chronic childhood asthma, offers the advantage of extended dosing intervals, and encourages improved patient cooperation in drug compliance.

Adolescent↗