Showing papers by "Saint Louis University published in 1988"

Determination and characterization of a cannabinoid receptor in rat brain.

Abstract: The determination and characterization of a cannabinoid receptor from brain are reported. A biologically active bicyclic cannabinoid analgetic CP-55,940 was tritium-labeled to high specific activity. Conditions for binding to rat brain P2 membranes and synaptosomes were established. The pH optimum was between 7 and 8, and specific binding could be eliminated by heating the membranes to 60 degrees. Binding to the P2 membranes was linear within the range of 10 to 50 micrograms of protein/ml. Specific binding (defined as total binding displaced by 1 microM delta 9-tetrahydrocannabinol (delta 9-THC) or 100 nM desacetyllevonantradol) was saturable. The Kd determined from Scatchard analysis was 133 pM, and the Bmax for rat cortical P2 membranes was 1.85 pmol/mg of protein. The Hill coefficient for [3H]CP-55,940 approximated 1, indicating that, under the conditions of assay, a single class of binding sites was determined that did not exhibit cooperativity. The binding was rapid (kon approximately 2.6 x 10(-4) pM-1 min-1) and reversible (Koff approximately 0.016 min-1) and (koff' greater than 0.06 min-1). The two Kd values estimated from the kinetic constants approximately 55 pM and exceeded 200 pM, respectively. The binding of the agonist ligand [3H]CP-55,940 was decreased by the nonhydrolyzable GTP analog guanylylimidodiphosphate. The guanine nucleotide induced a more rapid dissociation of the ligand from the binding site, consistent with an allosteric regulation of the putative receptor by a G protein. The binding was also sensitive to MgCl2 and CaCl2. Binding of [3H]CP-55,940 was displaced by cannabinoid drugs in the following order of potency: CP-55,940 greater than or equal to desacetyllevonantradol greater than 11-OH-delta 9-THC = delta 9-THC greater than cannabinol. Cannabidiol and cannabigerol displaced [3H]CP-55,940 by less than 50% at 1 microM concentrations. The (-)-isomer of CP-55,940 displaced with 50-fold greater potency than the (+)-isomer. This pharmacology is comparable to both the inhibition of adenylate cyclase in vitro and the analgetic activity of these compounds in vivo. The criteria for a high affinity, stereoselective, pharmacologically distinct cannabinoid receptor in brain tissue have been fulfilled.

Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model.

Abstract: Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia. A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as "nonclassical" cannabinoid analgetics that conform to this agonist-receptor three-point interaction model. At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor. A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro. Enantio- and stereoselectivity were exhibited by the nonclassical cannabinoid compounds for both the analgetic response and the ability to inhibit adenylate cyclase. The magnitude of the enantioselective response was equal for both the biochemical and physiological endpoints. Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo. A conceptualization of the cannabinoid analgetic receptor is presented.

Test-retest reliability of the pain drawing instrument

Abstract: Test-retest reliability of a pain drawing instrument was investigated. Pain drawings of chronic pain patients (n = 51) were scored for percentage of total body surface in pain and location of pain. A test-retest reliability coefficient of r = 0.85 was calculated for a time interval that averaged 71 days. In addition, a percentage of agreement based on distribution of pain over time was calculated at 88.2%. The effect on reliability of age, gender and time-interval differences was investigated. The utility of the pain drawing instrument as a measure of extent of pain and location of pain over time is discussed.

Ventral striatopallidal parts of the basal ganglia in the rat i. neurochemical compartmentation as reflected by the distributions of neurotensin and substance p immunoreactivity

Abstract: The distribution of neurotensin immunoreactivity in the basal ganglia of the adult rat was evaluated by studying alternate serial vibratome sections that were exposed to antiserum against neurotensin, substance P, or cholecystokinin. It was observed that a heterogeneous distribution of neurotensin-immunoreactive fibers and terminals contributes to the neurochemical compartmentation of the ventral pallidum and ventral striatum, and that significant numbers of neurotensin-immunoreactive neurons occupy striatal districts of the olfactory tubercle, nucleus accumbens, and ventromedial caudate-putamen. An intense band of pallidal neurotensin immunoreactivity characterizes the medial part of the ventral pallidum adjacent to the nucleus accumbens, whose medial boundary is conveniently defined in sections incubated with cholecystokinin antiserum. Electron microscopic studies showed that the pallidal plexus of neurotensin-immunoreactive elements consists primarily of boutons, which contact large dendrites in arrangements that in all respects appear to be of the classical striatopallidal variety. A gradual decrease in immunolabel was observed approaching the lateral parts of the ventral pallidum, which display sparse neurotensin immunoreactivity. The results thus indicate the existence of a significant neurotensinergic striatopallidal pathway confined primarily, if not exclusively, to the medial part of the ventral striatopallidal system. The contribution of neurotensin-immunoreactive fibers and terminals to the compartmentation of ventral striatum is expressed most vividly in their exclusion from clusters of tightly packed medium-sized neurons, many of which are intensely substance P immunoreactive. Such clusters appear identical with those previously described as rich in opiate receptors and poor in acetylcholinesterase activity. In the ventral striatal region where the nucleus accumbens and ventromedial caudate-putamen merge, neurotensin-immunoreactive neurons are organized in clusters. Further rostral in the nucleus accumbens, they are more evenly distributed. Few were found in the dorsolateral quadrant of the neostriatum.

Operational Criteria for the Determination of Suicide

Abstract: Suicide is an important public health problem for which we have an inadequate public health database. In the United States, decisions about whether deaths are listed as suicides on death certificates are usually made by a coroner or medical examiner. These certification decisions are frequently marked by a lack of consistency and clarity, and laws and procedures for guiding these decisions vary from state to state and even from county to county. Without explicit criteria to aid in this decision making, coroners or medical examiners may be more susceptible to pressures from families or communities not to certify specific deaths as suicide. In addition, coroners or medical examiners may certify similar deaths differently at different times. The degree to which suicides may be underreported or misclassified is unknown. This makes it impossible to estimate accurately the number of deaths by suicide, to identify risk factors, or to plan and evaluate preventive interventions. To remedy these problems, a working group representing coroners, medical examiners, statisticians, and public health agencies developed operational criteria to assist in the determination of suicide. These criteria are based on a definition of suicide as “death arising from an act inflicted upon oneself with the intent to kill oneself.” The purpose of these criteria is to improve the validity and reliability of suicide statistics by: (1) promoting consistent and uniform classifications; (2) making the criteria for decision making in death certification explicit; (3) increasing the amount of information used in decision making; (4) aiding certifiers in exercising their professional judgment; and (5) establishing common standards of practice for the determination of suicide.

Gc-globulin (vitamin D-binding protein) enhances the neutrophil chemotactic activity of C5a and C5a des Arg.

Abstract: Several serum proteins have been shown to be important in modulating leukocyte chemotaxis and inflammation. We investigated the possibility that the multifunctional serum protein Gc-globulin (vitamin D-binding protein) may also enhance the neutrophil chemotactic activity of complement-derived peptides. Purified Gc-globulin by itself did not induce chemotaxis of human neutrophils. However, as little as 0.01 nM Gc-globulin greatly enhanced the neutrophil chemotactic activity of C5a and its derivative, C5a des Arg over a wide concentration range. The effect was most pronounced at nonchemotactic doses of C5a (0.01 nM) and C5a des Arg (1 nM). Gc-globulin was unable to augment the neutrophil chemotactic activity of FMLP and leukotriene B4. This enhancing activity was not due to a nonspecific effect of anionic proteins since other purified serum proteins, of similar size and charge as Gc-globulin (alpha 1 acid glycoprotein, alpha 2 HS glycoprotein, alpha 2 histidine-rich glycoprotein), could not increase the chemotactic activity of C5a des Arg. Serum depleted of Gc-globulin by immunoaffinity chromatography totally lacked chemotactic enhancing activity for C5a des Arg. Gc-globulin-depleted serum activated with zymosan also had significantly less chemotactic activity than control- (sham-depleted) activated serum. Finally, radioiodinated C5a or C5a des Arg formed a 1:1 complex with purified Gc-globulin when analyzed by gel filtration chromatography. These results indicate that Gc-globulin is the major chemotactic enhancing factor in serum and may function as an up-regulator of the chemotactic activity of C5-derived peptides.

Four types of social phobia in a community sample.

Abstract: Point prevalence rates and demographic characteristics associated with four specific forms of social phobia (public speaking/performing, writing in front of others, eating in restaurants, and use of public restrooms) were examined in a sample of adult residents of the greater St. Louis area. Diagnos

Increased concentrations of leukotrienes in bronchoalveolar lavage fluid of patients with ARDS or at risk for ARDS.

Abstract: The sulfidopeptide leukotrienes (LT) C4 and D4 have been reported to promote the formation of pulmonary edema when administered into the pulmonary circulation of laboratory animals. As a first step in the evaluation of the hypothesis that these leukotrienes participate in the edema formation of the adult respiratory distress syndrome (ARDS), we investigated whether LTC4 and LTD4 were present in the bronchoalveolar lavage (BAL) fluid of patients with ARDS compared to nonsmoker control subjects and to patients with acute respiratory failure exhibiting no radiographic evidence of widespread pulmonary infiltrates but having a clinical predisposition for developing ARDS, i.e., the “at risk” group. Bronchoscopic lavage was performed with sterile 0.9% NaCl on 32 control subjects, nine patients with ARDS, and nine patients “at risk” for ARDS. Leukotrienes were measured in BAL fluid by radioimmunoassay after methanol extraction and HPLC purification of a 20-ml aliquot of the BAL sample. LTC4 and LTD4 (mean ± SE) i...

Effect of conduction defects on the signal-averaged electrocardiographic determination of late potentials.

Abstract: To determine the effect of cardiac conduction defects on the signal-averaged electrocardiogram (ECG) and on its ability to noninvasively identify patients predisposed to ventricular tachycardia (VT), standard 12-lead ECGs and signal-averaged ECGs were obtained in 213 patients with normal conduction and 186 patients with various conduction defects. Sustained VT was induced by programmed stimulation or occurred spontaneously in 122 patients. Two-way analysis of variance showed that conduction defects and VT were associated with changes in 3 signal-averaged ECG parameters: duration of the filtered QRS, duration of the terminal QRS under 40 microV and the mean amplitude of the terminal 40 ms of the QRS. Stepwise multiple logistic regression identified 3 variables that distinguished the patient with VT with a sensitivity of 62%, a specificity of 63% and a positive predictive accuracy of 63%. These 3 variables, listed in order of importance, were conduction defect score, duration of the filtered QRS and mean amplitude of the terminal 40 ms of the QRS. These data indicate that conduction defects have systematic effects on signal-averaged ECG parameters independent of those seen in patients predisposed to VT. These effects mandate the adjustment of the definitions of late potentials in the presence of conduction defects.

Polymorphous low-grade adenocarcinoma of minor salivary gland. An immunohistochemical and clinicopathologic study.

Abstract: Polymorphous low-grade adenocarcinoma (PLGA) is a minor salivary gland carcinoma usually arising intraorally, primarily in the palate. It is characterized by cytologic uniformity, histologic blandness, and a variable, infiltrating growth pattern. To date, 117 tumors have been reported but the immunohistochemical features of this neoplasm have not been adequately described. This report describes the immunohistochemical distribution of epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), high-molecular-weight keratin, muscle-specific actin (MSA), and S-100 protein in four palatal polymorphous low-grade adenocarcinomas arising in two men and two women. Three patients were treated with a combination of radiation and surgery, and one was treated with just surgery; none of the tumors recurred or metastasized. More than 90% of tumor cells in all four tumors stained with S-100 and EMA, while 75 to 95% stained with keratin. MSA staining intensity was variable; it ranged from less than 10% to 67% of tumor cells staining positively. CEA staining also was markedly variable; it ranged from very focal luminal positivity to 75% of tumor cells staining positive. The diffuse staining pattern of EMA and S-100 and the difference in staining patterns of EMA and CEA in PLGA is distinct from that found in adenoid cystic carcinoma. In the latter neoplasm, EMA and CEA staining patterns are similar and they are localized to ductal lumina; S-100 stains much less diffusely. These differences are useful in the differential diagnosis between these two tumors.

Increased frequency of restenosis in patients continuing to smoke cigarettes after percutaneous transluminal coronary angioplasty.

Abstract: The influence of continued cigarette smoking on restenosis after percutaneous transluminal coronary angioplasty (PTCA) was retrospectively determined through a study of 160 patients with primary success who underwent follow-up angiography after a mean of 7 ± 7 months. The average number of narrowings at risk for restenosis was 1.7/patient in the 84 patients who continued to smoke (group 1) and 1.9/patient in the 76 patients who stopped smoking at the time of PTCA (group 2) (difference not significant). The 2 patient groups at baseline were similar with respect to gender, frequency of diabetes mellitus, number of pack/year smoking, angina class and number of diseased coronary arteries. The location of the dilated narrowings, the residual luminal diameter stenosis and the transstenotic gradient after the procedure were similar in both groups. The recurrence of angina ≥ class II was the reason for restudy in 43% and 36% of group 1 and group 2 patients, respectively. Restenosis, defined as the presence of ≥50% narrowing at the site of previous successful dilatation at follow-up angiography, was significantly higher in group 1 compared with group 2 patients (55% vs 38%, p = 0.03). Continued smoking was selected as an independent predictor of restenosis by logistic regression analysis. The incidence of coronary artery disease progression (14% vs 10%) was not significantly different between the 2 groups. In conclusion, continued smoking after successful PTCA is associated with an increased risk of restenosis. The higher restenosis rate in smokers emphasizes the need to strengthen educational programs after PTCA.

A pathologic study of allergic bronchopulmonary aspergillosis.

Abstract: A lung biopsy specimen was obtained from a 10-year-old boy with cystic fibrosis and allergic bronchopulmonary aspergillosis. Light microscopy revealed a marked inflammatory process that was largely bronchocentric. Infiltrating cells included lymphocytes, plasma cells, monocytes, and numerous eosinophils. Elastin layers were intact in blood vessels and markedly disrupted in bronchioles. By immunofluorescent, major basic protein was demonstrated in eosinophils, was freely deposited outside of eosinophils, especially in the interlobular septum, and was taken up by macrophages. A number of lymphocytes stained positively for IgE. Through an immunoperoxidase stain, septate hyphae of Aspergillus were clearly observed in the lung parenchyma. A significant increase in interleukin-2 positive-staining T cells was observed with an approximate 2:1 ratio of helper to suppressor cells. The use of newer immunohistologic techniques has enabled us to gain additional insights into the pathogenesis of allergic bronchopulmonary aspergillosis.

Sinusitis in adults and its relation to allergic rhinitis, asthma, and nasal polyps

Abstract: Sinusitis, an infection of the paranasal sinuses, has been linked to allergic rhinitis, asthma, and nasal polyps. Sinusitis is a common complication of allergic rhinitis, which can lead to inflammation of the sinus mucosa, obstruction of the sinus opening or ostium, and generally favorable conditions for bacterial growth. Sinusitis can trigger asthma. Stimulated nerves in an infected sinus may result in parasympathetic stimulation to the bronchial tree and in smooth muscle contraction. Sinusitis may be a cause of nasal polyps, which are common when sinusitis complicates allergic rhinitis and even more common in nonallergic rhinitis. Treatment of sinusitis strives to eliminate infection and promote drainage. Ampicillin or amoxicillin is the antibiotic of choice. All patients with sinusitis should be treated with antibiotic to encourage drainage. Fluids, expectorants, and decongestants, both oral and topical, should be used. As many as half of patients with sinusitis also have marked rhinitis (either allergic or nonallergic), nasal polyps, or swollen, edematous mucosa; these patients should also receive topical steroids, such as flunisolide. Flunisolide promotes drainage and aeration by decreasing inflammation, swelling, and the influx of white blood cells. Persistent sinusitis may need to be treated surgically.

Insulin synthesis by isolated rabbit neurons.

Abstract: Insulin has been identified in the central nervous system of a number of vertebrate species, but the site of synthesis as yet remains unresolved. Two previous studies reported the presence of insulin mRNA in neural tissue, but related efforts to confirm and better localize the cellular origin of the hormone have yielded equivocal results. In the present study we have attempted to clarify this issue by employing both immunocytochemistry and in situ hybridization on isolated enriched cultures of rabbit brain neurons and glia. Our data show that a subset (3-5%) of neurons is positively immunoreactive for insulin, but all of the glial cells are negative. The level of staining intensity can be increased by preincubating the neurons with monensin (a Na+ ionophore that prevents cell secretory activity), but not the fraction of positive cells. Similarly, in situ hybridization reveals the presence of mRNA in 3-5% of neurons; but no such signal is detected in glia. Thus, our data not only confirm previous reports o...

Properties of Emerging Organizations

Abstract: Using organization theory, the properties of emergingorganizations are explored, as well as the opportunities for further researchin this area. Understanding the properties that an organization possesses as itis created will aid in identifying a framework for determining whenorganization creation may occur. Previous research has often focused only onstructure or on process -- this framework attempts to integrate theseapproaches. McKelvey's definition of organization is used to identify theproperties of emerging organizations. These properties are intentionality,resources, boundaries, and exchange. They represent the minimum characteristicsnecessary for identifying the existence of an organization, and help to focuson the interactions of agents and the environment. These characteristics may not become visible at the same time. Consequently,choosing one particular property as the sampling variable can dramaticallyimpact the point at which newly created organizations are identified. The useof these four properties will impact the methods and theory in organizationtheory and entrepreneurship. The use of each property to identify nascentorganizations is illustrated, and examples of previous research utilizing theseproperties are provided. Focusing on the period when a preorganizationmoves to a new organization will help to better explain the concept ofemergence and the manner in which organizations come into existence.(SRD)

Osteosarcomas arising on the surfaces of long bones.

Abstract: Malignant bone-forming tumors that arise from the surfaces of long bones are far less common than those that arise from within bone. These surface osteosarcomas are clinically and radiographically similar, yet histologically they are quite distinct. In reviewing the literature, we classified the tumors according to three subgroups: parosteal (juxtacortical) osteosarcoma, periosteal osteosarcoma, and high-grade surface osteosarcoma. We also studied the clinical, radiographic, and histological findings in eighty patients who had been treated for an osteosarcoma over a forty-four-year period. Adequate follow-up data existed for forty-eight of the eighty patients. The duration of follow-up ranged from two to fifteen years after the initial operation (amputation or resection). Patients who had a parosteal osteosarcoma had the best prognosis; those who had a periosteal osteosarcoma, the next best; and those who had a high-grade surface osteosarcoma, the poorest. Because of these widely varying prognoses, the lesions require different treatment.