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Biomedical subjects

J L Black

Publications and source records attributed to J L Black.

At least 19 recordsLinked to original sources
PubMed1992

Obsessive compulsive disorder: a clinical update.

Recent epidemiologic studies have indicated that obsessive compulsive disorder is a fairly common psychiatric condition. In this article, obsessive compulsive disorder, its subtypes, and epidemiologic features are described. The common obsessions and compulsions are discussed, as are the comorbid conditions. Currently, etiologic hypotheses revolve around serotonergic and dopaminergic neurotransmitter systems. Management of patients with obsessive compulsive disorder involves education, pharmacotherapy, and behavior therapy, and recent advances in such treatments offer patients hope. Psychotherapy has not proved useful. In refractory cases, psychosurgical intervention remains an option.

Behavior Therapy↗
PubMed1992

A retinitis pigmentosa register for western Australia.

This paper describes the main elements of the Western Australian retinitis pigmentosa register including details of the data stored on the register, aspects of the coding systems used and some description of the tests employed in diagnosis of retinitis pigmentosa. The register is family based and contains data on affected individuals and on their unaffected relatives. As at November 1991, the register contained data for 391 individuals from 207 separate families. Of the 391 individuals, 240 had definite or probable retinitis pigmentosa and 26 were possibly affected. The remainder were unaffected family members. In many cases, both affected and unaffected family members are being studied serially and the register is designed to store and easily retrieve serial data to allow study of disease progression for individuals and within families.

Australia↗
PubMed1992

Phosphoramidon potentiates the contractile response to endothelin-3, but not endothelin-1 in isolated airway tissue.

1. Phosphoramidon (10 microM) markedly increased the contractile response to endothelin-3 in human and rabbit bronchus in vitro. In human tissue the contractile response to 0.3 microM endothelin-3 was significantly increased from 54 +/- 12% to 137 +/- 34% (of the response to 1 nM acetylcholine) in the presence of phosphoramidon. Similarly, in rabbit isolated bronchus, the endothelin-3-induced response was increased from 34 +/- 5% to 61 +/- 7%. 2. In addition, the potency (as measured by EC30 values) of this peptide in human and rabbit airways was significantly augmented in the presence of the enzyme inhibitor. The geometric mean EC30 value was decreased from 53 nM (95% CI:15, 190) to 8 nM (95% CI:3, 23) in human bronchus and from 150 nM (95% CI:89, 250) to 23 nM (95% CI:11, 50) in rabbit tissue. 3. Neither the potency nor the response (at 0.3 microM) to endothelin-3 in canine bronchial rings was altered after incubation of the tissue in phosphoramidon. 4. A previous study carried out in human airways has implied that the difference in potency between endothelin-1 and endothelin-3 may be attributed to a heterogeneous endothelin receptor population. The results of our study, while also demonstrating this difference in potency, have shown that this marked difference, as well as that obvious in rabbit airway tissue can be abolished in the presence of phosphoramidon. 5. Phosphoramidon produced no change in the cumulative concentration-response curve for endothelin-1 in airway tissue from the three species studied. 6. These results suggest that a phosphoramidon-sensitive enzyme (probably neutral endopeptidase) found in lung, may be responsible for local degradation of endothelin-3, but not endothelin-l in human and rabbit isolated bronchus.

Animals↗
PubMed1992

Tachykinin receptors in rabbit airways--characterization by functional, autoradiographic and binding studies.

1. In many species, both NK1 and NK2 tachykinin receptors appear to be important in mediating the contraction of airway smooth muscle. We have examined the distribution and characterization of receptors for tachykinins in rabbit airways using functional length tension studies, autoradiography and radioligand binding studies. 2. Contractile responses to tachykinins were elicited in four different areas of the respiratory tree--trachea, and three progressively more distal areas of the right bronchus. The NK2 receptor-preferring agonists, neurokinin A (NKA), neuropeptide gamma (NP gamma) and the NK2-selective [Lys5 MeLeu9, Nle10]-NKA(4-10) [NKA (4-10) analogue] produced similar contraction in all four areas. Substance P (SP) and the NK1-selective [Sar9,Met(O2)11]-SP (Sar-SP) exhibited a marked location-dependence in the magnitude of contraction, producing minimal contraction in the trachea and more proximal bronchi with contractions becoming progressively larger in the more distal airways. Senktide (which is selective for the NK3 receptor) produced negligible contraction in all areas. 3. The NK2-selective antagonist, MDL29,913, was a weak antagonist of NKA and NKA(4-10) analogue. At a concentration of 2 microM, it produced a small but significant shift in the response curve to NKA and a greater shift (8 fold) in the curve to NKA(4-10) analogue, but it had no effect on responses to Sar-SP. The non peptide NK1 receptor antagonist, CP-96,345, was also unexpectedly weak in this preparation. The pD2 value for Sar-SP was decreased 27 fold by CP-96,345 at a concentration of 1 microM, without alteration in the maximum response.4. Autoradiographic binding sites to ['251I]-NKA were sparse over smooth muscle in proximal airway preparations and markedly increased in density in the more distal airways. There was negligible binding over vascular smooth muscle and epithelium.5. Radioligand binding studies revealed binding to ['251I]-NKA which was 82% specific. The order of potency for inhibition of ['251I]-NKA binding was SP> = Sar-SP> NKA = NPy>CP-96,345> NKA(4-10) analogue >NKB>>>MEN 10207 (the NK2 subtype selective antagonist) >MDL 29,913> senktide. This profile indicates binding predominantly to NK, receptors.6. These results suggest that there are at least two types of tachykinin receptors in rabbit airways, a population of NK, receptors, the density of which is greatest in the periphery and, in addition, NK2 receptors which are uniformly distributed throughout the airways. These receptors have unusual characteristics in that the NK, antagonist, CP-96,345 and the NK2 antagonist, MDL 29,913 respectively exhibited only weak potency.

Amino Acid Sequence↗
PubMed1992

Platelet-activating factor-induced contraction of human isolated bronchus.

In recent years, platelet-activating factor (PAF) has been strongly implicated as a mediator involved in asthma. In non-asthmatic subjects, aerosolized PAF has been shown to cause bronchoconstriction. The mechanism of this in vivo effect is unknown. We have previously shown that PAF causes a contraction of human isolated bronchus that varies in magnitude between patients, and within tissues from the same patient. To examine the possibility that this variability in contraction was secondary to PAF-induced release of mediators from inflammatory or epithelial cells within the tissue, we examined the relationship between contractile responses to PAF and the presence of inflammatory or epithelial cells. We studied eight tissues from five patients. Of the eight tissues, four contracted, whilst four failed to contract, to PAF (7 x 10(-7) M). After the contractile response to PAF had been assessed by observing changes in isometric tone in vitro, bronchial rings were examined histologically to enable the quantification of inflammatory cell numbers and intact epithelium. No significant correlation was observed between the magnitude of contractions and numbers of eosinophils, neutrophils, lymphocytes, plasma cells, total cells or percentage intact epithelium. We conclude that it is unlikely that the variability in response to PAF in human isolated airways is related to the variability in inflammatory cell numbers or to the presence of epithelium. Thus, the contraction induced by PAF is probably not mediated via the release of a secondary mediator from the particular cells examined in this study.

Bronchi↗
PubMed1992

Auditory P300 studies in schizophrenic subjects and their first degree relatives.

Nineteen subjects with schizophrenia, 6 subjects with related disorders (schizophrenic spectrum disorders (S.S.D.)), and 20 unaffected first degree relatives from a sample of schizophrenic pedigrees, together with 35 normal control subjects, had auditory P300 evoked responses measured, using the "odd-ball" paradigm for stimulation. Bipolar recording on the midline (CZOZ) and two contralateral sites (CZ-mastoid) was carried out. It was found that approximately 40% of schizophrenics/S.S.D.'s had abnormal P300 responses. Abnormalities were seen in latency, RMS response voltage and in the left side response--right side response cross correlation coefficient. Schizophrenics/S.S.D.s showed responses which were topographically different than those of normal controls. Significant left-side/right-side response voltage asymmetry was not observed. In our study, only 10% of unaffected relatives of schizophrenics/S.S.D.'s showed abnormal P300 responses.

Adolescent↗
PubMed1991

Beta-adrenoceptors in human airway tissue: relationship between functional responsiveness and receptor number.

Functional organ bath experiments and radiolabelled ligand binding studies were used to investigate the relationship between beta-adrenoceptor-mediated relaxation and the total number of beta-adrenoceptors in human lung parenchymal tissue and bronchial tissue. Sensitivity to the beta-adrenoceptor agonist isoprenaline (pD2) varied almost 10-fold (pD2 values 6.00 to 6.85) for lung parenchymal preparations and 35-fold for bronchial preparations (pD2 values 6.16 to 7.67) between patients. The total number of [3H] DHA labelled beta-adrenoceptors (Bmax) varied almost 6-fold for lung parenchymal membrane preparations (Bmax 164 to 936 fmol/mg protein) and less than 2-fold for bronchial tissue membrane preparations (Bmax 188 to 342 fmol/mg protein) between patients. Comparison of sensitivity to isoprenaline and beta-adrenoceptor number for lung parenchymal tissue from the same patient demonstrated a negative correlation (r = -0.80 [95% confidence intervals: -0.13, -0.96], 6 d.f., P less than 0.05), suggesting that beta-adrenoceptor-mediated sensitivity of lung parenchymal tissue is inversely related to the number of beta-adrenoceptors. However, there was an absence of correlation between sensitivity to isoprenaline and beta-adrenoceptor number in bronchial tissue from the same patient. Thus, the findings of the present study do not support the possibility of a direct relationship between the beta-adrenoceptor-mediated responsiveness and the beta-adrenoceptor number of human airway preparations.

Aged↗
PubMed1991

Neuropeptide gamma, the most potent contractile tachykinin in human isolated bronchus, acts via a 'non-classical' NK2 receptor.

Cumulative contractile response curves to neurokinin A (NKA) and neuropeptide gamma (NP gamma) were obtained in human isolated bronchus, in the presence of phosphoramidon 10 microM. NP gamma was approximately 10-fold more potent than NKA (pD2 values 8.6 +/- 0.4 and 7.3 +/- 0.3 respectively, n = 6; P less than 0.01). The NK1-selective agonist [Sar9, Met(O2)11]-SP and the NK3 selective agonist senktide produced negligible contraction. Response curves to NP gamma and NKA were unaffected by the NK2 subtype-selective antagonist MDL 29913 at 2 microM, but NP gamma-induced contraction was markedly inhibited by 20 microM MDL 29,913. Thus NP gamma is the most potent tachykinin in human isolated bronchus and its effects are mediated at a receptor which is not of the 'classical' NK2 subtype found in hamster urinary bladder.

Amino Acid Sequence↗
PubMed1991

Functional and autoradiographic studies of endothelin-1 and endothelin-2 in human bronchi, pulmonary arteries, and airway parasympathetic ganglia.

We compared the contractile potency and efficacy of two of the forms of endothelin (endothelin-1 and endothelin-2) on human bronchi and pulmonary arteries in vitro and examined the effects of sarafotoxin on the bronchial preparations. In addition, we used autoradiographic methods to investigate the location of binding sites for both forms of endothelin within human lung. Endothelin-1 (ET-1) was 2.5 times more potent than endothelin-2 (ET-2) in both the airway and vascular tissues, and both forms of the peptide were 5 times more potent in the isolated pulmonary artery than in the bronchial tissue. There were no differences in the magnitude of the contractions generated by ET-1 and ET-2 in either tissue type. Sarafotoxin also produced a contractile response in the bronchi that was equipotent to ET-1 but of a greater magnitude. Specific binding on the smooth muscle of bronchus, pulmonary artery, and alveolar walls to both ET-1 and ET-2 was detected in autoradiographic studies. In addition, binding sites for both forms of the peptide were localized to parasympathetic ganglia within the airways, where the presence of muscarinic receptors was also confirmed with [3H]QNB. There appeared to be no difference between the endothelins in the location or the density of binding sites. These results indicate that endothelin may have a neuromodulatory role in the airways as well as a direct contractile action on the bronchial and arterial smooth muscle.

Autoradiography↗
PubMed1991

Nedocromil sodium inhibits substance P-induced potentiation of cholinergic neural responses in the isolated innervated rabbit trachea.

1. Sensory neuropeptides such as substance P may be implicated in the pathophysiology of asthma. 2. It has been proposed that nedocromil sodium may inhibit the effects of neuropeptides. 3. In this study, using an isolated innervated preparation of rabbit trachea, substance P, 10(-6) M, potentiated contractions induced by parasympathetic stimulation. The effect of substance P at the preganglionic site (307 +/- 38% of control, n = 5), was similar to that at the postganglionic site (307 +/- 61% of control, n = 5). 4. Nedocromil sodium, 10(-7) M, significantly inhibited the substance P-induced potentiation preganglionically (199 +/- 44%, n = 4, P less than 0.05) but not postganglionically (356 +/- 118%, n = 4). 5. These results suggest that nedocromil sodium may modify neuropeptide action selectively at a preganglionic site and that this may contribute to its therapeutic efficacy.

Animals↗
PubMed1991

The mechanism of action of endothelin in human lung.

1 The peptides endothelin-1 (ET-1) and endothelin-2 (ET-2) elicited potent and sustained contractions of human isolated bronchus and pulmonary artery. 2 ET-1 is one of the most potent contractile agonists investigated in these tissues with an EC50 value of 18.3 nM (95% confidence interval: 12.9, 25.9 nM: n = 26) in bronchus and 3.2 nM (95% confidence interval: 0.4, 23.9 nM; n = 5) in the arterial preparation. 3 ET-1 is 2.5 times more potent than ET-2 in both the airway and vascular tissues, and both forms of the peptide have geometric mean EC50 values 5 times greater than in the isolated bronchial tissue than in the pulmonary artery. 4 Neither pretreatment with the voltage-dependent calcium (VDC) channel antagonist verapamil (10 microM) nor with indomethacin (25 microM) significantly altered the response curve to ET-1 in human isolated bronchus. Removal of calcium from the Krebs-Henseleit solution did not affect ET-1-induced responses. 5 Specific binding on the smooth muscle of human airway and pulmonary arterial tissue to both ET-1 and ET-2 was detected in autoradiographic studies. There appeared to be no difference between the peptides in the location nor the density of binding sites. 6 We conclude that contraction of human bronchial tissue by ET-1 is not dependent upon influence of extracellular calcium nor release of prostaglandins or thromboxane A2. It is likely that the action of ET-1 in this tissue is due to binding of this peptide to specific receptors located on the smooth muscle.

Binding Sites↗
PubMed1991

A national survey on pediatric training and activities in school health.

National trends in school health practice and training were assessed 10 years after the report of the 1978 American Academy of Pediatrics Task Force on Pediatric Education. A questionnaire was sent to 2,237 randomly selected AAP Fellows and was returned by 1,068 (48%). Seventy-seven percent of practicing pediatricians reported involvement in some type of school-based or school consultant activity. Those having residency training in school health and those practicing in rural areas were most likely to be involved. The most common types of activity were school-based pre-athletic exams (56%), consultant to special education placement (26%), and game/event physician (23%). Pediatricians were paid for 20% of sports-related school consultation and 25% of nonsports school health activities. Didactic or clinical training in school health was offered during residency to 19%. Specific didactic topics in school health included learning and attention deficit disorders (32%), physician role in health education (15%), and sports medicine (12%). Preathletic participation exams were the most commonly performed school health activity during residency (23%), followed by serving as a school consultant (11%), and attending an individual education plan meeting (7%). Most pediatricians engaged in school health activities. However, they did so without preparation during residency and without payment for their services.

Chi-Square Distribution↗
PubMed1991

Substance P-induced contraction of rabbit airways: mechanism of action.

The mechanism by which substance P induces contraction of airway smooth muscle has been the subject of numerous reports. It has been suggested that in rabbit airways the action of substance P is indirect, via the release of endogenous acetylcholine, whereas this is not so in other species. The present detailed study investigated whether substance P-induced contraction in rabbit isolated bronchus and trachea is due to the release of endogenous acetylcholine or in bronchus is due to histamine release and whether substance P is metabolized by the enzymes enkephalinase and acetylcholinesterase. Isometric contraction to cumulative addition of substance P was measured in the presence of 10(-6) and 10(-4) M atropine, 10(-6) M pyrilamine, 10(-5) M phosphoramidon, or 3 x 10(-7) M neostigmine. Neither atropine nor pyrilamine had any effect on the substance P responses. Phosphoramidon, however, produced a 12-fold shift to the left in the response curve with a decrease in the 50% effective concentration from 7.0 x 10(-8) to 6.1 x 10(-9) M (n = 4 control and 5 treated; P less than 0.05). In contrast, neostigmine at a concentration that produced a sixfold shift to the left in the acetylcholine response curve had no effect on substance P responses. We conclude that, in rabbit airways in vitro, substance P-induced contraction is not mediated by release of endogenous acetylcholine or histamine. In addition, endogenous enkephalinase but not acetylcholinesterase may be involved in the degradation of substance P. Our results show that, in contrast to previous studies in rabbits, the mechanism of action of substance P may resemble that described in humans.

Animals↗
PubMed1991

Pharmacology of airway smooth muscle in chronic obstructive pulmonary disease and in asthma.

Only a small number of studies investigating the in vitro pharmacologic properties of airway smooth muscle in asthma and well-characterized COPD have been performed. Further detailed studies on well-defined patient groups are required. The majority of available evidence would suggest that once airway smooth muscle is removed from its in vivo milieu, it loses the characteristics of hyperresponsiveness. This would explain why there are no clear differences in the pharmacologic responsiveness of tissue from patients with asthma or COPD and those with no obstructive disease. Future in vitro studies should be directed towards reproducing the in vivo environment. this would entail the establishment of a chronic inflammatory condition created by the continuous presence of neural and humoral factors.

Asthma↗
PubMed1990

Neurokinin A with K+ channel blockade potentiates contraction to electrical stimulation in human bronchus.

This study investigated the effects of neurokinin A (NKA) on cholinergic neural responses in human bronchus. NKA (0.1 nM) did not alter the contractile response to submaximal electrical field stimulation. However, K+ channel blockade with 4-aminopyridine (4-AP) (0.1 mM) potentiated the response to electrical field stimulation (to 182 +/- 25% of control, n = 4, P less than 0.05) and subsequent addition of NKA in the presence of 4-AP produced further potentiation (to 123 +/- 6% of the response to 4-AP n = 4, P less than 0.05). Neither 4-AP (0.01 or 0.1 mM) nor NKA in the presence of 4-AP potentiated the actions of exogenous acetylcholine but in these experiments 4-AP itself produced a marked direct contractile response. Thus NKA in the presence of K+ channel blockade potentiates cholinergic neural response in human bronchus and this occurs at a prejunctional site.

4-Aminopyridine↗
PubMed1990

Effect of sensitization and aerosol antigen challenge in guinea-pigs--studies of airway receptor function and characteristics.

Immunological sensitization of guinea-pigs and subsequent antigen inhalation challenge has provided an animal model which has several features in common with human asthma. Impairment of beta-adrenoceptor-mediated function and mechanisms have been postulated to contribute to the hyperreactivity to contractile agonists demonstrated in vivo and in vitro in these animals. Functional and receptor radioligand binding studies were carried out on airway tissue from: non-sensitized; sensitized; sensitized saline challenged; sensitized antigen challenged guinea-pigs. Sensitization did not alter responsiveness of airway tissue to carbachol, although subsequent antigen challenge did increase carbachol sensitivity of peripheral airway tissue six-fold. Neither sensitization itself nor subsequent antigen challenge altered binding characteristics of the muscarinic cholinoceptor ligand [3H]quinuclidinyl benzilate ([3H]QNB) to peripheral airway tissue, suggesting that mechanisms responsible for increases in carbachol sensitivity are distal to these receptors. Relaxation of airway preparations to isoprenaline was not altered by sensitization or further antigen challenge of the animals. However, sensitization significantly reduced affinity but not the total number of binding sites in peripheral airway tissue for the beta-adrenoceptor ligand [3H]dihydroalprenolol ([3H]DHA). Antigen challenge of the animals did not further alter beta-adrenoceptor ligand binding characteristics. These results suggest that airway hyperreactivity in this model is not a function of alteration in receptor characteristics, or impairment of relaxation mechanisms.

Aerosols↗