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Biomedical subjects

M Wise

Publications and source records attributed to M Wise.

At least 55 records · Page 3Linked to original sources
PubMed1992

The use and reliability of psychiatric diagnosis in forensic settings.

The clinical professional encounters conflict whenever he or she enters the courtroom. The psychiatrist's approach must not be simply diagnostic or simply legal. We cannot shed our clinical identity; indeed, the court depends on our clinical identity and expertise in its search for the truth. The psychiatric expert must be able to translate his or her findings for the court, but these findings must come from clinical experience, not some solely legal perspective. The legal system needs our knowledge about the interfaces of mental illness, function, and behavior. After we provide our opinions, however, the legal issues must be left to the lawyers and the final determinations left to the judge or jury.

Criminal Law↗
PubMed1991

Intervertebral disk prolapse and diskospondylitis in a horse.

Intervertebral disk prolapse was diagnosed in a mature horse with clinical signs of caudal ataxia. Radiography and myelography demonstrated a collapsed intervertebral space and loss of the dorsal and ventral dye columns. Results of CSF analysis were normal, as were a CBC and serum biochemical profile. High CSF WBC count and high CSF creatine kinase activity were noticed following acute neurologic deterioration. While common in certain breeds of dogs, intervertebral disk prolapse is rarely reported in horses. It should be considered in the differential diagnosis of horses with caudal ataxia.

Animals↗
PubMed1991

Triple therapy.

Explore the source record for details and available documents.

Animals↗
PubMed1990

Induction of tolerance in peripheral T cells with monoclonal antibodies.

Our goal has been to develop ways to tolerize the mature immune system to any defined antigen. In this report we show that peripheral (post-thymic) T cells of mice can become tolerant to a range of antigens (human and rat immunoglobulins, and bone marrow and skin grafts that differ at multiple minor transplantation antigens). In the case of human gamma globulin (HGG), this required that the antigen be given under the cover of a short course of non-depleting anti-CD4 antibody, while for tolerance to skin and marrow grafts anti-CD8 antibody was also required. Tolerance to HGG could be reinforced by repeated injections of HGG, but was lost in the absence of any further exposure to antigen. This reversal of tolerance with time was due to new T cells being exported from the thymus, as it was not observed in tolerized, adult thymectomized mice. In contrast, tolerance to marrow and skin grafts was permanent, presumably because the established grafts acted as a continuous source of antigen to reinforce the tolerant state. Tolerance could not be broken by the infusion of unprimed spleen cells and in one example (tolerance to Mls-1a) there was clear evidence that specific peripheral T cells were anergic. We propose that anergic cells may themselves participate in reinforcing the tolerant state by competing at sites of antigen presentation.

Animals↗
PubMed1987

Multisubstrate inhibitors of dopamine beta-hydroxylase. 2. Structure-activity relationships at the phenethylamine binding site.

1-Aralkylimidazole-2-thiones have been shown to be potent multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1). In the present study, a series of 1-benzylimidazole-2-thiones was prepared to explore the effects of substitution in the benzyl ring on the inhibition of DBH. A detailed structure-activity relationship for in vitro activity was discovered and this was shown by a modified Hansch analysis to correlate (r = 0.91) with four key structural features of the benzyl ring: the presence of a hydroxyl at the 4-position, molar refractivity at the 3-, 4-, and 5-positions, inductive effects of the substituents at the 3-, 4-, and 5-positions, and pi-electron density. The affinity (Kis) of eight substituted inhibitors for DBH was shown to correlate (r = 0.75) with the affinity (KD) of comparably substituted tyramines for the ternary DBH-oxygen-tyramine complex. This correlate is used to support the hypothesis that binding of inhibitor to DBH occurs in a fashion that mimics the binding of tyramine substrates. The most potent inhibitors were selected for study in vivo in the spontaneously hypertensive rat model of hypertension. The changes in vascular dopamine and norepinephrine levels that resulted from oral administration of the inhibitors corresponded to the observed reduction in mean arterial blood pressure. A divergence between in vitro potency and in vivo efficacy upon oral dosing was noted and is suggested to result from an in vivo metabolic conjugation of the phenolic group of inhibitor.

Animals↗
PubMed1987

Synthesis, conformation, and dopaminergic activity of 5,6-ethano-bridged derivatives of selective dopaminergic 3-benzazepines.

To probe the suggestion that D-1 (DA1) dopamine receptors might possess an accessory pi-binding site in a location complementary to a suitably oriented aromatic ring (i.e., in an axial orientation approximately orthogonal to the catechol nucleus) in agonists such as 2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine-7,8-diol (1) and 3',4'-dihydroxynomifensine (2) that are selective for this subtype, cis- and trans-2,3,4,8,9,9a-hexahydro-4-phenyl-1H-indeno[1,7-cd]azepine-6,7-diol were prepared. These compounds are 5,6-ethano-bridged derivatives of the D-1 selective dopamine receptor agonist 1. Introduction of the bridge reduces the conformational mobility of the parent molecule. Comprehensive conformational analyses by molecular mechanical methods indicated that both the cis and trans isomers could attain a conformation that places the phenyl substituent in an axial orientation. X-ray analysis of the trans isomer showed an axial disposition of the phenyl ring; however, NMR studies suggest that this conformation is fixed in the trans isomer, but not in the cis. The dopamine receptor binding affinity and intrinsic activity of the cis isomer were considerably greater than those of its trans counterpart; the cis isomer also demonstrated a high degree of selectivity for the D-1 subtypes. One possible explanation of these results, suggested by the molecular modeling studies, is that both the axial orientation of the phenyl postulated to be required for binding to the receptor and a putatively requisite location of the nitrogen in approximately the plane of the catechol ring can be attained only by the cis isomer in which the tetrahydroazepine ring is in a twist conformation. Conversely, these results might simply suggest a preference of the D-1 receptors for benzazepine agonists having the phenyl group in an equatorial orientation. Still another possibility is that the D-1 receptor binding site is in a sterically hindered area accessible only to compounds that are relatively planar. However, it requires an axial 1-phenylbenzazepine for strong binding. Thus, a conformationally flexible cis isomer could more readily achieve the different conformations required to both gain access to and bind with the D-1 site.

Animals↗
PubMed1986

Synthesis and dopaminergic binding of 2-aryldopamine analogues: phenethylamines, 3-benzazepines, and 9-(aminomethyl)fluorenes.

A series of 2-aryldopamine analogues were synthesized and evaluated for their effects on D1 and D2 dopamine receptors. The 2-phenyldopamine and 6-phenylbenzazepine analogues exhibited weak binding to both D1 and D2 receptors. The 9-(aminomethyl)fluorenes also exhibited weak D2 binding; however, 2,5,6-trihydroxy-9H-fluorene-9-methanamine (4b) exhibited D1 binding comparable to apomorphine. The binding activity has been correlated with the calculated torsion angle of the biphenyl portion of these molecules. Good D1 dopamine binding occurs when the aromatic rings approach coplanarity; poor binding occurs when the aromatic rings are orthogonal.

Animals↗
PubMed1983

Suspected villonodular synovitis in a dog.

Progressive bilateral juxta-articular osteolytic lesions were detected in the coxofemoral joints of a dog. The differential diagnoses included neoplasia or an inflammatory process of periarticular tissue. The clinical signs, radiographic findings, and gross and microscopic appearance of the lesions were similar to the inflammatory changes of villonodular synovitis.

Animals↗