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D L Evans

Publications and source records attributed to D L Evans.

At least 163 records · Page 9Linked to original sources
PubMed1992

A function-associated molecule on rat natural killer cells identified by anti-idiotypic monoclonal antibodies.

Monoclonal antibodies were generated against idiotopes on an NK target antigen-specific IgM monoclonal antibody (mab). This mab (18C2) was originally produced against (NC-37) human EBV-transformed B cells. The 18C2 mab inhibits natural killer cell lysis of NC-37 and other target cells by preventing conjugate formation. Anti-18C2(id) mabs were tested for binding to effector cells and screened by ELISA, flow cytometry, and by inhibition of NK cytotoxicity. Two of the anti-18C2(id) (anti-id) mabs (12H1.C5 and 6D9.B11) were chosen for further study. The idiotypic specificity of these anti-id mabs was confirmed by testing their binding to 18C2 hybridoma cells in the presence of homologous and heterologous "cold" inhibitor mabs. Experiments were also conducted to determine the functional properties of these mabs. Anti-18C2(id) mab 12H1.C5 inhibited the cytotoxic activity of rat splenic NK (nylon wool nonadherent cells, NWNA) and rat ALAK cells. Flow cytometric (FCM) analysis of the binding of the anti-18C2(id) mabs demonstrated that mab 12H1.C5 bound 75.43% rat NWNA spleen cells, 43.74% rat ALAK cells, and 74.33% rat CRC- cells. Anti-id mab 6D9.B11 bound 45.20% NWNA cells, 70.45% rat ALAK cells, and 55.86% CRC- cells. Two-color FCM analysis demonstrated that the anti-id mabs not only bound to the same molecule on NK cells, but also these mabs bound to the same molecule as 5C6, an anti-NK cell mab. Biochemical analysis of the antigen recognized by mab 12H1.C5 was determined by Western blotting. The determinant on NWNA cells recognized by mab 12H1.C5 had an M(r) of 40 kDa and appeared to be identical to that recognized by mab 5C6. The same experiment using a transformed rat RNK-16 (CRC-) cell extract and Western blot analysis, demonstrated an M(r) of 42 and 48 kDa in the presence of mabs 5C6 and 12H1.C5. Monoclonal antibody 5C6 was previously shown to recognize a vimentin-like function-associated molecule on NK cell membranes. The anti-id mabs were also shown to have cross-reactivity with the intermediate filament vimentin as determined by Western blot analysis.

Animals↗
PubMed1992

Relationship of object loss during development to hypothalamic-pituitary-adrenal axis function during major affective illness later in life.

Although many studies have attempted to determine whether early object loss influences the risk of developing major affective illness in adulthood, there are few empirical data relating early loss to subsequent hypothalamic-pituitary-adrenal (HPA) axis dysfunction in adulthood. Forty-five psychiatric inpatients admitted for an active major affective illness, all of whom had a previous history of a significant permanent object loss (by death only), were studied retrospectively in this preliminary investigation to examine whether the type and timing of object loss experienced earlier in life would discriminate affectively ill patients who exhibit HPA dysfunction. Several loss variables were found to be statistically significant predictors of cortisol responses following glucocorticoid challenge. A median split of the distribution was used to classify patients into early loss (< or = 19 years) and late loss (> or = 20 years) groups. Analyses for all subjects, early and late loss combined, showed that late loss was associated with higher 11 p.m. cortisol levels. Within the early loss group, however, age of first loss was the most significant predictor of 4 p.m. cortisol levels after dexamethasone challenge. Consistent with the hypothesis that childhood object loss may be associated with long-term alterations in HPA axis function, younger age of loss correlated significantly with higher 4 p.m. cortisol responses. These preliminary data suggest that future prospective investigation of the neurobiological as well as psychosocial consequences of various types of early loss warrant further study.

Adult↗
PubMed1992

Serpins: implications of a mobile reactive centre.

The serpins are unique among the families of serine proteinase inhibitors in having a reactive centre that is situated on a mobile loop. The structures of three alternative conformations are now known, and it can be deduced that the active form involves the partial insertion of the loop into the A sheet of the molecule. The ability of the loop to move in and out of this sheet has been adapted by evolution to allow the modulation of inhibitory activity. Manipulation of the structure of the loop and of other functional domains in the serpin superfamily enables the production of serpins with tailor-made activities. The ability of the loop to lock in latent conformations or to take part in intermolecular polymerization has implications for the production and stabilization of recombinant serpins. This review has been adapted from Current Opinion in Structural Biology 1992, 2:438-446.

Amino Acid Sequence↗
PubMed1992

The natural killer cell-like lytic activity expressed by cytolytic T lymphocytes is associated with the expression of a novel function-associated molecule.

Experiments were performed to analyse the natural killer cell (NK)-like cytotoxicity frequently expressed by human antigen-specific cytolytic T lymphocytes (CTL). To this end, several monoclonal antibodies (MoAbs) previously shown to identify a novel function-associated molecule (FAM) involved in human NK function were utilized. Flow cytometry revealed that these MoAbs reacted with the majority of human NK, but only with a subpopulation of CTL isolated from primary mixed lymphocyte cultures. Preincubation of CTL with the MoAbs inhibited the NK-like lysis of K562 targets. Experiments with anti-CD3 MoAb demonstrated that neither the NK-like cytotoxicity of CTL nor the lytic activity of NK were mediated by the CD3 complex. Expression of the novel FAM was found to develop in T-cell cultures at the time that NK-like cytotoxicity was observed. Repeated in vitro antigenic stimulation of CTL was shown to result in loss of NK-like cytotoxicity, as well as loss of the FAM on the CTL surface. Thus, NK-like cytotoxicity displayed by antigen-specific CTL appears to be mediated by a novel FAM that is identical to that structure found on NK.

Adolescent↗
PubMed1992

Coping with the threat of AIDS: the role of social support.

OBJECTIVE: There has been relatively little clinical research on how asymptomatic HIV-positive men cope with the threat of AIDS. The present study was intended to 1) describe the coping strategies used by asymptomatic HIV-positive homosexual men, 2) examine the relationship of coping to dysphoria and self-esteem, and 3) explore how race and social support correlate with coping. METHOD: The study group was composed of 52 asymptomatic HIV-positive homosexual men. A group of 53 HIV-negative homosexual men was used for descriptive comparison. Data on coping, social support, dysphoria, and self-esteem came from self-report measures; depression was also determined by interviews with the Hamilton Rating Scale for Depression. RESULTS: The authors found that 1) subjects primarily coped with the threat of AIDS by adopting a fighting spirit, reframing stress to maximize personal growth, planning a course of action, and seeking social support; 2) more helpless coping, less fighting spirit, and less personal growth were related to dysphoria and poor self-esteem, whereas denial was related to more depression, anger, and helpless coping; 3) satisfaction with one's social support networks and participation in the AIDS community were related to more healthy coping strategies (e.g., fighting spirit, personal growth); and 4) black subjects expressed more denial, more helplessness, and less social support. CONCLUSIONS: These results suggest that health professionals should encourage more adaptive coping strategies, help patients use existing sources of positive social support, and assist patients, particularly black patients, in finding community support networks.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Abnormal diurnal variation in circulating natural killer cell phenotypes and cytotoxic activity in major depression.

This investigation tested the hypothesis that depressed patients have abnormal diurnal variation of natural killer (NK) cell measures. The diurnal variation of levels of Leu-11 NK cells and NK cytotoxic activity was significantly less in 24 patients with major depression than in 24 normal comparison subjects. These findings provide evidence that aspects of immune, as well as neural and endocrine, chronobiology are abnormal in depression.

Adult↗
PubMed1992

Neurobehavioral functioning in a nonconfounded group of asymptomatic HIV-seropositive homosexual men.

Neurobehavioral functioning was tested in 34 asymptomatic HIV-seropositive and 43 HIV-seronegative male homosexual subjects without substance abuse and CNS disorders. The HIV-positive subjects exhibited mild motor slowing compared to the seronegative subjects. These differences remained after controlling for potential cofactors. Early neurobehavioral impairment in HIV infection seems limited to subclinical motor deficits and attributable to HIV rather than possible confounding factors.

Adolescent↗
PubMed1992

Neuroendocrine effects of intravenous clomipramine in depressed patients and healthy subjects.

OBJECTIVE: Neuroendocrine challenge paradigms have been used to asses serotonergic systems in depression, but limitations in the specificity of many of these tests have been noted. In this study, the neuroendocrine responses to acute intravenous administration of the serotonin (5-HT) reuptake inhibitor clomipramine were assessed in depressed patients and matched control subjects. METHODS: Thirty hospitalized patients who met DSM-III-R criteria for major depression, and 30 healthy control subjects who were matched for age, sex, and season of year for the time of study, received 12.5 mg of intravenously administered clomipramine. RESULTS: The depressed patients demonstrated significant blunting of prolactin responses to clomipramine, as well as trends toward blunted ACTH and cortisol responses. There was no difference between the patient and control groups in growth hormone responses, plasma clomipramine levels, or self-reports of side effects. CONCLUSIONS: These data support the hypothesis that depressed patients have abnormal neuroendocrine responses to the intravenous administration of the 5-HT reuptake inhibitor clomipramine. Further study is required to delineate the mechanisms responsible for the abnormal response to intravenously administered clomipramine in depression.

Adolescent↗
PubMed1992

Intrinsic activity determinations at the dopamine D2 guanine nucleotide-binding protein-coupled receptor: utilization of receptor state binding affinities.

Guanine nucleotide-binding protein-coupled receptors have been shown to exist in both a high affinity agonist (HiAg) and a low affinity agonist (LowAg) state. The formation of the HiAg state is promoted by agonists, and the formation of this state of the receptor appears to be a critical factor in the generation of the effector-activating complex G alpha.GTP.Mg2+ and in the production of a stimulus. The magnitude of the difference in the affinity a compound has for the HiAg versus the LowAg state of the receptor has been related to the intrinsic activity of the compound. In this paper the HiAg and LowAg affinities (Ki) of full and partial dopamine agonists of varying levels of intrinsic activity were determined using membranes from Chinese hamster ovary cells stably transfected with the D2i receptor. The HiAg state was defined using the recently described dopamine agonist ligand [3H]U-86170, and the LowAg state was defined using [3H] raclopride plus 600 microM GTP. The LowAg/HiAg ratios for apomorphine (43), HW-165 (12.5), (-)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(-)-3-PPP] (4.5), terguride (1.6), SDZ-208-911 (1.2), and SDZ-208-912 (0.3) were found to correlate well with their electrophysiologically derived intrinsic activities (r = 0.92). Using this relationship, the intrinsic activity for compounds such as (+)-3-PPP (112%), quinpirole (104%), U-68553B (102%), and U-86170 (95%) was predicted to be high (greater than 90%); (-)-apomorphine (73%) was of high/moderate intrinsic activity, HW-165 (52%), (+)-apomorphine (51%), and (-)-3-PPP (34%) were in the intermediate range, and terguride (16.5%), SDZ-208-911 (11.7%), and SDZ-208-912 (-12%) were at the lower end of the intrinsic activity spectrum. The receptor state binding-determined intrinsic activity values for quinpirole (100%), U-86170F (94.8%), HW-165 (52.1%), (-)-3-PPP (34.3%), SDZ-208-911 (11.7%), and SDZ-208-912 (-12%) were found to correlate well (r = 0.908) with their maximum response (intrinsic activity), as determined using ATP-mediated increases in arachidonic acid release from CHO-D2i cells. In addition, the maximal effect of several of these compounds on rat striatal homovanillic acid (HVA) levels was determined. The drug-induced changes in tissue HVA levels were found to be consistent with the affinity-derived intrinsic activities of the drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoquinolines↗
PubMed1992

A flexible automated data acquisition system for ophthalmic electrophysiology.

An automated system for performing VER, ERG and EOG measurements has been developed and is now in clinical use. Considerable effort has been made to retain the flexibility of non-automated systems while providing an easily followed procedure for standard tests which can be undertaken by staff with minimal training. Clinical experience has shown that the standard parameters for data acquisition which are optimal for normal subjects are not always suitable for patients who are uncooperative or have poor vision. These parameters are under software control and can be amended interactively if necessary. The five main functions of the software, namely data acquisition, data selection and commentary, report generation, patient database operation and waveform archiving are written as separate modules and called as required. During data acquisition the software rejects gross artefacts and in the case of EOG's warns of patient non-cooperation. After an ERG or VER has been acquired the operator identifies features in the waveforms and the computer measures them whereas for EOG's the measurement process has been automated. When the waveforms are subsequently reviewed by the operator they are presented in a logical sequence, a sequence which does not depend on the order in which they were acquired, and this sequence is maintained when they are printed out later in the completely automated report phase.

Adult↗
PubMed1992

Thermal and electrical characteristics of thermal dilution cardiac catheter systems.

A combination of cooling systems for the injectate used in thermal dilution cardiac output measurements is shown to quickly cool the thermal indicator to a low homogeneous temperature. The variability of the physical constants characterizing the catheter thermistors are found to be adequately compensated for by the calibration resistors incorporated in the catheters. The calibration resistors are found to have a magnitude approximately 20 times the differential resistivity of the thermistors and this linear relationship is validated on theoretical grounds.

Cardiac Catheterization↗
PubMed1992

Psychopharmacological screening criteria. APA Committee on Research on Psychiatric Treatments.

This chapter includes a revision of psychopharmacological screening criteria originally developed in 1977-78 by the American Psychiatric Association (APA) and the National Institute of Mental Health (NIMH). This recent revision by the APA Committee on Research on Psychiatric Treatments provides criteria that are of considerable help in carrying out drug usage evaluations. Also included are useful suggestions for medical record documentation of specific classes of drugs, as well as for identification of adverse drug reactions. Thresholds for review are suggested.

Ambulatory Care↗
PubMed1991

Protease specificity and heparin binding and activation of recombinant protease nexin I.

Structural and functional properties of alpha-protease nexin I (alpha-PNI) expressed in Chinese hamster ovary cells were studied. All three cysteines were in the reduced form, showing that the potential disulfide bridge between residues Cys117 and Cys131 was not formed. Heparin association rate enhancements were from ka = 8.3 x 10(5) to 0.7-1.6 x 10(9) M-1 s-1 for the interaction of PNI with thrombin, from ka = 5.1 x 10(3) to 3.5 x 10(5) M-1 s-1 for interaction with Factor Xa, and from ka = 2.2 x 10(6) to 1.0 x 10(7) M-1 s-1 for interaction with trypsin; there was no rate enhancement of the plasmin interaction (ka = 1.0 x 10(5) M-1 s-1). The minimal heparin pentasaccharide had no effect on these interactions. Cleavage of the reactive center loop of PNI by three different proteases gave the typical stressed to relaxed change in thermal stability, but unlike with antithrombin III, there was no loss of heparin affinity. A similar difference from antithrombin was that PNI-thrombin complexes retained normal heparin affinity. These results are compatible with a role for protease nexin I as a cell-associated thrombin inhibitor that remains bound to the cell surface even after complexing with the protease, as compared with the role of antithrombin III as a circulating inhibitor of thrombin that becomes activated on binding to the microvasculature and is released on complex formation.

Amino Acid Sequence↗
PubMed1991

Mobile reactive centre of serpins and the control of thrombosis.

Two protease inhibitors in human plasma play a key part in the control of thrombosis: antithrombin inhibits coagulation and the plasminogen activator inhibitor PAI-1 inhibits fibrinolysis, the dissolving of clots. Both inhibitors are members of the serpin family and both exist in the plasma in latent or inactive forms. We show here that the reactive centre of the serpins can adopt varying conformations and that mobility of the reactive centre is necessary for the function of antithrombin and its binding and activation by heparin; the identification of a new locked conformation explains the latent inactive state of PAI-1. This ability to vary conformation not only allows the modulation of inhibitory activity but also protects the circulating inhibitor against proteolytic attack. Together these findings explain the retention by the serpins of a large and unconstrained reactive centre as compared to the small fixed peptide loop of other families of serine protease inhibitors.

Amino Acid Sequence↗
PubMed1991

Dopamine D2 receptor binding properties of [3H]U-86170, a dopamine receptor agonist.

U-86170F, an imidazoguinolinone, is a potent dopamine D2 agonist, binding with high affinity to the dopamine D2 receptor. A Kd of 0.99 nM was determined in membranes from Chinese hamster ovarian (CHO) cells transfected with the D2 receptor and a Kd of 1.72 nM was obtained in rat striatal homogenates. GTP sensitivity was demonstrated when its addition (300 microM) reduced [3H]U-86170 binding by 60%. This agonist ligand is especially effective in identifying agonists and partial agonists, as well as antagonists, and affords a more precise evaluation of their affinity for the dopamine D2 receptor, without the use of multiple site analysis, than does an antagonist [3H]-ligand.

Aminoquinolines↗
PubMed1991

Identification of an evolutionarily conserved, function-associated molecule on human natural killer cells.

Nonspecific cytotoxic cells (NCC) in teleost fish are analogous to human natural killer (NK) cells and spontaneously lyse a variety of transformed human cell lines sensitive to human NK cell lysis. Monoclonal antibodies (mAbs) made against these NK-like effector cells inhibited their lytic activity. These anti-NCC mAbs were examined with human NK cells for their effects. It was observed that these mAbs bound specifically to a small percentage of peripheral blood lymphocytes (5-15%) and to the majority (greater than 85%) of CD3- NK cells. The mAbs inhibited human NK cell lysis against a variety of transformed cell lines. Single-cell assays showed that the mAbs exerted their effects through inhibition of conjugate formation (recognition). However, the mAbs did not inhibit NK cell-mediated antibody-dependent cell-mediated cytotoxicity. Biochemical analysis of the NK cell molecule revealed that a dimeric structure was involved (distinct from antigen receptors on T cells). Thus, this molecule appears to be a candidate NK cell antigen receptor.

Antibodies, Monoclonal↗