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Biomedical subjects

C A Martin

Publications and source records attributed to C A Martin.

At least 19 recordsLinked to original sources
PubMed1992

Influence of (+/-)-CP-96,345 and SR 48968 on electrical field stimulation of the isolated guinea-pig main bronchus.

The aim of this study was to investigate the effects of (+/-)-CP-96,345 and SR 48968, two new nonpeptide antagonists of neurokinin NK1 and NK2 receptors, respectively, on the response of isolated guinea pig main bronchi to electrical field stimulation (EFS). Bronchi were stimulated transmurally with biphasic pulses (16 Hz, 1 ms, 320 mA for 10 s) in the presence of indomethacin (10(-6) M) and propranolol (10(-6) M). Two successive contractile responses were observed. Both responses were abolished by tetrodotoxin (10(-6) M) whereas only the first rapid phase was abolished by atropine (10(-6) M). The late and prolonged second phase was strongly reduced by the neurokinin A (NK2) receptor antagonist SR 48968 (10(-11) to 10(-8) M) with an EC50 of 0.056 nM and a maximal inhibition of 83.3 +/- 10.8% (10(-8) M, n = 4). This second response was partially inhibited by the substance P (NK1) receptors antagonist (+/-)-CP-96,345 (10(-8) to 10(-6) M). An incubation of 2 h was necessary for SR 48968 to inhibit the EFS-evoked noncholinergic contraction. These results confirm that EFS of guinea-pig bronchi involves stimulation of cholinergic and noncholinergic excitatory nerves and demonstrate that the new developed tachykinin receptors nonpeptide antagonists (+/-)-CP-96,345 and especially SR 48968 are potent inhibitors of the noncholinergic contraction induced by EFS of the isolated guinea-pig main bronchus.

Animals↗
PubMed1992

Experimental allergic encephalomyelitis mediated by cloned T cells specific for a synthetic peptide of myelin proteolipid protein. Fine specificity and T cell receptor V beta usage.

Proteolipid protein (PLP) is the major protein of central nervous system myelin. SJL (H-2s) mice immunized with a synthetic peptide corresponding to PLP residues 139-151 develop acute EAE. In this study, 6 IAs-restricted, CD4+, TCR alpha beta-bearing T cell clones were derived from SJL/J mice after immunization with this synthetic peptide. The clones responded in in vitro proliferative assays to the whole PLP molecule and to PLP peptide 139-151, but not to irrelevant Ag. They also responded to truncated and overlapping forms of the peptide but five distinct reactivity patterns were observed using these peptides. A panel of anti-TCR V beta mAb and TCR V beta-specific cDNA probes were used to determine the TCR V beta usage of the clones. Five clones were found to use four different V beta (V beta 2, V beta 6, V beta 10, or V beta 17a), whereas the V beta on the sixth clone could not be identified. Five of the clones induced EAE of varying severity upon adoptive transfer into naive syngeneic mice or mice pretreated with irradiation and pertussis and one clone was nonencephalitogenic. The Ag-specific proliferative response of all but the nonencephalitogenic clone could be blocked by an anti-CD4 mAb. Thus, the clones showed differences in their fine specifity, TCR V beta usage, sensitivity to antibody blocking, and encephalitogenic potency. These data demonstrate that the T cell response to the encephalitogenic PLP peptide 139-151 is heterogeneous.

Amino Acid Sequence↗
PubMed1991

Differential regulation of interleukin-6, macrophage inflammatory protein-1, and JE/MCP-1 cytokine expression in macrophage cell lines.

Activated macrophages produce a number of proinflammatory cytokines including IL-6, JE, MIP-1 alpha and MIP-1 beta. The induction requirements for production of either IL-6 or the MIP-1 related inflammatory proteins (MIP-1 alpha, MIP-1 beta, and JE) have been analyzed independently using fibroblasts, monocytes, or endothelial cells. However, little is known about the regulation of these cytokines in macrophages. Since activated macrophages produce prostaglandins (PGE2) which may participate in the autoregulation of cytokine production by stimulation of adenylate cyclase and the induction of cAMP-dependent signal pathways, we determined the effects of PGE on the production of IL-6 and MIP-1-related proteins. Murine macrophage cell lines were incubated with PGE1, PGE2, cholera toxin, or dibutyryl cAMP in the presence of absence suboptimal doses of LPS. Pharmacologic agents alone did not induce IL-6 production but incubation of macrophages with combinations of adenylate cyclase stimulators and LPS or dcAMP and LPS led to the dose-dependent enhancement of IL-6 secretion and mRNA expression. In contrast, PGE1 inhibits LPS-induced JE, MIP-1 alpha, and MIP-1 beta mRNA expression and this inhibition is partially dependent on a cAMP-mediated pathway of signal transduction. In previous work we demonstrated that IFN-gamma and PMA do not stimulate the production of IL-6 by macrophages. Here we show that incubation of macrophages with either IFN-gamma or PMA induces the expression of JE, MIP-1 alpha and MIP-1 beta mRNA expression. JE mRNA expression is much more responsive to the stimulatory effects of IFN-gamma than are the MIP-1 genes. Finally, PGE inhibits PMA and IFN-gamma-induced JE and MIP-1-related mRNA expression.

Alprostadil↗
PubMed1991

Unrecognized left ventricular dysfunction in an apparently healthy alcohol abuse population.

To examine effects of chronic alcohol abuse on left ventricular function, 162 otherwise relatively healthy alcohol abusers, having been admitted to a rehabilitation program, underwent cardiac evaluation including chest X-ray, electrocardiogram, and radionuclide angiography after 2 weeks abstinence. Twenty-nine of the 162 alcoholic subjects (18%) with left ventricular dysfunction were identified. Twenty-two had regional wall motion abnormalities, suggesting a localized process, of whom 12 also had depressed ejection fractions. Seven others had a depressed ejection fraction alone with a more global myopathic process. Only 4 of these 29 patients had any history suggesting prior heart disease. Two of the 29 had Q-waves greater than or equal to 0.4 s and 8 had an abnormal cardiothoracic ratio on chest X-ray. Chronic alcohol abusers appear to be at relatively high risk for left ventricular dysfunction; most of which is unrecognized. Routine screening methods failed to identify 85% of our subjects who later were recognized by radionuclide angiography. Since historical and electrocardiographic abnormalities are often absent in this population, detection of left ventricular dysfunction by other methods such as radionuclide angiography must be used.

Adult↗
PubMed1991

Twenty years of gerontological education: a report on the experience of one program.

The Center for Studies in Aging at the University of North Texas has been in existence for over 20 years. Data were collected from 339 of the 493 students who completed its program between 1967 and 1987. Data suggest that: levels of both initial employment and retention in the field of aging are high; gender differences in salaries exist among program concentrations and year of completion; and former students report high levels of involvement in collateral activities.

Curriculum↗
PubMed1991

The development of the woman child psychiatry researcher--a review.

Greater efforts should be made to recruit women into child psychiatry research. Women's tendencies to minimize their creativity and to avoid competition and criticism and women's underrepresentation and isolation in research and academia should be addressed. Nontraditional lateral tracks should be developed for women during phases of intense professional and personal demands. Mentorships, stimulating collegial relationships, and open forums at local and national levels to address these issues may encourage women's growth as child psychiatry researchers. In addition, changes for improving hiring, promoting, and facilitating career development for women are mandated.

Career Choice↗
PubMed1991

Physicians' psychologic reactions to malpractice litigation.

A questionnaire investigating the psychologic sequelae of malpractice litigation was administered to sued and nonsued physicians through a major malpractice insurer in a rural southern state. Factor analysis showed clusters of symptoms, including psychologic trauma, job strain, shame/doubt, and active coping. Psychologic stress decreased with time (but did not return to baseline after 2 years), with winning a case, and with increased age. Stress was increased among those with cases pending or multiple suits. Female physicians used more active coping strategies, and being in a high-risk specialty led to greater job strain and active coping, regardless of litigation experience. Malpractice litigation is a major life trauma that should be dealt with as any other trauma, including use of positive coping strategies such as knowledge of the psychologic sequelae, cognitive reframing, and collegial and personal support systems.

Adaptation, Psychological↗
PubMed1991

Imipramine treatment of ADHD in a fragile X child.

Fragile X syndrome, an X-linked genetic disorder, is the third most common cause of mental retardation. The following is a case of a 6-year-old boy with fragile X syndrome and its characteristic cognitive and behavioral symptomatology, including attention deficit hyperactivity disorder. In addition, this child experienced initial insomnia and nocturnal enuresis, problems not previously reported with fragile X. Previous pharmacological treatment of the syndrome's behavioral difficulties and attention deficit has included stimulants, folic acid, and neuroleptics. This is the first report of the successful use of imipramine. Imipramine also improved the boy's insomnia and enuresis, whereas methylphenidate caused an overall worsening of his condition.

Attention Deficit Disorder with Hyperactivity↗
PubMed1990

Antigen-specific and antibody-mediated growth inhibition of suppressor T cell hybridomas. Roles of H-2 and the CD3-T cell receptor-alpha/beta complex.

Eight different Ts cell hybridomas (including inducer (Ts1) and effector (Ts3) suppressor cells) specific for the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten were tested for their ability to respond to Ag or anti-CD3 antibody in a growth-inhibition assay. Results suggest that the expression of the TCR-CD3 complex on Ts hybridomas is required for the Ag or anti-CD3-mediated growth inhibition. One of the CD3+, Ts hybridomas (CKB-Ts3-9.H3) was tested in detail; this CD4- effector suppressor cell hybridoma showed specific inhibition of growth in the presence of NP or NIP-coupled protein conjugates but not in the presence of other irrelevant hapten-protein conjugates. In addition, growth of this hybridoma was specifically inhibited by anti-CD3 and anti-TCR-alpha/beta antibodies but not by control hamster antibodies. In order to study the role of MHC molecules in Ag-mediated growth inhibition, Ts cell hybridomas were incubated with Ag (NP-keyhole limpet hemocyanin) in the presence of spleen cells from various H-2 congenic strains. The results suggest that the Ts hybridomas that express donor Ts-derived TCR beta-chain recognize Ag in an MHC-restricted manner, whereas the two Ts3 hybridomas that utilize BW5147-derived TCR-beta recognize Ag in H-2 unrestricted way. Co-incubation of anti-CD3 and anti-TCR-alpha/beta antibodies with specific Ag enhanced the Ag-mediated growth inhibition, whereas anti-LFA-1 antibody completely blocked the Ag-mediated effect. The combined data suggest that, like Th hybridomas, expression of CD3-associated-TCR complex is essential for the Ag responsiveness of Ts cell hybridomas.

Animals↗
PubMed1990

Enhanced expression of c-fos is not obligatory for retinoic acid-induced F9 cell differentiation.

c-fos was studied in F9 cells to determine whether changes in its expression are an early and/or obligatory event in retinoic acid-induced F9 cell differentiation. Induction of c-fos transcripts was not observed at times early or late during retinoic acid-promoted differentiation, but a decrease in c-myc mRNA was noted as early as 1 h after retinoic acid dosing. Induction of a rapid and transient change in c-fos expression in F9 cells was observed only in response to serum stimulation. Therefore, although expression of c-fos may be involved in the cellular growth and proliferation of F9 cells, as indicated by the response to serum, an increase in c-fos is not required for retinoic acid-induced differentiation.

Blood↗
PubMed1990

A refractive and histopathologic study of excimer laser keratectomy in primates.

Using a 193-nm excimer laser, we produced wide-area, refractive keratectomies on 18 cynomolgus monkey corneas and followed them up for up to 18 months. All corneas developed some subepithelial haze by one month. Electron microscopy disclosed epithelial thickening, absence of Bowman's layer, and subepithelial activated fibroblasts surrounded by disorganized collagen. By six months, the haze faded to a variable degree, the epithelium regained normal thickness, and the collagen was more organized. Persistent corneal haze at 12 months in some corneas correlated with electronlucent spaces in the subepithelial zone. Corneas were 90 microns thinner centrally two weeks after myopic ablation, but returned to preoperative thickness by six months. Myopic flattening and hyperopic steepening of 6 diopters were targeted, and over 7 diopters of each were achieved initially. Regression of induced curvature stabilized over several months. At 18 months, 4.4 diopters of myopic flattening and 5.2 diopters of hyperopic steepening remained.

Animals↗
PubMed1990

Enhancement of in vivo cell-mediated immune responses by three distinct cytokines.

The ability of recombinant/purified cytokines to augment delayed-type hypersensitivity (DTH) responses was investigated. Suboptimal doses of haptenized SC were treated in vitro with purified or recombinant derived cytokines and tested for their ability to enhance DTH in vivo. With the use of this protocol, it was shown that both human and mouse rIL-6, as well as mouse rTNF-alpha, potentiated DTH in a dose-dependent manner. In accordance with these data, IL-6/TNF-alpha-containing supernatant from long term nonlymphoid cell lines also possessed the ability to augment DTH. By using the same protocol, we have also identified T cell hybridomas that produce DTH-augmenting activity constitutively. The hybridoma-derived factor, termed the T cell enhancing factor (TCEF), was functionally distinguishable from the defined cytokines IL-1 through IL-6, IFN-gamma, and TNF by bioassay. Furthermore, RNA derived from the hybridoma failed to hybridize with cDNA probes specific for IL-1 to IL-6, IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF. Further characterization of the serum-free conditioned media derived from the hybridoma indicated that the TCEF was a soluble acid labile glycoprotein (Mr greater than 30,000). Finally, we investigated the cellular requirements for DTH augmentation by IL-6, TNF-alpha, and TCEF; all are dependent upon the presence of T cells in the immunizing inoculum. We propose that these cytokines play a critical role in the development of DTH responses in vivo.

Animals↗
PubMed1990

Unrecognized left ventricular dysfunction in an apparently healthy cocaine abuse population.

To determine the frequency and severity of clinically unrecognized left ventricular (LV) dysfunction related to cocaine use, 84 asymptomatic cocaine abusers underwent cardiac evaluation which included chest x-ray, electrocardiography (ECG), and radionuclide angiography after a two-week abstinence from cocaine use. LV dysfunction was discovered in 6/84 (7%). Regional wall motion abnormalities suggesting a localized myocardial abnormality were found in 2, whereas an ejection fraction less than 50% suggesting a more global process was noted in 4. An abnormal chest x-ray was found in only 1 subject and none had abnormal ECGs. In each of these cases, repeated and protracted use of cocaine was documented and the suggestion of cardiac dysfunction was supported by at least one other independent abnormal finding. In these 6 cases, the dysfunction was clinically unrecognized and unsuspected after routine evaluation. The significance of subclinical LV dysfunction in this population has not been determined and requires long-term study.

Adult↗
PubMed1990

Interleukin-6 production by murine macrophage cell lines P388D1 and J774A.1: stimulation requirements and kinetics.

The murine macrophage tumor lines, P388D1 and J774A.1 were stimulated with LPS, IL-6, IL-1 alpha, TNF-alpha, IFN-gamma, PMA, or combinations of these reagents to induce the production of IL-6, IL-1, and TNF-alpha. Using Northern blot analysis and bioassays for the detection of cytokine production, it was noted that identical stimuli induced all three inflammatory mediators. However, unlike fibroblasts or endothelial cells, neither P388D1 nor J774A.1 macrophages respond to IL-1 alpha or TNF-alpha by producing IL-6. The results imply that these cytokines are not autoregulatory for macrophages and may be tissue-specific in their stimulatory effects. IFN-gamma and PMA synergize with LPS in the production of IL-6 as well as IL-1 and TNF-alpha. These observations suggest that IFN-gamma may mediate amplification pathways important in the production of inflammatory mediators. Kinetic studies on the transcription of mRNA and secretion of IL-6, IL-1, and TNF-alpha revealed that TNF-alpha mRNA transcription and cytokine production occur very rapidly. TNF-alpha mRNA accumulation peaked 1-2 hr after stimulation and maximum concentrations of cytokine are found in supernatants collected after 2-4 hr of culture. IL-6 and IL-1 alpha mRNA accumulation peaked simultaneously after 4-8 hr. However, IL-6 bioactivity peaks between 8 and 12 hr whereas maximum concentrations of IL-1 bioactivity are not detected in supernatants from stimulated cells collected prior to 12 hr of culture. Thus even though TNF-alpha production precedes that of IL-1 and IL-6, and stimulates IL-6 production in fibroblasts, there is no evidence that TNF-alpha acts to amplify the production of IL-6 or IL-1 by murine macrophage cell lines. The results suggest differential regulation of IL-6 expression between fibroblasts and macrophages.

Animals↗
PubMed1990

Retinoic acid, dibutyryl-cAMP, and differentiation affect the expression of retinoic acid receptors in F9 cells.

Expression of the retinoic acid receptors alpha and beta (RAR-alpha and RAR-beta) was examined in F9 cells, an embryonal carcinoma cell model established for the study of retinoid metabolism and function. Addition of retinoic acid to F9 cell medium caused a dose-dependent increase in RAR-beta mRNA within 3 hr that reached 5- to 30-fold greater than the constitutively expressed mRNA by 24 hr. The elevation in mRNA resulted from increased transcription, as demonstrated by nuclear run-on transcription, did not require protein synthesis, and required the constant presence of retinoic acid. N6,O2'-Dibutyryl-cAMP attenuated the retinoic acid-induced increase in RAR-beta mRNA by a post-transcriptional mechanism. In contrast, RAR-alpha mRNA in F9 stem cells was affected less (1.2- to 1.4-fold increase) by retinoic acid and decreased 3-fold transiently when fresh serum was added to the medium. Differentiation of F9 cells resulted in increased steady-state levels of RAR-beta mRNA in primitive (4-fold), parietal (3-fold), and visceral (8-fold) endoderm but decreased steady-state levels of RAR-alpha mRNA in primitive (2-fold), parietal (3-fold), and visceral (1.4-fold) endoderm. These data demonstrate that RAR-beta is a primary target gene for retinoic acid in a characterized model of retinoid function, indicate that constitutive expression of both RAR-beta and RAR-alpha is dependent upon the differentiation state, and suggest hormonal modulation of RAR-beta by cAMP and modulation of RAR-alpha by serum factors. These results distinguish the effects of serum, cAMP, and retinoic acid on the expression of RAR from the effects mediated by differentiation.

Animals↗
PubMed1990

Alcoholism treatment: a ten-year follow-up study.

Two hundred male and female patients, selected at random from all patients admitted to an inpatient alcoholism treatment facility in 1973-1974, were surveyed 10 years following treatment. Response rate was 80%, and a validity check was done. Of the 158 unstable responses, 61% reported complete or stable remission of their alcoholism for at least 3 years prior to the survey and 84% reported stable psychosocial status. Successful outcome was possible regardless of severity of drinking history or psychosocial status. Seventy-six percent (76%) of those still alive at follow-up reported remission; at most, 23% of the deceased were reported in remission prior to death. Involvement in Alcoholics Anonymous (AA) predicted abstinence, suggesting successful outcome for patients who undergo a treatment regimen, which bridges patients into AA involvement. Of those respondents who continued to sponsor other AA members throughout the follow-up period, 91% were in remission at the time of survey.

Adult↗