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Biomedical subjects

A Singer

Publications and source records attributed to A Singer.

At least 55 records · Page 3Linked to original sources
PubMed1990

Segmented turboFLASH: method for breath-hold MR imaging of the liver with flexible contrast.

A method called segmented turboFLASH imaging allows high-resolution, multisection, short-inversion-time (TI) inversion-recovery (STIR), T1- or T2-weighted magnetic resonance (MR) studies of the liver to be completed within a breath-hold interval. The method was applied in a phantom and in 19 patients with hepatic lesions. Sequence comparisons were performed among segmented turboFLASH, single-shot turboFLASH, T1-weighted gradient-echo with ultrashort echo time, and T2-weighted spin-echo (SE) techniques. Signal from fat and liver could be nulled with the segmented turboFLASH method, with TIs of 10 and 300 msec, respectively; signal from these tissues could not be eliminated with the single-shot approach. Signal-difference-to-noise ratios and contrast for the best segmented sequences were comparable with those of the best T2-weighted SE and T1-weighted gradient-echo techniques. It is concluded that it is feasible to obtain breath-hold images with arbitrary tissue contrast by means of segmented turboFLASH imaging. The method may prove helpful for the detection and characterization of hepatic lesions and will likely have applications to other anatomic regions such as the chest and pelvis.

Adenoma, Bile Duct↗
PubMed1990

Regulation of plasma ANF after increases in afterload in conscious dogs.

Although atrial stretch is the primary stimulus for atrial natriuretic factor (ANF) secretion, hormones may directly affect ANF secretion or may indirectly influence ANF by changing left ventricular afterload, thereby altering atrial stretch. To determine whether direct effects are important for the release of ANF in vivo, we measured changes in plasma ANF and in atrial wall function in the conscious dog after the administration of vasopressin, angiotensin II, and phenylephrine and by mechanically increasing left ventricular afterload by partial aortic occlusion. Injections of phenylephrine, angiotensin II, and arginine vasopressin (AVP) that were chosen to cause similar changes in systemic arterial pressure resulted in similar changes in atrial pressure and diameter. Maximum V wave atrial wall stress increased to 283 +/- 12, 311 +/- 41, 327 +/- 24, and 277 +/- 22 g/cm2 for AVP, angiotensin, phenylephrine, and occlusion, respectively, and plasma ANF increased to 242 +/- 81, 248 +/- 62, 299 +/- 95, and 190 +/- 53 pg/ml. There were significant linear correlations between left ventricular afterload and left atrial pressure, and each method for increasing left ventricular afterload shifted the position to the left on an atrial pressure-diameter, compliance curve, by a similar degree. Thus changes in left ventricular afterload result in changes in atrial wall function and similar changes in plasma ANF. No hormonal-specific increase in plasma ANF was found in conscious dogs after increases in afterload.

Angiotensin II↗
PubMed1990

Neuropsychological assessment and brain imaging technologies in evaluation of the sequelae of blunt head injury.

A 43 year old man with a traumatic amnesic syndrome experienced only a brief, if any, loss of consciousness following an injury to the head. Four years after this injury, his results on standard psychometric assessment were normal. Long-latency evoked response potentials results were normal, and the neurological examination and computed tomography scans were unhelpful in explaining his amnesic symptoms. He had no history of alcohol abuse, yet his neuropsychological profile was that of a Korsakoff-like amnesia with frontal lobe features. Magnetic-resonance images demonstrated evidence of extensive frontal lobe damage, while cerebral blood flow studies provided additional evidence of bilateral frontal lobe dysfunction. The case highlights the need for those giving opinions in medico-legal head trauma cases to go beyond a reliance on routine indicators, such as duration of coma, results of standard psychometric assessment and computed tomography scans, to more specialised neuropsychological evaluations and magnetic-resonance imaging scans.

Adult↗
PubMed1989

Octadeca-9,11-dienoic acid in cervical intraepithelial neoplasia: a colposcopic study.

488 women were studied to evaluate the use of the molar ratio (%MR) of octadeca-9,11-dienoic acid (18:2(9, 11] to linoleic acid (18:2(9, 12] as a new screening method for cervical cancer and pre-cancer. A combination of Papanicolaou cytology, colposcopy and %MR 18:2(9, 11)/18:2(9, 12) were employed. 86 women (17.6%) were found to have histologically proven cervical intraepithelial neoplasia (CIN). The %MR was obtained in 452 cases (92%). There was no significant difference in %MR in cervical cell scrapes from women with or without CIN. The %MR of cervical scrapes in some women with anaerobic vaginosis was significantly elevated suggesting bacterial generation of 18:2(9, 11). The %MR of 18:2(9, 11)/18:2(9, 12) is unsuitable for the diagnosis of cervical intraepithelial neoplasia.

Adult↗
PubMed1989

Intrathymic signalling in immature CD4+CD8+ thymocytes results in tyrosine phosphorylation of the T-cell receptor zeta chain.

Thymic selection of the developing T-cell repertoire occurs in immature CD4+CD8+ double-positive thymocytes and is thought to be mediated by signals transduced by T-cell antigen receptor (TCR) molecules and possibly by CD4 and CD8 accessory molecules as well. It is not known, however, which signal-transduction mechanisms function in immature CD4+CD8+ thymocytes on engagement of TCR, CD4 or CD8 molecules. In mature T cells, CD4 and CD8 molecules are each associated with the src-like protein tyrosine kinase p56 lck and signals transduced by TCR and CD4 activate tyrosine kinases that phosphorylate TCR-zeta chains and other intracellular substrates. Consequently, we examined whether tyrosine kinases could be similarly activated in immature CD4+CD8+ thymocytes. Unexpectedly, we found that TCR-zeta chains from CD4+CD8+ thymocytes were already phosphorylated in vivo, and that dephosphorylation of this TCR subunit occurred on removal of CD4+CD8+ cells from their intrathymic environment. Rephosphorylation of TCR-zeta in cultured CD4+CD8+ thymocytes occurred rapidly in vitro, either in response to cross-linking of TCR, CD4 or CD8 by specific monoclonal antibodies, or on cell-cell contact. These observations indicate that tyrosine kinases are activated in vivo in immature CD4+CD8+ thymocytes undergoing thymic differentiation and selection. They also indicate that TCR, CD4 and CD8 molecules can function in CD4+CD8+ thymocytes as signalling molecules to activate tyrosine kinases and that phosphorylated TCR-zeta serves as a marker of these signalling events.

Animals↗
PubMed1989

Rejection of skin allografts by CD4+ T cells is antigen-specific and requires expression of target alloantigen on Ia- epidermal cells.

The effector mechanism of skin allograft rejection has been characterized as Ag specific, rejecting cells that express the target alloantigen but sparing those that do not. However, the rejection of MHC class II disparate skin grafts, in which very few cells (Langerhans cells) actually express the target Ia Ag could conceivably proceed by either one of two distinct rejection mechanisms. One possibility is that Ia- cells are destroyed by a sequence of events in which CD4+ T cells, activated by Ia+ LC, elaborate soluble factors that are either directly cytolytic or that recruit and activate non-specific effector cells. The alternative possibility is that activated CD4+ T cells elaborate soluble factors which induce Ia expression on Ia- cell populations, and that these Ia+ cells are subsequently destroyed by effector cells specific for the induced Ia alloantigens. We found that rejection of Ia+ LC was not of itself sufficient to cause rejection of skin grafts, indicating that skin allograft rejection is contingent on the destruction not only of LC but of other graft cell populations as well. We then investigated whether CD4+ T cells rejected allogeneic skin grafts in an antigen specific fashion. To do so, we engrafted immunoincompetent H-2b nude mice with trunk skin grafts from B6----A/J allophenic mice because such skin is composed of mutually exclusive cell populations expressing either H-2a or H-2b histocompatibility Ag, but not both. The engrafted mice were subsequently reconstituted with H-2b CD4+ T cells. The CD4+ T cells destroyed keratinocytes of A/J origin but spared keratinocytes of B6 origin, even though neither cell population constitutively expresses target IAk alloantigen. The targeted rejection of A/J keratinocytes but not of B6 keratinocytes indicates that the target Ia alloantigen must have been induced on Ia- A/J keratinocytes, rendering them susceptible to destruction by anti-Iak-specific CD4+ effector cells. These data demonstrate that CD4+ T cell rejection of skin allografts is mediated by Ag-specific CD4+ cytolytic T cells and hence, requires the induction of target Ia alloantigens on epidermal cells within the graft.

Animals↗
PubMed1989

Characterization of primary T cell subsets mediating rejection of pancreatic islet grafts.

The cellular mechanisms by which pancreatic islet grafts are rejected have not been clearly defined. In order to address the roles of CD4+ and CD8+ T cells in pancreatic islet rejection, we used an adoptive transfer model in which H-2b nude mice were reconstituted with negatively selected H-2b CD4+ or CD8+ T cell subpopulations and engrafted with fully allogeneic pancreatic islet grafts. We found that primary (unprimed) CD4+ T cells mediated the rejection of pancreatic islet grafts, whereas, primary CD8+ T cells failed to do so, even though both T cell subpopulations were competent to reject skin allografts. These data indicate that primary CD4+ T cells are necessary for rejection of allogeneic pancreatic islet grafts, whereas primary CD8+ T lymphocytes are not. Implications concerning the nature of the APC involved in the initiation of the rejection response to islet allografts and the expression of MHC Ag by pancreatic islet cells are discussed.

Animals↗
PubMed1989

Characterization of anti-CD8-resistant cytolytic T lymphocytes induced by multivalent cross-linking of CD8 on precursor cells.

The lytic activity of most CD8+ MHC class I allospecific CTL generated in vitro can be inhibited by anti-CD8 antibodies. Such inhibition has led to hypotheses that CD8/class I interactions normally contribute to the triggering of CTL with low or moderate avidity Ag-specific TCR by providing those CTL with auxiliary binding avidity. However, CD8 has also been proposed to play an active signaling role in T cell activation. We have recently reported that multivalent cross-linking of CD8 on CTL precursors in MLC does appear to mediate activation signals, and induces the generation of CD8+ MHC class I allospecific CTL whose lytic activity cannot be blocked by anti-CD8 antibodies. In our present study, we have further characterized such anti-CD8 uninhibitable effector cells. These CTL are resistant to blocking of their lytic function by anti-Lyt-3 mAb as well as anti-Lyt-2 mAb, but remain sensitive to blocking by anti-LFA-1 mAb, indicating that they do use non-CD8 cell adhesion molecules during target cell recognition and lysis. As a consequence of mAb-induced multivalent CD8 cross-linking during their generation, anti-CD8 uninhibitable CTL significantly reduce their cell surface expression of CD8, which permits their identification and facilitates their purification from heterogeneous MLC populations. Such anti-CD8 uninhibitable effector cells can be maintained as stable CTL lines, in the absence of anti-CD8 mAb after the initial induction period. The in vitro generation of anti-CD8 uninhibitable CTL, which may be highly enriched for cells bearing high affinity TCR, could represent a new experimental approach to studies of TCR gene usage and repertoire, as well as a potentially important strategy for the deliberate generation of high affinity effector cells for adoptive immunotherapy.

Animals↗
PubMed1989

Cell surface comodulation of CD4 and T cell receptor by anti-CD4 monoclonal antibody.

In our study we have used anti-CD4 mAb to investigate the cell surface association between CD4 and the Ag-specific TCR complex on mature peripheral T cells. Anti-CD4 mAb was administered in vivo and in vitro and its effects on CD4 and CD3 cell surface expression were determined. In vivo, anti-CD4 mAb reduced cell surface expression of its ligand, CD4, and secondarily also reduced cell surface expression of CD3/TCR on CD4+ splenic T cells. In vitro, multivalent cross-linking of CD4 by anti-CD4 mAb and either FcR+ cells or anti-Ig mAb also resulted in decreased surface expression of CD4 and specific comodulation of CD3/TCR. The secondary reduction in cell surface CD3/TCR expression induced by CD4 cross-linking could be pharmacologically disrupted by high doses of PMA, indicating that the comodulation of CD3 with CD4 was dependent upon intracellular mediators, possibly including protein kinase C. These results demonstrate that, in the presence of anti-CD4 mAb, CD4 is functionally associated with the CD3/TCR complex, and that this association is dependent upon the activity of intracellular mediators. Such intracellular mediators might induce the coordinate down-modulation of physically unassociated CD4 and CD3/TCR molecules, or, alternatively, might promote a physical interaction between CD4 and CD3/TCR molecules.

Adjuvants, Immunologic↗
PubMed1989

Role of CD4 in thymocyte selection and maturation.

We examined the possible role of CD4 molecules during in vivo and in vitro fetal thymic development. Our results show that fetal thymi treated with intact anti-CD4 mAbs fail to generate CD4 single-positive T cells, while the generation of the other phenotypes remains unchanged. Most importantly, the use of F(ab')2 and Fab anti-CD4 mAb gave identical results, i.e., failure to generate CD4+/CD8- T cells, with no effect on the generation of CD4+/CD8+ T cells. Since F(ab')2 and Fab anti-CD4 fail to deplete CD4+/CD8- in adult mice, these results strongly argue that the absence of CD4+/CD8- T cells is not due to depletion, but rather, is caused by a lack of positive selection, attributable to an obstructed CD4-MHC class II interaction. Furthermore, we also observed an increase in TCR/CD3 expression after anti-CD4 (divalent or monovalent) mAb treatment. The TCR/CD3 upregulation occurs in the double-positive population, and may result from CD4 signaling after mAb engagement, or may be a consequence of the blocked CD4-class II interactions. One proposed model argues that the CD3 upregulation occurs in an effort to compensate for the reduction in avidity or signaling that is normally provided by the interaction of the CD4 accessory molecule and its ligand. As a whole, our findings advocate that CD4 molecules play a decisive role in the differentiation of thymocytes.

Animals↗
PubMed1989

Role of lymphokine-secreting CD8+ T cells in cytotoxic T lymphocyte responses against vaccinia virus.

The present study has examined the relative role of CD4+ and CD8+ Th cells in the generation and reactivation of antivaccinia virus memory CTL responses. We show that mice primed in vivo to vaccinia virus generate in vitro antivaccinia virus memory CTL responses through both CD4+ and CD8+ Th cell pathways, with the CD4+ Th pathway being the more prominent of the two. In addition, we show that vaccinia virus-specific CD8+ Th cell function is mediated through production of lymphokines, including IL-2, and that the CD8+ Th cell component in the CTL response is labile, decreasing progressively with increasing time after in vivo priming. Thus, this study demonstrates the existence of two phenotypically distinct Th cell pathways in the generation of antivirus CTL responses.

Animals↗
PubMed1989

Inhibition of allorecognition by an H-2Kb-derived peptide is evidence for a T-cell binding region on a major histocompatibility complex molecule.

The class I and class II major histocompatibility complex (MHC) antigens are polymorphic cell-surface glycoproteins that present antigenic peptides to T lymphocytes in the generation of immune responses. While much is known about the recognition and processing of antigens, the nature of T-cell recognition sites on MHC molecules is poorly understood. Both structural and functional studies have suggested that the two major alpha-helical regions of the class I MHC molecule not only define the site for binding of antigenic peptide but also provide potential sites for interaction of the MHC molecule with the T-cell receptor. A peptide derived from one of these regions on the H-2Kb molecule, peptide Kb163-174, was previously shown to specifically inhibit the stimulation of an alloreactive T-cell hybridoma. To further investigate the role of this region in the recognition of H-2Kb, the effects of peptide Kb163-174 on allospecific T-cell lines and clones were studied. When peptide Kb163-174 was cocultured with either an H-2Kbm10 anti-H-2Kb cytotoxic T-lymphocyte (CTL) clone or a CTL line, this peptide inhibited lysis of H-2Kb targets. Pretreatment experiments showed that the blockade was due to interaction of the peptide with the effector T cells. Surprisingly, peptide Kb163-174 also inhibited lysis of H-2Kb targets by H-2Kbm1-, H-2Kbm3-, H-2Kbm6, and H-2Kbm8-anti-H-2Kb CTLs. These CTLs, which identify multiple antigenic sites on H-2Kb in the alpha 1 and alpha 2 domains, are not directed against amino acid residues 163-174 of H-2Kb. In addition, peptide Kb163-174 specifically blocked lysis of only H-2Kb and not H-2Ld targets by a single bulk CTL culture that was alloreactive on both H-2Kb and H-2Ld. These results indicate that peptide Kb163-174 interferes with T-cell receptor engagement of a contact site on the H-2Kb molecule. Thus, amino acid residues 163-174 define a site used by many alloreactive T cells to engage the H-2Kb molecule.

Amino Acid Sequence↗
PubMed1989

The effect of the Vietnam War on numbers of medical school applicants.

Among the little-noticed but far-reaching side effects of the Vietnam War was its impact on the higher education system. This often-unpopular war, coupled with the military draft and student deferment policies, led many young men to enter educational institutions of all types. Beginning around 1964, there was a surge of enrollments and degrees granted in higher education that began to abate only after the draft ended in 1973. The leading edge of the post-World War II "baby-boom" also became of college age in the mid-1960s and undoubtedly contributed to elevated levels of enrollments and degrees in higher education. But the Vietnam War had an impact over and above the purely demographic, as can be seen when population effects are factored out. This effect largely explains why the numbers of bachelor's degrees and doctorates (Ph.D. degrees and equivalent) granted to men suddenly stopped increasing in 1974 even though the relevant population groups continued to grow throughout the 1970s. The patterns of enrollments and degrees attained by women are quite different from the men's patterns, and they serve to reinforce the evidence of a draft effect. Students in health professions schools of all types were given special consideration under the deferment policies established by the Selective Service System, leading to rapid increases in applications to medical, dental, and other health professions schools during the period 1968-1974. Since then, the health professions schools have had quite similar experiences with applications--those from men have generally declined while those from women have generally increased. Also, career choices are shifting.(ABSTRACT TRUNCATED AT 250 WORDS)

Career Choice↗
PubMed1989

Regional cerebral blood flow measurements in the diagnosis of dementia.

The Xenon-133 regional cerebral blood flow technique (rCBF) was used to assess cortical perfusion in a group of 15 elderly patients (mean age = 79.1, SD = 8.7) with a probable diagnosis of Dementia of the Alzheimer type (DAT). Nine had mild DAT and six were in the moderate stages of DAT. These patients were compared with 15 age and sex matched normal elderly controls (mean age = 75.1, SD = 5.6). RCBF was measured in each patient and control at rest with eyes closed. The DAT patients had significantly lower mean global CBF than normal controls (t = -4.63, p less than 0.0001). In addition, a further 15 normal elderly subjects aged 60 to 92 were assessed and combined with the original 15 to allow calculation of a normal range of rCBF for elderly individuals. Seventy-three per cent of the DAT patients fell below the lower limit of the normal range (39.3 - 59.3 ISI units). These results show the possible usefulness of rCBF as an aid in the diagnosis of early DAT.

Aged↗