Search PubMed⌕ Search

Biomedical subjects

L A Jones

Publications and source records attributed to L A Jones.

At least 127 records · Page 7Linked to original sources
PubMed1991

Selective effects of preeclamptic sera on human endothelial cell procoagulant protein expression.

Current concepts of preeclampsia suggest that dysfunction of maternal vascular endothelium in vivo is a central pathogenetic feature of this syndrome. This hypothesis is suggested by the activation of the coagulation cascade associated with preeclampsia and evidence for a role of endothelium in maintaining thromboresistance. Previous in vitro studies with monolayers of human umbilical vein endothelial cells demonstrated direct cytotoxic effects of sera from preeclamptic parturients. In the current studies, we have examined the in vitro expression of three procoagulant protein activities regulated by endothelial cells: cellular fibronectin, an important mediator of platelet aggregation known to be elevated in preeclamptic women in vivo; tissue factor, the most potent endogenous procoagulant activity; and von Willebrand factor, a major component of coagulation factor VIII. Monolayer cultures of human umbilical vein endothelial cells were incubated with pregnancy sera for 24 hours before these proteins and activities were quantified. Exposure of identical endothelial cell cultures to predelivery preeclamptic sera caused significantly greater release of cellular fibronectin than postdelivery preeclamptic or predelivery or postdelivery normal pregnancy sera (p less than 0.05). However, neither tissue factor activity nor von Willebrand factor expression appeared to be increased preferentially by preeclamptic sera. The data indicate that sera from women with preeclampsia induce a selective, but not a generalized, activation of endothelial cell procoagulant protein production.

Adult↗
PubMed1991

High plasma cellular fibronectin levels correlate with biochemical and clinical features of preeclampsia but cannot be attributed to hypertension alone.

Current concepts of the pathogenesis of preeclampsia involve the generalized dysfunction of maternal vascular endothelial cells. We measured the endothelial isoform of fibronectin as a marker of endothelial cell injury throughout pregnancy in a prospective, case-control study. Nineteen women met strict criteria for the diagnosis of preeclampsia. Nineteen normal pregnant women, and 19 women with gestational hypertension but without other stigmata of preeclampsia (transient hypertension) were selected from the same cohort and matched according to race, age, nulliparity, and gestational age at delivery. Plasma levels of cellular fibronectin were significantly elevated in women meeting strict clinical and biochemical criteria for preeclampsia but not in women with normal pregnancies or transient hypertension. Moderate but significant elevations in mean levels were found in the second trimester in women destined to have preeclampsia, as compared with matched normal and transient hypertension groups (p less than 0.05). The results indicate that elevated plasma levels of cellular fibronectin are not simply the result of increased blood pressure but reflect a maternal insult specific to the syndrome of preeclampsia. Elevation of the mean concentration during the midtrimester is consistent with the hypothesis that endothelial cell injury is a specific lesion that occurs early in the course of preeclampsia, before clinical signs and symptoms.

Adult↗
PubMed1991

Amyloidosis.

Amyloidosis is a disease involving the fibrillar deposition of proteins in a manner that uniformly leads to the presence of green birefringence on polarization microscopy after staining the involved tissues with Congo red. In the year summarized, a wide range of new information has accumulated about this disease. In this article, attention has been paid to several newly described proteins now known to precipitate into amyloid deposits, including the proteins transthyretin, apolipoprotein A-1, cystatin C, gelsolin, amyloid beta protein, beta 2-microglobulin, scrapie protein, and islet amyloid polypeptide. The number of these amyloid-related proteins has resulted in the need for a revised nomenclature and classification scheme. The results of a recent international symposium addressing this issue are summarized in table form. The varied clinical manifestations of amyloidosis are described according to organ system, with unusual or unique areas of involvement noted. Finally, the treatment of amyloidosis and its prognosis are addressed, and new areas of possible intervention suggested.

Amyloid↗
PubMed1991

Alteration of proto-oncogene c-fos expression in neonatal estrogenized BALB/c female mice & murine cervicovaginal tumor LJ6195.

Experiments were performed to determine the effect of neonatal estrogen treatment on the expression of the proto-oncogene c-fos in the BALB/c mouse cervicovaginal tract. Estradiol induces the expression of c-fos in the normal mouse cervicovaginal tract. However, c-fos expression was not stimulated by estradiol in the cervicovaginal tracts of mice that received neonatal estrogen treatment. In addition, the level of expression of c-fos by the estrogen- and progesterone-induced murine cervicovaginal LJ6195 tumor was similar to that in the normal vaginal tract following estradiol stimulation and was not regulated by estradiol.

Animals↗
PubMed1991

Proline at position 36: a new transthyretin mutation associated with familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is associated with the deposition of an abnormal transthyretin (TTR) molecule. We have studied DNA from a family of Greek descent with FAP. The proband's TTR gene was asymmetrically amplified by using PCR and then was sequenced directly, to reveal a cytosine-for-guanine substitution in codon 36. This substitution removes a recognition site for endonuclease Fnu4HI. Allele-specific PCR was employed for diagnosis of the mutation. The predicted amino acid change of alanine to proline at position 36 was confirmed by protein sequencing of the proband's plasma TTR.

Adult↗
PubMed1991

CD4 and CD8 act as co-receptors during thymic selection of the T cell repertoire.

The selection of T cell receptor specificities must logically not only involve the alpha beta-TCR but, also the CD4 and CD8 molecules, as antigen recognition by the alpha beta-TCR on mature T cells is facilitated by the CD4 and CD8 co-receptors. In this review, the studies that provided key advances in our understanding of the possible role of CD4 and CD8 in T cell development will be discussed.

Animals↗
PubMed1990

Peripheral clonal elimination of functional T cells.

A major mechanism for generating tolerance in developing T cells is the intrathymic clonal deletion of T cells that have receptors for those self antigens that are presented on hematopoietic cells. The mechanisms of tolerance induction to antigens not expressed in the thymus remain unclear. Tolerance to self antigens can be generated extrathymically through the induction of clonal nonresponsiveness in T cells with self-reactive receptors. A second mechanism of extrathymic tolerance was identified: clonal elimination of mature T cells with self-reactive receptors that had previously displayed functional reactivity.

Animals↗
PubMed1990

Failure of clonal deletion in neonatally thymectomized mice: tolerance is preserved through clonal anergy.

Self-tolerance is achieved in part through intrathymic deletion of self-reactive T cells. The necessity of the thymus for this process is suggested by the development of autoimmune diseases in neonatally thymectomized (neoTx) mice and by the failure of clonal deletion in nude mice. Indeed, the present study demonstrates that neonatal thymectomy on day 3 after birth results in the failure of clonal deletion of V beta 11+ T cells in BALB/c mice and V beta 5+ and V beta 6+ T cells in DBA/2 mice. However, these potentially autoreactive cells are nonfunctional as measured by proliferation and lymphokine production after stimulation with appropriate anti-V beta mAbs or stimulator cells. It appears that this induction of nonresponsiveness may have occurred extrathymically: the early neonatal thymus (presumably the source of the peripheral T cells observed in neoTx mice) also contains T cells with self-reactive receptors, but these cells are fully functional. Therefore, neonatal thymectomy aborts deletion of self-reactive T cells, but self-tolerance is maintained through functional inactivation of potentially self-reactive clones.

Animals↗
PubMed1990

In vivo induction of anergy in peripheral V beta 8+ T cells by staphylococcal enterotoxin B.

We have developed a model of peripheral in vivo T cell tolerance that is induced by administration of the protein superantigen staphylococcal enterotoxin B (SEB). Rather than activating V beta 8+ T cells, in vivo administration of SEB induced in them a profound state of anergy. This was shown by their failure to proliferate to subsequent in vitro restimulation with SEB or to anti-V beta 8 antibodies. This unresponsiveness was V beta 8 specific since T cells from SEB-immunized mice responded normally to other antigens. 8 d after SEB administration, there was no reduction in the number of V beta 8+ T cells or in the intensity of V beta 8 T cell receptor (TCR) expression. Although a portion of the V beta 8+ T cells from SEB-primed mice were able to express interleukin 2 receptors (IL-2Rs), they failed to proliferate in response to exogenous IL-2, indicating they were defective in their IL-2 responsiveness. 2-4 wk after SEB administration, there was a reduction of approximately 50% in the number of V beta 8+ cells in immunized compared with control animals. There was, however, no reduction in the level of TCR expression on the remaining V beta 8+ cells. These data demonstrate that proteins that activate T cells in vitro in a V beta-specific manner can induce a state of anergy in peripheral T cells in vivo and may possibly further mediate clonal deletion in a portion of the tolerized cells.

Animals↗
PubMed1990

CD8 is required during positive selection of CD4-/CD8+ T cells.

Interactions between self-MHC molecules and T cells are necessary for the proper development of mature T cells, in part due to an absolute requirement for self-MHC-TCR interactions. Recently, we showed that CD4-mediated interactions also participate in shaping the T cell repertoire during thymic maturation. We now examine the possible role of the CD8 molecule during in vivo T cell development. Our results demonstrate that perinatal thymi treated with intact anti-CD8 mAb fail to generate CD8 single-positive T cells, while the generation of the other main phenotypes remains unchanged. Most importantly, the use of F(ab')2 anti-CD8 mAb fragments gave identical results, i.e., lack of generation of CD4-/CD8+ cells, with no effect on the generation of CD4+/CD8+. Furthermore, selective blocking of one CD8 allele with F(ab')2 mAbs in F1 mice expressing both CD8 alleles did not interfere with the development of CD4-/CD8+ cells, demonstrating that the absence of CD8+ T cells in homozygous mice is not due to depletion, but rather is caused by a lack of positive selection. This is most likely attributable to a deficient CD8-MHC class I interaction. Our findings strongly advocate that CD8 molecules are vital to the selection process that leads to the development of mature single-positive CD8 T cells.

Animals↗
PubMed1990

Influence of the mechanical properties of a manipulandum on human operator dynamics. 1. Elastic stiffness.

An active servo-system was used to change the stiffness of a manipulandum used in a position-control pursuit-tracking task. The elastic stiffness of the manipulandum connected to the forearm was set by a computer at one of five levels ranging from 0 N/m to 2000 N/m. Subjects were required to track, either by moving their forearm or by generating a force isometrically, a visually presented target whose position changed randomly every second for 100 s. Nonparametric and parametric impulse response functions were calculated between the input (target) and output (force or position) in each tracking condition, and revealed that for all subjects force control was faster than position control when the stiffness of the manipulandum was set at 0 N/m. Subjects were also consistently faster in reaching the target when the stiffness was greater than zero, and were more accurate (steady-state response) when the stiffness of the manipulandum was set at lower rather than higher amplitudes. The parametric impulse response functions revealed that the human operator system was underdamped (0.7) with a natural frequency of approximately 8 rad/s. These findings were interpreted in terms of the responses of the various subsystems (visual, cognitive, contractile, limb mechanics) that comprise the human operator's response.

Adult↗
PubMed1990

A perceptual analysis of stiffness.

The perception of stiffness was studied in ten human subject using two servo-controlled electromagnetic linear motors with computer-controlled stiffness, one motor coupled to each wrist of the subject. Using the contralateral limb-matching procedure in which subjects adjusted the stiffness of the motor connected to one (matching) arm until it was perceived to be the same as that connected to the other (reference) arm, a psychophysical function for stiffness was calculated. Eight different stiffness intensities were matched by subjects with five repetitions at each stimulus amplitude. The relation between the stiffness of the reference and matching motors was linear, and the accuracy with which subjects could match stiffness paralleled that reported previously for force and displacement. The Weber fraction for stiffness was 0.23 which is three times that reported for elbow flexion forces and forearm displacement. These findings were interpreted as indicating that subjects can perceive changes in the stiffness of mechanical devices used to effect action in the environment and that these perceptions are based on sensory signals conveying force and movement information.

Adult↗
PubMed1990

In vivo regulation of the murine syngeneic mixed lymphocyte reaction.

Previous work from this laboratory has suggested that a CD8+ T suppressor (Ts) cell network regulated the murine syngeneic mixed lymphocyte reaction (SMLR). We have attempted to disrupt this network by the inoculation of anti-CD8 monoclonal antibodies (mAb) in vivo. Intraperitoneal inoculation of three mAbs resulted in a marked increase in the proliferation of CD4+, self-Ia-reactive splenic T cells in vitro to syngeneic, but not to allogeneic, spleen cells. Suppression was not limited to a specific mouse strain as the enhanced SMLR was reproducible following anti-CD8 treatment of three strains of mice. In vivo depletion of CD8+ T cells was not a prerequisite for enhancement of the SMLR as several mAb to CD8 augmented the SMLR independent of their capacity to cause CD8 T cell depletion. Moreover, enhancement of the SMLR could be mimicked in vitro by inclusion of anti-CD8 mAb in in vitro cultures of responder T cells and irradiated Ia+ syngeneic stimulators. Since the in vitro SMLR was enhanced following mAb treatment, it was expected that the in vivo SMLR would also be increased. However, no evidence of increased in vivo autoreactivity could be detected following in vivo treatment with anti-CD8 mAb, indicating that other mechanisms in addition to CD8+ regulatory T cells acted to regulate the in vivo activity of autoreactive T cells.

Animals↗
PubMed1989

Thymic requirement for clonal deletion during T cell development.

During T cell differentiation, self tolerance is established in part by the deletion of self-reactive T cells within the thymus (negative selection). The presence of T cell receptor (TCR)-alpha beta + T cells in older athymic (nu/nu) mice indicates that some T cells can also mature without thymic influence. Therefore, to determine whether the thymus is required for negative selection, TCR V beta expression was compared in athymic nu/nu mice and their congenic normal littermates. T cells expressing V beta 3 proteins are specific for minor lymphocyte stimulatory (Mlsc) determinants and are deleted intrathymically due to self tolerance in Mlsc+ mouse strains. Here it is shown that V beta 3+ T cells are deleted in Mlsc+ BALB/c nu/+ mice, but not in their BALB/c nu/nu littermates. Thus, the thymus is required for clonal deletion during T cell development.

Animals↗
PubMed1989

Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.

Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.

Animals↗
PubMed1989

The assessment of hand function: a critical review of techniques.

The tests and procedures used to evaluate the sensory and motor capabilities of the hand are reviewed in the context of normative studies that provide evidence of their reliability and validity. Three broad areas of assessment are distinguished, ranging from the measurement of strength and joint motion to the evaluation of the functional capacity of the hand. The strengths and limitations of the techniques used to evaluate hand function are examined, and the importance of considering a number of variables (e.g., hand preference, age) when interpreting test results from patients is discussed. The problems in predicting the functional capacity of the hand from scores on specialized sensory and motor tests suggest that more versatile measuring instruments are required. This issue is addressed with reference to recent studies of prehension in normal subjects.

Biomechanical Phenomena↗
PubMed1989

Matching forces: constant errors and differential thresholds.

A contralateral limb-matching procedure was used to study the perception of forces generated by the elbow flexor muscles. Subjects were required to generate forces ranging from 15 to 85% of their maximum voluntary contraction (MVC range: 169-482 N), and after achieving the target force to produce a force of the same perceived intensity with their contralateral arm. Under these conditions, subjects consistently overestimated the amplitude of the two lowest forces, and the most accurate matching of forces occurred in the middle of the response range (around 50% MVC). This pattern of constant errors could be explained in terms of an artifact of the starting position, which has been shown to influence the accuracy of judgements of stimulus magnitude. The Weber fraction for force calculated from the matching data was 0.07, which is within the range reported previously for weight. These thresholds are, however, considerably lower than those described for friction and the moment of inertia, the perception of which also involves the proprioceptive system.

Adult↗