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Biomedical subjects

S Adams

Publications and source records attributed to S Adams.

At least 163 records · Page 9Linked to original sources

Late potentials and their relation to ventricular function in human immunodeficiency virus infection.

Signal-averaged electrocardiograms were performed in 225 patients with serologic evidence of human immunodeficiency virus infection as part of a prospective longitudinal study of patients with HIV-associated heart disease and 12 seronegative control subjects. The duration of signal-averaged QRS vector, root-mean-square voltage of the terminal 40 ms of the vector magnitude and the duration of the low-amplitude (less than 40 microV) signal were determined during serial visits at 4-month intervals. One or more of these variables was abnormal on initial visit in 59 of patients (26%); QRS duration was greater than 114 ms in 9 patients (4%), root-mean-square voltage less than 20 microV in 55 patients (24%) and low-amplitude signal duration greater than 39 ms in 43 (19%). In contrast, none of the seronegative control subjects had any abnormal variables (p less than 0.03). During follow-up (mean 10 +/- 8 months), 26 patients with initially normal studies developed abnormal variables and 24 with abnormal signal-averaged electrocardiograms reverted to normal. Left ventricular contractility was assessed by echocardiography using the rate-corrected velocity of fiber shortening-end-diastolic wall stress relation. Late potentials were not related to contractile abnormalities. Clinical arrhythmias were rare and did not appear more frequent among patients with late potentials. Thus, late potentials were both common and evanescent in patients infected with human immunodeficiency virus.

Adult↗

The interaction of caldesmon with the COOH terminus of actin.

Caldesmon interacts with the NH2-terminal region of actin. It is now shown in airfuge centrifugation experiments that modification of the penultimate cysteine residue of actin significantly weakens its binding to caldesmon both in the presence and absence of tropomyosin. Furthermore, as revealed by fluorescence measurements, caldesmon increases the exposure of the COOH-terminal region of actin to the solvent. This effect of caldesmon, like its inhibitory effect on actomyosin ATPase activity, is enhanced in the presence of tropomyosin. Proteolytic removal of the last three COOH-terminal residues of actin, containing the modified cysteine residue, restores the normal binding between caldesmon and actin. These results establish a correlation between the binding of caldesmon to actin and the conformation of the COOH-terminal region of actin and suggest an indirect rather than direct interaction between caldesmon and this part of actin.

Actins↗

Immunochemical evidence for the binding of caldesmon to the NH2-terminal segment of actin.

The binding of caldesmon and its actin-binding fragments to actin was studied by using peptide antibodies directed against two actin sites implicated in actomyosin interactions. Antibodies against residues 1-7 on skeletal alpha-actin strongly inhibited the binding of caldesmon to actin and perturbed to a smaller extent the interaction between actin and the actin binding fragments. Carbodiimide coupling of ethylenediamine to the NH2-terminal acidic residues on actin inhibited the binding of caldesmon and its fragments to actin to a similar extent as the (residues 1-7) antibodies. Antibodies against residues 18-28 showed only limited competition with caldesmon for the binding to actin. These results lead to the following conclusions. (i) The NH2-terminal residues on actin play an important role in the binding of caldesmon to actin, (ii) residues 18-28 on actin do not form a major caldesmon interaction site, and (iii) the actin-binding fragments do not contain the full actin-binding interface. These conclusions and other literature data suggest that caldesmon regulates the actomyosin ATPase by competing with myosin.ATP for the NH2-terminal segment on actin.

Actins↗

T cell receptor V beta genes expressed by IgG anti-DNA autoantibody-inducing T cells in lupus nephritis: forbidden receptors and double-negative T cells.

In the (SWR x NZB)F1 (SNF1) model of lupus nephritis, pathogenic variety of IgG anti-DNA autoantibodies are induced by certain T helper (Th) cells that are either CD4+ or CD4-CD8- (double negative; DN) in phenotype. From the spleens of eight SNF1 mice with lupus nephritis, 149 T cell lines were derived and out of these only 25 lines (approximately 17%) were capable of augmenting the production of pathogenic anti-DNA autoantibodies. Herein, we analyzed the T cell receptor (TcR) V beta genes used by 16 such pathogenic autoantibody-inducing Th cell lines. Twelve of the Th lines were CD4+ and among these five lines expressed V beta 8 (8.2 or 8.3). The V beta 8 gene family is contributed by the NZB parent to the SNF1 mice, since it is absent in the SWR parental strain. Three other CD4+ Th lines expressed V beta 4, another was V beta 2+ and one line with poor autoantibody-inducing capability expressed V beta 1. Four autoantibody-inducing Th lines from the SNF1 mice had a DN phenotype and these lines were also autoreactive, proliferating in response to syngeneic spleen cells. Among these DN Th lines, two expressed V beta 6 and one expressed V beta 8.1 TcR. Both of these are forbidden TcR directed against Mls-1a (Mlsa) autoantigens expressed by the SNF1 mice and such autoreactive T cells should have been deleted during thymic ontogeny. Thus, the DN Th cells of non-lpr SNF1 mice are different from the DN cells or MRL-lpr which lack helper activity and do not express forbidden TcR. The spleens of 6 out of 19 nephritic SNF1 animals tested also showed an expansion of forbidden autoreactive TcR+ cells that were mainly DN. Two of these animals expressed high levels of V beta 6 (anti-Mlsa) and V beta 11 (anti-I-E) TcR+ cells, three others had high levels of V beta 11+ cells alone and one animal had an expanded population of V beta 17a+ (anti-I-E) cells. The I-E-reactive TcR again should have been eliminated in the SNF1 thymus, since they express I-E molecules contributed by the NZB parent. The SWR parents of SNF1, are I-E-; moreover, they lack the V beta 11 gene but they express V beta 17a in peripheral T cells. Whereas the NZB parents are I-E+, they lack a functional V beta 17a gene and they delete mature V beta 11+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A prospective survey of reactions to blood tests by children and adolescents.

A sample of 171 children and adolescents aged 3-17 years requiring venepuncture for blood sampling were asked to report on their pain and anxiety and were observed immediately before and during blood drawing. Depending on the measures used, 36-64% of children from 3 to 6 years old experienced moderate to severe distress from blood drawing. Multiple regression analysis revealed that age and the parents' prediction of how upset the child would feel before the blood test was a significant predictor of the observed distress and the self-report of pain. Experience with previous needle procedures did not add significantly to the prediction of distress. Identification of children at high risk to respond poorly to painful medical procedures is discussed.

Adolescent↗

Oral structure nonspeech motor control in normal, dysarthric, aphasic and apraxic speakers: isometric force and static position control.

This study investigated the isometric force and static position control of the upper lip, lower lip, tongue, jaw, and finger in four subject groups (normal control, apraxia of speech, conduction aphasia, and ataxic dysarthria) at two force and displacement levels. Results from both the force and position tasks suggested that the apraxic and dysarthric groups tended to produce significantly greater instability than the normal group, although the pattern of instability across articulators was not systematic within or across the force and position experiments for subjects within or between groups. The conduction aphasic group produced force and position stability that typically was not significantly different from any of the remaining three groups, suggesting that their force and position stability as indexed in the present study fell somewhere between that of the normal group and the apraxic and dysarthric groups. It is suggested that other analyses of force and position control, such as descriptive accounts of the trial-by-trial time histories, might shed additional light on the speech and orofacial sensorimotor control deficits in persons with apraxia, dysarthria, and conduction aphasia.

Adult↗

Statistical comparison of movement amplitudes from groupings of normal geriatric speakers.

An implicit assumption of many studies of articulatory kinematics is that all normal speakers are equivalent, at least in a statistical sense. The present report investigated this assumption by performing post hoc analyses on random groups of 8 normal, geriatric males. Results of these analyses suggest that, at least for the geriatric population, small numbers of subjects may not represent the parent population adequately, especially when the unit of statistical analysis is the individual trial. These findings have implications for the types of generalizations that can be made from studies with small samples and suggest the need for more comprehensive investigations of speech kinematics.

Aged↗

Noninvasive monitoring of human cardiac allograft rejection.

The frequency of donor-reactive cytolytic T lymphocytes was measured in the peripheral blood mononuclear cell population of a group of 12 cardiac allograft recipients immediately before and at various time points after transplantation. At each of the time points after transplantation the donor heart was biopsied and the rejection status of the graft was determined by applying standard histological criteria. The results of this study showed that the preoperative frequency of donor-reactive cytolytic T lymphocytes in the blood was not predictive of a future tendency toward graft rejection. However, when all the data were examined it was apparent that the frequency of donor-reactive cytolytic T lymphocytes was significantly higher (P less than 0.05) in blood samples from patients whose simultaneous biopsy showed histological evidence of acute cardiac allograft rejection than in blood samples from transplant patients showing no evidence of rejection.

Adult↗

Regulation of human lung fibroblast collagen production by recombinant interleukin-1, tumor necrosis factor, and interferon-gamma.

Several cytokines have been shown to modulate the synthesis of matrix molecules, but few reports have defined how the cytokines interact with one another in mediating these regulatory effects. To define the cytokine network regulating collagen production, we have studied the effects of interferon-gamma, interleukin-1, and tumor necrosis factor on collagen synthesis by cultured human lung fibroblasts. Confluent cells were treated with cytokines for 24 h in the absence of serum or in media containing 1% serum. In the absence of serum, IL-1 and TNF each dose-dependently stimulated types I and III collagen production, with a maximal 2-4-fold increase in collagen accumulation being observed. Cells treated with IL-1 and TNF in combination showed less stimulation than with either cytokine alone. IFN-gamma also diminished the stimulatory effects of both IL-1 and TNF. In contrast, in 1% serum IL-1 and TNF individually had relatively minor effects, while IFN-gamma inhibited collagen production. However, the combination of IL-1 and TNF inhibited collagen production. Generally, these effects were achieved through control of mRNA levels. These studies demonstrate the existence of a cytokine network regulating fibroblast collagen production and suggest that cytokine effects in vivo may vary depending upon the constellation of factors present in the tissue.

Adult↗

[Activities of the International Committee for Prevention and Treatment of Depression].

During recent decades depressive states, mainly those of a psychogenic nature, have been encountered with ever increasing frequency; somatization of depressive syndromes has also been on the increase. Since the number of psychiatrists available had become hardly sufficient to cope with all the depressed patients, it proved possible--thanks to progress in the diagnosis and management of depression--also to enlist the aid of general practitioners in treatment for depression on an ambulant basis. The general practitioner is in fact usually the first person to whom depressed patients, including especially those with physical complaints, turn for help; it is he who must then decide whether the patient is suffering from depression and, if so, whether he himself will treat the case or refer the patient to a practising psychiatrist or to a hospital. In order to contribute to the postgraduate instruction of non-psychiatrists working in everyday practice by enlightening them on the problem of depression, an "International Committee for Prevention and Treatment of Depression" (P.T.D. Committee) was founded some 15 years ago.

Brazil↗

Permanent alteration of the murine Ly-1 B repertoire due to selective depletion of Ly-1 B cells in neonatal animals.

Studies presented here demonstrate that paternal allotype Ly-1 B cells are permanently depleted following neonatal treatment with antibodies to the paternal IgM allotype. Paternal allotype conventional B cells, in contrast, are temporarily depleted by treatment with either anti-IgM or anti-IgD allotype antibodies and return rapidly to normal frequencies once the antibody treatment disappears. These differences are explained by basic developmental differences between Ly-1 B and conventional lineage B cells. That is, the conventional B cell population is replenished from Ig- precursors throughout life and, therefore, is only temporarily affected when depleted in neonates. The Ly-1 B cell population, in contrast, develops from Ig- progenitors during the prenatal and neonatal life but survives because it is exclusively self-replenishing in adults. Therefore, elimination of a population of Ly-1 B cells from neonates is tantamount to removing it forever. These findings suggest that while conventional B cells turn over rapidly and have an effectively unlimited repertoire, Ly-1 B cells express a repertoire whose composition is strongly influenced by neonatal conditions that favor or select against the retention of cells producing certain antibody molecules. Thus, Ly-1 B cells play a unique role in the immune system in that they retain indefinitely the history of the neonatal animal's immunological experience.

Animals↗

Feedback regulation of murine Ly-1 B cell development.

Studies presented here, conducted with allotype homozygotes, demonstrate the existence of a feedback mechanism that regulates development of Ly-1 B cells from immature progenitors. In the preceding study (P. A. Lalor et al., Eur. J. Immunol. 1989. 19:501), conducted with allotype heterozygotes, we showed that treating neonates with monoclonal antibody to the paternal allotype IgM depletes roughly half of the neonatal B cell population (i.e. those expressing the paternal IgM allotype) and that paternal allotype Ly-1 B cells specificically remain depleted for the life of the animal. Here we show that treating allotype homozygotes with the same antibody depletes all (rather than half) of the B cells and that, under these conditions, relatively normal numbers of Ly-1 B cells reappear shortly after the treatment antibody disappears. The recovery, we also show, is prevented by restoring allotype-congenic Ly-1 B cells to the treated homozygotes, i.e. by reconstituting treated neonates with allotype-congenic peritoneal cells, sorted Ly-1 B cells or a monoclonal population of Ly-1 B "tumor" cells. These findings in essence reveal a feedback mechanism through which mature Ly-1 B cells prevent further Ly-1 B cell development from Ig- precursors. This feedback regulation is independent of Ig secretion by the mature Ly-1 B cells, since the monoclonal Ly-1 B "tumor" population that prevents endogenous Ly-1 B development does not secrete Ig. Furthermore, it appears to be independent of Ly-1 B surface Ig specificity, since a monoclonal population is sufficient to block all Ly-1 B cell development. This mechanism appears to operate normally to fix the composition of the Ly-1 B population, which survives through self-replenishment in adults, in accord with conditions that influence Ly-1 B development during neonatal life.

Animals↗

Post-infarction ventricular septal defect: the importance of site of infarction and cardiogenic shock on outcome.

Sixty-eight patients operated upon for post-infarction VSD from 1980-1987 have been reviewed to identify incremental risk factors which influence survival. Univariate and multivariate analysis was performed on 19 parameters and showed the following in decreasing order of importance to be significantly associated with non-survival: (1) operation within 24 h of occurrence of the VSD; (2) inferior infarct preceding the VSD; (3) requirement for inotropic support preoperatively; (4) preoperative cardiogenic shock; (5) a lower mean pulmonary artery pressure; (6) a lower mean wedge pressure; (7) a lower mean systolic pressure. The presence of a graft to the right coronary artery was associated with a better prognosis. Age, sex, diastolic blood pressure, balloon pumping, mean plasma urea, right atrial pressure, extent of coronary disease, number of coronary grafts, grafts to the left coronary system and method of myocardial preservation had no influence on survival.

Aged↗

Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity.

Long term B lineage chimeras are used here to study the origin of plasma cells in the mouse. Chimeric mice are constructed by reconstituting lethally irradiated mice with peritoneal cells (PerC) and bone marrow cells from congenic pairs of mice differing in Igh-C allotype. All conventional B cells in these mice express the allotype of the bone marrow donor and nearly all Ly-1 B lineage cells express the allotype of the PerC donor. FACS analysis and immunohistology of these mice shows that virtually all (sig+) B cells in peripheral lymphoid organs are derived from the bone marrow donor. However, despite this overwhelming number of bone marrow-derived B cells in these animals, immunohistological staining of lymphoid organs and gut shows that nearly half of the IgM, IgG, and IgA plasma cells derive from the PerC donor. These data demonstrate that the peritoneal cavity contains a major reservoir of self-replenishing cells that play a significant role in the mucosal immune response. The possibility that these are B cells that belong to the Ly-1 B lineage is discussed.

Animals↗

Enhanced immunogenicity of a T cell immunogenic peptide by modifications of its N and C termini.

The modification of the terminal ionizable charges of an immunogenic peptide, HEL (46-61), was found to greatly increase the immunogenicity of the peptide. The modified peptide had 100- to 1000-fold enhanced activity in both in vitro and in vivo T cell assays. The mechanism of the enhancement was investigated by determining the binding affinities to I-Ak as well as circular dichroism (CD) studies. The native and enhanced peptides had indistinguishable binding affinities, as well as similar kinetics. The CD studies revealed that in aqueous solution, neither peptide had any detectable helicity; however, the addition of trifluoroethanol did result in significant helicity; with the two peptides being indistinguishable. These same modifications were also shown to enhance other immunogenic peptides if they contained a basic carboxy-terminal amino acid residue. Thus, by modifying the termini of T cell epitopes, their immunogenicity can be dramatically increased, but the molecular basis for this enhancement is still unclear.

Amino Acid Sequence↗