Search PubMed⌕ Search

Biomedical subjects

J Slack

Publications and source records attributed to J Slack.

At least 19 recordsLinked to original sources
PubMed2001

Skinny dipping for stem cells.

Stem cells have been big news for the past couple of years and yet they remain remarkably inscrutable in terms of declaring their true nature and identity. On pages 778-784 of this issue, Toma et al. describe the identification of a new type of stem cell from the dermis of ths skin, called skin-derived precursor (SKP) cells. These can be converted into several differentiated cell types in vitro, including neurons, and might become a source of cells for therapeutic tissue repair.

Animals↗
PubMed2001

Zero-sum politics, the Herbert thesis, and the Ryan White CARE Act: lessons learned from the local side of AIDS.

This study examines the dynamics of grass-roots decision-making processes involved in the implementation of the Ryan White CARE Act. Providing social services to persons with HIV/AIDS, the CARE act requires participation of all relevant groups, including representatives of the HIV/AIDS and gay communities. Decision-making behavior is explored by applying a political (zero-sum) model and a bureaucratic (the Herbert Thesis) model. Using qualitative research techniques, the Kern County (California) Consortium is used as a case study. Findings shed light on the decision-making behavior of social service organizations characterized by intense advocacy and structured on the basis of volunteerism and non-hierarchical relationships. Findings affirm bureaucratic behavior predicted by the Herbert Thesis and also discern factors which seem to trigger more conflictual zero-sum behavior.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Effects of dexamethasone on development of immunoglobulin G subclass responses following vaccination of horses.

OBJECTIVE: To determine the effects of dexamethasone on development of IgG subclass responses following vaccination of healthy horses. ANIMALS: 11 mature Thoroughbreds. PROCEDURE: Horses received 2 IM injections at 2-week intervals of a vaccine containing inactivated infectious bovine rhinotracheitis, bovine viral diarrhea, and parainfluenza-3 viral antigens and were then randomly assigned to 2 groups. Six horses received dexamethasone (0.2 mg/kg of body weight, IM) twice weekly for 8 weeks starting the day of the first vaccination. Five control horses received an equivalent volume of saline (0.9% NaCl) solution. Antigen-specific serum IgG subclass titers were determined weekly after vaccination by use of an ELISA. RESULTS: Vaccination resulted in similar antigen-specific serum IgG(T) titers in dexamethasone-treated and control horses. In contrast, although control horses developed IgGa and IgGb responses after vaccination, corticosteroid administration completely inhibited these responses in treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Cortico steroids can have profound effects on primary immune responses in horses and can significantly affect IgG responses to inactivated vaccines. Corticosteroid treatment regimens commonly used to treat diseases in horses may result induction of a nonprotective IgG subclass response, leaving treated horses susceptible to disease. Additionally, mechanisms regulating IgGa and IgGb responses appear to differ from those regulating IgG(T) responses. Further defining these mechanisms is a critical step in designing effective vaccines, and corticosteroid-induced immunomodulation may be a valuable tool for studying immune responses in horses.

Animals↗
PubMed1999

Tissue plasminogen activator (tPA) as therapy for hepatotoxicity following bone marrow transplantation.

The treatment of established veno-occlusive disease (VOD) of the liver with tissue plasminogen activator (tPA) has been disappointing. In attempts to improve upon these results we identified a subgroup of patients with consistently elevated bilirubin levels who did not meet conventional criteria for VOD (Susp VOD) but who had a significant risk of later developing clinical VOD. In January 1994 we began to treat patients who developed Susp VOD with tPA rather than waiting until they developed clinical VOD. We now report on the results of the first 37 patients who ultimately developed clinical VOD and received tPA therapy prior to Susp VOD, or at the time they had established VOD. Significant bleeding complications occurred in 13 (35%) patients but resolved with discontinuation of therapy in all but one. We found that patients treated early in the course of hepatotoxicity prior to the development of overt VOD had a significantly higher response rate and 100 day survival than patients treated at the time of established VOD. Given the poor results seen in treating late VOD, we suggest that early treatment with tPA may improve the outcome in patients who develop signs of hepatotoxicity following marrow transplantation.

Adolescent↗
PubMed1995

Training obstetricians and midwives to present screening tests: evaluation of two brief interventions.

The objective of this study was to assess the effects of two brief training interventions to improve obstetricians' and midwives' explanations to patients of a routine prenatal screening test. Health professionals were randomly allocated to one of two intervention groups or a control group. Information-giving about the test and communication skills were assessed at baseline, post-training and 3-month follow-up from audiotaped consultations. Both intervention groups received a 1-h training session involving small group discussions focused around a video. In addition, one group received individual feedback on their baseline and post-training consultations. Twenty-six midwives and nine obstetricians completed the study according to the protocol. Changes between baseline and post-training, and between baseline and follow-up, were computed. Information-giving and communication skills improved significantly in subjects receiving training and feedback on their performance, with the greatest improvements occurring before feedback was given. Those receiving training without feedback significantly improved their communication skills and showed some improvement in information-giving. These results show that modest improvements in communication can be made with relatively brief training. Greater and more sustained improvements may be found if all staff were trained, and trained on a regular basis.

Communication↗
PubMed1994

Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses.

Two types of cellular IL-1Rs have been characterized and cloned from both human and murine sources. The type II IL-1R has a very short cytoplasmic domain and does not seem to participate in IL-1 signaling. We demonstrate that type II IL-1Rs are released from the surface of neutrophils in response to treatment with TNF or endotoxin. In addition, serum from patients with sepsis syndrome contains elevated levels of soluble type II IL-1Rs. Neutrophils isolated from patients with sepsis have greatly enhanced expression of type II IL-1R mRNA and cell surface receptors and are therefore a likely source for the shed receptors in serum. Of the three forms of IL-1, soluble type II IL-1R binds IL-1 beta with highest affinity and also selectively inhibits IL-1 beta activity. We propose that increased cell surface expression and rapid release of preformed type II IL-1R from neutrophils, as a soluble IL-1 beta binding protein, represents a mechanism that has evolved for regulating IL-1 activity in sepsis.

Blotting, Northern↗
PubMed1994

Helper T cell-independent proliferation of CD8+ cytotoxic T lymphocytes transduced with an IL-1 receptor retrovirus.

Although the proliferation of CD8+ CTL typically requires cytokine support provided by helper T cells, a subset of naturally occurring CD8+ CTL are capable of proliferating independently of T cell help. Such helper-independent CTL have previously been shown to possess IL-1 receptors (IL-1R) and to proliferate in response to IL-1 through endogenous production of IL-2. In this study, we have transduced conventional helper-dependent CTL clones with a retroviral vector encoding the murine type I IL-1R. Transduced CTL selected in G418 expressed vector-derived transcripts encoding IL-1R and displayed approximately 1000 cell surface receptors with an IL-1 affinity typical for the type I IL-1R. In contrast to parental cells, transduced CTL proliferated in response to IL-1 in the presence of Ag, without a requirement for helper T cells, IL-2, or other cytokine support. Stimulation with both IL-1 and Ag was necessary for the proliferative response. No endogenous synthesis of IL-2 could be detected in the IL-1R transduced cells in response to IL-1 stimulation, in the presence or absence of Ag. The IL-1R-induced phenotype was demonstrated in two independent T cell clones, both of which retained Ag-specific cytolytic activity. No such conversion to a helper-independent phenotype was induced by a retroviral vector encoding only the neo gene. The behavior of the IL-1R-transduced CTL in proliferation assays thus resembled that of the naturally occurring helper-independent CTL.

Animals↗
PubMed1994

Role of fibroblast growth factors as inducing agents in early embryonic development.

To assess the potential role of a molecule in development we need to know three things: 1) what are the biological activities of the molecule, 2) what is its expression pattern, and 3) what are the consequences of removing it from the embryo? In the case of the FGF family in Xenopus embryos we have quite a lot of information about all three questions. Most members of the family can induce mesoderm from isolated animal caps, thus mimicking the natural "ventral vegetal" inducing signal operative in the blastula. This activity can be exerted on isolated, disaggregated cells and does not involve a change in division rate. When overexpressed from injected mRNA, the activity of FGFs depends largely on whether or not they possess a signal sequence, showing the importance of secretion in the inductive process. In addition to the mesoderm-inducing activity, there are effects of overexpression on whole embryos which lead to a suppression of anterior structures. Three types of FGF have so far been cloned from Xenopus: direct homologs of each of the mammalian types FGF-2 and FGF-3, and eFGF ("embryonic FGF"), which is equidistant in sequence from mammalian FGF-4 and FGF-6. Attempts to find homologs of mammalian FGF-5 and FGF-7 in Xenopus have proved unsuccessful. All three types of Xenopus FGF are expressed in early development. FGF-2 and eFGF are present in the oocyte and fertilized egg, and are thus both available at the time of mesoderm induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Lack of knowledge in health professionals: a barrier to providing information to patients?

OBJECTIVE: To assess obstetricians' and midwives' knowledge of routine prenatal screening tests for fetal abnormality and factors associated with such knowledge. DESIGN: Questionnaire assessment of antenatal clinic staff. SETTING: Six hospitals within the United Kingdom (four district general hospitals in London, one district general hospital in Wales, and one teaching hospital in Wales), offering routine prenatal screening tests. SUBJECTS: 29 obstetricians and 97 midwives were invited to participate, of whom 21 and 70 respectively responded to the questionnaire. MAIN MEASURES: Knowledge of prenatal tests, according to 19 item multiple choice questionnaire, reluctance to disclose uncertainty, and clinical experience. RESULTS: The overall response rate was 72% (91/126). In all, 43% of midwives and 14% of obstetricians obtained correct responses on fewer than half the items. Reluctance to disclose uncertainty to patients was associated in obstetricians with having less knowledge about prenatal testing (r = -0.50; p < 0.025, Pearson product moment correlation) and in midwives with more clinical experience (r = 0.43; p < 0.001). CONCLUSIONS: Lack of knowledge and greater clinical experience seem to be important barriers to providing patients with information about prenatal screening tests.

Communication Barriers↗
PubMed1993

Murine T helper cell-2 lymphocytes express type I and type II IL-1 receptors, but only the type I receptor mediates costimulatory activity.

The role of IL-1 in augmenting the Ag receptor-initiated activation program was evaluated in IL-4-producing (Th2) CD4+ murine T lymphocytes. Northern blot and 125I-labeled IL-1 alpha cross-linking analyses demonstrated that Th2 lymphocytes express both type I and type II IL-1R. The expression of both IL-1R isoforms on the surface of the Th2 cells is coordinately up-regulated in response to anti-CD3 cross-linking in the absence of detectable accessory cells. Analyses of the kinetics of IL-1R acquisition demonstrated that the peak level of type I and type II IL-1R mRNA expression occurs after the peak expression of mRNA encoding IL-2R alpha and IL-4, which are two IL-1-responsive events in the Th2 activation program. Type I IL-1R ligand-binding antagonists, IL-1R antagonist and anti-type I mAb, were used to evaluate the functional significance of Th2 cell expression of two IL-1R isoforms. The addition of either IL-1R antagonist or anti-type I mAb completely inhibited the IL-1 alpha-augmented component of the proliferative response stimulated by anti-CD3 plus exogenous IL-1 alpha. Together, these studies indicate that, although Th2 clones express inducible levels of both type I and type II IL-1R isoforms, the IL-1-induced intracellular signals involved in augmenting an anti-CD3-stimulated proliferative response are mediated solely through the type I IL-1R.

Animals↗
PubMed1993

Independent binding of interleukin-1 alpha and interleukin-1 beta to type I and type II interleukin-1 receptors.

Interleukin (IL)-1 refers to a group of three polypeptide hormones with a wide range of cellular targets. Two types of IL-1 receptor have been identified and characterized by cDNA cloning. Both human type I and type II IL-1 receptors contain extracellular domains of approximately 310 residues and a single membrane-spanning region. The type I receptor contains a cytoplasmic domain of 213 residues. The cytoplasmic region of the type II receptor is 29 residues in length. It has been found recently that a number of cells express both forms of receptor. By analogy with other cytokine receptor systems, the two IL-1 receptors might be expected to form a heterodimeric complex, the type II receptor being an alpha-chain-like structure, functioning only to bind ligand, and associating with the type I receptor (a beta-chain-like structure) which would transduce signals. In this report we show that this is not the case, but rather that IL-1, when complexed to type II receptor, cannot bind type I receptors, and vice versa. These data show that the complex patterns often observed for IL-1 binding to cells cannot be accounted for by the same type of mechanism that underlies the behavior of, for example, the IL-2 system.

Antibodies, Monoclonal↗
PubMed1992

The psychological effects of false-positive results in prenatal screening for fetal abnormality: a prospective study.

The purpose of the study was to describe the impact of false-positive results from initial maternal serum alpha-fetoprotein (MS-AFP) screening. The analyses compared two groups of women, those receiving a negative result (n = 346) and those receiving an initial positive result (n = 26), over four time points--prior to testing, immediately after testing, later in pregnancy, and in the post-partum period. Receiving an abnormal result was associated with high levels of anxiety which were reflected in increased worry about the baby's health and a more negative attitude towards the pregnancy and the baby. Women who had an initial abnormal result were offered a variety of further tests. Those women who went on to have amniocentesis were less worried about their baby's health in the third trimester and also less anxious post-partum than those who did not have amniocentesis. In view of the increasing number of screening tests available, it is necessary to establish whether and how these levels of distress can best be reduced.

Adult↗
PubMed1992

Psychological effects of having amniocentesis: are these due to the procedure, the risk or the behaviour?

The purpose of the study was to examine the impact of amniocentesis on women at risk for having a baby with Down's syndrome because of raised maternal age. Fifty-four of the study participants had amniocentesis and nine did not. At the time of the procedure, those having amniocentesis were significantly more anxious, less certain about the baby's health, and held more negative attitudes towards the baby than women who did not undergo amniocentesis. For women undergoing amniocentesis there was a positive association between perceived risk of having an abnormal baby and anxiety. After the baby's birth, women who had undergone amniocentesis held less positive attitudes to the baby and were significantly more worried about the baby's health. These results suggest that the anxiety surrounding amniocentesis is related both to the procedure and to the perceived likelihood of an abnormal result. The differences between the groups after the birth seem more likely to reflect pre-existing attitudinal differences between the two groups, than the effects of amniocentesis.

Adaptation, Psychological↗
PubMed1992

Use of family history in a screening clinic for familial ovarian cancer.

We have estimated the risks of ovarian and other types of cancer in first-degree relatives of women who have developed the disease (the index patients). The number of deaths from each type of cancer was determined from pedigrees taken from 391 self-referred, asymptomatic women attending a screening clinic for familial ovarian cancer. These values were compared with the expected number of deaths for women in the general population (calculated from life tables), and the relative risks were used to estimate lifetime risks. The overall relative risk were 4.5, 1.4, 1.3, and 1.1 for ovarian, stomach, breast, and endometrial cancers, respectively. The risks were invariably higher if the index patient was < 55 years old. Ovarian cancer appeared to have no clear inheritance pattern in 290 pedigrees and there was no increased risk for the first-degree relatives. Eighty-two pedigrees were compatible with a diagnosis of a multiple-site cancer family syndrome and the relative risks were 6.1, 2.8, 3.7, and 2.7 for ovarian, breast, stomach, and colorectal cancer, respectively. There was evidence of site-specific ovarian cancer in 19 families; the relative risk for the first-degree relatives was 39.1 and the lifetime risk 1 in 2. We believe that family history can be used to identify women who are at a high risk of developing ovarian and certain other types of cancer. This information can be used to counsel women attending ovarian cancer screening clinics and to maximize the usefulness of current resources.

Female↗
PubMed1992

Correlation in ages at death from familial ovarian cancer among sisters.

The analysis of pedigrees taken from 97 of 1466 women attending a screening clinic for early familial ovarian cancer showed that there was a strong correlation in the ages at death from the disease among sisters (r = 0.68, confidence limits 0.51-0.82, P < 0.001), but not between mothers and daughters. This information can be used to help counsel women who are considering the appropriate time for more intensive screening or prophylactic oophorectomy.

Adult↗
PubMed1992

Presenting a routine screening test in antenatal care: practice observed.

People's knowledge of screening tests for which they are eligible and which they may have undergone is frequently low. The aim of the current study is to determine the extent to which this is due to how a test is offered and explained. Routine consultations (n = 102) between midwives, obstetricians and pregnant women were tape-recorded to determine how a routine screening test for fetal abnormalities (maternal serum alpha-fetoprotein) is presented. The test was presented in the vast majority of consultations. Overall, little information was provided about the test, the conditions screened for, and the meaning of either a positive or a negative result. Screening was presented in such a way as to encourage women to undergo the test. The way in which routine prenatal screening is presented is unlikely to maximise informed decisions about whether to participate in this screening programme. Factors likely to be influencing test presentation include knowledge, attitudes and skills of staff, as well as the attitudes of pregnant women. The results of this study highlight a need to train the heath professionals implementing screening programmes in how to inform people fully about low probability but serious events without alarming them unduly, or reassuring them falsely.

Down Syndrome↗