PubMed Health⌕ Search

Biomedical subjects

G Kay

Publications and source records attributed to G Kay.

At least 19 recordsLinked to original sources
PubMed2006

Human embryo: a biological definition.

This paper defines a human embryo from a biological standpoint that takes into account emerging technologies in reproductive science. The paper does not consider legal, moral, religious or social views. As the definition of a human embryo must reflect the multifactorial processes of development, an approach has been adopted which combines recognition of observed events with potential for further development. This acknowledges that fertilization and development are not static processes, and as such embryo status can only be defined by observation of specific markers. The following biological definition of 'human embryo' is proposed. A human embryo is a discrete entity that has arisen from either: the first mitotic division when fertilization of a human oocyte by a human sperm is complete or any other process that initiates organized development of a biological entity with a human nuclear genome or altered human nuclear genome that has the potential to develop up to, or beyond, the stage at which the primitive streak appears, and has not yet reached 8 weeks of development since the first mitotic division.

Beginning of Human Life↗
PubMed2004

Estimation of the liveweight of working mules in Morocco from their body measurements.

During March 2001, 117 working mules, randomly chosen from four markets in Morocco, were weighed and a series of body measurements recorded; their age and body condition score were also recorded. Linear regression techniques were used to derive a 'best fit' equation for predicting liveweight from the other variables. For the working mules weighing between 131 and 391 kg the best prediction equation using two variables was: liveweight (kg) = -33 + 2.8 x heart girth (cm)+1.36 x length (cm). Other prediction equations available for estimating the liveweight of equidae were tested on the data, but in all cases they significantly overestimated the weights of the Moroccan mules.

Animals↗
PubMed2004

Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study.

This study was designed to evaluate the effect of stabilized oral reduced nicotinamide adenine dinucleotide (NADH) on cognitive functioning in patients with Alzheimer's disease (AD). NADH is a coenzyme that plays a key role in cellular energy production and stimulates dopamine production. In previous trials NADH has been shown to improve cognitive functioning in patients with Parkinson's disease, depression and AD. The present trial was a randomized, placebo-controlled, matched-pairs, double-blind, 6-month clinical study. Patients with probable AD (n = 26) were randomized to receive either stabilized oral NADH (10 mg/day) or placebo. Twelve pairs of subjects were matched for age and baseline total score on the Mattis Dementia Rating Scale (MDRS) and the Mini Mental State Examination. After 6 months of treatment, subjects treated with NADH showed no evidence of progressive cognitive deterioration and had significantly higher total scores on the MDRS compared with subjects treated with placebo (p < 0.05). Analysis of MDRS subscales revealed significantly better performance by NADH subjects on measures of verbal fluency (p = 0.019), visual-constructional ability (p = 0.038) and a trend (p = 0.08) to better performance on a measure of abstract verbal reasoning. There were no differences between groups in measures of attention, memory, or in clinician ratings of dementia severity (Clinical Dementia Rating). Consistent with earlier studies, the present findings support NADH as a treatment for AD.

Administration, Oral↗
PubMed2003

Ovarian steroids reduce apoptosis induced by trophic insufficiency in nerve growth factor-differentiated PC12 cells and axotomized rat facial motoneurons.

Previous studies have demonstrated that ovarian steroids exert neuroprotective effects in a variety of in vitro and in vivo systems. The mechanisms underlying these effects remain poorly understood. In the present study, the neuroprotective effects of estradiol (E(2)) and progesterone (P) were examined in two models of apoptosis induced by growth factor insufficiency: partially nerve growth factor (NGF)-differentiated PC12 cells, after serum and NGF withdrawal; and axotomized immature rat facial motor motoneurons. E(2) and P both increased the survival of trophically withdrawn NGF-differentiated PC12 cells, at physiologically relevant concentrations. However, neither steroid had a significant effect on the survival of PC12 cells that had not been NGF treated. Exposure to NGF had no effect on the expression of estrogen receptor (ER)beta, but markedly increased the levels of ERalpha and altered the expression of the progesterone receptor (PR) from predominantly PR-B in NGF naive cells, to predominantly PR-A after NGF. The survival promoting effects of E(2) and P were blocked by the specific steroid receptor antagonists Faslodex (ICI 182780) and onapristone (ZK98299), respectively. Inhibitors of RNA (actinomycin D) or protein (cycloheximide) synthesis also abrogated the protective effects of both steroids. In immature rats, E(2) and P both significantly increased the numbers of surviving facial motor neurons at 21 days after axotomy. These data demonstrate significant protective effects of E(2) and P in two well-characterized models of apoptosis induced by trophic withdrawal and suggest that, at least in PC12 cells, the effects of the steroids are mediated via interaction with nuclear steroid receptor systems. The lack of steroid responsiveness in NGF-naive PC12 cells despite the presence of abundant ERbeta and PR-B are consistent with the view that ERalpha and PR-A may be particularly important as mediators of the neuroprotective effects of their corresponding hormonal ligands.

Animals↗
PubMed2001

Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype.

ATM, the gene mutated in the human immunodeficiency disorder ataxia-telangiectasia (A-T), plays a central role in recognizing ionizing radiation damage in DNA and in controlling several cell cycle checkpoints. We describe here a murine model in which a nine-nucleotide in-frame deletion has been introduced into the Atm gene by homologous recombination followed by removal of the selectable marker cassette by Cre-loxP site-specific, recombination-mediated excision. This mouse, Atm-DeltaSRI, was designed as a model of one of the most common deletion mutations (7636del9) found in A-T patients. The murine Atm deletion results in the loss of three amino acid residues (SRI; 2556-2558) but produces near full-length detectable Atm protein that lacks protein kinase activity. Radiosensitivity was observed in Atm-DeltaSRI mice, whereas the immunological profile of these mice showed greater heterogeneity of T-cell subsets than observed in Atm(-/-) mice. The life span of Atm-DeltaSRI mice was significantly longer than that of Atm(-/-) mice when maintained under nonspecific pathogen-free conditions. This can be accounted for by a lower incidence of thymic lymphomas in Atm-DeltaSRI mice up to 40 weeks, after which time the animals died of other causes. The thymic lymphomas in Atm-DeltaSRI mice were characterized by extensive apoptosis, which appears to be attributable to an increased number of cells expressing Fas ligand. A variety of other tumors including B-cell lymphomas, sarcomas, and carcinomas not seen in Atm(-/-) mice were observed in older Atm-DeltaSRI animals. Thus, expression of mutant protein in Atm-DeltaSRI knock-in mice gives rise to a discernibly different phenotype to Atm(-/-) mice, which may account for the heterogeneity seen in A-T patients with different mutations.

Animals↗
PubMed2001

Healthy public relations: the FDA's 1930s legislative campaign.

In this article, I argue that the Food and Drug Administration (FDA) is an oft-overlooked government agency that acts to preserve and secure the public's health. From its early years as an agency charged with enforcement of the 1906 Pure Food and Drugs Act, the FDA not only protected the public's health but also made the public aware of its mission, using methods as diverse as displays at county fairs and at the 1933 Chicago World's Fair, radio programming, and active correspondence. The agency encouraged the public to protect itself, particularly in those arenas in which the FDA had no regulatory authority. In addition, it may have overstepped its boundaries when it actively solicited public support for a bill submitted to Congress in the early 1930s. In the dark days of the Great Depression, the FDA contended not only with limited resources and its own feelings of inadequacy in terms of what could and could not be done to protect the populace, but also with "guinea pig" books that horrified and angered many readers. By 1938, when the agency prevailed and the revisions to the 1906 Act passed Congress and were signed into law by President Franklin D. Roosevelt, the FDA had done all that a responsible public health agency should do, and more.

Health Education↗
PubMed2000

Inhibition of degranulation and interleukin-6 production in mast cells derived from mice deficient in protein kinase Cbeta.

The antigen-mediated activation of mast cells by means of IgE antibodies bound to the cell surface leads to direct interactions between FcepsilonRI receptor cytoplasmic domains and various intracellular proteins. These interactions initiate diverse signal-transduction pathways, and the activation of these pathways results in the immediate release of proinflammatory agents. A delayed response also occurs and includes the release of various cytokines. It is clear that the activation of kinases is a requirement for the exocytosis observed in mast cells. In addition to the tyrosine phosphorylation of the affected system by soluble tyrosine kinases, activity of protein kinase C (PKC) results in serine or threonine phosphorylation of multiple protein substrates. In this study, we found that mast cells derived from PKCbeta-deficient mice produce less interleukin 6 in response to IgE-Ag. The inhibition of exocytosis in the PKCbeta-deficient mast cells occurred whether the stimuli were due to the aggregation of the mast cell surface FcepsilonRI or to the calcium ionophore, ionomycin. However, no significant changes were observed in the proliferative response of the mast cells to interleukin 3 (IL-3) or in their apoptotic rate after IL-3 depletion. (Blood. 2000;95:1752-1757)

Animals↗
PubMed2000

Inhibition of melanin synthesis by cystamine in human melanoma cells.

In studies to determine whether pigmentation can be regulated physiologically by thiols, human melanoma cells (MM418c5) and melanocytes were found to become depigmented when cultured continuously in 50 microM cystamine. Cystamine was depleted from the culture medium and the treatment was nontoxic and reversible. Cysteamine, dithiothreitol, and phenylthiourea were less effective, and glutathione, cysteine, and cystine were inactive. Tyrosinase (dopa oxidase) activity was not greatly affected except for induction of a lag period. In contrast, tyrosinase activity in an amelanotic melanoma cell line (MM96L) was rapidly inhibited without consumption of cystamine/cysteamine, in association with the generation of free thiol in the culture medium, and could be enhanced by the cystine transport inhibitor, glutamate. Tyrosinase expressed by a recombinant vaccinia virus was inhibited by cystamine treatment of MM96L and HeLa cells. Cystamine treatment lowered the degree of cross-linking of the pigmentation antigen gp75/TRP-1 in MM418c5 cells. Tyrosinase protein and mRNA levels in MM418c5 cells were not affected by cystamine. The results show that cystamine at a concentration close to physiologic levels has multiple effects on the melanogenic pathway. In amelanotic cells, tyrosinase has a short half-life and is readily inhibited by cystamine/cysteamine whereas tyrosinase in the more mature melanosomes of the pigmented cell appears to be less accessible to proteolytic and thiol attack. Inhibition of melanin synthesis in the latter cell type may arise to a significant degree from reduction of cystamine to cysteamine, which sequesters quinones.

Cystamine↗
PubMed1999

The proliferation-associated nuclear protein Ki-67 in the bovine system: partial characterisation and its application for determination of the proliferation of Theileria-infected bovine cells.

Theileria annulata-infected bovine cells as well as mitogen-stimulated bovine peripheral blood mononuclear cells (PBMC) express a proliferation-associated nuclear protein equivalent to the human Ki-67 protein. In analogy to the human system, the expression of the bovine Ki-67 protein is restricted to proliferating cells only, since (a) Ki-67 expression paralleled [3H]-thymidine incorporation in concanavalin A (Con A)-stimulated bovine PBMC, (b) Ki-67 was not detectable in quiescent bovine cells, and (c) Ki-67 expression in Theileria-infected cells is related to the presence of the parasites within the cytoplasm of the host cells; upon treatment with the theilericidal drug buparvaquone the parasites are destroyed and the cells cease to proliferate and to express the Ki-67 protein. Western-blot analysis of lysates of proliferating bovine cells revealed that the prototype monoclonal antibody Ki-67 and the new equivalent antibody MIB-1 detected one prominent protein band with an apparent molecular weight of 430 kDa. Two cDNA clones (pUC18.B1.Ki-67 and pUC18.B2.Ki-67) were isolated from a lambdagt11 cDNA library of T. annulata-infected bovine cells by immunoscreening with the monoclonal antibody MIB-1. Comparison of these cDNA sequences with those of the human Ki-67 protein revealed 60-70% identity. Within the "Ki-67 motif", identity proved to be 80% at the amino acid level. The remarkable identity between bovine and human Ki-67 proteins suggests that MIB-1 can be used as a marker for cell proliferation in animal research. In this context we could identify proliferating cells in lymph nodes of Theileria-infected animals and, furthermore, we could distinguish between infected and uninfected proliferating cells using MIB-1 and an antiserum against a recombinant parasite protein designated SA288.

Amino Acid Sequence↗
PubMed1998

Nuclear translocation of upstream stimulating factor 2 (USF2) in activated mast cells: a possible role in their survival.

Multiple transcription factors are activated in the cytoplasm and translocated to the nucleus where they exert positive or negative control over cellular genes. Such subcellular traffic of transcription factors usually requires the presence of a positively charged nuclear localization sequence (NLS). Upstream stimulating factor 2 (USF2) is one of the few transcription factors that contain two potential domains for nuclear localization. In addition to the conventional basic NLS, USF2 contains a highly conserved USF-specific region that is involved in its nuclear translocation. In the present work, the induction of translocation of USF2 into the mast cell nucleus was observed and found to be dependent on activation of the cells either by IL-3 or IgE-Ag. It was also observed that the prevention of the translocation of USF2 to the nucleus, using a peptide derived from the specific USF-NLS region, significantly inhibited their IL-3-mediated survival. Thus, our findings show a direct connection between mast cell surface receptor-mediated USF2 nuclear translocation and cell viability.

Amino Acid Sequence↗
PubMed1998

Prenatal stress depresses immune function in rats.

The aim of the present study was to determine the effect of prenatal stress on immune function in rats. Pregnant rats were stressed by noise and light, three times weekly throughout pregnancy. Experiments were performed on male and female offspring aged 2 months. Cellular immune responses of splenic lymphocytes to B-cell (pokeweed mitogen (PWM) and T-cell (phytohemagglutinin (PHA)) mitogens were measured by [3H]thymidine uptake, and natural killer (NK) cell cytotoxicity in blood and splenic lymphocytes was measured against the murine T-cell lymphoma, YAC-1, by a 4-h [51Cr] release assay. Prenatal stress suppressed immune function as shown by a) decreased NK cytotoxicity in splenic and blood lymphocytes, indicating that the effect was not confined to a particular immune compartment, and b) decreased rate of proliferation of splenic lymphocytes to PWM and a smaller depressant effect on their response to PHA. The suppression of B-cell proliferation was more marked in the female and that of NK cell cytoxicity, in the male. Prenatal stress did not alter the distribution of subsets of lymphocytes, in either the spleen or blood, indicating that the reduction in proliferative and cytotoxic activity resulted from functional modifications of effector mechanisms in the cells rather from alterations in their migration between immune compartments. The mechanisms underlying this effect of prenatal stress are not clear but could result from an action of maternal stress hormones on the developing fetal neuroendocrine system.

Animals↗
PubMed1996

Role of experimental conditions in determining differences in exploratory behavior of prenatally stressed rats.

The effect of prenatal stress was determined on exploration in situations that induce different levels of fear. Dams (12) were stressed by noise and light thrice weekly on an unpredictable basis throughout pregnancy, and 12 controls were left undisturbed. The time spent by different groups of their adult offspring of both sexes in exploration was assessed during 4 min in a plus maze; large, well-lit open field (1), and open field (2) after prior exposure to a small, dark holebox. Prenatal stress resulted in a significant reduction in the number of arm entries in the plus maze and amount of time spent in the open arms. Locomotion and rearing were also reduced in Open Field 1 and 2, but these activities and hole poking were unchanged in the holebox. It is concluded that prenatal stress renders the animal more fearful to a novel, intimidating environment, which may be expressed as a suppression of exploratory activity.

Animals↗
PubMed1995

Clinical aspects of preconditioning and implications for the cardiac surgeon.

Ischemic preconditioning is one of the most powerful means to reduce myocardial ischemic cell death in the experimental laboratory. Data are now emerging suggesting that ischemic preconditioning also can occur in the human heart. Studies performed on human myocardial biopsies, angioplasty studies, clinical studies assessing acute tolerance to angina, and some studies evaluating the effect of angina prior to myocardial infarction, lend support to the concept that the human heart can be preconditioned. The ultimate objective is to develop preconditioning-mimetic agents that can be administered prophylactically prior to the time of cardiopulmonary bypass surgery or administered to hearts that have been harvested for transplant in order to better preserve the ischemically jeopardized myocyte.

Angina Pectoris↗
PubMed1995

Immune responsiveness in mutant mice lacking T-cell receptor alpha beta+ cells.

Immune responses of mice with T-cell receptor (TCR)gamma delta+ T cells but lacking TCR alpha beta+ cells because of a disruption in the TCR alpha gene, were analysed against alloantigens, soluble protein antigen, killed Mycobacterium tuberculosis and exogenous superantigen. Rejection of skin allografts mismatched for classical major histocompatibility complex (MHC) plus multiple minor H antigens was virtually abrogated but the presence of mismatched Qa-1 non-classical MHC antigens on donor tissue resulted in a significant proportion of TCR alpha-/- mice rejecting such grafts. In view of the proposed role for gamma delta T cells in mycobacterial responses, and particularly against self- or mycobacterial heat-shock protein HSP 65, we examined these responses in TCR alpha-/- mice. Local responses after immunization were low in lymph nodes and no component of these was directed against mycobacterial HSP 65. However, splenic T cells from mutant mice responded strongly to either purified protein derivative (PPD) or M. tuberculosis. Our findings indicate that TCR alpha-/- mice are selectively compromised: while responses to (undefined) mycobacterial antigens were substantial, responses to some other target antigens such as MHC alloantigens and HSP 65, believed to be preferentially recognized by gamma delta receptors, were poor or absent. However, the fact that the mutant mice more readily rejected allografts that are mismatched for the non-classical MHC antigen Qa-1 in addition to classical MHC and minor-H incompatibility, indicates that in some mice the residual immune response, presumed to be by gamma delta cells, is sufficient to cause skin graft rejection and that recognition of non-classical MHC antigens may play an important part in the response.

Animals↗