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Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 145 records · Page 8Linked to original sources
PubMed1999

Intraovarian regulation of luteolysis.

The corpus luteum is a transient gland, which is only functional for 17-18 days in the cyclic cow or for up to 200 days in the pregnant cow. Regression of the corpus luteum is essential for normal cyclicity as it allows the development of a new ovulatory follicle, whereas prevention of luteolysis is necessary for the maintenance of pregnancy. Evidence acquired over the past three decades indicated that PGF2 alpha is the luteolytic hormone in ruminants. Nevertheless, the detailed mechanisms of PGF2 alpha action are just beginning to be clarified. A pivotal role for an endothelial cell product endothelin 1 (ET-1) has been documented in PGF2 alpha-induced luteal regression. ET-1 inhibited progesterone production by luteal cells in a dose-dependent manner via selective ET-1 binding sites (ETA). The inhibitory action of PGF2 alpha on progesterone secretion (in vivo and in vitro) was blocked by a selective ETA receptor antagonist. This implied that ET-1 (through ETA receptors present on steroidogenic cells) may have mediated the inhibitory effect of PGF2 alpha. The involvement of ET-1 in luteal regression was also suggested by the observation that the highest concentrations of ET-1 coincide with uterine PGF2 alpha surges. Furthermore, PGF2 alpha administration upregulated ET-1 expression within the corpus luteum. Later stages of luteal regression, which involve programmed cell death (PCD), are presumably mediated by immune cells. ET-1 may also be involved in this process by promoting leukocyte migration and stimulating macrophages to release tumour necrosis factor alpha (TNF alpha). The TNF alpha receptor type 1 (p55) is present on luteal cells (endothelial and steroidogenic cells) and could initiate PCD and the structural demise of the corpus luteum.

Animals↗
PubMed1998

Retinoic acid enhances neuronal proliferation and astroglial differentiation in cultures of CNS stem cell-derived precursors.

Stem cells isolated from the embryonic day 14 mouse striatum proliferate in response to epidermal growth factor (EGF). These stem cells produce clonally derived clusters of undifferentiated cells (spheres) which, in turn, produce neurons, astrocytes, and oligodendrocytes. Reverse transcription followed by polymerase chain reaction showed that EGF-generated spheres express several of the retinoid receptors. Thus, we asked whether all-trans retinoic acid (ATRA) could regulate the differentiation or proliferation of central nervous system stem cell-derived progeny. Under conditions that promote differentiation, cultures of dissociated spheres showed a dose-dependent increase in neuron numbers in response to ATRA. At the most effective neurogenic concentration (0.1 microM ATRA), neuron production increased two- to threefold. However, no difference in the total numbers of control and treated cells was observed. Delayed addition experiments suggest that responsive cells must be exposed to ATRA within the first 24 h in culture. Bromodeoxyuridine incorporation labeling indicates that the ATRA-generated neurons are derived from a mitotically active population of cells. Under conditions that promote glial progenitor cell division, however, ATRA attenuated proliferation (maximum of 60% decrease with 0.1 microM ATRA), accompanied by an increase in the number of glial fibrillary acidic protein-immunoreactive astrocytes. These results suggest that retinoids can regulate the proliferation of mitotically active EGF-responsive stem cell progeny to enhance neurogenesis and astrocyte differentiation.

Animals↗
PubMed1998

A microsatellite-based multilocus phylogeny of the Drosophila melanogaster species complex.

Uncovering the genealogy of closely related species remains a major challenge for phylogenetic reconstruction. It is unlikely that the phylogeny of a single gene will represent the phylogeny of a species as a whole [1], but DNA sequence data across a large number of loci can be combined in order to obtain a consensus tree [2]. Long sequences are needed, however, to minimize the effect of (infrequent) base substitutions, and sufficient individuals must be sequenced per species to account for intraspecific polymorphisms, an overwhelming task using current DNA sequencing technology. By contrast, microsatellites are easy to type [3], allowing the analysis of many loci in multiple individuals. Despite their successful use in mapping [4,5], behavioural ecology [6] and population genetics [7], their usefulness for the phylogenetic reconstruction of closely related taxa has never been demonstrated, even though microsatellites are often conserved across species [8-10]. One drawback to microsatellite use is their high mutation rate (10(-4)-10(-2)), combined with an incomplete understanding of their mutation patterns. Many microsatellites are available for Drosophila melanogaster, and they are distributed throughout the genome [11]. Most can be amplified in the D. melanogaster species complex [12,13] and have low mutation rates [14, 15]. We show that microsatellite-specific distance measurements [16] correlate with other multilocus distances, such as those obtained from DNA-DNA hybridization data. Thus microsatellites may provide an ideal tool for building multilocus phylogenies. Our phylogenetic reconstruction of the D. melanogaster complex provides strong evidence that D. sechellia arose first, followed by a split between D. simulans and D. mauritiana.

Animals↗
PubMed1998

Semiconductor nanocrystals as fluorescent biological labels.

Semiconductor nanocrystals were prepared for use as fluorescent probes in biological staining and diagnostics. Compared with conventional fluorophores, the nanocrystals have a narrow, tunable, symmetric emission spectrum and are photochemically stable. The advantages of the broad, continuous excitation spectrum were demonstrated in a dual-emission, single-excitation labeling experiment on mouse fibroblasts. These nanocrystal probes are thus complementary and in some cases may be superior to existing fluorophores.

3T3 Cells↗
PubMed1998

Antagonist peptide selects thymocytes expressing a class II major histocompatibility complex-restricted T cell receptor into the CD8 lineage.

CD4/CD8 lineage decision is an important event during T cell maturation in the thymus. CD8 T cell differentiation usually requires corecognition of major histocompatibility complex (MHC) class I by the T cell receptor (TCR) and CD8, whereas CD4 T cells differentiate as a consequence of MHC class II recognition by the TCR and CD4. The involvement of specific peptides in the selection of T cells expressing a particular TCR could be demonstrated so far for the CD8 lineage only. We used mice transgenic for an MHC class II-restricted TCR to investigate the role of antagonistic peptides in CD4 T cell differentiation. Interestingly, antagonists blocked the development of CD4(+) cells that normally differentiate in thymus organ culture from those mice, and they induced the generation of CD8(+) cells in thymus organ culture from mice impaired in CD4(+) cell development (invariant chain-deficient mice). These results are in line with recent observations that antagonistic signals direct differentiation into the CD8 lineage, regardless of MHC specificity.

Animals↗
PubMed1998

The role of the bacterial membrane protein ActA in immunity and protection against Listeria monocytogenes.

ActA, an essential virulence factor of Listeria monocytogenes, is an integral membrane protein that is required for intracellular motility, cell-to-cell spread, and rapid dissemination of the bacteria in the infected host. To reveal cytotoxic T cell responses against ActA we introduced a recombinant soluble form of ActA into the MHC class I-processing compartment of APC using a variant of listeriolysin mutated within its immunodominant MHC class I epitope. With this experimental system we demonstrate that T cells are induced against ActA during a sublethal infection with L. monocytogenes. However, adoptively transferred cytotoxic CD8+ T cells specific for ActA did not protect mice against a subsequent challenge with this pathogen. This was due to an inability of APC to present ActA by either MHC class I or class II molecules as long as ActA remained tethered to the surface of intracellular viable bacteria. ActA was only presented when L. monocytogenes were engineered to secrete ActA or when the bacteria were killed by antibiotics during the assay. These findings raise questions on the general use of membrane proteins of pathogens as candidates for subunit vaccines.

Adoptive Transfer↗
PubMed1998

Relation of nutrition to bone lead and blood lead levels in middle-aged to elderly men. The Normative Aging Study.

The relations of nutritional factors to lead accumulation in the body were examined cross-sectionally among 747 men aged 49-93 years (mean 67 years) in the Normative Aging Study in 1991-1995. Means (standard deviations) for blood lead, tibia lead, and patella lead were 6.2 (4.1) microg/dl, 21.9 (13.3) microg/g, and 32.0 (19.5) microg/g, respectively. In multiple regression models adjusting for age, education level, smoking, and alcohol consumption, men in the lowest quintile of total dietary intake levels of vitamin D (including vitamin supplements) (<179 i.u./day) had mean tibia and patella lead levels 5.6 microg/g and 6.0 microg/g higher than men with intake in the highest quintile (> or =589 i.u./day). Higher calcium intake was associated with lower bone lead levels, but this relation became insignificant when adjustment was made for vitamin D. The authors also observed inverse associations of blood lead levels with total dietary intake of vitamin C and iron. When analyses were controlled for patella lead, age, smoking, and alcohol consumption, men in the lowest vitamin C intake quintile (<109 mg/day) had a mean blood lead level 1.7 microg/dl higher than men in the highest quintile (> or =339 mg/day), while men in the lowest iron intake quintile (<10.9 mg/day) had a mean blood lead level 1.1 microg/dl higher than men in the highest quintile (> or =23.5 mg/day). This study suggests that low dietary intake of vitamin D may increase lead accumulation in bones, while lower dietary intake of vitamin C and iron may increase lead levels in the blood.

Aged↗
PubMed1998

[The family physician and prevention of alcohol-related problems].

Involvement of the family physician in the prevention of alcohol-related problems is described. Advice about risks in low-risk drinking is presented, as well as non-laboratory assessment of alcohol-dependency and of patients with increased risk of developing alcohol-related problems. The CAGE questionnaire, patterns of alcohol intake, and brief intervention among low-risk and high-risk patients are discussed.

Alcohol-Related Disorders↗
PubMed1998

Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans.

The molecular basis for autosomal dominant progressive nonsyndromic hearing loss in an Israeli Jewish family, Family H, has been determined. Linkage analysis placed this deafness locus, DFNA15, on chromosome 5q31. The human homolog of mouse Pou4f3, a member of the POU-domain family of transcription factors whose targeted inactivation causes profound deafness in mice, was physically mapped to the 25-centimorgan DFNA15-linked region. An 8-base pair deletion in the POU homeodomain of human POU4F3 was identified in Family H. A truncated protein presumably impairs high-affinity binding of this transcription factor in a dominant negative fashion, leading to progressive hearing loss.

Adult↗
PubMed1998

Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: distinct actions from those of brain-derived neurotrophic factor.

Insulin-like growth factor-I (IGF-I) has been reported previously to promote the proliferation, survival, and maturation of sympathetic neuroblasts, the genesis of retinal neurons, and the survival of CNS projection and motor neurons. Here we asked whether IGF-I could promote the in vitro differentiation of postmitotic mammalian CNS neuronal precursors derived from multipotent epidermal growth factor (EGF)-responsive stem cells. In the absence of IGF-I, virtually no neurons were present in cultured stem cell progeny, whereas IGF-I increased neuron number by eight- to 40-fold. Brief exposures (2 hr) to IGF-I were sufficient to allow for neuronal differentiation without affecting proliferation or survival. IGF-I actions could be mimicked by insulin and IGF-II at concentrations that correspond to the pharmacology of the IGF-I receptor, the latter for which the mRNA was detected in undifferentiated stem cell progeny. Although ineffectual alone at low concentrations (10 nM) that would activate its own receptor, insulin was able to potentiate the actions of IGF-I by acting on mitotically active neural precursors. When neuronal precursor differentiation by IGF-I was examined in relation to brain-derived neurotrophic factor (BDNF), two important observations were made: (1) BDNF could potentiate the differentiating actions of IGF-I plus insulin, and (2) BDNF could act on a separate population of precursors that did not require IGF-I plus insulin for differentiation. Taken together, these results suggest that IGF-I and BDNF may act together or sequentially to promote neuronal precursor differentiation.

Animals↗
PubMed1998

Interferon-beta is required for interferon-alpha production in mouse fibroblasts.

The type I interferons--interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta)--are critical for protection against viruses during the acute stage of viral infection [1,2]. Furthermore, type I interferons have been implicated as important mediators in the regulation of lymphocyte development [3], immune responses [4,5] and the maintenance of immunological memory of cytotoxic T cells [6,7]. The different IFN-alpha subtypes are encoded by 12 genes in the mouse [8] whereas IFN-beta is encoded by only one gene [9]. IFN-alpha and IFN-beta have a high degree of sequence homology and are thought to interact with the same surface receptor on target cells [10,11]. As an approach to analysing the different biological functions of IFN-alpha and IFN-beta, we have generated a mouse strain with an inactivated IFN-beta gene. We report here that embryonic fibroblasts from such mice produce neither IFN-beta nor IFN-alpha upon Sendal virus infection, whereas the production of IFN-alpha by leukocytes from the same strain of mice is intact. IFN-alpha production in embryonic fibroblasts from IFN-beta-/- mice could be rescued by 'priming' the cells using exogenous IFN-beta. These results imply a unique role for IFN-beta in the induction of type I interferons in peripheral tissues.

Animals↗
PubMed1998

Temporal relations between obesity and insulin: longitudinal data from the Normative Aging Study.

Although obesity and insulin levels are generally associated in cross-sectional data, the temporal and causal nature of their association is not yet clear. Increased obesity may have preceded increased insulin levels or vice versa. The authors examined the temporal relations between fasting insulin blood levels and weight in longitudinal data from the ongoing Normative Aging Study. Two insulin measurements from which a rate of change (delta Insulin) could be calculated were available from 376 non-diabetic male subjects (mean age = 62.1 years). Rate of change in weight could be calculated for the previous inter-examination period (delta Weight1), the contemporaneous period (delta Weight2), and the inter-examination period following the second insulin measurement (delta Weight3). delta Weight2 was a significant predictor (p = 0.0005) of delta insulin in multiple linear regression models that included control for potential confounders (body mass index, waist-to-hip ratio, antihypertensive and diuretic medication use, and age) and for correlation between the initial level and change in insulin (mean fasting insulin). delta Weight1 was added to the model and was found not to be statistically significant (p = 0.15). When the model was stratified by age tertile, the regression coefficient on delta Weight1 was -0.44 (p = 0.018) for the youngest stratum, -0.06 (p = 0.72) for the middle stratum, and 0.21 (p = 0.19) for the oldest men. Similarly, delta Insulin was a significant predictor of delta Weight3 (p = 0.026) in a separate regression model. These findings are consistent with both possible temporal sequences of association between changes in insulin and obesity. The intricate homeostatic mechanisms that regulate changes in insulin and obesity may not be readily amenable to description in terms of cause and effect.

Aged↗
PubMed1998

CNS stem cells: where's the biology (a.k.a. beef)?

Central nervous system (CNS) stem cells have become the subject of many laboratories' efforts, presentations, and publications. Yet, in the stem cell world, CNS cells are viewed with skepticism. This is likely due to a dearth of biology (in vivo function) to accompany a flurry of phenomenological and restorative neurology studies. In this article, we compare and contrast the biological knowledge of adult forebrain epidermal growth factor-responsive neural stem cells that has emerged from our laboratories with that of hematopoietic stem cells, using two recent papers in the latter field as specific examples. A comparison of stem cell location, lineage, and repopulation suggests that our understanding of CNS stem cell biology is immature. We conclude that a greater focus on in vivo biology will enhance our knowledge and understanding of CNS stem cells.

Aging↗
PubMed1998

Expression level of a transgenic lambda2 chain results in isotype exclusion and commitment to B1 cells.

Two new lambda2 chain-transgenic mouse lines were established, both of which showed stable transgene expression during aging of the mice. The line L23, which expressed the transgene at low levels, exhibited normal B cell development, antibody responses and serum Ig levels. Most of the B cells in this mouse line co-expressed the transgenic lambda2 chain together with an endogenous kappa chain, thus showing poor allelic exclusion of endogenous L chains. On the other hand, high expression of the transgenic lambda2 chain in the other mouse line, L2, resulted in nearly complete exclusion of endogenous L chain isotypes. In this line, the lambda2 transgene was already detectable in the cytoplasm of all preB-II cells and some pro/preB-I cells. Its expression during these early phases obviously inhibited development of conventional B2 cells, since the B cells in the periphery of these mice were almost exclusively of the B1 type. This finding was confirmed by adoptive transfer of transgenic bone marrow into lethally irradiated recipients. Very few B cells were present in the spleen of such recipients. The serum IgM levels of L2 mice were close to normal and the majority of these IgM were associated with the transgenic lambda2 chain. Antibody responses to thymus-dependent antigens in such mice were almost exclusively found to be of IgM class. Together, these findings indicate a developmental bias leading to a predominance of B1 cells in the L2 line.

Adoptive Transfer↗
PubMed1998

Efficient induction of cytotoxic CD8+ T cells against exogenous proteins: establishment and characterization of a T cell line specific for the membrane protein ActA of Listeria monocytogenes.

The property of listeriolysin (LLO) to introduce soluble passenger proteins into the cytosol of antigen-presenting cells allows the induction of CD8+ cytotoxic T cells against such antigens. To overcome the potential problem of presentation of the immunodominant epitope LL091-99 by H-2Kd, a variant LLO92A was established in which Tyr 92 was replaced by Ala. Immunization of BALB/c mice with purified LLO92A failed to stimulate cytotoxic T cells specific for either the epitope LLO91-99 or for any other LLO-derived peptide. Injection of mixtures of purified LLO92A and soluble nucleoprotein (NP) of influenza virus into mice resulted in a strong cytotoxic T cell response exclusively directed against NP. The LLO92A variant was successfully used to generate, propagate and characterize a CD8 T cell line specific for the membrane-bound virulence factor ActA of Listeria monocytogenes. Interestingly, wildtype ActA bound to the surface of live L. monocytogenes was not presented by MHC class I molecules to the CD8+ T cell line.

Animals↗
PubMed1998

[Indications and technique of bone cutting].

For cutting bones different tools and techniques are available. The question which method is most advantageous depends on the basic surgical concept, the location of the bone cut and the choice of the subsequent implant. The biological activity of the anatomical site of the cut determines how much the tissue needs to be protected, taking into consideration the vascularity of the bone and avoiding heat transfer. The surgical approach depends on the implant and should be used also for the bone cut. Specific indications are given for the oscillating saw, the Gigli saw, the osteotome, drill holes and the medullary saw.

Equipment Design↗