PubMed Health⌕ Search

Biomedical subjects

M M Reynolds

Publications and source records attributed to M M Reynolds.

8 recordsLinked to original sources
PubMed2003

Overdominant lethals as part of the conifer embryo lethal system.

In pines, self-pollination rates can be as high as 34% yet only 5% of viable seed is a product of self-fertilization. This decline in selfed seed viability is the consequence of post-fertilization exclusion mechanisms operating via the embryo lethal system. Recent molecular marker dissection studies suggest that the embryo lethal system is composed of semilethal factors dispersed across the genome, but it is not clear whether overdominant lethal factors are rare or representative. The study objective was to determine if overdominance was rare for the embryo lethal system in conifers. Three cohorts of selfed offspring from a single Pinus taeda parent were genotyped for nuclear microsatellites. Maximum likelihood tests based on distorted segregation ratios for single markers and for interval mapping were used to infer the degree of dominance. Four hypotheses about overdominance lethal factors were tested: (1) overdominant lethal factors rarely occur within the embryo lethal system, (2) overdominant lethal factors are rarely detected because they are transient and display stage-specific expression, (3) overdominant lethal factors are rarely detected due to tight linkage with rare marker alleles and (4) dominance estimation is unbiased by gametic selection. Four out of the seven chromosomal segments were linked to an overdominant lethal factor. One of these four segments had symmetric overdominance, an effect which persisted from embryo maturity through germination. Four overdominant lethal factors were linked to common and rare marker alleles. Gametic selection was not a source of bias in dominance estimation. Overdominant or pseudo-overdominant lethal factors are a common component of the conifer embryo lethal system.

Chromosome Segregation↗
PubMed1997

Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase.

The epidermal growth factor receptor (EGFR) is overexpressed in a significant percentage of carcinomas and contributes to the malignant phenotype. CP-358,774 is a directly acting inhibitor of human EGFR tyrosine kinase with an IC50 of 2 nM and reduces EGFR autophosphorylation in intact tumor cells with an IC50 of 20 nM. This inhibition is selective for EGFR tyrosine kinase relative to other tyrosine kinases we have examined, both in assays of isolated kinases and whole cells. At doses of 100 mg/kg, CP-358,774 completely prevents EGF-induced autophosphorylation of EGFR in human HN5 tumors growing as xenografts in athymic mice and of the hepatic EGFR of the treated mice. CP-358,774 inhibits the proliferation of DiFi human colon tumor cells at submicromolar concentrations in cell culture and blocks cell cycle progression at the G1 phase. This inhibitor produces a marked accumulation of retinoblastoma protein in its underphosphorylated form and accumulation of p27KIP1 in DiFi cells, which may contribute to the cell cycle block. Inhibition of the EGFR also triggers apoptosis in these cells as determined by formation of DNA fragments and other criteria. These results indicate that CP-358,774 has potential for the treatment of tumors that are dependent on the EGFR pathway for proliferation or survival.

Adenosine Triphosphate↗
PubMed1992

Large pericardial effusions in the acquired immunodeficiency syndrome.

The increasing importance of the acquired immunodeficiency syndrome (AIDS) as a cause of large, clinically significant pericardial effusions has not been well documented. To determine the frequency and characteristics of large AIDS-associated pericardial effusions, we reviewed the records of 50 consecutive patients undergoing pericardiocentesis between 1985 and 1990; AIDS was the most common underlying illness and was present in 14 patients (28 percent). The pericardial fluid was diagnostic in three (21 percent) of the 14 cases (one bacterial, one positive for acid-fast bacilli, and one lymphoma). Of the 11 patients with nondiagnostic fluid, one underwent a pericardial biopsy which revealed granuloma consistent with mycobacterial disease, four had active pulmonary tuberculosis (TB), and two responded clinically to anti-TB therapy. Thus, in 8 (57 percent) of the 14 patients with AIDS, there was either definitive or suggestive evidence of mycobacterial disease. We conclude that AIDS is now a common underlying illness associated with large pericardial effusions and that mycobacterial disease may frequently be the etiology.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Interleukin-1 and tumor necrosis factor synergistically stimulate lung fibroblast interleukin-1 alpha production.

We determined whether normal human lung fibroblasts expressed cell-associated thymocyte-stimulating activity in response to recombinant interleukin-1 (rIL-1) (alpha and beta) and recombinant tumor necrosis factor (rTNF). Individually, rIL-1 and rTNF induced fibroblast expression of thymocyte-stimulating activity, with rIL-1 being significantly more potent. Importantly, combining rIL-1 and rTNF resulted in a synergistic increase in fibroblast thymocyte-stimulating activity. This synergistic interaction was dose dependent for both cytokines and was not noted when gamma-interferon was combined with rIL-1 or rTNF. In all cases, the thymocyte-stimulating activity was the result of an IL-1 alpha-like moiety whose maximal production required protein synthesis. IL-1 alpha activity could be detected after as little as 4 h, peaked after 24 h, and returned toward normal with longer periods of cytokine-fibroblast incubation. However, cytokine-stimulated fibroblasts that no longer expressed IL-1 alpha activity could be induced to re-express this activity with repeat cytokine challenge. Induction of fibroblast IL-1 alpha by IL-1 and/or TNF may be an important mechanism amplifying IL-1-mediated biologic events at sites of local inflammation.

Cell Adhesion↗
PubMed1989

Fibroblast interleukin 1 beta: synergistic stimulation by recombinant interleukin 1 and tumor necrosis factor and posttranscriptional regulation.

To understand the role fibroblasts play in mediating and amplifying the effects of inflammatory cytokines, we determined whether recombinant interleukin 1 (IL-1) and recombinant tumor necrosis factor (TNF), alone and in combination, stimulated fibroblasts to produce IL-1 beta. Recombinant IL-1 (alpha and beta) stimulated fibroblast IL-1 beta mRNA accumulation, whereas recombinant TNF did not. In addition, simultaneous stimulation with recombinant IL-1 (alpha or beta) and recombinant TNF resulted in a synergistic increase in IL-1 beta mRNA levels. However, in all cases, IL-1 beta mRNA accumulation was not associated with fibroblast production of soluble IL-1 beta protein. Lysates of unstimulated, recombinant IL-1-stimulated, and recombinant TNF-stimulated fibroblasts did not contain IL-1 beta prohormone. In contrast, IL-1 beta prohormone was detected in lysates of fibroblasts incubated simultaneously with recombinant IL-1 and recombinant TNF. These studies demonstrate that recombinant IL-1 stimulates fibroblast IL-1 beta mRNA accumulation and that recombinant IL-1 and recombinant TNF synergize to further up-regulate IL-1 beta mRNA levels. In addition, they show that IL-1 beta production by human lung fibroblasts is inhibited at a posttranscriptional level. Translational control appears to be important in recombinant IL-1-stimulated fibroblasts and posttranslational control is important in fibroblasts stimulated simultaneously with recombinant IL-1 and recombinant TNF.

Antibodies↗
PubMed1977

The role of social workers in medical education: a historical perspective.

Although the number of social workers participating in medical education is increasing, there is a need to review and evaluate their roles in such educational activities. Information is needed about how social workers participate in medical education in order to plan how to make a more effective contribution. This article describes how the role of social workers in medical education evolved, and gives examples of what social workers have done in the past and are doing today.

Education, Medical↗
PubMed1976

Professional review of health care services.

The question of professional accountability has frequently been raised with regard to the provision of health care services. Various systems, among them peer review, utilization review, and the PSRO, have accordingly been introduced to monitor the quality and the cost of health care. Social workers will have increased opportunities to participate in these review systems and, thus, to improve health care delivery.

Allied Health Personnel↗