Biomedical subjects

Miriam Davis

Publications and source records attributed to Miriam Davis.

5 recordsLinked to original sources

PubMed2006

A role for transcription factor NF-kappaB in autoimmunity: possible interactions of genes, sex, and the immune response.

Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases. The mechanism of hormonal action in autoimmunity is unknown. Drawing on genetic studies of autoimmune disease, this article discusses how both genes and sex hormones may exert their effects through the same general mechanism, dysregulation of transcription factor NF-kappaB, an immunoregulatory protein. Gene and hormone alterations of the NF-kappaB signaling cascade provide a unifying hypothesis to explain the wide-ranging human and murine autoimmune disease phenotypes regulated by NF-kappaB, including cytokine balance, antigen presentation, lymphoid development, and lymphoid repertoire selection by apoptosis.

Animals↗

PubMed2005

A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia.

OBJECTIVE: On April 23, 2004, a joint meeting of the FDA, NIMH, MATRICS investigators, and experts from academia and the pharmaceutical industry was convened to develop guidelines for the design of clinical trials of cognitive-enhancing drugs for neurocognitive impairments in patients with schizophrenia. METHOD: Experts were asked to address specific questions relating to clinical trial design of adjunctive/co-treatment and broad spectrum agents. At the workshop, experts reviewed relevant evidence before offering the discussion panel proposed guidelines for a given subset of questions. The discussion panel, which consisted of presenters and representatives from FDA, NIMH, academia, and industry, deliberated to reach consensus on suggested guidelines. When evidence was insufficient, suggested guidelines represent the opinion of a cross-section of the presenters and discussion panel. RESULTS: Guidelines were developed for inclusion criteria, the use of co-primary outcome measures, and statistical approaches for study design. Consensus was achieved regarding diagnostic and concomitant medication inclusion criteria and on the use of cognitive screening measures. A key guideline was to limit the trial to patients in the residual phase of their illness, who have a predefined level of positive, negative, and affective symptoms. The most difficult issues were the feasibility of including a co-primary measure of functional improvement and the choice of comparator agent for a trial of a broad spectrum agent (with antipsychotic and cognitive-enhancing effects). CONCLUSIONS: The suggested guidelines represent reasonable starting points for trial design of cognitive-enhancing drugs, with the understanding that new data, subsequent findings, or other methodological considerations may lead to future modifications.

Antipsychotic Agents↗

PubMed2005

Diabetes and stem cell researchers turn to the lowly spleen.

The spleen gets no respect. Long seen as superfluous, the adult spleen of the mouse has recently been shown to hold stem cells that, in diabetic mice or genetically altered mice that lack a pancreas, effectively regenerate insulin-producing islet cells of the pancreas. Stem cells of the spleen express Hox11, a highly conserved transcription factor that plays a major role in the development of organs in vertebrate and invertebrate embryos. Hox11 and other members of the Hox family of genes may give stem cells of the spleen the capacity to mature into cell types other than islet cells, including neurons and bone cells. Multilineage splenic stem cells may trace to the embryogenesis and possible persistence into adulthood of a fetal stem cell region called the aorta-gonad-mesonephros (AGM). This Perspective calls for reappraisal of the lowly spleen for treating diabetes and other diseases of aging.

Aging↗

PubMed2005

Regenerative medicine: a radical reappraisal of the spleen.

The spleen has long been considered a dispensable organ. Recent research, however, has found that the spleen of adult mice holds a reservoir of stem cells that can rapidly and robustly differentiate into functional cells of diverse lineages. Splenic stem cells express Hox11, a key embryonic transcription factor that regulates organogenesis. The presence of multi-lineage stem cells in the spleen might represent lifelong persistence of cells from a primitive embryonic region called the aorta-gonad-mesonephros. By bringing together findings from diverse disciplines, we propose that the adult spleen is an important source of multi-lineage stem cells for future cellular therapies for diabetes and other diseases.

Animals↗

PubMed2003

Confronting depression and suicide in physicians: a consensus statement.

OBJECTIVE: To encourage treatment of depression and prevention of suicide in physicians by calling for a shift in professional attitudes and institutional policies to support physicians seeking help. PARTICIPANTS: An American Foundation for Suicide Prevention planning group invited 15 experts on the subject to evaluate the state of knowledge about physician depression and suicide and barriers to treatment. The group assembled for a workshop held October 6-7, 2002, in Philadelphia, Pa. EVIDENCE: The planning group worked with each participant on a preworkshop literature review in an assigned area. Abstracts of presentations and key publications were distributed to participants before the workshop. After workshop presentations, participants were assigned to 1 of 2 breakout groups: (1) physicians in their role as patients and (2) medical institutions and professional organizations. The groups identified areas that required further research, barriers to treatment, and recommendations for reform. CONSENSUS PROCESS: This consensus statement emerged from a plenary session during which each work group presented its recommendations. The consensus statement was circulated to and approved by all participants. CONCLUSIONS: The culture of medicine accords low priority to physician mental health despite evidence of untreated mood disorders and an increased burden of suicide. Barriers to physicians' seeking help are often punitive, including discrimination in medical licensing, hospital privileges, and professional advancement. This consensus statement recommends transforming professional attitudes and changing institutional policies to encourage physicians to seek help. As barriers are removed and physicians confront depression and suicidality in their peers, they are more likely to recognize and treat these conditions in patients, including colleagues and medical students.

Adult↗