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Biomedical subjects

W J Simmons

Publications and source records attributed to W J Simmons.

16 recordsLinked to original sources
PubMed2001

META-controlled env-initiated transcripts encoding superantigens of murine Mtv29 and Mtv7 and their possible role in B cell lymphomagenesis.

Spontaneous germinal center (GC)-derived B cell lymphomas of SJL mice (RCS) transcribe a 1.8-kb Mtv-29 mRNA under control of the META-env promoter. The encoded vSAg29 stimulates syngeneic Vbeta16(+) CD4(+) T cells, thereby acquiring T cell help necessary for RCS growth. Other strains of B cell lymphoma-prone mice include Mtv29(+) C57L and MA/MyJ, and the Mtv29(-) Mtv7(+)-recombinant inbred strain, SW x J-1. The lymphomas of these mice produce similar mouse mtv-vSAg-encoding mRNA, as characterized by Northern blotting, PCR, and RNase protection. A 1.8-kb mRNA in C57L/J and MA/MyJ lymphomas hybridized with an Mtv29-specific oligonucleotide, whereas SW x J-1 lymphomas produced 1.8-kb transcripts hybridizing with an Mtv7-specific oligonucleotide. Similar META-env-initiated transcripts were absent from LPS-activated B cells from any strain examined but were detected in Peyer's patch RNA from SJL mice. Like typical SJL-derived RCS, all these lymphomas stimulated syngeneic CD4(+) T cells and Vbeta16(+) T hybridoma cells. Immunohistochemical staining of primary tumors showed the presence of peanut agglutinin binding (PNA(+)) highly mitotic lymphoblasts, suggesting their GC derivation. The findings indicate that this novel mRNA for Mtv29 is present in B cell lymphomas from several Mtv29(+) mouse strains. Additionally, this is the first description of the ability of Mtv7 to produce transcripts that are controlled and spliced identically to those of Mtv29 and that are expressed in SW x J-1, I-A(s+), lymphomas that also stimulate Vbeta16(+) T cells. Our results suggest an important role for mouse mtv-vSAgs and Vbeta16 T cell stimulation in the development of GC-derived murine B cell lymphomas.

Animals↗
PubMed2001

Appearance of Langerhans cells in the epidermis of Tgfb1(-/-) SCID mice: paracrine and autocrine effects of transforming growth factor-beta 1 and -beta 2(1).

A striking immunologic abnormality of normal and SCID Tgfb1(-/-) mice is the total absence of Langerhans cells in their epidermis. Here we show that transfer of Tgfb1(+/-) SCID bone marrow causes, within a few weeks, the appearance of Langerhans cells in the epidermis of gamma-irradiated and unirradiated Tgfb1(-/-) SCID recipients. In addition, local injection of 2 x 10(5) latent transforming growth factor-beta1 cDNA-transduced cloned CD4+ T lymphocytes causes the appearance of Langerhans cells in the ear epidermis of Tgfb1(-/-) SCID mice. This effect is enhanced by antigen-specific activation of these T cells. Injection of recombinant active transforming growth factor-beta 2 into the ear of Tgfb1(-/-) SCID mice also results in the migration of Langerhans cells into the epidermis locally, but no epidermal Langerhans cells are seen after systemic injections of transforming growth factor-beta 2. Our results suggest that transforming growth factor-beta can act in paracrine as well as autocrine fashion to induce the differentiation of precursors into Langerhans cells. Furthermore, these results indicate that the relative roles of different transforming growth factor-beta isoforms in vivo may be influenced by their local availability and/or the regulation of their conversion from latent into active form.

Animals↗
PubMed2001

Induction of germinal centers by MMTV encoded superantigen on B cells.

It has not been established whether an endogenous superantigen (SAg) expressed on B cells can induce germinal centers (GCs). An interesting model is that of mammary tumor virus encoded viral SAgs, which induce vigorous T cell proliferation and are predominantly expressed on activated B cells. We have used this model to analyze the possibility that direct stimulation of Mtv7+ DBA/2 B cells by vSAg-responsive (Vbeta6+) BALB/c T cells can give rise to GCs. Injection of BALB/c SCID mice i.v. with 2 x 10(6) DBA/2 B cells, together with LPS, followed by 2 x 10(6) BALB/c T cells induces numerous large splenic GCs within 3-5 days. The GCs are still large on day 7, but are very much reduced by day 10. B cell activation with LPS is needed for this effect. These GCs form in spite of the apparent absence of follicular dendritic cells (FDCs) as judged by staining for several FDC surface markers. Control mice receiving either BALB/c T or DBA/2 B cells + LPS alone or DBA/2 T + B cells + LPS fail to exhibit any GCs on days 3-7. Numerous small clusters of PNA+ cells, but few large GCs are observed when TNF-R(p55)-Ig is also injected, whereas LTbetaR-Ig treatment impeded the formation of aggregations of these cells even further, leaving scattered PNA+ single cells and very small clumps throughout the white pulp of the spleens. Anti-TNFalpha had no effect. These results suggest that endogenous vSAg mediated GC formation is independent of antigen trapping by FDCs.

Animals↗
PubMed1999

Modulation by cytokines of induction of oral tolerance to type II collagen.

OBJECTIVE: To determine whether the simultaneous administration of drugs and/or cytokines such as transforming growth factor beta (TGFbeta) can render oral tolerance to type II collagen (CII) more effective in causing resistance to collagen-induced arthritis (CIA) in mice, and to investigate whether oral tolerance can still be induced when high levels of anti-CII are present. METHODS: Tolerance was induced by intragastric feeding of low-dose CII to DBA/1 mice during a 2-week period, either before immunization with CII in Freund's complete adjuvant or after initiation of arthritis. Some mice were simultaneously injected with TGFbeta1 or with the H2 receptor agonist dimaprit. RESULTS: Both TGFbeta1 and dimaprit increased the degree of oral tolerance obtained. TGFbeta1 augmented the induction of immunoregulatory CD8 T cells, which transferred the resistance to CIA induction to normal recipients. Feeding of CII for 2 weeks, starting after the onset of arthritis, still significantly ameliorated the course of CIA. CONCLUSION: Administration of TGFbeta1 or dimaprit, both of which are believed to promote the development of immunoregulatory T cells, may reinforce induction of oral tolerance, even after the onset of arthritis.

Adjuvants, Immunologic↗
PubMed1998

Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta1.

A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was transduced with cDNA for murine latent transforming growth factor-beta1 (TGF-beta1) by coculture with fibroblasts producing a genetically engineered retrovirus. When SJL x BALB/c F1 mice, immunized 12-15 days earlier with proteolipid protein in complete Freund's adjuvant, were injected with 3 x 10(6) cells from MBP-activated untransduced cloned Th1 cells, the severity of experimental allergic encephalomyelitis (EAE) was slightly increased. In contrast, MBP-activated (but not resting) latent TGF-beta1-transduced T cells significantly delayed and ameliorated EAE development. This protective effect was negated by simultaneously injected anti-TGF-beta1. The transduced cells secreted 2-4 ng/ml of latent TGF-beta1 into their culture medium, whereas control cells secreted barely detectable amounts. mRNA profiles for tumor necrosis factor, lymphotoxin, and interferon-gamma were similar before and after transduction; interleukin-4 and -10 were absent. TGF-beta1-transduced and antigen-activated BALB/c Th1 clones, specific for hemocyanin or ovalbumin, did not ameliorate EAE. Spinal cords from mice, taken 12 days after receiving TGF-beta1-transduced, antigen-activated cells, contained detectable amounts of TGF-beta1 cDNA. We conclude that latent TGF-beta1-transduced, self-reactive T cell clones may be useful in the therapy of autoimmune diseases.

Animals↗
PubMed1998

The transprofessional model: blending intents in terminal care of AIDS.

Current terminal care services present dying patients and their families with a dichotomy in service delivery and the intent care between curative treatments and palliative treatments. This arbitrary dichotomy reduces patients' quality of life in many cases and robs patients and families of benefiting from the psychosocial aspects of treatment until the last few weeks of life. This article presents a blended model of care, the Transprofessional Model, in which patients receive both curative and palliative service throughout their care process. The blended intent model differs from traditional home care in that services are provided by a care coordination team composed of nurses and social workers; the traditional model of care is often case managed by a single, registered nurse. The combination of the multi-disciplinary approach to care coordination and training in both curative and palliative services in the Transprofessional Model demonstrates that this blended model of care produces a bio-psychosocial focus to terminal care as compared to a primary focus on curative services present in the traditional model of home care.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Ambulatory elderly patients of primary care physicians: functional, psychosocial and environmental predictors of need for social work care management.

With increasing numbers of elderly people, and the escalating costs of health care, screening becomes increasingly important for identifying those older people with social health care needs who appear in their primary care physicians' offices. Many people are not aware of available social services. Families with serious social problems are not finding the help they need. The aim of this study was to develop and refine a questionnaire as a screening tool to identify elderly outpatients in primary care settings who are at high risk for psychological, social or environmental needs. This study identified those ten factors at each site which were most indicative that further intervention was needed. There were consistencies among the coordinators across sites in terms of what factors triggered intervention. Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs) were more likely to be predictive of the coordinator's intervention than were other factors.

Activities of Daily Living↗
PubMed1994

A role for case managers in the physician office.

Independent primary care physicians continue to be important gatekeepers for health care services needed by older patients. There is a natural role for case management in the physician office as a link to nonmedical support services that can help the elderly maintain their independence. In this article, the authors describe a model partnership between primary care physicians and a community-wide case management program that was developed to enhance the continuum of care and improve integration of service systems. Rapid response for assessments, brief interventions, and linkage to home and community services are provided through a case manager/liaison who is on-call to physician offices. Patients are seen in the physician office or in their homes or contacted by telephone. The liaison assesses and provides immediate information and referral, maintains short-term contact, or refers patients with complex situations or long-term case management needs to agency or community case management programs. The liaison also makes regular office rounds to maintain visibility, discuss cases, and educate staff about patient risk factors. Physicians and patients have been pleased with the model.

Aged↗
PubMed1986

Planning for discharge with the elderly.

This article examines key issues in acute hospital care for the elderly and discusses their implications for discharge planning and quality assurance activities. Because the present emphasis on cost containment has led to earlier discharges, more comprehensive planning with home care and community-based services is necessary to ensure continuity of care and patient safety.

Aged↗
PubMedDate not supplied

Managed care and case management: an overview.

This article presents a brief overview of managed care and discusses the role of case management. Characteristics of each are given along with a brief history, description of current models, and a forecast of the next generation. Major issues and implications for social work and discharge planning are also covered.

Financing, Organized↗
PubMedDate not supplied

The impact of managed care on cancer care. Review and recommendations.

PURPOSE: The authors review the opportunities and challenges to quality cancer clinical care presented by the rise of managed care. OVERVIEW: The impact of managed care is apparent in every aspect of cancer care: research and clinical trials, practitioner training, prevention and early detection, treatment decisions, palliation and psychosocial support, and timely referral to hospice. The little research that has been done indicates that the transformation wrought by managed care has resulted in mixed consequences for oncology healthcare providers and patients alike. CLINICAL IMPLICATIONS: Whether cancer care will deteriorate or will improve in response to the advent of managed care depends largely on the oncology community's response. The opportunities for betterment include agreement on the quantifiable definition of excess care and the curbing of practices falling within that definition; greater emphasis on palliation and psychosocial support; flexible provider roles that may improve continuity of care and fit between patient and family need and practitioner behavior; reallocation of research dollars to reward innovation and reduce project duplication; and a diffusion of medical education into community settings.

Delivery of Health Care↗