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Biomedical subjects

S S Morse

Publications and source records attributed to S S Morse.

At least 19 recordsLinked to original sources
PubMed1999

Virus and autoimmunity: induction of autoimmune disease in mice by mouse T lymphotropic virus (MTLV) destroying CD4+ T cells.

Neonatal infection of the mouse T lymphotropic virus (MTLV), a member of herpes viridae, causes various organ-specific autoimmune diseases, such as autoimmune gastritis, in selected strains of normal mice. The infection selectively depletes CD4+ T cells in the thymus and periphery for 2-3 wk from 1 wk after infection. Thymectomy 3 wk after neonatal MTLV infection enhances the autoimmune responses and produces autoimmune diseases at higher incidences and in a wider spectrum of organs than MTLV infection alone. On the other hand, inoculation of peripheral CD4+ cells from syngeneic noninfected adult mice prevents the autoimmune development. These autoimmune diseases can be adoptively transferred to syngeneic athymic nude mice by CD4+ T cells. The virus is not detected by bioassay in the organs/tissues damaged by the autoimmune responses. Furthermore, similar autoimmune diseases can be induced in normal mice by manipulating the neonatal thymus/T cells (e.g., by neonatal thymectomy) without virus infection. These results taken together indicate that neonatal MTLV infection elicits autoimmune disease by primarily affecting thymocytes/T cells, not self Ags. It may provoke or enhance thymic production of CD4+ pathogenic self-reactive T cells by altering the thymic clonal deletion mechanism, or reduce the production of CD4+ regulatory T cells controlling self-reactive T cells, or both. The possibility is discussed that other T cell-tropic viruses may cause autoimmunity in humans and animals by affecting the T cell immune system, not the self Ags to be targeted by the autoimmunity.

Adoptive Transfer↗
PubMed1997

The public health threat of emerging viral disease.

"Emerging diseases" are those that either have newly appeared in the population or are rapidly increasing their incidence or expanding their geographic range. Emerging viruses usually have identifiable sources, often existing viruses of animals or humans that have been given opportunities to infect new host populations ("viral traffic"). Environmental and social changes, frequently the result of human activities, can accelerate viral traffic, with consequent increases in disease emergence. Host factors, including nutrition, have often received less attention in the past but are of considerable importance. These factors, combined with the ongoing evolution of viral and microbial variants, make it likely that emerging infections will continue to appear and probably increase, emphasizing the need for effective surveillance.

Animals↗
PubMed1996

Patterns and predictability in emerging infections.

Many seemingly novel infections have a long history as zoonoses, and perhaps in sporadic human hosts; they gain access to new host populations through ecologic changes and human activity. identification of patterns in the emergence of such illnesses--ranging from influenza and Lyme disease to Ebola fever and AIDS--suggests that worldwide surveillance may be more feasible than once thought.

Acquired Immunodeficiency Syndrome↗
PubMed1996

T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases.

This paper shows that elimination of a small subpopulation of peripheral T cells can elicit activation/expansion of self-reactive T cells from the remaining T cells and produce a wide spectrum of organ-specific and systemic autoimmune diseases in normal mice; reconstitution of the eliminated T-cell population prevents autoimmune development. This regulatory T-cell population expresses the CD25 molecule, apparently includes 'activated' T cells, and suppresses immune responses to non-self as well as self antigens in an antigen-nonspecific manner. Although the degree of abnormality in the T-cell regulation significantly influences the spectrum, incidence, and severity of autoimmune disease, the T-cell abnormality itself cannot determine the specificities of the elicited autoimmune responses since a comparable degree of abnormality causes different autoimmune diseases depending on the mouse strains used. Host genetic elements thus significantly contribute to determining the specificities. These findings taken together indicate that one aspect of natural self-tolerance is maintained by a T cell-mediated or -dependent control of potentially pathogenic self-reactive T cells in the periphery, and that defective control, caused by environmental insults or genetic abnormalities, suffices to activate self-reactive T cells, eliciting various autoimmune diseases depending on the genetic makeup of the host.

Animals↗
PubMed1996

ProMED global monitoring of emerging diseases: design for a demonstration program.

The emergence and reemergence of infectious diseases, as the result of recent and ongoing social and environmental changes, urgently calls for a global surveillance system, so that unusual outbreaks can be recognized and controlled at an early stage. ProMED, an international non-governmental group of infectious disease experts, was organized by the Federation of American Scientists to promote the establishment of a global Program to Monitor Emerging Diseases. ProMED proposes the establishment of a demonstration program by prioritizing a small number of strategically-located institutions in the developing world, mainly those least in need of upgrading, for development as sentinel centers. In this way a functional, although limited, network with capabilities for monitoring both endemic and emerging diseases could be rapidly established at minimal cost. The network would serve as an experimental model for future expansion. Initially, each center would develop its own local/regional network with which it would exchange information and assistance, and through which it would collect clinical data and specimens for monitoring the emergence of a limited number of defined syndromes. A central program office would provide protocols, assistance, training, quality assurance, communications, etc. and would coordinate fundraising and program activities. If successful, the syndromes monitored would be expanded and additional institutions strengthened to become new network centers.

Communicable Disease Control↗
PubMed1995

Superantigens and conventional antigens induce different responses in alpha beta T-cell receptor transgenic mice.

While superantigens such as staphylococcal enterotoxin B (SEB) have been shown to induce both clonal deletion and clonal anergy, it is still not known why tolerance rather than memory is induced. To address this issue, we tested the proliferative capacity of T cells from ovalbumin (OVA)-specific alpha beta T-cell receptor transgenic mice primed with either SEB emulsified in complete Freund's adjuvant (CFA) or with OVA peptide, the specific antigen, in CFA. By contrast cells from mice primed with SEB in CFA appeared to be anergic in that they were hyporesponsive to OVA peptide as well as to SEB. The anergic cells could respond to phorbol myristate acetate (PMA) and ionomycin, suggesting that a proximal signal transduction step was affected. Cells from transgenic mice primed with OVA peptide and CFA were not anergic and in fact displayed an enhanced response when they were challenged with OVA in vitro. Thus, when the two antigens are emulsified in CFA and then injected subcutaneously, they behave very differently: the superantigen SEB induces anergy whereas the conventional antigen OVA induces a memory type of response.

Animals↗
PubMed1994

Prediction and biological evolution. Concept paper.

The major issue addressed was how to introduce evolutionary thinking into epidemiology, and the appropriate approach to "evolutionary epidemiology." There was general agreement that disease emergence is not a static but a dynamic process, and that dynamic approaches should therefore be emphasized.

Biological Evolution↗
PubMed1994

The CD28/B7 pathway costimulates the response of primary murine T cells to superantigens as well as to conventional antigens.

While the CD28/B7 pathway has been shown to play an important costimulatory role in the response of T cells to conventional antigens, its role in superantigen-mediated T cell activation has not been as clear. In this report, we used CD4+ T cells from ovalbumin-specific alpha beta-TCR-transgenic mice (DO11.10) to compare the ability of this pathway to costimulate the response of primary T cells to conventional antigens and superantigens. We show that either the addition of anti-CD28 monoclonal antibody or presentation with a B7 transfected cell line enhances the proliferative and interleukin-2 secretion response of DO11.10 CD4+ cells to both the conventional antigen, ovalbumin peptide (OVA 323-339), and the superantigen SEB. This implies that CD28-mediated costimulation plays a role in the response of murine T cells to superantigens as well as to conventional antigens.

Animals↗
PubMed1993

Preoperative evaluation of patients for liver resection. Appropriate CT imaging.

OBJECTIVE: The authors determined which combination of computed tomography scans is most helpful for preoperative assessment of patients with liver tumors. SUMMARY BACKGROUND DATA: Multi-institutional studies have shown that the most important prognostic factors for selection of patients with metastatic colorectal cancer considered for liver resection are: Dukes' stage of primary tumor, the number of hepatic metastases if greater than 3, the presence of extrahepatic cancer, and the ability to resect tumors with an adequate margin (> 1 cm.) Therefore the ability to predict the presence of extrahepatic disease and the number and location of hepatic tumors are important in these patients. METHODS: One hundred and nine consecutive patients with evidence of hepatic tumors were evaluated by computed tomography with arterial portography (CTAP) and abdominal computed tomography after a 4-hour delay (CT-D). Results of these studies and conventional computed tomography (CT-C) were compared with findings at operation. RESULTS: CTAP proved to be the most sensitive test for assessing distribution of intrahepatic disease. CT-D was no more sensitive than CT-C for the detection of hepatic or extrahepatic disease. CONCLUSIONS: CT-C in concert with CTAP provides the most reasonable CT evaluation of patients considered for operation for the treatment of hepatic tumors.

Humans↗
PubMed1992

Identification and evaluation of new primer sets for the detection of lentivirus proviral DNA.

We have developed sets of degenerate oligonucleotides designed to detect pol gene sequences from any member of the lentivirus subfamily when used as primers in amplification techniques such as the polymerase chain reaction (PCR). This pan-lentivirus-specific primer set (PLSPS) consists of primers, LV1, LV2, and LV3, based on conserved regions common to lentiviruses only. Our protocol is based on primary amplification with LV1 and LV2 followed by secondary amplification with a nested primer set based on the YM/VDD motif found in all reverse transcriptases (or "DDMY," in the opposite direction), and LV3, a block of lentivirus homology nested just downstream of LV1. PLSPS-PCR analysis of DNA from cells infected with HIV-1, HIV-2, SIVmac239, BIV, visna, EIAV, CAEV, OPPV, or FIV resulted in the amplification of appropriately sized products. Sequence analysis of the LV1/2 products, cloned into pBluescript (pBS), indicated that at least 20% (most often, > 80%) contained the predicted lentivirus pol sequence. Greater than 95% of the LV3/DDMY products contained the expected lentiviral sequences. Using the PLSPS, lentivirus pol sequences could typically be detected at levels of one copy in 2 x 10(6) cells after secondary amplification. No specific lentiviral PCR products were detected in DNA from uninfected human or mouse monocytes, feline or bovine leukocytes, mouse, rat or human fibroblast cell lines, chicken embryo fibroblasts, Tahr lung cells, or cell lines infected with the following retroviruses which are not lentiviruses: Rous sarcoma virus, Moloney leukemia virus or Kirsten sarcoma virus, mouse mammary tumor virus, human T-cell lymphotropic virus I, and feline leukemia virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Evolving views of viral evolution: towards an evolutionary biology of viruses.

Despite considerable interest in viral evolution, at least among virologists, viruses are rarely considered from the same evolutionary vantage point as other organisms. Early work of necessity emphasized phenotype and phenotypic variation (and therefore arguably was more oriented towards the broader biological and ecological perspectives). More recent work (essentially since the development of molecular evolution in the 1960's but beginning earlier) has concentrated on genotypic variation, with less clarity about the significance of such variations. Other aspects of evolutionary theory, especially considerations of natural selection and of evolutionary constraints, have not widely been applied to viruses, and an evolutionary framework for virology has long been lacking. This becomes apparent in considering 'emerging' viruses, which have often been treated on an ad hoc basis. It was often felt that, because previously unrecognized viruses are involved, mechanisms of viral emergence must mirror the unpredictability of mutations in the viral genome. However, most examples of viral emergence are independent of mutation, at least initially, and are often pre-existing viruses in changed circumstances ('viral traffic'). This conclusion also readily follows from ordinary Darwinian premises, which would require that, like other living species, 'new' organisms are descended only from existing species. In this respect, from a Darwinian perspective, viruses would appear to resemble other organisms.

Biological Evolution↗
PubMed1992

Percutaneous nephrostomy and ureteral stenting in gynecologic malignancies.

OBJECTIVE: To identify the indications, complications, and efficacy of percutaneous nephrostomies and ureteral stents in women with gynecologic cancer. METHODS: In a retrospective study, 40 women underwent urinary diversion with percutaneous nephrostomy and ureteral stents. Nine had ureteral stenosis on initial presentation, 18 had persistent or recurrent cancer, nine had no evidence of disease, and four had operative ureteral damage. Of the nine who were without disease, seven had a urinary conduit. RESULTS: Thirty-five patients had ureteral stenosis, which was bilateral in 24, and five had a ureteral fistula. Sixteen had a unilateral and 22 had bilateral percutaneous nephrostomies, with two cases having stents only. The most common complication was hematuria. Thirteen women were later hospitalized for pyelonephritis. Twenty-nine (72.5%) had ureteral stents, which were bilateral in 12. Renal function was abnormal in 26, but improved in 14 and returned to normal in six. Five fistulas were managed with ureteral stents alone and four were closed. The median time to death (N = 22) was 5.5 months, 12 months in primary cases versus 5.5 months in recurrent cases. Twelve of the remaining 18 were alive without evidence of disease at a median of 38 months, five were alive with disease at a median of 16 months, and one was lost to follow-up. CONCLUSIONS: These techniques are safe and often improve renal function. The procedures have different roles in women with primary and recurrent gynecologic cancer, in those without evidence of recurrent disease, and in those with urinary conduits.

Adolescent↗