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Biomedical subjects

A Ben-Yehuda

Publications and source records attributed to A Ben-Yehuda.

At least 55 records · Page 3Linked to original sources

Dehydroepiandrosterone (DHEA) treatment reverses the impaired immune response of old mice to influenza vaccination and protects from influenza infection.

Dehydroepiandrosterone (DHEA) is a native steroid with an immunomodulating activity. Recently it was suggested that its age-associated decline is related with immunosenescence. To examine whether DHEA administration could effectively reverse the age-associated decline of immunity against influenza vaccine, aged mice were simultaneously vaccinated and treated with DHEA. Reversal of the age-associated decline and a significant constant increase of humoral response was observed in treated mice. Increased resistance to post-vaccination intranasal challenge with live influenza virus was observed in DHEA-treated aged mice. Thus, DHEA treatment overcame the age-related defect in the immunity of old mice against influenza.

Adjuvants, Immunologic↗

Successful treatment of pure red cell aplasia in systemic lupus erythematosus with erythropoietin.

We describe a 32-year-old woman who developed severe anemia due to pure red cell aplasia in the course of systemic lupus erythematosus (SLE). After failure of therapy with high doses of glucocorticoids and immunoglobulins, and despite high levels of endogenous erythropoietin, she was treated with human recombinant erythropoietin with dramatic and sustained improvement. Based on this case and on the literature review of erythropoietin therapy in pure red cell aplasia, we suggest that erythropoietin should be used in SLE associated pure red cell aplasia before cytotoxic therapy.

Adult↗

Bone marrow declines as a site of B-cell precursor differentiation with age: relationship to thymus involution.

The rearrangement of immunoglobulin genes in B-lymphocyte precursors requires the expression of the recombination activating genes (Rag), which leads to the generation of a highly diverse B-cell repertoire. We can use the level of Rag-1 mRNA in the bone marrow as an index of its capacity to support the maturation of B lymphocytes as all detectable bone marrow Rag-1 mRNA is expressed by B-cell precursors. In mouse bone marrow, Rag-1 mRNA increases during the first 2 months of life to reach its maximal level at 2 months of age. This level is maintained until 5 months of age and thereafter declines to a minimum level by 10 months of age. Thus, bone marrow Rag-1 mRNA is highest at the time when thymic function is maximal in euthymic mice. An association between thymic activity and bone marrow Rag-1 gene expression was supported by showing a low level of bone marrow Rag-1 mRNA in athymic nude mice at an age when this gene is maximally expressed in euthymic mice. Another characteristic of B cells in nude mice is their preferential rearrangement of diversity region (D)-proximal heavy-chain variable region (VH) genes. We demonstrated that injection of syngeneic splenic T cells into nude mice not only stimulates an increase in Rag-1 mRNA in their bone marrow B-cell precursors but also restores their random use of VH genes. Most interestingly, injection of supernatant medium from phytohemagglutinin-activated splenic T-cell cultures from young euthymic mice also induces both Rag-1 mRNA in bone marrow B-cell precursors and random use of VH genes. These findings suggest that thymic function can regulate both Rag-1 gene expression and VH gene use by bone marrow B-cell precursors.

Aging↗

Age-associated changes in the B-cell repertoire: effect of age on RAG-1 gene expression in murine bone marrow.

The available repertoire of B cells that develop early or late in life reflects the restricted recombination of 5' immunoglobulin heavy chain variable region genes. In addition, autoantibody reactivity is overrepresented in the preferentially recombined 3' Vh gene families, resulting in over representation of autoreactive antibody specificities. The preferential utilization of 3' Vh gene families is associated with, and perhaps caused by, the reduced expression of the RAG-1 gene. One can only speculate what effect the induction of RAG-1 activity in the bone marrow of old mice would have on their antibody repertoire.

Aging↗

[Long-term weight changes after Roux-en-Y gastric bypass for morbid obesity].

100 patients were followed for 6-9 years after Roux-en-Y gastric bypass for morbid obesity. They were randomly selected from 600 patients operated on between 1980-85. Their initial weight averaged 118 +/- 16 kg, which was 196 +/- 25% of their ideal body weight. They reached their lowest weight during an average of 15.5 months after surgery, at which time 37% were at their ideal weight, 42% were 110-130% of their ideal weight and 21% were 131-192% of their ideal weight. 90% had lost more than 50% of their excess weight. 24% had lost all their excess weight or even more, which could jeopardize nutritional status. Longer follow-up of 6-9 years showed weight gain, with 24% having become morbidly obese again, 74% having lost more than 50% of their excess weight and only 7% having lost all their excess weight. We conclude that Roux-en-Y gastric bypass induces long term weight loss and largely prevents return of morbid obesity, as long as 6-9 years after surgery.

Adult↗

Recombinant vaccinia virus expressing the PR/8 influenza hemagglutinin gene overcomes the impaired immune response and increased susceptibility of old mice to influenza infection.

Elderly humans have increased morbidity and mortality after viral influenza despite immunization. A mouse model of influenza infection was used to search for a more effective way to induce immunity to influenza. Old (18 months) BALB/c mice were more susceptible to influenza pneumonia than young (2 months) BALB/c mice after intranasal challenge with PR/8 influenza virus despite prior immunization with influenza virus. The decreased resistance to live influenza virus challenge was associated with an impaired generation of anti-hemagglutinin antibody and cytotoxic T lymphocytes in old mice. In contrast, immunization of old mice with a recombinant vaccinia virus expressing the PR/8 influenza hemagglutinin gene protected them from intranasal challenge with live influenza virus and generated high levels of anti-PR/8 influenza virus hemagglutinin antibody and PR/8-specific cytotoxic T cells. Recombinant vaccine overcame the age-associated immune defect that follows the administration of conventional viral vaccine.

3T3 Cells↗

Effect of age on the expressed B cell repertoire: role of B cell subsets.

Aged humans and experimental animals are impaired in their responses to most foreign antigens although they produce greater amounts of autoantibodies. We have examined the effect of age on the production of antibodies to a prototypic foreign antigen, sheep erythrocytes (SRBC), and to a prototypic autoantigen, bromelain-treated mouse erythrocytes (BrMRBC), in young and old mice before and after immunization with SRBC. Old mice express more anti-BrMRBC plaque-forming cell (PFC) antibodies before and an even greater number after immunization with SRBC than young mice. Conversely, old mice produce far fewer anti-SRBC PFC than young mice following immunization with SRBC. We hypothesized that the differences in the responses of old mice to BrMRBC and SRBC reflects differences in the activity of CD5+ and CD5- B cells. To test this hypothesis we immunized young and old mice with foreign antigens reported (and confirmed in our studies) to stimulate CD5+ B cells [TNP-ficoll and phosphorylcholine-keyhole limpet hemocyanin (KLH)] or CD5- B cells (SRBC and TNP-KLH). We found that the PFC response of old mice to antigens mediated by CD5+ B cells was equal to or greater than that of young mice. In contrast the PFC response of old mice induced by antigens mediated by CD5- B cells was only 10% that of young mice. Thus it appears that the immune response of old mice is well maintained for antigens which elicit a CD5+ B cell response but not for those which elicit a CD5- B cell response.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Immune senescence: mechanisms and clinical implications.

There are many changes in the immune response with age, most of which can be related to the involution of the thymus gland and alteration of the distribution and function of T lymphocytes. These changes indirectly influence B-cell function, which not only amplifies the immune deficits, but leads to the increased production of autoantibodies and monoclonal immunoglobulins with age. Thus, immune senescence is characterized by both an immune deficiency and an immune dysregulated state.

Aging↗

Host resistance and the immune system.

Elderly persons are more susceptible and vulnerable to many infections compared with young adults. This phenomenon can be attributed to a decline in host defense mechanisms, particularly altered immune function. The effects of aging on T- and B-lymphocyte function; antigen-presenting cells, natural killer cells, and granulocytes; and organ-specific host resistance are discussed in this article.

Aged↗