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Biomedical subjects

R M Lewis

Publications and source records attributed to R M Lewis.

At least 91 records · Page 5Linked to original sources
PubMed1989

Bidirectional regulatory circuit between the immune and neuroendocrine systems.

The immune system and the neuroendocrine system affect each other via molecules and receptors shared by both systems. Activation of the neuroendocrine system results in a generalized alteration in host homeostasis and immune response. The interaction appears to be a complete circuit in that products of the immune system can also modulate nervous and neuroendocrine system responses. Since different hormones/soluble mediators are produced by neuroendocrine and immune cells, the particular alteration is a function of the induction stimulus.

Animals↗
PubMed1989

Ultrastructure of cultured canine oral keratinocytes.

Keratinocytes from explants of the oral mucosa of dogs were grown in culture for five passages. The ultrastructure of primary cultures and fully developed subcultures passaged 1, 3, and 5 times was examined. At every stage, the cells had the morphologic characteristics of epithelial cells and formed a multilayered squamous epithelium. The basal cells had the characteristics of metabolically active cells, whereas the suprabasal cells and the cells at the media interface expressed many, but not all, of the organelles and cell surface characteristics associated with keratinocyte differentiation. Keratohyalin granules were located in the suprabasal and superficial cells. Cell size and shape and the relationship between cells in the layers also reflected the morphologic characteristics of the parent tissue. Cells maintained this typical structure through all passages and the cultures changed minimally for up to a week after development.

Animals↗
PubMed1988

The impact of cytomegalovirus infection on seronegative recipients of seropositive donor kidneys versus seropositive recipients treated with cyclosporine-prednisone immunosuppression.

To assess the impact of cytomegalovirus (CMV) infection in D+R- patients treated with cyclosporine (CsA)-prednisone immunosuppression, we compared the incidence of CMV infection, severity of disease, and the 1, 2, and 3-year actual graft and patient survival rates of CMV-infected D+R- patients with R+ patients from a group of 516 renal allograft recipients at our center. CMV infection occurred more frequently in 27/56 D+R- patients (48%) versus 111/376 R+ patients (29%) (P less than 0.01). The incidence of CMV was also significantly greater in D+R- versus R- patients receiving CAD grafts (59% vs. 32%, P less than 0.01) and first transplants (47% vs. 30%, P less than 0.05). There were no significant differences in CMV disease severity between the aggregate D+R- and R+ patient groups and when subgroups of these patients receiving cadaveric donor (CAD), living-related donor (LRD), first, or retransplant allografts were compared. The actual 1, 2, and 3-year graft survival rates for D+R- patients (68%, 58%, 68%) were not significantly different from rates in R+ patients (83%, 77%, 63%) with CMV infection. When the 1, 2, and 3-year actual graft survival rates in subgroups of D+R- and R+ patients were compared in CAD, LRD, and first and retransplants, there were no significant differences. The actual 1, 2, and 3-year patient survival rates were not significantly different between D+R- (89%, 92%, 100%) and R+ patients (94%, 91%, 86%) with CMV infection, nor were they different when CMV infected D+R- and R+ patients with CAD, LRD, first or retransplant grafts were compared. These data do not support the policy of denying a seropositive kidney to a seronegative recipient, since the severity of CMV disease and the impact of CMV infection is not significantly different comparing D+R- and R+ patients receiving CsA-prednisone immunosuppression.

Adolescent↗
PubMed1988

The impact of HLA A, B, and DR blood transfusions and immune responder status on cardiac allograft recipients treated with cyclosporine.

From July 1982 to August 1986, 137 patients received heart allografts at our transplant (Tx) center. Recipients were treated postoperatively with cyclosporine (CsA) and prednisone (Pred), with a minority of patients receiving CsA, Pred, and azathioprine (Aza) as immunosuppression. The impact of pre-Tx immune factors on survival was evaluated, including HLA A, B, and DR mismatches (MM), blood transfusions (BT), immune responder status, crossmatch results, and donor and recipient AIDS-virus (human immunodeficiency virus, HIV-1) status. The overall patient survivals were 75%, 68%, and 62% at one, two, and three years respectively. Pre-Tx, 15/137 (11%) recipient sera and 5/137 (3.6%) donor sera were HIV-1 reactive in both enzyme immunoassay (EIA) and Western blot antibody assays. Two of the 5 recipients of HIV-1 (+) donor allografts are alive 11 and 29 months post-Tx, whereas the other 3 recipients died at 1, 31, and 36 months post-Tx from diseases unrelated to AIDS. All 5 were pre-Tx HIV-1 nonreactive. The survivals for the 15 recipients who tested pre-Tx HIV-1 (+) were 87%, 87%, and 69% at 1, 2, and 3 years, respectively, comparable to the overall group survivals. Pre-Tx strong and weak immune responders had comparable 12-month survivals of 73% and 80%, respectively. Six patients displayed a positive pre-Tx donor crossmatch, two were attributed to autoantibody, and 4 were attributed to donor T cell reactivity. Five of the six patients presently survive 14, 16, 30, 36, and 44 months post-Tx. Recipients treated pre-Tx with 1-4 BTs displayed significantly better 12-month survival (81% vs. 69%, P less than 0.05) and fewer rejections (1.3 +/- 0.9 vs. 1.9 +/- 1.0, P less than 0.05) than untransfused recipients. Recipients of a 0-1 vs. 2 DR donor antigen-mismatch experienced fewer rejections (1.3 +/- 1.0 vs. 1.8 +/- 1.1, P less than 0.05). Evaluation of the combined influence of HLA DR as well as pre-Tx BTs suggested a significantly improved survival (80% vs. 61%, P less than 0.05) and fewer rejection episodes (1.4 +/- 0.9 vs. 2.0 +/- 1.1, P less than 0.05) for 29 well-matched, transfused (0-1 DR MM and 1-4 BT) compared with 43 poorly matched, untransfused (2 DR MM and 0-BT) heart allograft recipients. Moreover, the benefit of DR matching was only observed in untransfused, but not transfused, cardiac recipients.

Adolescent↗
PubMed1988

The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients.

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.

Acute Disease↗
PubMed1988

Short-term and long-term function of cadaveric kidneys from pediatric donors in recipients treated with cyclosporine.

Short and long-term renal function of 67 cyclosporine-prednisone (CsA-Pred)-treated recipients of pediatric cadaveric donor kidneys followed for up to 68 months (mean 16 months) were compared with 67 recipients of adult kidneys (group 3), who were demographically matched for recipient age, sex, race, cause of disease, HLA compatibility, ABO blood type, and retransplant status. Thirty-seven of the pediatric kidneys came from donors less than or equal to 10 years old (group 1) and 30 from donors 11-16 years old (group 2). Group 1 displayed impaired short-term graft function: a significantly higher mean value of the nadir serum creatinine (SCr; 2.35 versus 1.63 mg/dl), a lower maximal creatinine clearance during the first 30 days (50.3 versus 65.7 ng/dl/1.73 m2), and a longer time to achieve the nadir creatinine (22.1 versus 17.2 days). Group 1 transplants also had a higher mean nadir creatinine at 3 months and a lower mean creatinine clearance (CCl) at 3 and 6 months. By 12 months the values in the group 1 pediatric kidneys were similar to those using the group 3 adult grafts. Therefore, CsA therapy did not preclude compensatory graft function. Group 2 grafts showed intermediate short-term function relative to groups 1 and 3. Mean SCr and CCl showed progressive improvement over time, significantly better than adult kidneys at two years. Graft loss was significantly greater at two years in pediatric compared with adult grafts, but significantly better than our historical controls using azathioprine-prednisone immunosuppression.

Adolescent↗
PubMed1988

Immune serum increases arenavirus replication in monocytes.

The U937 monocytic cell line was used to determine whether antibodies could facilitate infection and replication of the arenaviruses, Pichinde virus (PV) and Lassa fever virus (LFV). When high dilutions of PV-immune serum were added to cultures simultaneously with PV inoculum, virus replication was dramatically (1000-fold) increased. Low dilutions of this antiserum neutralized the virus. LFV also replicated in U937 cells. The presence of LFV-specific immune serum in the growth medium increased the viral titre as much as 10,000-fold. Addition of heat-aggregated IgG partially inhibited antibody-mediated enhancement, probably by inhibiting the binding of immune complexes to the monocytic cells.

Arenaviridae↗
PubMed1988

Immunostimulatory capabilities of highly enriched Langerhans cells in vitro.

Langerhans cells (LC) are epidermal antigen-presenting cells capable of inducing allogenic, antigen-specific, and cytotoxic T cell proliferation. Previous studies have examined the dynamics of LC maintained in vitro in crude epidermal cell (EC) suspensions in which the major cell type is the keratinocyte (KC). To avoid the confounding effects of KC and other immunoregulatory cells on LC dynamics in vitro, highly enriched murine LC (85%) were studied, through 72 h of incubation in vitro, for their ability to present alloantigen (in a primary allogenic proliferation assay) and foreign antigen (in a secondary autologous proliferation assay). The results were compared to similar studies using crude EC suspensions. Freshly prepared LC are very poor stimulators of a primary allogenic proliferation response, with a 12- to 16-fold increase in stimulatory capacity by 72 h using panned-enriched and crude EC suspensions, respectively. Similarly, freshly prepared LC are weak stimulators of a secondary autologous proliferation response, with a 2.5- to 6-fold increase in immunostimulatory capability by 72 h. The overall increased stimulatory effect observed with the crude EC suspensions compared to highly enriched LC is most likely attributed to the effect of KC on T cell proliferation, rather than to a maturation effect of KC on LC during the 72 h of in vitro incubation. Using back-scattered electron imaging, the surface density of MHC-class II molecules (Ia) increased three- to fourfold through culture, which parallels the increase in functional ability. This study demonstrates that LC in either a crude or highly enriched cell suspension mature into potent immunostimulatory cells after incubation in vitro with an increased surface expression of Ia molecules. Keratinocytes are not necessary for LC maturation in vitro, but seem to exert some stimulatory effect by enhancing lymphocyte proliferation in the functional assay system.

Animals↗
PubMed1988

Neuroendocrine-immune interactions: immunoregulatory signals mediated by neurohumoral agents.

While we generally think of the brain and nervous system as central to most basic life processes, the concept of immune regulation or modulation is a relatively new idea. The novelty of such an association may be rooted in classic concepts of neurologic function describing direct innervation of controlled tissues and stimulation across synapses. The involvement of the neuroendocrine system in the precise control of metabolic and a variety of cellular functions should preface its involvement in defense against and/or surveillance for aberrant cell replication. Moreover, a principal characteristic of any control mechanism is feedback from the affected system (be it an organ or single cell). In this framework, it is not unreasonable to expect bidirectional interactions between the nervous and immune systems. Direct innervation of lymphoid tissues was described a number of years ago. More recently, immunoregulatory function has been demonstrated in vitro with a variety of neuroendocrine molecules such as the biogenic amines, SP, CGRP, SOM, vasopressin, ACTH, the endorphins, enkephalins, neurotensin, NGF and VIP. Now it has been shown that many of these same or similar neuroregulatory molecules are produced by cells of the immune system. The possibility that neurotransmitters or peptides, or both, may play a role in vivo in the maintenance of immunocompetence is supported by the finding that specific receptors for the neurohumoral modulators are present on the surface of immunocompetent cells. Current hypotheses speculate that feedback control mechanisms are manifested through the production of lymphokines, PGs and leukotrienes. Though it has not been possible to clearly demonstrate the reciprocal interaction between the neuroendocrine and immune systems in vivo, the evidence to date points to its inevitability.

Animals↗
PubMed1988

Blood transfusion experience for cyclosporine/prednisone-treated renal allograft recipients at the University of Texas Medical School at Houston.

Our data indicate that CsA-P-treated primary recipients of cadaveric donor renal allografts as well as haploidentical living-related donor allograft recipients enjoy prolonged, successful patient and graft survivals whether conditioned with pretransplant transfusions or not. The data are important because they reflect clinical results from a single transplant center wherein the recipients have been immunosuppressed for approximately 7 years with little change in protocol. This is an important point since utilizing maximum therapeutic immunosuppressive efficacy will result in prolonged graft and patient survival.

Azathioprine↗
PubMed1988

Successful transplantation of 100 untransfused cyclosporine-treated primary recipients of cadaveric renal allografts.

This report examines the effect of pretransplant (pre-Tx) blood transfusions (BT) on the patient and graft survival results of 320 cyclosporine (CsA) and prednisone (Pred)-treated primary (1 degree) recipients of cadaveric (CAD) donor renal allografts. The 320 CsA-Pred treated 1 degree-CAD recipients included 100 pre-Tx untransfused (O-BT) and 220 transfused patients. The overall patient survival at 12, 24, and 36 months post-Tx were 94%, 94%, and 93%, respectively. There were no differences observed in graft survivals at 12, 24, or 36 months post-Tx whether patients received 0, 1-4, greater than or equal to 5-10 or greater than 10 pre-Tx BTs. A mean serum creatinine of 1.9 +/- 0.7 mg/dl was comparable among all BT groups at 12, 24, and 36 months post-Tx. The frequency of rejection episodes--namely, 37% for O-BT and 36% for greater than O-BT were identical. High-risk patients (greater than 45 years of age, diabetics, or blacks) were comparably distributed in O-BT and greater than O-BT groups and did not impact on the data. Similarly, increasing panel-reactive antibodies (PRA), associated with increasing numbers of pre-Tx BTs, did not influence the data. When HLA A, B, and DR matching results were combined with the BT groupings no differences were observed in patient or graft survivals. Poorly matched and untransfused recipients did as well as well-matched, transfused recipients. These findings suggest that CsA-Pred immunosuppressive therapy allows for successful 1 degree-CAD renal allograft transplantation without the need for pretransplant blood transfusion conditioning or matching of donor HLA A, B, and DR antigens to recipients.

Blood Transfusion↗