Search PubMed⌕ Search

Biomedical subjects

T M Phillips

Publications and source records attributed to T M Phillips.

At least 55 records · Page 3Linked to original sources
PubMed1993

Inhibition of tumor necrosis factor-alpha by thalidomide in magnesium deficiency.

The effect of thalidomide on circulating cytokines and myocardial lesion formation was investigated in Mg-deficient rats. After two weeks on a Mg-deficient diet, rats show an increase in circulating levels of tumor necrosis factor-alpha and interleukin 1. Thalidomide (1 mg/day) caused a complete inhibition of the increase in circulating tumor necrosis factor-alpha levels, without having an effect on interleukin 1. However, a marked increase in cardiomyopathic lesion formation was observed in Mg-deficient animals treated with thalidomide; possible mechanisms for thalidomide's enhancement of myocardial injury are discussed.

Animals↗
PubMed1993

HIV-associated immune-mediated renal disease.

Although focal glomerulosclerosis is the most common renal disease, other proliferative glomerulonephritides are encountered in HIV-infected patients. We studied four HIV-infected patients with renal insufficiency, proteinuria, and proliferative glomerulonephritis, consistent with immune-mediated disease, to investigate the role of the virus and immune complexes in the pathogenesis of the nephropathy. Circulating immune complexes (CICs) and HIV-reactive antibodies were measured and characterized in each patient. Renal biopsy tissue was acid eluted, and the eluate analyzed. DNA extracted from biopsies was subjected to the polymerase chain reaction (PCR) to detect HIV genome. CICs were detected in each patient: an IgA-p24 HIV antigen complex and an IgG antibody-gp 120 HIV antigen complex in two patients; two patients had an IgG-p24 HIV antigen complex. Identical complexes were eluted from renal tissue in the first three patients; p24 HIV antigen, and complement from the fourth. The eluted antibodies reacted with the HIV antigens from the isolated CICs. Direct immunofluorescence for viral antigen in the eluted glomerular tissue revealed HIV antigens; PCR confirmed the presence of gag genome in all four biopsies. We conclude both circulating and in-situ HIV antigen-specific immune complexes may be associated with glomerulonephritis in HIV infected patients. Viral incorporation into renal tissue may be important in the pathogenesis of HIV-associated renal disease.

AIDS-Associated Nephropathy↗
PubMed1993

Presence of anti-pituitary hormone antibodies in patients with empty sella syndrome and pituitary tumours.

OBJECTIVE: We evaluated the presence of anti-pituitary hormone autoantibodies (APHA) in patients with primary empty sella syndrome and pituitary tumours and examined the correlation of positive antibodies with the hormonal deficiencies. DESIGN: Case-control, retrospective study. PATIENTS: Eleven patients were identified with primary empty sella syndrome or a pituitary tumour by magnetic resonance imaging or computed tomography scanning. Six healthy, normal subjects without evidence of a pituitary problem served as the control group. MEASUREMENTS: Anti-pituitary hormone autoantibodies against purified pituitary hormones were measured in all subjects utilizing an immunoblotting technique. All patients with pituitary disease had their medical records reviewed for any hormonal evaluation. RESULTS: All of the normal subjects were negative for antipituitary hormone antibodies. Forty-five per cent of patients with pituitary disease (pituitary tumours or primary empty sella syndrome) had positive antipitutary hormone antibodies. Of the five patients with positive antipituitary hormone antibodies, anti-ACTH antibodies were the most common (5/5) followed by anti-TSH and anti-GH antibodies (2/5 for each). The hormonal deficiencies failed to correspond with the antipituitary hormone antibodies. Anti-ACTH antibody had a sensitivity of 50% with a specificity of 56%. The anti-TSH antibody yielded a sensitivity of 67% with a specificity of 100%. The anti-FSH/LH antibody reported a 0% sensitivity. CONCLUSIONS: Detection of antipituitary hormone antibody was unable to discriminate between empty sella syndrome and pituitary tumours. The presence of these antipituitary hormone antibodies were neither specific for, nor predictive of, the endocrine deficiencies.

Adenoma↗
PubMed1993

Modulation of cytokines and myocardial lesions by vitamin E and chloroquine in a Mg-deficient rat model.

Antioxidant treatment with alpha-tocopherol did not affect the level of the "inflammatory cytokines" in Mg-deficient animals, although it diminished the extent of the myocardial lesions. In another group of Mg-deficient animals chloroquine treatment diminished significantly the levels of circulating cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) and also resulted in a major decrease in myocardial lesions. These results raise the question of the role of these inflammatory cytokines in the formation of lesions in Mg-deficient myocardium. Because these cytokines are able to stimulate free radical production in various cell types, we postulate that Mg deficiency involves free radical mechanisms that can be amplified by inflammatory cytokines; whether these cytokines initiate lesion formation is unclear. Although our data do not confirm either possibility, we submit that these results implicate a role for the inflammatory cytokines in the cardiac pathology of Mg deficiency.

Animals↗
PubMed1992

Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin.

We have developed two rodent models of diet-induced magnesium-deficiency in which histologically defined cardiac lesions can be induced within two to three weeks. During the development of these lesions, the magnesium-deficient animals exhibit circulating cytokine levels which are indicative of a generalized inflammatory state. Dramatic elevations of the macrophage-derived cytokines, IL-1, IL-6, and TNF-alpha together with significantly elevated levels of the endothelial cell-derived cytokine, endothelin, were detected in the plasma of these animals. We believe that the pathophysiological effects caused by the action of these cytokines may play a role in the promotion of cardiovascular pathology associated with magnesium deficiency.

Animals↗
PubMed1992

Gonadotropins enhance HLA-DR antigen expression in human granulosa cells.

OBJECTIVES: To determine whether HLA-DR expression in the human ovary is controlled by endocrine or immune mediators, we examined the effects of several lectins, lymphokines, and hormones on granulosa cells in vitro. STUDY DESIGN: HLA-DR antigens were detected by indirect immunofluorescence on granulosa cells obtained at oocyte retrieval for in vitro fertilization. RESULTS: When cultured with concanavalin A, pokeweed mitogen, phytohemagglutinin, interleukin-1, or interleukin-2, granulosa cells failed to express HLA-DR antigens. Both interferon alfa and interferon beta induced only a modest expression of HLA-DR molecules (4.1% +/- 0.9% and 2.5% +/- 0.8%, respectively) in comparison with the marked increase in HLA-DR expression (25.2% +/- 2.8%), when granulosa cells were exposed to interferon gamma. The gonadotropins follicle-stimulating hormone and human chorionic gonadotropin alone were unable to induce HLA-DR antigens, but acted synergistically with interferon gamma to enhance expression in a dose-dependent manner. The addition of 0.1 and 10 IU/ml of follicle-stimulating hormone with 10,000 IU/ml of interferon gamma significantly increased expression by 11.5% +/- 2.5% and 15.5% +/- 2.7%, respectively, over that of interferon gamma alone. Similarly, 1 and 10 IU/ml of human chorionic gonadotropin produced a 7.8% +/- 2.0% and 12.4% +/- 2.2% increase in HLA-DR expression over baseline. CONCLUSION: These studies demonstrate that factors from both the immune and endocrine systems can interact to control HLA-DR expression in the ovary.

Adult↗
PubMed1992

Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis.

During the progression of Mg deficiency in a rodent model, we have observed dramatic increases in serum levels of inflammatory cytokines [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] after 3 wk on a Mg-deficient diet. Sequential analyses of these cytokine changes in the serum of rats revealed an initial rise at day 12, followed by a major elevation in all three cytokine levels by day 21. Of greater interest was an early peak in the serum level of the neuropeptide substance P after only 5 days on the diet. This "neuronal" tachykinin is thought to be released from neural tissues, and it is known to stimulate production of certain cytokines, including IL-1, IL-6, and TNF-alpha. In addition, there was a concomitant increase in histamine levels, which may have resulted from stimulation and degranulation of mast cells by substance P. Thus we hypothesize that the release of substance P may be the earliest pathophysiological event leading to stimulation of the inflammatory cytokines, which may then stimulate the free radical mechanisms of injury previously confirmed by our work.

Animals↗
PubMed1992

Eosinophilia and cellular cytokine responsiveness in hemodialysis patients.

Eosinophilia in hemodialysis (HD) patients has been associated with allergy to dialyzers and exaggerated activation of complement during HD. Its etiology, however, remains unknown. Complement activation can lead to cytokine production, and interleukin-2 (IL-2) administration has been shown to cause eosinophilia. Because abnormalities in cellular cytokine production in renal patients were previously demonstrated, the relationship between dialysis-associated eosinophilia and IL production in this HD population was studied. Twelve patients on chronic HD therapy with normal eosinophil counts (mean, 0.23 +/- 0.03 cells/nL) were compared with nine patients with eosinophilia (mean, 0.85 +/- 0.17 cells/nL). Measurements of cellular IL-1 and IL-2 production were performed before (pre) and after (post) HD with cuprammonium dialyzers. In patients with eosinophilia, stimulated cellular IL-1 production increased by 117 +/- 40% (P < 0.01) when post-HD measurements were compared with pre-HD values and IL-2 production increased by 127 +/- 65% (P < 0.05). In contrast, there was no difference in stimulated cellular cytokine production when values before and after HD were compared in patients without eosinophilia. Individual responses were reproducible during subsequent dialysis. It was concluded that cellular cytokine production in response to HD is not uniform. Eosinophilia is a clinically useful marker of exaggerated HD-associated cytokine production. Cytokine production depends on individual responsiveness and is probably related to atopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Isolation of an interleukin 2-binding receptor from activated lymphocytes by high-performance immunoaffinity chromatography.

Isolation of a lymphokine-binding receptor, from activated lymphocyte membranes, can be achieved by high-performance immunoaffinity chromatography (HPIAC), using immobilized antibodies against human interleukin 2 (IL-2), as the ligand and natural IL-2 as the receptor probe. Activated lymphocytes were reacted with IL-2, sonically disrupted and their membranes solubilized, prior to passage through the HPIAC column. The IL-2 acted as an efficient receptor probe, which helped to maintain the integrity of the receptor during the isolation procedure and also acted as an attachment antigen for the immunoaffinity ligand. Recovery of the bound receptor was achieved by dissociation of the receptor-antigen-immobilized ligand complex by the action of chaotropic ions and collection of the released receptor from the column effluent during the elution phase of the separation.

Antibodies, Monoclonal↗
PubMed1990

Isolation of anti-idiotypic antibodies by immunoaffinity chromatography on Affinichrom beads.

Anti-idiotypic antibodies are important regulators of the immune system but they are difficult to isolate and monitor. We have developed a technique for isolating specific auto-anti-idiotypic antibodies by high-performance immunoaffinity chromatography using immobilized autologous anti-tumor antibodies as the affinity ligand. The isolated anti-idiotypes demonstrated the ability to react with the original antitumor antibodies and inhibit their reactivity against autologous tumor cells. This technique can be used to monitor regulatory antibodies in cancer patients receiving immune modulation therapy.

Antibodies↗
PubMed1990

Effect of renal replacement therapy on cellular cytokine production in patients with renal disease.

To evaluate the effect of renal replacement therapy on cellular cytokine production in patients with renal disease, we studied interleukin 1 (IL-1) and interleukin-2 (IL-2) production by target cells stimulated with supernatants from cultured peripheral blood mononuclear cells from patients with end-stage renal disease, who were treated with hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) before and after hemodialysis or a peritoneal dialysate exchange, compared to normal subjects used as time controls, and patients with chronic renal insufficiency. Initial cellular IL-2 production was increased in patients with hemodialysis, compared to normal controls. The ratio of pretreatment cellular IL-2 and IL-1 production was increased in all patient groups compared to normal subjects. Both hemodialysis and CAPD treatments resulted in increased cellular IL-1 (51.7%, P less than 0.007, and 42.8%, P less than 0.002, respectively) and IL-2 production (50.5%, P less than 0.015, and 33.3%, P less than 0.0008, respectively). The hemodialysis group had significantly higher cellular IL-2 production compared with normal controls' after treatment. After treatment, the IL-2/IL-1 ratio remained elevated in all groups with renal disease compared with normal subjects. We conclude patients with renal disease have an abnormal functional relationship between IL-1 and IL-2, characterized by increased IL-2 production per level of IL-1, unaffected by type or presence of renal replacement therapy.

Biological Assay↗
PubMed1990

Persistent cutaneous insulin allergy resulting from high-molecular-weight insulin aggregates.

Cutaneous insulin allergy remains a clinical problem despite the use of highly purified human insulins. We used in vitro lymphocyte-transformation studies to examine the reactivity of various insulin formulations in diabetic patients with (n = 4) and without (n = 8) cutaneous allergies. Nonspecific response to concanavalin A demonstrated a greater than 40-fold response in both groups. Control patients did not respond to the addition of commercial insulin preparations (stimulation index [SI] less than 4), whereas allergic patients had an 11-fold response to beef (P less than 0.01), a 10-fold response to pork (P less than 0.01), and a 6-fold response to human (P less than 0.01) insulins. This response was limited to a single insulin manufacturer's preparations and was uniform in all three species tested. Efforts to identify the offending agent revealed no lymphoblast transformation when crystalline insulin was used or when commercial preparations were purified to a single peak by high-performance liquid chromatography (HPLC). Pure crystalline insulin dimers of beef, pork, and human species were tested; control subjects responded with mean SIs of 1.9, 1.9, and 1.8, respectively, whereas allergic patients showed greater reactivity to beef (SI 7.3) and pork (SI 14.8). The lymphoblast-transformation response to crystalline human dimer was dose dependent with mean SIs of 0.9 at low concentration (2.8 ng/ml) and 19.2 at a higher concentration (20.4 ng/ml). The commercial insulin preparations were run on size-exclusion HPLC to determine high-molecular-weight aggregate content. Independent of species, a single manufacturer had products demonstrating aggregate levels 3- to 6-fold higher than those found in other manufacturers' preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Concanavalin A↗
PubMed1990

Update on topical cyclosporin A. Background, immunology, and pharmacology.

Systemic cyclosporin A (CsA) is currently being used for immunosuppression in solid organ transplantation. Its unique mechanism of action and low myelotoxicity have vastly improved the prognosis for patient survival. A reversible and irreversible nephrotoxicity has complicated its use. CsA works via the inhibition of both lymphokine release and subsequent activation of cytotoxic T cells. The corneal allograft model presents several unique features that make it amenable to local immunosuppressant therapy. Following topical application, CsA corneal levels have been obtained above the experimentally determined levels necessary for local immunosuppression. CsA represents one of a new class of specific, potent immunomodulators, which may improve the prognosis for patients at high risk for allograft rejection.

Administration, Topical↗
PubMed1989

Isolation of a specific membrane protein by immunoaffinity chromatography with biotinylated antibodies immobilized on avidin-coated glass beads.

Avidin-coated, solid glass beads have been used as an immobilization support for attaching biotinylated antibodies. These beads have been packed into analytical, semi-preparative and preparative columns and used to isolate the B27 histocompatibility anigen (HLA) from human lymphocytes. The beads provided a suitable column material for all three chromatographic procedures and, depending on the size of the immunoaffinity column, B27 antigen could be isolated in nanogram to microgram quantities. Polyacrylamide gel electrophoresis demonstrated the presence of only a single band in the immunoaffinity peaks isolated by all three procedures. Enzyme-linked immunosorbent assay analysis of these immunoaffinity-isolated materials revealed that they were biologically active and could be used to determine the levels of anti-B27 antibodies in clinical studies.

Antibodies, Monoclonal↗
PubMed1989

Sperm antibodies in vasectomized men and their effects on fertilization.

Sera (vbs, n = 25) and seminal plasma (vsp, n = 21) from vasectomized men (n = 25) were analyzed for cross-reaction with lithium diiodosalicylate (LIS)-solubilized human sperm extract, protamine, and fertilization antigen (FA-1) with an enzyme-linked immunosorbent assay (ELISA). Among the vbs tested, 44% reacted with human sperm extract, 28% reacted with protamine, and 44% reacted with FA-1 for at least one class of antibodies (IgG, IgA, or IgM). In contrast to the sera, the seminal plasma showed minimal reactions. Neither the vbs nor vsp were found to contain immune complexes, indicating that the antibodies were present in free form. Vasectomized sera that reacted with FA-1 showed a significant (p less than 0.0001) inhibition of human sperm penetration of zona-free hamster ova. The immunoabsorption of FA-1-positive sera with purified FA-1 significantly increased the penetration rates. Affinity-purified human immunoglobulins reactive with FA-1 and not those reactive with protamine reduced sperm penetration rates. Thus, antibodies in vbs reactive with FA-1 are relevant to infertility, causing an inhibition of fertilization. These data will have clinical relevance for diagnosis and treatment of infertility after successful vasovasostomy.

Adult↗
PubMed1989

Biochemical classification of circulating immune complexes in human malignant melanoma and hematologic neoplasms.

Circulating immune complexes (CIC) in human cancer are known to be very heterogeneous in size and composition. In 95 staged malignant melanoma patients and 71 individuals with leukemia and lymphoma, this heterogeneity was analyzed biochemically in sera positive for CIC. CICs were measured by a multiassay system and individual complexes were isolated and analyzed by immunological and biochemical methods. Analyses of sera from 100 normal individuals, from 25 rheumatoid women, and a group of 12 laboratory staff who work with human melanoma were included for comparison. Three basic patterns of complexes were identified circulating in the sera of the cancer patients. Type I are medium-sized (17-23S), complement-fixing complexes usually occurring in combinations. The prototype in melanoma contained IgG antibody and additional glycoprotein components and bound complement by the classical pathway. In hematological malignancies four subtypes could be identified depending on whether the antibody class was IgG or IgM, the nonimmunoglobulin component was glycoprotein or protein, and whether complement fixation occurred by the classical or alternate pathway. Type II complexes were noncomplement-fixing, medium-sized complexes (15-21S), which in melanoma contained IgG antibody and additional protein components. In the hematologic malignancies two subtypes could be identified depending on whether the antibody class was IgG or IgM. Both subtypes contained a glycoprotein nonimmunoglobulin component. Both melanoma and hematologic tumors had type III heavy complexes (36-44S) which were noncomplement-fixing and contained only immunoglobulin components, either IgG-IgG or IgM-IgG. As expected the rheumatoid arthritis patients frequently had both 7S and 21-23S CICs containing IgG as well as IgM rheumatoid factor with complement fixation via the classical pathway. No CICs were detected in normal young men and women (20-30 years); a few individuals in middle age (31-50 years) had small (7-11S) CICs which bound complement by the classical pathway and contained IgG and a protein nonimmunoglobulin component. The frequency of these 7S complexes increased with advancing age, with the appearance of 23S IgG-IgG or IgM-IgG complexes. IgG antibodies from only the melanoma patients reacted with cytoplasmic components of fresh melanoma cells, except the laboratory workers where all of their isolated CIC antibodies also reacted with melanoma cells. Thus the heterogeneity of complexes in melanoma is not random, but can be classified into three basic biochemical patterns. The hematologic group provides a slightly richer variation of subtypes within this basic scheme.

Adolescent↗