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H M Fillit

Publications and source records attributed to H M Fillit.

30 records · Page 2Linked to original sources
PubMed1990

Elevated circulating levels of tumor necrosis factor in severe chronic heart failure.

BACKGROUND AND METHODS: Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. RESULTS: Mean (+/- SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115 +/- 25 U per milliliter) than in the healthy controls (9 +/- 3 U per milliliter; P less than 0.001). Nineteen of the patients with chronic heart failure had serum levels of tumor necrosis factor greater than or equal to 39 U per milliliter (greater than 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82 +/- 3 vs. 95 +/- 6 percent of ideal body weight, respectively; P less than 0.05) and had more advanced heart failure, as evidenced by their higher values for plasma renin activity (2.92 +/- 0.53 vs. 1.06 +/- 0.53 ng per liter per second [10.5 +/- 1.9 vs. 3.8 +/- 1.9 ng per milliliter per hour]; P less than 0.01) and lower serum sodium concentration (135 +/- 1 vs. 138 +/- 1 mmol per liter; P less than 0.05). The group with high levels of tumor necrosis factor also had lower hemoglobin levels (7.82 +/- 0.2 vs. 8.69 +/- 0.4 mmol per liter [12.6 +/- 0.4 vs. 14.0 +/- 0.6 g per deciliter]) and higher values for blood urea nitrogen (19.5 +/- 2.2 vs. 12.5 +/- 1.8 mmol per liter) than the group with low levels of tumor necrosis factor (P less than 0.05 for both). The high levels of tumor necrosis factor were not due solely to decreased renal clearance, however, since the levels in the patients with heart failure were considerably higher than those in the nine patients with chronic renal failure (115 +/- 25 vs. 45 +/- 25 U per milliliter; P less than 0.05). CONCLUSIONS: These findings indicate that circulating levels of tumor necrosis factor are increased in cachectic patients with chronic heart failure and that this elevation is associated with the marked activation of the renin-angiotensin system seen in patients with end-stage cardiac disease.

Adult↗
PubMed1988

Immunogenicity of liposome-bound hyaluronate in mice. At least two different antigenic sites on hyaluronate are identified by mouse monoclonal antibodies.

Hyaluronate (HA) was previously demonstrated to be immunogenic in rabbits. The immunogenicity of HA in mice was studied. Hyaluronidase-digested streptococcal HA (IA1) covalently linked to liposomes (IA1-liposomes) were produced for immunization. Mice immunized with IA1-liposomes developed measurable serum antibodies to IA1, while mice immunized with IA1 in Freund's adjuvant did not. mAbs produced by two stable hybridomas (10G6 and 5F11) from mice immunized with IA1-liposomes produced IgG antibody reactive with HA in ELISA. 10G6 had a much higher avidity for liposome-bound IA1 than free IA1, while 5F11 did not, suggesting that the mode of presentation of IA1 is important in HA immunogenicity and antigenicity. Both mAbs recognized terminal HA immunodeterminants exposed by hyaluronidase treatment. Sonication had no effect on HA reactivity for either mAb. However, ascorbic acid treatment significantly reduced the antigenicity of HA for mAb 5F11, but not 10G6. Only 10G6 was inhibited by glucuronic acid. Electrostatic forces appear to play a role in the binding site of 5F11, but not 10G6. 5F11 crossreacts with heparan sulfate and phosphorylcholine, while 10G6 did not crossreact with any glycosaminoglycans or phosphorylated compounds tested. These results confirm that HA is immunogenic. They suggest that the mode of presentation of HA is important for the induction of the immune response, and in HA antigenicity. At least two different antigenic sites on HA were demonstrated. 10G6 recognizes a terminal HA antigenic site expressed on IA1-liposomes that contains glucuronic acid in its immunodominant site. 5F11 recognizes an HA antigenic site in which electrostatic forces appear to play a role, is sensitive to ascorbic acid treatment, and is crossreactive with heparan sulfate. The use of mAbs should facilitate immunologic studies of HA.

Animals↗
PubMed1988

Monoclonal antibodies to heparan sulfate proteoglycan: development and application to the study of normal tissue and pathologic human kidney biopsies.

Monoclonal antibodies (mAbs) (4F2 and 7E12) were prepared against heparan sulfate proteoglycan (HSPG) isolated from bovine glomeruli. Enzyme linked immunosorbent assays (ELISA) and immunoblotting demonstrated that the mABs reacted with HSPG. Indirect immunofluorescence (IF) showed that the mAbs stained renal basement membranes (BMs) and BMs in other organs of normal bovine and human tissues in patterns typical of HSPG. Immunoinhibition studies, and immunoblotting of heparan lyase digested HSPG, indicated that the mAbs recognize HSPG core protein. In kidney biopsies from patients with acute poststreptococcal GN, intact linear glomerular BM (GBM) staining for HSPG was noted despite markedly widened capillary loops. In membranous and in diffuse proliferative lupus GN, loss of HSPG staining was demonstrated at sites of immunodeposition of IgG or C3, while increased staining for HSPG was noted in areas of newly formed GBM. Extensive loss of HSPG was seen in areas of glomerular sclerosis and necrosis. In biopsies from patients with minimal change glomerulonephritis (GN) and mesangioproliferative lupus GN, a normal linear GBM distribution of HSPG was noted. The findings are discussed in the context of current knowledge regarding the pathogenesis of glomerular injury. MAbs to BM HSPG should prove useful for future immunochemical studies, and for the study of diseases of the basement membrane.

Animals↗
PubMed1987

Antivascular antibodies in the sera of patients with senile dementia of the Alzheimer's type.

We have investigated the specificities of antibrain antibodies in the sera of patients with senile dementia of the Alzheimer's type (SDAT). Using indirect immunofluorescence, we observed a vascular pattern of staining in 6 of 16 sera from patients with typical SDAT. None of 14 sera from age matched controls demonstrated this pattern of staining. The vascular pattern of staining seen with SDAT sera was identical to the immunofluorescent staining of brain by a monoclonal antibody to vascular basement membrane heparan sulfate proteoglycan. Immunoabsorption of SDAT sera with purified vascular proteoglycan abolished the staining of brain vessels. Using an enzyme linked immunoassay, 3 of the 6 vascular-reactive SDAT sera, and none of the 24 sera from aged controls, were shown to contain antibodies to purified vascular heparan sulfate proteoglycan. Proteoglycans play an important role in the barrier function of the blood-brain barrier. Autoimmune injury to the blood-brain barrier by antivascular antibody may play a role in the pathogenesis of dementia by permitting the passage of injurious substances into the brain.

Aged↗
PubMed1986

Induction of antibodies to hyaluronic acid by immunization of rabbits with encapsulated streptococci.

The immunogenicity of hyaluronic acid was investigated. Rabbits were immunized with encapsulated group A and C streptococci. Intact long-chain hyaluronate was conjugated to BSA for use as antigen in an ELISA. Antibodies to the hyaluronate-BSA conjugate were detected in peak immune sera. The specificity of the antibodies for both mammalian and streptococcal hyaluronate was shown by inhibition studies. To further confirm the presence of antihyaluronate antibodies, hyaluronidase-digested streptococcal hyaluronate was conjugated to biotin and used as an antigen in the ELISA. A clear immunization effect was shown for each rabbit by the study of preimmune and postimmunization bleedings. Titers for each rabbit increased by greater than 32 - 256 - fold. Inhibition studies using hyaluronidase-digested hyaluronate and periodate-treated hyaluronate showed that the immunodominant site of antibody reactivity was a terminal glucuronic acid residue. Further studies showed that the carboxyl group of the terminal glucuronide was the major immunoreactive site. Both mammalian and streptococcal hyaluronate inhibited the immune rabbit sera reaction to streptococcal hyaluronate, demonstrating crossreactivity of these molecules. Thus, hyaluronate was shown to be immunogenic in rabbits.

Agglutination Tests↗
PubMed1982

In vitro correlates of endothelial injury and repair.

The effects of immune complexes, microbial components, and glomerular basement membrane on cultured human umbilical endothelial cells were assessed in vitro using phase contrast microscopy, cell counts, 51Cr release, and terminal tritiated thymidine-labeling assays. Neither heat-aggregated IgG nor bovine serum albumin-antibovine serum albumin immune complexes altered endothelial cell growth as measured by cell counts, thymidine labeling, and phase contrast microscopy, nor did immune complexes induce cytotoxicity as measured by 51Cr release. Some microbial components appeared cytotoxic to endothelial cells, other microbial components had no effect, and one, clostridial neuraminidase, induced proliferation of endothelial cells as measured by phase contrast microscopy, cell counts, and thymidine labeling. Native and glycosidase-altered glomerular basement membrane also enhanced endothelial cell thymidine labeling. These studies show that microbial components directly alter endothelial cell growth in vitro, whereas immune complexes by themselves do not. Thus, in vivo microbial components by themselves may directly affect endothelial cells and cause vascular pathology, whereas immune complexes presumably must recruit other inflammatory systems to affect endothelial cells. Alterations of basement membrane during inflammation may also affect endothelial growth and, thus, vascular pathology.

Antigen-Antibody Complex↗
PubMed1978

Cellular reactivity to altered glomerular basement membrane in glomerulonephritis.

Glomerular basement membrane may be altered during glomerulonephritis, exposing antigens that are recognized as foreign. Immunochemical studies suggest that removal of peripheral glycopeptides from the basement membrane with glycosidase mimics this pathogenetic event. To examine these hypotheses, we studied 24 patients with biopsy-proved glomerulonephritis by means of the lymphocyte-blast-transformation assay. Three preparations of normal glomerular basement membrane were used: two mimicked the native state for the peripheral glycopeptides, and one was altered by glycosidases. Results showed minimal differences in responses to native glomerular basement-membrane preparations among patients with glomerulonephritis and control groups. However, patients with glomerulonephritis had a significant blastogenic response to the glycosidase-treated glomerular basement membrane as compared to patients with nonglomerular renal disease and normal controls (P less than 0.0005). These studies suggest that cellular reactivity to altered glomerular basement-membrane antigens can be detected in certain forms of progressive glomerulonephritis.

Antigens↗
PubMedDate not supplied

Public attitudes about genetic testing for Alzheimer's disease.

In a general population survey (N = 314), 79 percent of respondents stated that they would take a hypothetical genetic test to predict whether they will eventually develop Alzheimer's disease. The proportion fell to 45 percent for a "partially predictive" test (which had a one in ten chance of being incorrect). Inclination to obtain testing was similar across age groups. Respondents were willing to pay $324 for the completely predictive test. Respondents stated that if they tested positive, they would sign advance directives (84 percent), get their finances in order (74 percent), and purchase long-term care insurance (69 percent). Only a third of respondents expressed concern about confidentiality. The results suggest that people value genetic testingfor personal and financial reasons, but they also underscore the need to counsel potential recipients carefully about the accuracy and implications of test information.

Adult↗