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Biomedical subjects

J C Hoffmann

Publications and source records attributed to J C Hoffmann.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid arthritis (RA).

Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS-PAGE, and Western blotting. Gel filtration gave similar peaks at 95-125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2+ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation.

Adult↗
PubMed1996

Detection of soluble adhesion molecules in pleural effusions.

PURPOSE: Multiple immune functions such as activation of T cells and monocytes or cytolysis of tumor cells are mediated via the adhesion receptor/ligand pairs CD2/LFA-3 and LFA-1/ICAM-1. Because soluble forms of LFA-3 (sLFA-3) and ICAM-1 (sICAM-1) can interfere with these functions, we asked whether increased levels of sLFA-3 and/or sICAM-1 can be found in malignant or inflammatory effusions compared with transudates. METHODS: sLFA-3 and sICAM-1 levels were measured by enzyme-linked immunoassays in pleural effusions from 70 patients (6 transudates, 10 inflammatory, 47 malignant, and 7 other effusions). Twenty pleural fluid samples were tested in parallel for the complete sLFA-3 molecule or sLFA-3-domain 1 only. RESULTS: Increased levels of sICAM-1 were found in all types of exudates compared with transudates. Highest levels of sICAM-1 were measured in malignant exudates, particularly in effusions caused by mesotheliomas, non-small lung cancers, and gynecologic malignancies. This was also true for sLFA-3. However, sLFA-3 levels were not increased in inflammatory effusions. sLFA-3 levels correlated significantly with protein, cholesterol, lactate dehydrogenase, and sICAM-1 levels. Comparison of sLFA-3-domain 1 and the complete sLFA-3 molecule revealed identical sLFA-3 levels, suggesting the absence of nonfunctional split products. CONCLUSIONS: Elevated levels of the complete sLFA-3 molecule were found in malignant pleural effusions, while sICAM-1 level was elevated in both inflammatory and malignant effusions. Secretion of sICAM-1 and sLFA-3 by tumor cells might block T-cell-mediated immune functions such as tumor cytotoxicity. Alternatively, secretion of soluble adhesion molecules might reflect the generalized inflammation within the pleural space.

Adult↗
PubMed1996

Reduced serum levels of a soluble form of the human adhesion receptor CD58 (LFA-3) in patients with inflammatory bowel disease.

The activation of monocytes, neutrophils, and B cells by T-lymphocytes appears to play a pivotal role in the pathophysiology of inflammatory bowel disease. The pan T cell marker CD2 and its ligand CD58 mediate these immune function. We asked whether serum levels of a soluble form of CD58 is altered in patients with inflammatory bowel disease. Soluble CD58 was measured in sera from 41 patients with Crohn's disease, 19 patients with ulcerative colitis, and 24 normal controls. Soluble CD58 levels were significantly decreased in sera from patients with ulcerative colitis and even more with Crohn's disease when compared to controls (p = 0.025 and p < 0.0001, respectively). Reduction of soluble CD58 serum levels correlated significantly with various humoral (e.g. erythrocyte sedimentation rate: r = -0.48, p = 0.0002) and clinical parameters of disease activity (e.g. CDAI: r = -0.44, p = 0.005). In conclusion, serum levels of soluble CD58 are reduced in patients with inflammatory bowel disease. Since soluble CD58 can block the CD2/CD58 interaction further studies have to show whether the reduction of soluble CD58 in patients with inflammatory bowel disease contributes to T cell adhesiveness in the mucosa.

Adolescent↗
PubMed1995

Lyme disease in a 74-year-old forest owner with symptoms of dermatomyositis.

We describe a 73-year-old forest owner with widespread erythema, myalgia, and proximal muscle weakness. The clinical signs and the results of electromyography, magnetic resonance imaging, and a muscle biopsy were consistent with dermatomyositis. However, serology was positive for Borrelia burgdorferi. More importantly, B burgdorferi DNA was detected in skin by polymerase chain reaction techniques, and spirochete-like organisms were detected in the muscle by silver staining. Lyme disease with muscle involvement can mimic or trigger dermatomyositis and should be considered in the differential diagnosis of dermatomyositis.

Aged↗
PubMed1993

A soluble form of the adhesion receptor CD58 (LFA-3) is present in human body fluids.

The human adhesion receptor CD58 (LFA-3) is expressed on most human cell types. Here we report on a soluble form of CD58 (sCD58) in human serum, human urine, and culture supernatants of several cell lines. sCD58 partially purified from human serum, from supernatant of the Hodgkin cell line L428, and purified sCD58 from human urine were found to have a molecular mass of 40-70 kDa under denaturating conditions (sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting). However, gel filtration of sCD58 purified from human urine gave a molecular mass of 118-166 kDa, suggesting a noncovalent homotrimer conformation or its association with other molecules. Using an enzyme-linked immunosorbent assay specific for CD58 we found that sera from patients suffering from different forms of hepatitis contained elevated sCD58 levels (n = 108). Accordingly, there was a fivefold increase of supernatant sCD58 when the hepatocellular carcinoma cell line Hep G2 was incubated with 25 ng/ml recombinant tumor necrosis factor-alpha in vitro. In contrast, sCD58 serum levels of 337 additional patients suffering from various other immunological disorders were not found to be raised. At high concentrations sCD58 binds to CD2-positive cells and inhibits rosette formation of human T cells to human erythrocytes. Thus, local release of large quantities of naturally occurring sCD58 may interfere with intercellular adhesion in vivo.

Antibodies, Monoclonal↗
PubMed1993

Biological response modifiers render tumor cells susceptible to autologous effector mechanisms by influencing adhesion receptors.

Adhesion molecules such as CD2 and its ligand CD58 (LFA-3), as well as CD11a/18 (LFA-1) and CD54 (ICAM-1) regulate not only cell to cell attachment but also participate in lymphocyte activation, recirculation, and effector function including cytolytic activity towards tumor cells. We have investigated the role of CD2/CD58 and CD11a/18/CD54 interactions in cellular immune responses directed towards freshly recovered human T cell leukemias. Downregulation of CD54 and CD58 were observed to correlate with enhanced numbers of blasts in circulation and lack of susceptibility to killing by autologous cytotoxic lymphocytes. Furthermore, culturing tumor cells with recombinant TNF-alpha conditioned medium resulted in reinduction of CD54 and CD58 expression and susceptibility to lymphocyte mediated resulted in reinduction of CD54 and CD58 expression and susceptibility to lymphocyte mediated lysis in vitro. Our findings support the view that adhesion molecules play a pivotal role for tumor cell biology in vivo and stress the point that successful immunotherapy of malignant disease may be facilitated by influencing not only the immune response itself but also adhesion molecules on the malignant tumor targets.

Antigens, CD↗
PubMed1992

Structural and functional epitopes of the human adhesion receptor CD58 (LFA-3).

CD58 (LFA-3), a heavily glycosylated protein of 40-70 kDa, is expressed on a broad range of hematopoietic and non-hematopoietic cells. It serves as a physiological ligand of the CD2 receptor, present on T cells and natural killer cells, and plays, thus, an important role in lymphocyte adhesion and T cell activation through CD2. Whereas several epitopes and their respective function are known for CD2, a similarly detailed characterization of CD58 is still lacking. We raised a panel of novel murine monoclonal antibodies (mAb) against recombinant human CD58 and describe here the identification of six structurally and/or functionally distinct epitopes on the CD58 molecule. All epitopes were found to be present in equal numbers on a wide range of CD58+ cells, none of them being differentially up-regulated following cell activation or malignant transformation. Two of these epitopes represent functionally relevant sites, involved in binding of CD58 to CD2 and T cell activation via CD2. One further epitope appears to be selectively involved in CD58-mediated activation, whereas the other three displayed no functional effects. The new mAb allow for the first time the detection of CD58 in enzyme-linked immunosorbent assays and immunofluorescence while bound to its receptor CD2 in human serum or on freshly isolated blood cells. Finally, one mAb was found to specifically cross-react with T11TS, the equivalent of CD58 in sheep.

Animals↗
PubMed1987

Leptomeningeal metastasis: MR imaging.

Seven patients with central nervous system neoplasia and leptomeningeal metastases, proved either at initial diagnosis or on follow-up with contrast material-enhanced computed tomography (CT), were evaluated with magnetic resonance (MR) imaging. In two patients, diffuse sulcal enhancement on CT scans was inapparent on T1- or T2-weighted MR images. Likewise, in four patients diffuse cisternal enhancement on CT scans was not identifiable with MR. Nodular or focal cisternal masses were identified with both CT and MR imaging in three patients; in two, however, MR imaging provided less information. Ependymal and subependymal metastases identified with CT (two patients) were indistinguishable on MR images from periventricular abnormalities of radiation therapy and/or hydrocephalus. These findings suggest that leptomeningeal metastasis may be so subtle or inapparent as to be overlooked with MR imaging alone. Thus, CT and MR imaging should be considered complementary techniques for initial diagnosis and follow-up of tumors with a propensity for leptomeningeal metastasis.

Adult↗
PubMed1985

Multiple causes of pregnancy failure in hamsters precociously ovulated by human chorionic gonadotropin.

Cycling adult female hamsters can be induced to mate and ovulate 24 h early by the injection of 20 IU human chorionic gonadotropin (hCG) at 1500 h on Day 3 (day before proestrus), but pregnancy is not established. Although there is evidence of decreased sperm transport in precociously ovulated females, this does not appear to be the primary cause of infertility. Reduced size and vascularity of corpora lutea (CL) in treated females suggests incomplete or failed CL activation. Control and hCG-treated females were killed by exsanguination under ether anesthesia at intervals for the first 5 days after mating. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, estradiol, and progesterone were measured by radioimmunoassay. Luteinizing hormone in treated animals was very high at 2200 h on Day 1 after mating (31 h after the hCG injection), due to endogenous release, and dropped below control levels thereafter. Follicle-stimulating hormone, by contrast, was significantly lower than controls at 2200 h on Day 1 and remained low until 2200 h on Day 3 after mating. Prolactin in treated animals was not different from that in controls, except for 1000 h on Day 4, when it showed a significant dip. Estradiol in treated animals was significantly higher than in controls at 2200 h on Day 1 (when LH was also high and FSH was low), and remained high at 1000 h and 2200 h on Day 2, dropping thereafter to control levels. Progesterone was initially at control levels but had dropped significantly by 1000 h on Day 2 and remained low for the next 24 h. These results suggest that pregnancy failure is due to inadequate activation of corpora lutea. This may be due to: 1) immaturity of follicles at the time of ovulation; 2) inappropriate timing of preovulatory events; 3) the luteolytic effects of high levels of LH or estradiol or both; 4) the low level of FSH in the early stages of corpus luteum development; or 5) a combination of the above. Abnormalities of prolactin secretion were not investigated in detail but cannot be ruled out at this time.

Animals↗
PubMed1984

Seasonal reproduction in the mongoose, Herpestes auropunctatus. IV. Organ weight and hormone changes in the female.

The mongoose, Herpestes auropunctatus, shows a well-defined breeding season in Hawaii. In this study, females were live-trapped throughout the year and sacrificed within 48 hr to obtain information about reproductive organ weights and gonadotropin levels. Pregnant females were found from February through September and lactating females from March through October. Body weight did not change significantly throughout the year, but anterior pituitary, adrenal, ovarian, and uterine weights were significantly reduced during the nonbreeding season. LH and FSH levels were extremely variable among individuals and, although mean values were higher during the breeding than during the non-breeding season, no significant differences could be demonstrated. After castration, there was not a clearcut rise in either LH or FSH, regardless of the season of the year, when animals were followed for up to l5 days. This contrasts with the male mongoose, where FSH rose significantly by 4 days after castration in either the breeding or nonbreeding season, while LH rose more slowly in the nonbreeding season but by l0 days after castration was significantly elevated and comparable to values in males castrated in the breeding season. We conclude that the female mongoose population shows less synchrony in changes in gonadotropin levels than the males, in spite of the well-defined breeding season.

Animals↗
PubMed1982

Role of daylength in the regulation of reproductive function in the male mongoose, Herpestes auropunctatus.

The male mongoose, Herpestes auropunctatus, displays a distinct seasonal reproductive rhythm in environments which show minimal changes in daylength. This investigation was designed to evaluate whether the reproductive system of the male mongoose was responsive to photoperiodic manipulations. Four experiments were conducted; two during the breeding season, one during the inactive season, and one during the recrudescence phase. Serum androgen levels and reproductive organ weights were similar in males exposed to either short (6L:18D) or control photoperiods (14L:10D) when the photoperiodic adjustment was initiated in April; however, serum androgen levels were significantly depressed after 60 days exposure to short photoperiods as were weights of prostate glands when the photoperiodic manipulation was initiated in May. An increase in the number of hours of light per day during the inactive season did not affect serum androgen levels or reproductive organ weights. Exposure to a very short photoperiod (2L:22D) during the recrudescence phase delayed, but did not prevent, the increase in serum androgen levels. Although the reproductive system of the male mongoose is responsive to daylength adjustments, the response is less pronounced when compared to the effects of photoperiod in other seasonal breeders.

Androgens↗
PubMed1979

Selective suppression of the primary surge of follicle-stimulating hormone in the rat: further evidence for folliculostatin in porcine follicular fluid.

Charcoal-extracted porcine follicular fluid (PFF), when injected at 1200 h on proestrus, blocked the primary FSH surge seen at 1700 and at 1830 h without affecting the LH surge. In contrast, if the injection was withheld until 1330 h, the FSH surge occurred in the normal way at 1700 h but was suppressed at the 1830 h autopsy. The suppression of FSH by 0.5 ml PFF at 1200 h had abated by 0400 h of estrus. The blockade of the primary surge of FSH at 1700 and 1830 h did not prevent ovulation, nor did it prevent the expected rise in serum progesterone or fall of estradiol levels. There appears to be a latency of at least 3.5 h, when PFF is administered ip, before FSH can be suppressed. This latency occurs whether the injection is carried out in intact proestrous rats or in acutely or chronically ovariectomized females.

Animals↗
PubMed1979

Pseudoaneurysm complicating superficial temporal artery--middle cerebral artery bypass.

A patient with transient ischemic attacks from occlusion of a left common carotid artery was treated with common carotid endarterectomy immediately followed by superficial temporal artery-middle cerebral artery bypass. Subsequent angiography demonstrated a pseudoaneurysm formation at the anastomotic site. To our knowledge, this is the first report of this complication occurring in a human being.

Cerebral Arteries↗