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Biomedical subjects

J C Hoffmann

Publications and source records attributed to J C Hoffmann.

At least 19 recordsLinked to original sources
PubMed2006

[An unusual case of upper GI bleeding: esophageal cancer metastasis at a percutaneous endoscopic gastrostomy site--case report and review of the literature].

We present the case of a patient with an esophageal squamous cell carcinoma, who was treated primarily by radiotherapy. Due to dysphagia, the patient received a percutaneous endoscopic gastrostomy (PEG) without any sign of tumour at that time. Five months later the patient presented with an upper GI bleeding from a gastric ulcer, which histologically turned out to be a metastasis of the previously diagnosed squamous cell carcinoma. So-called "implantation metastases" at the percutaneous endoscopic gastrostomy site are rare and most of the cases have been described in patients with head and neck tumours. Moreover, the presentation as an upper GI bleed is very uncommon and needs the attention of both endoscopists as well as gastrointestinal oncologists. Clinicopathological features of this case with a brief review of the literature are presented.

Carcinoma, Squamous Cell↗
PubMed2002

Unusual case of a large midoesophageal diverticulum mimicking unstable angina pectoris.

We describe a 77-year-old lady who presented with progressive retrosternal pain radiating to the left arm and the back. After exclusion of cardiac causes a large midoesophageal diverticulum was found on oesophago-gastro-duodenoscopy. Importantly, the retrosternal pain completely disappeared after endoscopic removal of impacted food from the diverticulum. After the surgical resection the patient became fully asymptomatic. This is the first example of angina-like chest pain which definitively resulted from a midoesophageal diverticulum. Therefore, midoesophageal diverticula should be considered as a rare differential diagnosis of exercise-induced retrosternal pain.

Aged↗
PubMed2001

Migration of T cells in vivo: molecular mechanisms and clinical implications.

T cells play an important role in the pathogenesis of chronic and autoimmune inflammatory diseases. They are found in high numbers in involved tissues, such as the lamina propria of the gut in patients with Crohn disease. Modifying T-cell number and function may therefore be of therapeutic value. In principle, two mechanisms may be responsible for the development of such T-cell infiltrates: 1) an increased rate of T-cell immigration into involved tissues or 2) an increased proliferation rate, decreased T-cell death (apoptosis) rate, and prolonged retention of T cells already in the tissue. Based on the theory that T cells selectively target affected tissues through organ-specific adhesion-molecule pathways, current anti-adhesion-molecule therapy aims to interfere selectively with T-cell entry to stop tissue damage. However, the traffic of labeled T cells in unmanipulated animals shows that the entry of T-cell subsets into tissues is not organ-specific, even under conditions of differing adhesion molecule and chemokine receptor expression. In contrast, within various tissues, both movement and survival of T-cell subsets differ considerably. These observations suggest that the differential expression of adhesion molecules and chemokine receptors on T cells serves at least two functions in vivo. First, during migration of T cells out of the bloodstream, the different adhesion-molecule pathways provide redundancy, which guarantees that T-cell subsets are able to enter the different tissues in sufficient numbers (security). Second, adhesion molecules and chemokine receptors mediate T-cell interactions within the tissue that are characteristic for each subset and each microenvironment and determine the nature of the ensuing immune response (selectivity). Shifting the focus of anti-adhesion-molecule therapy toward the T cells in diseased tissue may lead to new treatment options.

Animals↗
PubMed2001

Role of T lymphocytes in rat 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis: increased mortality after gammadelta T cell depletion and no effect of alphabeta T cell depletion.

BACKGROUND AND AIM: Indirect evidence suggests that CD4+ T cells have a pathogenic while gammadelta T cells have a protective role in the initiation and perpetuation of inflammatory bowel disease. To define the role of T cell subsets in a rat colitis model (2,4,6-trinitrobenzene sulphonic acid (TNBS)) we analysed colitis severity after effective depletion of T helper cells, alphabeta T cells, or gammadelta T cells. METHODS: T helper cells, alphabeta T cells, or gammadelta T cells were depleted using previously described monoclonal antibodies directed at the CD4 molecule (OX38), the CD2 molecule (OX34, both depleting CD4+ T cells), the alphabeta T cell receptor (R73), and the gammadelta T cell receptor (V65). Depletion was verified by flow cytometry and/or immunohistology. Colitis was induced using intracolonic application of TNBS. RESULTS: Surprisingly, depletion of T helper cells or alphabeta T cells had no influence on survival, macroscopic or microscopic scores, or myeloperoxidase activity following colitis induction. In contrast, depletion of gammadelta T cells resulted in significantly increased mortality (V65: 73%, n=15) compared with controls (30%, n=13; p<0.03). In addition, colitis was histologically more severe in the gammadelta T cell depleted group compared with controls (p<0.05). CONCLUSIONS: T helper cells or alphabeta T cells did not influence the initiation or perpetuation of rat TNBS colitis. In contrast, gammadelta T cells had a protective role in rat TNBS colitis as depletion caused increased mortality.

Animals↗
PubMed1999

Protection of trinitrobenzene sulfonic acid-induced colitis by an interleukin 2-IgG2b fusion protein in mice.

BACKGROUND & AIMS: We have shown in previous studies that an interleukin 2 (IL-2)-IgG2b fusion protein suppresses both humoral and cellular immune reactions in a murine model of DTH reaction. We now analyze the effects of IL-2-IgG2b in a model of intestinal inflammation in mice induced by the hapten reagent 2,4, 6-trinitrobenzene sulfonic acid (TNBS) that mimics immunologic characteristics of human Crohn's disease. METHODS: In TNBS-induced colitis, colonic and splenic T-cell subsets were characterized by immunohistochemistry and flow cytometry. Cytokine synthesis was studied by semiquantitative reverse-transcription polymerase chain reaction and intracellular cytokine staining in CD4(+) T cells. RESULTS: When mice were treated with IL-2-IgG2b, improvement in both wasting disease and histopathologic signs of colonic inflammation was observed. An increase in the number of colonic CD4(+)/CD25(+) T cells and increased synthesis of the immunosuppressive cytokine IL-10 also occurred. The protective role of IL-10 was demonstrated by the finding that neutralization of IL-10 in vivo using IL-10-specific antibodies inhibited the IL-2-IgG2b effects in TNBS-induced colitis. CONCLUSIONS: These studies show for the first time that the IL-2-IgG2b fusion protein can abrogate experimental colitis by local induction of IL-10-secreting T cells.

Animals↗
PubMed1998

Effects of the anti-CD2 mAb OX34 on in vivo proliferation.

In vitro studies indicate that CD2 plays an important role in the intestinal immune system with regard to T cell proliferation and T helper 2 differentiation. We asked whether anti-CD2 mAb induces T-cell proliferation in vivo. Rats received anti-CD2 mAb OX34 or control mAb over 3 days. Before exsanguination BrdU was injected. Lymphatic organs were processed for two-color immunohistology. OX34 depleted CD4+ but not CD8+ T cells in all organs. Remaining CD4+ T cells proliferated in the periarteriolar lymphocyte sheets. Surprisingly, OX34 led to strong proliferation of splenocytes in the red pulp. These cells were negative for markers of T cells, B cells, NK cells, macrophages, and myeloid cells. Taken together, the anti-CD2 mAb OX34 leads to proliferation of an as-yet-unidentified cell type in the red pulp of the spleen but not to proliferation of T cells.

Animals↗
PubMed1998

Human b cell differentiation: dependence on interactions with monocytes and T lymphocytes via CD40, CD80 (B7.1), and the CD2-Ligands CD48 and CD58 (LFA-3).

B cell differentiation depends on cellular interactions with T lymphocytes and monocytes via adhesion molecules (AM). In order to characterize AM which are required for B cell differentiation immunoglobulin production using unseparated peripheral blood mononuclear cells (PBMC) was studied. Unstimulated human PBMC were cultured for 9 days with mAb directed at CD2/CD48, /CD58, CD59, CD5/CD72, CD11a-CD18/CD54, CD28/CD80, CD86, CD40/CD40L, or rat CD2 (control). B cell differentiation was quantified measuring IgM and in some cases IgA, IgG, and IgE production. IgM levels were significantly reduced by mAb against CD40, CD48, CD58 and CD80. The reduction was not due to isotype switching to IgA, IgG or IgE. The role of CD40, CD48, CD58 and CD80 was further investigated after depletion of different cell types. Depletion of monocytes and NK cells resulted in no detectable IgM production irrespective of added mAbs. In contrast, IgM production was still present after depletion of T cells and NK cells. Only mAb against CD80 and CD48 significantly reduced IgM production, the reduction of IgM production by anti-CD40 mAb was less than in the presence of T cells. Importantly, anti-CD58 mAb had no effect on IgM production after T cell and NK cell depletion. Taken together, the AM CD40, CD48, CD58, and CD80 are involved in Ig production of unseparated PBMCs. In this model of B cell differentiation only the AM CD58 depend on the presence of T cells while CD48 and CD80 help was found to be T cell independent.

Animals↗
PubMed1998

Intestinal obstruction, progressive weight loss, and recurrent fever in two patients with mesenteric lesions.

We describe 2 patients who presented with fever and incomplete intestinal obstruction. Previously, both patients had had laparotomies showing unresectable lesions in the root of the mesentery which were histologically diagnosed as sclerosing mesenteritis in the first and mesenteric fibromatosis in the second patient. In spite of aggressive immunosuppressive therapy the first patient deteriorated with high-grade fever and progressive weight loss. Similar symptoms occurred in the second patient. Computed tomographic scanning revealed necrotic lesions in both patients which histologically were found to be an angiocentric T-cell lymphoma in the first and a superinfected necrotizing fibroma in the second patient. It is therefore clinically and radiologically impossible to distinguish between the different causes of mesenteric lesions. Reoperation for further biopsies needs to be considered if such patients do not respond to medical treatment.

Aged↗
PubMed1997

Elevated serum concentrations of soluble selectin and immunoglobulin type adhesion molecules in patients with inflammatory bowel disease.

Adhesion molecules mediate the extravasation of leukocytes and their accumulation in inflamed tissues. In the present study, serum concentrations of the selectin (sP- and sE-selectin) and immunoglobulin supergene family (sICAM-1 and sVCAM-1) of adhesion molecules were measured in 93 patients with inflammatory bowel disease (Crohn's disease, n = 65; ulcerative colitis, n = 28) and 58 age-matched normal controls. sP-selectin serum concentrations (mean +/- SEM ng/ml) of patients with Crohn's disease (399 +/- 33 ng/ml) and ulcerative colitis (385 +/- 42 ng/ml) were increased (P = 0.0067 and P = 0.0193, respectively) compared to controls (251 +/- 33 ng/ml). In contrast, E-selectin serum levels of patients with Crohn's disease (58 +/- 5 ng/ml) and ulcerative colitis (64 +/- 12 ng/ml) were not significantly higher than those of controls (53 +/- 5 ng/ml). sICAM-1 serum concentrations of patients with Crohn's disease (420 +/- 19 ng/ml) and those with ulcerative colitis (375 +/- 40 ng/ml) were elevated (P = 0.0001 and P = 0.0473, respectively) compared to controls (297 +/- 8 ng/ml). Further, sVCAM-1 levels of patients with Crohn's disease (664 +/- 43 ng/ml) and ulcerative colitis (963 +/- 162 ng/ml) were increased (P = 0.0222 and P = 0.0121, respectively) compared to controls (510 +/- 31 ng/ml). With few exceptions, serum levels of soluble adhesion molecules were not significantly correlated to disease activity indices or disease localization. Elevated circulating selectin and immunoglobulin supergene type adhesion molecules may compete with membrane-bound forms for their cognate ligands and thereby limit the rolling and stable adhesion of leukocytes.

Adolescent↗
PubMed1997

Anti-CD2 (OX34) MoAb treatment of adjuvant arthritic rats: attenuation of established arthritis, selective depletion of CD4+ T cells, and CD2 down-modulation.

Anti-CD2 MoAbs have previously been shown to induce tolerance and to block B cell differentiation, T cell and monocyte activation. Since these immune functions are important in joint inflammation, we asked whether administration of the anti-CD2 MoAb OX34 has a beneficial effect on established rat adjuvant arthritis, a model of human rheumatoid arthritis, and how it affects CD2-bearing leucocyte subsets. Female Lewis rats with established adjuvant arthritis received a total of 5 mg OX34 or isotype-matched control MoAb starting on day 15 after adjuvant injection. Weight and arthritis score (AS) were measured in a blinded fashion. Peripheral blood cells were analysed for numbers of leucocyte subsets at various time points. Animals were killed on day 30 and lymphatic organs were processed for immunohistology. Clinically, OX34 treatment led to increased body weight and reduced AS. Although OX34 binds to CD4+ and CD8+ T cells in a comparable fashion, OX34 treatment reduced CD4+ T cells, but not CD8+ T cells. Among CD4+ T cells CD45RC+ ('naive') T cells virtually disappeared; CD45RC- ('recently activated') T cells were slightly reduced. A reduction of CD4+ T cells was also found in the lung, liver, bone marrow, spleen and lymph nodes. Down-modulation of the CD2 molecule by OX34, again, affected CD4+ T cells, suggesting a specific signal for CD4+ but not CD8+ T cells. In conclusion, the anti-CD2 MoAb OX34 attenuates established rat adjuvant arthritis. In spite of similar binding to CD4+ and CD8+ T cells, OX34 depletes only CD4+ T cells and down-modulates the CD2 molecule on these cells. These results suggest a therapeutic benefit from CD2-directed therapy for chronic types of arthritis.

Animals↗
PubMed1997

Initiation and perpetuation of rat adjuvant arthritis is inhibited by the anti-CD2 monoclonal antibody (mAb) OX34.

OBJECTIVE: The purpose of this study was to investigate the therapeutic potential of the anti-CD2 mAb OX34 first with regard to bone protection in established rat adjuvant arthritis (AA) and secondly with regard to prevention of AA induction. METHODS: Established AA was treated with dexamethasone (1 mg/kg body weight) for two days plus OX34 mAb or control mAb over three days (2 mg and then 1 mg) starting at different time points of the disease. For prevention studies animals were injected as above with mAb before induction of AA. Arthritis score (AS), hindpaw thickness, and body weight were blindly measured three times per week. Flow cytometry and hindpaw radiography were performed at the end of the study (day 29). RESULTS: Treatment of early AA with OX34 mAb combined with dexamethasone but not dexamethasone plus control mAb dramatically suppressed established AA as assessed by AS and hind paw thickness (> 65% and > 80% reduction, respectively; p < 0.05). Most importantly, early treatment in the course of AA almost completely prevented bone destruction in established AA. When given before AA induction OX34 alone prevented the initiation of arthritis compared with controls (AS reduction 83-95%, p < 0.05). In addition, OX34 plus dexamethasone treatment resulted in depletion of CD4+ T cells but not CD8+ T cells. IL2R+ and CD45RC- ('memory') T cells were significantly reduced. CONCLUSIONS: Anti-CD2 mAb treatment prevents AA induction confirming the role of CD4+ T cells in the induction phase of AA. In addition, early OX34 plus dexamethasone treatment resulted in pronounced clinical improvement and joint protection. OX34 treatment therefore inhibits the initiation and the perpetuation of rat AA.

Animals↗
PubMed1996

Detection of a soluble form of the human adhesion receptor lymphocyte function-associated antigen-3 (LFA-3) in patients with chronic liver disease.

BACKGROUND/AIMS: Multiple immune functions, such as cytotoxic reactions, B cell differentiation, and monocyte activation, are mediated via the adhesion receptor/ligand pairs CD2/lymphocyte function-associated antigen(LFA)-3 and LFA-1/ intercellular adhesion molecule(ICAM)-1. Since 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 can be found in patients with different forms of chronic liver disease and/or hepatocellular carcinoma. METHODS: sLFA-3 was measured in sera from 84 patients with chronic liver disease (39 with chronic viral liver disease, 30 with autoimmune liver disease, 12 with alcoholic cirrhosis, 3 with other causes of cirrhosis), 24 patients with hepatocellular carcinoma (15 with and 9 without cirrhosis), and 61 normal controls. From 36 of the patients with liver cirrhosis, arterial and hepatic venous serum samples were simultaneously obtained and tested for sLFA-3 and sICAM-1. RESULTS: In comparison to controls, sLFA-3 levels were elevated in patients with liver cirrhosis due to autoimmune liver disease (p < 0.0001) and viral liver disease (p = 0.001), but not in patients with alcoholic cirrhosis. Increased sLFA-3 levels were also found in patients with hepatocellular carcinoma and liver cirrhosis. However, sLFA-3 was not significantly elevated in sera from patients with autoimmune liver disease, viral liver disease, and hepatocellular carcinoma without concomitant liver cirrhosis. No difference was found between arterial and hepatic venous serum levels of sLFA-3 and sICAM-1. sLFA-3 levels correlated positively with aspartate transaminase, alkaline phosphatase, bilirubin, sICAM-1, and inversely with albumin and cholinesterase. CONCLUSIONS: Taken together, sLFA-3 serum concentrations of patients with liver cirrhosis due to autoimmune liver disease or viral liver disease and of patients with hepatocellular carcinoma and cirrhosis are significantly increased compared to controls. Elevated sLFA-3 and sICAM-1 levels might reflect the generalized inflammation in cirrhosis and by interference with cell-cell interactions sICAM-1 and sLFA-3 may limit the extent of inflammation.

Adult↗