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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 217 records · Page 12Linked to original sources
PubMed1995

Cytokine (IL-8, IL-6, TNF-alpha) and soluble TNF receptor-I release from human peripheral blood mononuclear cells after respiratory syncytial virus infection.

During the initial phase of respiratory syncytial virus (RSV) infection, when a low virus-cell ratio is most probable, signs of inflammation are detectable in the infected respiratory tissue. Therefore we analysed the release of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, tumour necrosis factor-alpha (TNF-alpha), and the soluble form of the TNF receptor-I (sTNFR-I), from peripheral blood mononuclear cells (PBMC) after exposure to low infectious RSV doses (multiplicity of infection, MOI, 0.001-1) and incubation times of up to 24 hr. The PBMC secreted IL-8 in a time- and virus dose-dependent fashion. As was verified by Northern blot analysis, the increased IL-8 secretion rate was accompanied by an enhanced IL-8 mRNA steady-state level. The infection of the PBMC after 4 hr post-RSV exposure was verified by detection of RSVSH genomic RNA and mRNA after reverse transcription and polymerase chain reaction (PCR) amplification. In addition, after 24 hr post-infection we determined the percentage of infected cells by specific immunofluorescence using monoclonal antibodies directed against the F- and G-proteins. After exposure of PBMC to inactivated RSV, we observed only RSVSH genomic RNA and a reduced IL-8 release. Thus, even the binding and/or phagocytosis of RSV by PBMC induced an IL-8 synthesis to some extent. Following an incubation time of 24 hr, PBMC exposed to small RSV doses synthesized and released high amounts of IL-6 into the cell supernatant. In contrast, only low amounts of TNF-alpha were released from PBMC. In addition to the release of the proinflammatory cytokines, an enhanced level of the sTNFR-I was measured in the cell supernatants at a MOI of 0.1. However, there was no correlation between TNFR-I membrane expression and cell supernatant concentration. Co-culture experiments performed with PBMC and human epithelial cells (A549) revealed that the enhanced IL-8 secretion profile observed in the coculture was partially dependent on the cytokines TNF-alpha, IL-1 beta and TNF-beta/lymphotoxin released by the cells themselves.

Antigens, CD↗
PubMed1995

In vivo/ex vivo T cell depletion for GVHD prophylaxis influences onset and course of active cytomegalovirus infection and disease after BMT.

Combined in vivo/ex vivo T cell depletion is effective in the prophylaxis of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), but influences the occurrence of active cytomegalovirus (CMV) infection and disease. Twenty nine patients receiving a T cell-depleted marrow graft (Campath-1M) after intravenous application of the monoclonal antibody Campath-1G prior to conditioning were monitored for virus shedding and antigenaemia from day -7 to day +100. In seropositive patients in this group active CMV infection occurred more frequently (10 of 16) and much earlier (nine of 10 until day +21) than in 27 seropositive patients (10 of 27, P < 0.02) receiving cyclosporin A and methotrexate (CsA/MTX). Early active CMV infection after in vivo/ex vivo T cell depletion correlated strictly with an early increase in blood lymphocyte counts (P < 0.01), with predominance of NK cells and/or CD8+ T cells. Three cases of very early interstitial pneumonitis (IP) occurred after in vivo/ex vivo T cell depletion compared with none in the CsA/MTX group. IP was fatal in the only patient with early active CMV infection, who remained lymphocytopenic till death on day +31. This may indicate that an early immune response against CMV is possible and essential for favourable clinical outcome.

Adolescent↗
PubMed1995

In vivo/ex vivo T cell depletion reduces the morbidity of allogeneic bone marrow transplantation in patients with acute leukaemias in first remission without increasing the risk of treatment failure: comparison with cyclosporin/methotrexate.

We have performed a non-randomised GVHD prophylaxis trial comparing cyclosporin/methotrexate with in vivo/ex vivo T cell depletion with the monoclonal antibodies Campath 1G/1M in patients with acute leukaemias in first complete remission. We observed significantly less acute and chronic GVHD, neutropenic fever and severe mucositis in the T cell depletion group. The incidence of graft rejection and relapses was no higher than in the cyclosporin/methotrexate group. There is a trend in favour of improved disease-free survival in the in vivo/ex vivo T cell depletion group (80% vs. 62%).

Acute Disease↗
PubMed1995

Successful therapy with donor buffy coat transfusions in patients with relapsed chronic myeloid leukemia after bone marrow transplantation is associated with high frequencies of host-reactive interleukin 2-secreting T helper cells.

Six patients treated for relapsed chronic myeloid leukaemia after allogeneic bone marrow transplantation with donor buffy coat transfusions were investigated. In the 5 patients who achieved molecular remission high frequencies of host-reactive interleukin 2-secreting T helper cell precursors (Th-p) were detectable by limiting dilution analysis. In four of the patients the presence of Th-p was associated with a clinical syndrome similar to transfusion GVHD suggesting a T cell response to minor histocompatibility antigens (minor H) expressed by both malignant haemopoiesis and host tissues. In the fifth responding patient no GVHD or bone marrow hypoplasia was observed. The nature of the antigens recognised by these donor Th-p remains unknown. No host-reactive Th-p were detectable in the non-responder and host-reactive cytotoxic T cell precursors (CTL-p) were not consistently detectable in the responding patients.

Adult↗
PubMed1995

Presence of host-specific interleukin 2-secreting T helper cell precursors correlates closely with active primary and secondary chronic graft-versus-host disease.

We investigated the role of interleukin 2 (IL-2)-secreting T helper cell precursors (Th-p) in primary and secondary chronic graft-versus-host disease (GVHD). Twelve patients with chronic GVHD (8 primary and 4 secondary chronic GVHD) and 8 patients without chronic GVHD were investigated using a sensitive limiting dilution assay. High frequencies of host-reactive interleukin 2-secreting T helper cell precursors were detectable in all patients with chronic GVHD irrespective of the mode of onset. Host-reactive IL-2-secreting T helper cell precursors disappeared in patients whose GVHD resolved. Host-reactive IL-2-secreting T helper cell precursors were never found in the control patients without chronic GVHD. Host-reactive cytotoxic T cell precursors (CTL-p) were not consistently detectable in patients with chronic GVHD and were occasionally found in patients without GVHD. No autoreactive IL-2-secreting T helper cell precursors or cytotoxic T cell precursors were detectable in either group. The absence of autoreactive IL-2-secreting T helper cell precursors in patients was confirmed by clonal specificity analysis in 4 patients. These data suggest a role for host-reactive IL-2-secreting T helper cell precursors in the initiation and maintenance of chronic GVHD as previously shown for acute GVHD.

Adolescent↗
PubMed1995

Smoking as a risk factor for duodenal ulcer relapse. RUDER Study Group.

This study reports the influence of smoking on the two-year relapse rate of duodenal ulcers under treatment with ranitidine. 1899 patients with a healed duodenal ulcer received 150 mg ranitidine daily for one year, 1671 patients for two years. During this time period 23.4% of smokers relapsed compared with 26.3% of ex-smokers and 18.0% of non-smokers. The difference between smokers and ex-smokers versus non-smokers was statistically significant. There were significantly fewer relapses among smokers who stopped smoking (14.2%) compared with smokers who continued to smoke (25.2%) during maintenance treatment. These results show that continued and past smoking significantly increase the two-year relapse rate of duodenal ulcers during maintenance treatment with ranitidine.

Adult↗
PubMed1995

Use of a titanium-reinforced membrane in periodontal regeneration: a case report.

One of the most important principles of guided tissue regeneration is space creation and maintenance in the early stages of wound healing. Many devices have been tested to provide such space during this stage, some of which include various bone grafts, resorbable pins, and stainless steel fixation screws and tentpoles. A recently developed membrane fulfils such requirements. A case describes the use of this new membrane to treat a combined dehiscence and interproximal osseous defect. This technique was proven to have the potential to eliminate deep osseous defects and allow new attachment of soft tissue on the tooth surface.

Alveolar Bone Loss↗
PubMed1994

Distribution and chemical phenotypes of neuroendocrine cells in the human anal canal.

The presence, morphology and distribution of anal neuroendocrine cells were investigated with a panel of antisera and antibodies for neural markers, biogenic amines, and neuropeptides by the sensitive streptavidin-biotin-peroxidase immunocytochemistry, and coexistence patterns of neurochemically characterized neuroendocrine cells were examined by double immunofluorescence cytochemistry. In the colorectal zone, endocrine-like cells were immunoreactive for chromogranin A (CGA), serotonin (5-HT), pancreastatin (PST), peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and somatostatin (SOM). Coexistence patterns of endocrine-like cell phenotypes with CGA and GLP-1 were heterogeneous. In the anal transitional zone (ATZ), endocrine-like cells were immunoreactive for CGA, 5-HT and PST. Furthermore, six new phenotypes of endocrine-like cells were characterized by their immunoreactivity for PYY, GLP-1, protein gene product 9.5 (PGP), calcitonin gene-related peptide (CGRP), neurotensin (NT), and SOM. All endocrine-like cell types in the ATZ were immunoreactive for CGA. In the squamous zone and perianal skin, CGA-immunopositive Merkel cells were also immunoreactive for CGRP, PST, NT and PGP. Neuroendocrine cells in the anal canal exhibit epithelial zone-related diversities in their neurochemical phenotypes and coexistence patterns, which may indicate specific regulatory functions. In the epithelium of the ATZ, which is regarded as metaplastic, endocrine-like cells expressed phenotypes characteristic of the neuroendocrine cells of the colorectal zone and the squamous zones, indicating a possible metaplastic origin of these cells.

Adolescent↗
PubMed1994

[Diagnosis and therapy of active endocrine pancreatic tumors].

Diagnosis of endocrine pancreatic tumor syndromes is based on the characteristic spectrum of symptoms and the demonstration of inappropriately high serum levels of the tumor's secretory products. Available imaging methods cannot visualize pancreatic tumors with a diameter of less than 1 cm and are diagnostic in 50 to 60% only. With the introduction of endoscopic sonography and somatostatin receptor scintigraphy, detection of tumors has been improved. Therapeutic principles include surgical extirpation, primarily in the absence of metastases, and medical control of symptoms. In the case of metastatic disease, tumor growth and symptoms can be controlled by a variety of procedures including somatostatin analogs with and without additional alpha-interferon, polychemotherapy, embolization, surgical tumor debulking and liver transplantation.

Adenoma, Islet Cell↗
PubMed1994

Hepatitis C virus infection is a risk factor for liver failure from veno-occlusive disease after bone marrow transplantation.

The contribution of hepatitis C virus (HCV) infection to liver disease after bone marrow transplantation (BMT) was retrospectively evaluated in 61 patients treated with BMT. HCV genome, as well as antibodies to HCV, was analyzed in sera collected before and serially after BMT. Six patients had been infected with HCV before BMT and three patients acquired the infection during or shortly after BMT. All patients infected before BMT died within 10 weeks after transplantation. Five of these six patients (83%) died of veno-occlusive disease (VOD), compared with nine of 52 patients (17%) not infected with HCV (P < .005). Risk factors for VOD other than HCV were not more prevalent in these patients compared with uninfected patients. Parallel to the development of VOD, replication of HCV increased, as demonstrated by rising concentrations of viral RNA in serum. HCV infection acquired during or after BMT caused only mild acute hepatitis C, which progressed to chronic hepatitis C in one patient surviving 10 years after BMT. These data suggest that patients with liver disease caused by HCV infection are at high risk of developing lethal VOD after BMT.

Adolescent↗
PubMed1994

Glucagon-like peptide 1 immunoreactivity in gastroentero-pancreatic endocrine tumors: a light- and electron-microscopic study.

The preproglucagon gene encodes, in addition to glucagon, two smaller peptides with structural similarity: glucagon-like peptides 1 and 2. Glucagon-like peptide 1 (GLP-1) 7-36 amide is the most powerful incretin candidate. In the present study, GLP-1 immunoreactivity was investigated in tissue specimens of various types of gastroenteropancreatic tumors, and the serum-levels of GLP-1 were assayed. Immunohistochemical staining of 88 tumors revealed GLP-1 immunoreactivity in 17 neoplasias (19.3%), viz., in 7 out of 33 non-functioning tumors, 4 out of 20 gastrinomas, 4 out of 13 insulinomas, 1 out of 3 vasoactive-intestinal-polypeptide (VIP)omas and 1 adrenocorticotropic-hormone (ACTH)-producing tumor. In these tumors, GLP-1-immunoreactive cells were distributed either diffusely, arranged in clusters, or as single cells. All GLP-1-positive tumors were immunoreactive for glucagon or glicentin, 10 tumors were immunoreactive for pancreatic polypeptide, and 8 tumors for insulin. Ultrastructural analysis of 8 GLP-1-positive tumors, with the immunogold technique, demonstrated GLP-1 immunoreactivity mainly in cells resembling the A-cells of the pancreas or the L-cells of the gut. Of the 17 GLP-1-immunoreactive tumors, 15 were primarily located in the pancreas. Additionally, 2 non-functioning tumors of the rectum were GLP-1 immunoreactive. Five tumors were GLP-1 immunoreactive from 9 patients with multiple endocrine neoplasia I syndrome. Patients with GLP-1-immunoreactive tumors were characterized by a significantly lower rate of distant metastases (P < 0.01) and a higher rate of curative resections (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia.

The incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneic n = 271, autologous n = 27, syngeneic n = 5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.

Administration, Inhalation↗