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Biomedical subjects

J Beyer

Publications and source records attributed to J Beyer.

At least 127 records · Page 7Linked to original sources
PubMed1998

Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation.

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.

Adult↗
PubMed1998

Detection of tumor cells in peripheral blood samples from patients with germ cell tumors using immunocytochemical and reverse transcriptase-polymerase chain reaction techniques.

The aim of this study was to establish sensitive techniques for the detection of residual germ cell tumor cells in peripheral blood and progenitor cell harvests. For this purpose, we used immunocytochemical staining for cytokeratin filaments and reverse transcriptase-polymerase chain reaction (RT-PCR) for epidermal growth factor receptor (EGF-R) and germ cell alkaline phosphatase (GCAP). Germ cell tumor lines Tera-1 and Tera-2 were titrated into normal peripheral blood. Immunocytochemical staining allowed detection of one cytokeratin-positive tumor cell in 10(5) cells. RT-PCR for EGF-R revealed one tumor cell in 10 cells for Tera-1 and one tumor cell in 10(3) cells for Tera-2, while RT-PCR for GCAP displayed a sensitivity of one tumor cell in 10(6) cells for Tera-1, one tumor cell in 10(4) cells for Tera-2, and no positivity in normal mononuclear cells (n = 20) and progenitor cell harvests (n = 5). The analysis of peripheral blood and progenitor cell harvests from 20 patients with germ cell tumors revealed tumor cell contamination in three patients using immunocytochemical staining and in seven patients by RT-PCR for GCAP. We conclude that RT-PCR for GCAP appears to be suitable for the sensitive detection of residual germ cell tumor cells in peripheral blood and progenitor cell harvests.

Alkaline Phosphatase↗
PubMed1998

Skin microcirculation in patients with type I diabetes with and without neuropathy after neurovascular stimulation.

1. Neurovascular inflammation is impaired in patients suffering from diabetic neuropathy. The aim of our study was to evaluate the distribution of nutritive and total skin blood flow in diabetic patients with and without neuropathy after neurovascular stimulation with acetylcholine. 2. Twenty patients with Type I diabetes, 10 with and 10 without neuropathy, and 10 age-matched non-diabetic control subjects, underwent microvascular investigations before and after neurovascular stimulation by intracutaneous application of acetylcholine. The capillary blood cell velocity in the nailfold of the hallux was measured by videophotometric capillaroscopy, and the total skin microcirculation in the same area by laser Doppler flowmetry. 3. The increase in total skin blood flow was significantly impaired in the group of neuropathic diabetic patients compared with the non-neuropathic diabetic patients (17.5 +/- 8.3 versus 51.0 +/- 16.2; P < 0.05) and the non-diabetic subjects (17.5 +/- 8.3 versus 67.8 +/- 19.7; P < 0.01). The increase in capillary blood flow was not significantly impaired in Type I diabetes patients with neuropathy. 4. The ratio between capillary blood flow and total skin perfusion decreased significantly in the control group (from 0.82 +/- 0.15 to 0.47 +/- 0.11; P < 0.05) and in the Type I diabetes patients without neuropathy (from 0.79 +/- 0.12 to 0.43 +/- 0.12; P < 0.05), whereas the decrease in the neuropathic group was statistically insignificant (from 1.05 +/- 0.19 to 0.72 +/- 0.16). 5. Diminished total skin perfusion in the foot after intracutaneous stimulation with acetylcholine in Type I diabetes patients is associated with diabetic neuropathy, indicating a disturbance in the neurovascular reflex arc. This impaired neurovascular response is caused by a diminished total and subpapillary blood flow and not by a diminished nutritive capillary flow. There is no evidence of a diminished nutritive capillary blood flow during neurogenic inflammation in Type I diabetes patients suffering from diabetic neuropathy.

Acetylcholine↗
PubMed1998

Effect of long-term treatment with GH on bone metabolism, bone mineral density and bone elasticity in GH-deficient adults.

OBJECTIVE: Adults with GH deficiency (GHD) commonly have subnormal bone mineral density (BMD), and have been reported to have an increased risk of fractures. It has been suggested that GH replacement therapy may have beneficial effects on bone in such patients. The aim of this study was to investigate the effects of long-term GH replacement therapy on bone metabolism, BMD and bone elasticity in adults with GHD. DESIGN: At the start of the study, 20 adults with GHD were randomized to receive either GH, 0.25 IU/kg/week (the 'GH group') or placebo (the 'placebo group'). After 6 months, patients in the placebo group were switched to GH therapy, and all patients received GH for a further 42 months. PATIENTS: Of the 20 patients included in the study, 11 were male and nine were female. Mean age at the start of the study was 42.5 +/- 10.1 years. All patients had been GH-deficient for at least 2 years before the start of the study. MEASUREMENTS: Rates of bone resorption and formation were assessed by measuring serum levels of type I collagen carboxyterminal cross-linked telopeptide (ICTP) and carboxyterminal propeptide of type I procollagen (PICP), respectively. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the non-dominant forearm by single-photon absorptiometry (SPA). Bone elasticity was assessed by measuring apparent phalangeal ultrasound transmission velocity (APU). RESULTS: The main results in the GH group were as follows. The rate of bone resorption increased significantly during the first 6 months of treatment and remained significantly elevated above its baseline level thereafter. The rate of bone formation also rose during the first 6 months of treatment and remained elevated thereafter, but was significantly higher than at baseline only after 24 months of treatment. At both sites measured, BMD was subnormal at baseline, decreased during the first 6 months of treatment, and increased progressively for the rest of the study, eventually rising well above its baseline level. Bone elasticity decreased during the first 6 months of treatment, but had returned to its baseline level after 24 months. CONCLUSIONS: Our results support previous findings that BMD is subnormal in adults with GHD, that GH replacement therapy can stimulate bone turnover in such adults and that, in the long term, such stimulation results in a significant increase in BMD. In addition they show, for the first time, that BMD may continue to rise even after GH replacement therapy has been administered for 4 years, and indicate that bone elasticity is not adversely affected by long-term GH therapy.

Absorptiometry, Photon↗
PubMed1998

Endosonography of the adrenal glands: normal size--pathological findings.

Transabdominal sonography of the adrenal glands frequently is non-successful. It was the aim of this project to improve the imaging of the adrenal glands using high resolution sonography in order to obtain information about even small changes in these organs. Therefore, endosonographic imaging was investigated using an endosonoscope PENTAX FG32UA. The correct identification of the adrenal glands was examined in five human cadavers. A total of 58 patients with 113 adrenal glands (in 3 cases history of unilateral adrenalectomy) were investigated. 109 adrenal glands (97%) were identified and evaluated. Healthy adrenal glands are slightly hyperechoich and regarding their echogeneity comparable to other endocrine organs such as the testes or the thyroid. Adrenal size can be determined as largest cross sectional area and was found to be 216 +/- 93 mm2 right and 231 +/- 98 mm2 left. In the adrenal glands which could be imaged by endosonography, all findings detected by CT (n = 33) or MRI (n = 19) could also be demonstrated endosonographically. Additional information as compared to CT/MRI was obtained in 7 out of 33 and in 6 out of 19 patients. This concerns in particular differentiation between tumor and hyperplasia and detection of small adrenal adenomas. High resolution endosonography of the adrenal glands can provide information about adrenal gland morphology which cannot be obtained by any other diagnostic approach.

ACTH Syndrome, Ectopic↗
PubMed1998

The influence of advanced glycation endproducts (AGE) on the expression of human endothelial adhesion molecules.

Advanced glycation endproducts (AGEs) possibly play a dominant role in the pathogenesis of macrovascular disease in diabetes. Recent studies could demonstrate that glycated albumin (AGE-BSA) was able to stimulate vascular cell adhesion molecule-1 (VCAM.1) on endothelial cells. The aim of this study was to find out if AGE-BSA was not only able to enhance the expression of vascular cell adhesion molecule-1, but also of intercellular adhesion molecule-1 (ICAM-1) and E-Selectin on human endothelial cells. Stimulation of endothelial cells with AGE-BSA for six hours predominantly increased the expression of VCAM-1, but ICAM-1 and E-Selectin were also upregulated as shown by immunoilluminometric assay (ILMA).

Albumins↗
PubMed1998

Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals.

It is expected that microvascular blood flow might be affected by blood glucose, blood insulin and C-peptide levels. In our investigation skin microvascular blood flow (LDF) was measured using laser doppler fluxometry at skin temperatures of 37 degrees C and 44 degrees C during a 75 g oral glucose load (OGT) or water in ten healthy volunteers (6 male, 4 female, age: 28.1+/-4.0) who had fasted overnight. The transcutaneous oxygen tension (tcPO2) was measured using a transcutaneous oxygen electrode at a temperature of 44 degrees C. The microvascular response to acetylcholine was investigated before the start of the ingestion period and after 30 minutes. In addition, the capillary blood cell velocity (CBV) was measured using dynamic capillaroscopy. During OGT an increase in LDF could be observed at 37 degrees C (180%, p < 0.005) but only a slight increase was observed at 44 degrees C (86%, n.s.). The microvascular response to acetylcholine increased by 164% (p < 0.05) and the TcPO2 values increased by 30% (p < 0.01) during the OGT investigation. No significant changes in the microvascular measurements could be observed during the water experiment. No significant changes could be observed in the CBV measurements in any phase of the investigation. Plasma C-peptide and insulin levels exhibited an association with the LDF measurements at 37 degrees C (r = 0.22, p < 0.05; r = 0.30, p < 0.05; respectively), whereas blood sugar values showed an association with the TcPO2 measurements (r = 0.39, p < 0.01). After the ingestion of glucose a sophisticated modulation of microvascular blood flow was found in healthy volunteers. Further studies are necessary to investigate the role of a disturbed postprandial blood sugar control, insulin and C-peptide secretion in the development of microvascular dysfunction, especially in IDDM.

Acetylcholine↗
PubMed1998

New aspects on biological activity of C-peptide in IDDM patients.

C-peptide, which is released from the pancreatic beta cells into the circulation in amounts equimolar with insulin, fulfills an important function in the assembly of the two-chain insulin structure, but has otherwise been considered to be biologically inactive. However, during the last few years several experimental and clinical studies have demonstrated that replacement of C-peptide in patients with insulin-dependent diabetes mellitus elicits several physiological effects. Thus, during short-term substitution of C-peptide (1-3 h) decreased glomerular hyperfiltration, augmented whole body and skeletal muscle glucose utilisation, improved autonomic nerve function and a redistribution of microvascular skin blood flow could be observed. In addition, replacement of C-peptide during a period of 1-3 months has been shown to improve renal function as well as autonomic and sensory nerve function in IDDM patients. The mechanisms behind these effects remain unclear, but recent investigations have indicated that an increase in Na+K+ATPase activity and a stimulation of the endothelial nitric oxide synthase may contribute to the observed physiological effects of C-peptide. Not only the intact C-peptide molecule, but also fragments from the C-terminal and mid-portion of the molecule have been shown to exert biological effects. Further research will be necessary to evaluate the underlying mechanism and the clinical impact of C-peptide replacement in IDDM patients.

C-Peptide↗
PubMed1998

[Endosonographic imaging of the adrenal glands: a new method].

UNLABELLED: In contrast to the reliable imaging of the adrenal gland in infants and children, transabdominal sonography of the adrenal glands is often unsuccessful. AIM: To improve the imaging of the adrenal glands with high resolution in order to obtain information on even small changes in these organs. METHOD: Adrenal glands taken from human cadavers were investigated using a 7.5 MHz transducer. Thereafter, endosonographic imaging was investigated in 5 human cadavers using an endosonoscope PENTAX FG32 UA (longitudinal sector scanning. 7.5 MHz). Furthermore, the adrenal glands were imaged in a total of 30 patients with different indications for endosonography. RESULTS: The adrenal glands in 5 human cadavers could be identified in each case. This was proved in one human cadaver by endosonographically guided fine needle puncture with consecutive preparation of the tissue damage caused by the needle. In a total of 30 patients with 56 adrenal glands (in 4 cases preview history of unilateral adrenalectomy), 55 adrenal glands were correctly identified and evaluated. The only exception was the left adrenal gland of a patient with Billroth-II-stomach, which was slightly pulled to the right and very small. Healthy adrenal glands are slightly hyperechoic as compared to the parenchyma of the kidney and have echogeneity comparable to other endocrinal organs such as the testicles or the thyroid. Endosonographic imaging of the adrenal glands is far superior in resolution and determination to transabdominal sonography. In 18 of 30 patients (60%) endosonography provided additional diagnostic information compared to conventional sonography. CONCLUSION: Endosonography of the adrenal glands enables imaging of these organs with high resolution using a 7.5 MHz transducer from a distance of 1-2 cm.

Adenoma↗
PubMed1998

Analysis of CD34-expressing cells in clinical practice.

The flow cytometric determination of haemopoietic cells defined as CD34-expressing cells has greatly added to the improvement of the management of harvesting circulating haemopoietic cells for subsequent autologous reinfusion in the setting of high-dose chemo/(radio)-therapy. Additionally, this flow cytometric determination has replaced, in some institutions, the in-vitro culture test for CFU-GM as the measure to estimate the haemopoietic potential of the cells to be reinfused/transplanted.

Antigens, CD34↗
PubMed1998

Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors.

PURPOSE: High cumulative epipodophyllotoxin dosages are reported to be associated with an elevated risk for secondary acute myeloid leukemia (s-AML). This study examined the risk of s-AML following cumulative etoposide doses greater than 2 g/m2 in patients with metastatic germ cell tumors (GCT). PATIENTS AND METHODS: The incidence of s-AML was retrospectively assessed in patients treated within clinical trials between January 1986 and February 1996 at four university centers. All patients received high-dose chemotherapy (HDCT) plus autologous stem-cell support for metastatic GCT, including high cumulative etoposide doses (> 2 g/m2). Minimum patient follow-up was 12 months. Standardized morbidity ratio (SMR) was calculated to estimate the risk associated with high cumulative etoposide doses, as compared with the general population. RESULTS: A total of 302 patients with a median age of 29 years (range, 15 to 55) received a median cumulative etoposide dose of 5 g/m2 (range, 2.4 to 14 g/m2). Four cases of s-AML were observed, which resulted in a cumulative incidence of 1.3% (95% confidence interval [CI], 0.38% to 3.59%) at 52 months of median follow-up (range, 12 to 198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with primary mediastinal GCT. Based on the observed four cases of AML, which are most likely etoposide-related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7 to 411.2]) is significantly increased in comparison to the age-matched general population. CONCLUSION: Due to the low incidence of AML in the general population, the significantly elevated risk for developing s-AML affects only 1.3% of all patients who receive etoposide doses greater than 2 g/m2. HDCT, including etoposide doses greater than 2 g/m2, is associated with an acceptably low incidence of s-AML in patients with advanced GCT.

Acute Disease↗
PubMed1998

Iodide induces thyroid autoimmunity in patients with endemic goitre: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: Iodine is essential for normal thyroid function and the majority of individuals tolerate a wide range of dietary levels. However, a subset of individuals, on exposure to iodine, develop thyroid dysfunction. In this double-blind trial, we evaluated the efficacy and tolerability of low-dose iodine compared with those of levo-thyroxine (T4) in patients with endemic goitre. METHODS: Sixty-two patients were assigned randomly to groups to receive iodine (0.5 mg/day) or T4 (0.125 mg/day) for 6 months. Subsequently, both groups were subject to placebo for another 6 months. Thyroid sonography, determination of thyroid-related hormones and antibodies, and urinary excretion of iodine were carried out at baseline and at 1, 6 and 12 months. RESULTS: At 6 months, markedly increased urinary values of iodine were found in patients receiving iodine (36 microg/24 h at baseline, 415 microg/24 h at 6 months) compared with those receiving T4 (47 microg/ 24 h at baseline, 165 microg/24 h at 6 months; P < 0.0001 compared with iodine group). T4 administration engendered a greater (P < 0.01) decrease in thyroid volume (from 32 ml to 17 ml, P < 0.0001) than did intake of iodine (3 3 ml to 21 ml. P < 0.005). High microsomal and thyroglobulin autoantibody titres were present in six of 31 patients (19%) receiving iodine, and iodine-induced hypo- and hyperthyroidism developed in four and two of them, respectively. Fine-needle biopsy revealed marked lymphocyte infiltration in all six. After withdrawal of iodine thyroid dysfunction remitted spontaneously and antibody titres and lymphocyte infiltration decreased markedly. Follow-up of these six patients for an additional 3 years showed normalisation of antibody titres in four of them. CONCLUSION: Although nearly comparable results were obtained with both treatment regimens regarding thyroid size, partly reversible iodine-induced thyroid dysfunction and autoimmunity were observed among patients with endemic goitre.

Adult↗
PubMed1998

Establishment of a quantitative RT-pCR for detection of vascular cell adhesion molecule-1 transcripts in endothelial cells after stimulation with advanced glycation endproducts.

Advanced glycation endproducts (AGE) are supposed to increase endothelial expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1) by inducing an intracellular stress with subsequent activation of nuclear transcription factor NF-kappa-B. Quantitative analysis of VCAM-1-transcription has not been demonstrated concerning this topic. Thus, the aim of this study was to establish quantitative reverse transcription polymerase chain reaction (RT-PCR) assays using a spacer gene in order to measure the amounts of specific mRNA for VCAM-1 in human umbilical vein endothelial cells (HUVEC) which were stimulated with AGE-albumin (AGE-BSA). A recombinant RNA-standard was synthesized and used as internal RT-PCR standard. The amount of VCAM-1-mRNA in unstimulated HUVEC was found to be 2.2 +/- 2.7 copies per cell. After stimulation with AGE-BSA, mRNA-levels were elevated to 38.9 +/- 10.9 copies per cell. Positive controls (stimulated with lipopolysaccharide) revealed mRNA-levels of 78.7 +/- 27.5 copies per cell. We conclude that quantitative RT-PCR using the spacer gene technique is a valid and reliable method for the measurement of small amounts of specific

Cells, Cultured↗
PubMed1998

Prognostic factors in metastatic germ cell tumors.

Metastatic germ cell cancer is a very heterogeneous group with respect to prognosis under cisplatinum-based chemotherapy. The main determinants of complete response and survival are not only the extension of the metastases but much more the biology of the underlying tumor which is represented by the location of the metastases (pulmonary versus nonpulmonary visceral metastases (liver, bone, central nervous system) and the level of the marker elevation (AFG, HCG, LDH). Using these parameters patients with seminoma can be in two or three prognostic divided groups, depending on the model used; nonseminomatous germ cell cancer can be divided in three prognostic groups (good, intermediate and poor prognosis) with a 5 year survival of 90%, 70%, and 50%, respectively. The rate of marker decline and AFP- "surge" are not proven to be significant indicators of prognosis after the start of chemotherapy. Also, molecular markers i12p, p53, Rb, DNA-repair-capacity, etc, currently do not contribute to the prognostic models. In conclusion, with the present available prognostic models the patients with seminomatous as well as nonseminomatous cancer can be attributed to different prognostic groups for first-line as well as salvage treatment. This allows to the selection of patients for a risk adapted treatment and for the investigation of less toxic regimen for good prognosis patients and more aggressive protocols for intermediate and in particular poor risk patients.

Biomarkers↗
PubMed1998

Germ cell tumors: dose-intensive therapy.

Dose intensive chemotherapy in germ cell tumor patients has become a relatively safe procedure after the introduction of growth factors and the availability of autologous stem cells for hematopoietic rescue. Carboplatin and etoposide are the most active drugs available today, and are given in one or two subsequent cycles at dosages between 1000 and 2000 mg/m2 and 1200 and 2400 mg/m2, respectively. The potency of this approach is shown by the induction of long-term disease-free survival in a small proportion of patients with multiply relapsed or far advanced disease, deemed incurable with conventional chemotherapy. This observation indicates that cisplatin refractoriness can be overcome by high-dose carboplatin and etoposide. High-dose treatment (HDT) instituted earlier in the course of the disease, ie, for first-line salvage or even in first-line treatment of poor risk patients is better tolerated and is hoped to lead to superior tumor eradication. The value of HDT needs to be determined in randomized studies, some of which are under way.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

The use of dose-intensified chemotherapy in the treatment of metastatic nonseminomatous testicular germ cell tumors. German Testicular Cancer Study Group.

With the use of a cisplatin-based chemotherapy, metastatic testicular cancer has become a model for a highly curable malignant disease. Current data show that 70% to 80% of patients with this disease will achieve long-term survival following cisplatin/etoposide/bleomycin therapy. The role of high-dose chemotherapy with autologous stem cell support is being investigated in metastatic germ cell cancer in attempts to improve outcome for patients whose disease relapses after standard-dose chemotherapy and for those who present initially with advanced metastatic disease. Prognostic categories for patients receiving high-dose salvage chemotherapy have recently been developed: cisplatin-refractory disease, beta-human chorionic gonadotropin values greater than 1,000 U/L, and primary mediastinal germ cell tumors are factors characterizing patients who will derive less benefit from high-dose chemotherapy than those with chemosensitive disease at relapse. While standard-dose salvage chemotherapy achieves only a 20% long-term survival rate, high-dose salvage chemotherapy may yield a cure rate of approximately 40%. A randomized study comparing high-dose therapy with conventional-dose therapy (IT94 coordinated by the European Group for Blood and Marrow Transplantation) in patients with relapsed disease is ongoing to substantiate this observation. The use of dose-intensive therapy as first-line treatment is currently being studied by several institutions. High-dose therapy may be better tolerated when used first line compared with its use in the salvage situation, and may also achieve a rapid initial cell kill before cytostatic drug resistance develops. The German Testicular Cancer Study Group has developed a sequential high-dose combination regimen of cisplatin/etoposide/ifosfamide given with granulocyte colony-stimulating factor and peripheral blood stem cell support for four cycles every 3 weeks. This ongoing study, started in 1990, had accrued 218 patients with advanced testicular germ cell tumors as of June 1997. Of 141 evaluable patients receiving dose levels 1 through 5, 82 (58%) have achieved complete remission with no evidence of disease and 32 (23%) have achieved partial remission with marker normalization. The early death rate was 8%. Overall and event-free survival rates at 2 years are 78% and 73%, respectively, with a projected 5-year overall survival rate of 74%. Despite favorable preliminary results, this approach cannot be considered standard treatment. Currently, high-dose chemotherapy with peripheral blood stem cell transplantation should be administered to patients with testicular cancer only within controlled clinical trials to allow long-term cure rates and treatment-related late side effects to be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Arterivirus PRRSV. Experimental studies on the pathogenesis of respiratory disease.

Pigs were infected with the porcine respiratory and reproductive syndrome virus (PRRSV) by the oronasal route. We studied the development of histological lesions, sites of virus infection and of inflammatory infiltrates by quantitative evaluation of reactive cells. The animals developed a multifocal interstitial pneumonia. Clinical signs of pneumonia were observed from day 7 to 21. In the first stage, an acute alveolitis was found, which was characterised by a hyperplasia of type II pneumocytes within the septa and an accumulation of macrophages in the alveolar spaces. Within 2-4 days p.i., virus infected cells were prominent in lymphatic organs, but their number declined rapidly during the following days. In the following period, the number of virus antigen positive cells increased in the lung. An interesting discrepancy existed between the relatively small number of virus specific cells and the degree of intensive pneumonia. As a first step to analyse mechanisms leading to the induction of pneumonia, we studied transcriptional expression of cytokines and other immunomodulatory molecules by semiquantitative RT-PCR.

Animals↗