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Biomedical subjects

M Pedersen

Publications and source records attributed to M Pedersen.

At least 73 records · Page 4Linked to original sources

Amplification and sequencing of the control regions of BK and JC virus from human urine by polymerase chain reaction.

The various strains of BKV and JCV exhibit a remarkable degree of heterogeneity in the noncoding region near the origin of DNA replication. It is of great interest, therefore, to characterize the naturally occurring variants as a first step towards the attainment of an understanding of the origin and the biological significance of this hypervariability. In this paper we report the use of polymerase chain reaction for amplification and sequencing of the control regions of BKV and JCV DNAs from urines of AIDS patients, bone marrow transplantation recipients, and other patient groups. Our results support the conclusion that BK(WW) and its variants constitute the most prevalent strain in the human population tested so far. A new strain, designated BK(TU), was isolated from some patients from Norway. Urine inocula containing BK(WW) gave BK(TU) after propagation in cell culture, while BK(TU) did not change the sequence of its control region during the same procedure. The JCV isolates were almost identical with several strains molecularly cloned from the urine reported by Y. Yogo, T. Kitamura, C. Sugimoto, T. Ueki, Y. Aso, K. Hara, and F. Taguchi (J. Virol., 1990, 64, 3139-3143). This archetypal strain may represent the JCV circulating in the human population, from which various regulatory sequences of JCV isolates could have evolved by deletions and amplifications.

BK Virus

Paternity in patients with testicular germ cell cancer: pretreatment and post-treatment findings.

Paternity before and after treatment was investigated in 177 patients with unilateral germ cell tumours of the testis. Before the cancer was diagnosed, 51% had fathered at least 1 child, 9% had a history of infertility and 40% had not wanted to have children. It was estimated that 72% of the patients would have fathered at least 1 child at the age of 40 years. After treatment 41 patients had wished to have children. Infertility was still a problem 5 years after the end of treatment in 53% of these men. No significant differences was observed between patients treated with orchiectomy alone and patients treated with cisplatin-based chemotherapy or subdiaphragmatic irradiation. In 8 patients, infertility was present in spite of an evident recovery of spermatogenesis. Congenital malformations were recorded in 3.8% of the live-born children conceived before the orchiectomy. This incidence did not exceed the Danish national rate, the relative risk being 2.5 (95% confidence limits, 0.9-5.5). No malformations were observed in the 22 children conceived after ending treatment.

Adolescent

Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group.

In a Danish population-based non-Hodgkin lymphoma (NHL) registry, 1257 newly diagnosed NHL cases were registered over a 5-year period. Of these, 463 (37%) were extranodal. The gastrointestinal tract was the most common site of extranodal involvement (30% of the cases). Histologically, 44% of all extranodal NHL cases had high-grade, 17% intermediate and 27% low-grade features, while 12% were unclassified. The most common histological subtype (Kiel) was the centroblastic diffuse (23% of cases). 50% of all extranodal NHL were localised (stage IE or IIE) and 27% had B symptoms. Site-specific features included a strong age-correlation for thyroid and testes lymphoma (greater than 50 years) and a high prevalence of female cases in thyroid and salivary glands lymphomas (M/F 0.14 and 0.30, respectively). Overall 7-year survival for extranodal NHL was 46% (median 4.9 years). Poor prognosis patients could be identified by the presence of one or more of the following presentation characteristics: age greater than 65 years, B symptoms, high-grade histology, disseminated disease, elevated s-IgA and hyperuricaemia. Relative risk values ranged from 2.1 for age and B symptoms to 1.7 for hyperuricaemia.

Adolescent

Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes.

Histamine release induced by Staphylococcus aureus was examined in cells obtained by bronchoalveolar lavage (BAL) in non-atopic individuals. Approximately half of the individuals responded with mediator release to the bacterium, and the release was found to be time- and concentration dependent. No difference was found between the patients who responded and those who did not respond in regard to age, sex, smoker/non-smoker, % recovery of BAL-fluid, total cell count, differential cell counts, histamine content per mast cell, or diagnoses. Also stimulation of the BAL-cells with the calcium-ionophore A23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria-induced mediator release from superficially lying cells in the airways epithelium might be of importance for the precipitation or exacerbation of bronchial asthma in respiratory tract infections.

Adult

Cytokine-induced histamine release from basophils of AIDS patients. Interaction between cytokines and specific IgE antibodies.

Basophil leukocytes obtained from AIDS patients, allergic patients and healthy controls were stimulated in vitro with interleukin 4, lymphotoxin, tumour necrosis factor alpha and interferon gamma to examine the histamine releasing effect. The cytokines caused histamine release from the basophils of approximately half the AIDS patients and from 8-17% of the allergic patients. No response was obtained in the control group. Removal of cell surface immunoglobulins abolished the response to cytokines, indicating an Ig-dependent mechanism. Passive sensitization with cell-derived Ig, with Ig deprived of IgE, or with IgG, indicated that cell-bound IgE was responsible for the cytokine-induced histamine release in AIDS patients. This response may be mediated by cytokine-selective IgE antibodies.

Acquired Immunodeficiency Syndrome

HIV antigen-induced release of histamine from basophils from HIV infected patients. Mechanism and relation to disease progression and immunodeficiency.

Basophil leukocytes from 39 HIV-infected patients with various degrees of immunodeficiency and disease progression were stimulated with an HIV antigen preparation. Cells from 19 of 22 patients with AIDS and all of six patients with milder degrees of HIV-related disease showed significant histamine release. In contrast, cells from 11 asymptomatic HIV-infected patients and 11 healthy control persons released no histamine. The histamine release induced by HIV antigen was found to be inversely correlated to the number of CD4 positive T lymphocytes. These results indicate that the histamine release was related to both the clinical stage of disease and the degree of immunodeficiency. Passive sensitization experiments showed that IgE, but not IgG, was responsible for the induction of histamine release, indicating the reaction to be type 1 allergic. The histamine release caused by HIV might be involved in the development of disease because of the immunomodulating properties of this mediator.

Acquired Immunodeficiency Syndrome

Surveillance alone versus radiotherapy after orchiectomy for clinical stage I nonseminomatous testicular cancer. Danish Testicular Cancer Study Group.

From December 1980 to January 1984, all patients with stage I nonseminomatous testicular cancer in Denmark entered a randomized trial comparing surveillance only with radiotherapy after orchiectomy. One hundred fifty patients were assessable for the final analysis. Relapse occurred in 23 patients in the surveillance group and in 11 patients in the radiotherapy group. Radiotherapy completely prevented retroperitoneal relapse; 14 retroperitoneal relapses occurred in the surveillance-only group. All relapsing patients in the surveillance-only group are without evidence of disease with a median observation time after chemotherapy of 67 months. Two of the patients with relapse in the radiotherapy group died with disease; the others are alive without evidence of disease, with a median observation time after relapse treatment of 72 months. In the surveillance group, four relapses occurred later than 2 years after orchiectomy; only one such late relapse occurred in the radiotherapy group. Four of the retroperitoneal relapses occurred without concomitant increase in the serum marker levels (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]). It is concluded that surveillance only should replace radiotherapy after orchiectomy as standard treatment for clinical stage I nonseminomatous testicular cancer. Improved methods for control of retroperitoneal relapses, especially of embryonal carcinomas, are needed.

Adolescent

Virus enhances IgE- and non-IgE-dependent histamine release induced by bacteria and other stimulators.

Histamine release from human basophil leukocytes was triggered by Staph. aureus, Salmonella enteritidis, non-haemolytic streptococci, or E. coli. Influenza A virus was found to enhance the mediator release and the effect was caused by synergism, since the virus did not induce release of histamine per se. This potentiating effect of the virus was seen both when the bacteria-induced histamine release was IgE-dependent (i.e. patient sensitized to the bacterium) and when the bacterium caused mediator release by a non-immunological mechanism independent of IgE (putative sugar-lectin mediated). Histamine release induced by anti-IgE and calcium ionophore or agarose-beads was also enhanced in the presence of the virus. These findings indicate that influenza A virus potentiates both IgE- and non-IgE-mediated histamine release induced by bacteria and other stimulators.

Bacterial Infections

Cytokine-induced release of histamine from basophil leukocytes from AIDS patients.

Cytokine-induced histamine release from basophil leukocytes was examined in cell suspension from AIDS patients and compared with healthy controls. Cells from approximately half of the AIDS patients, in contrast to none from the control group, showed histamine release after stimulation with interleukin-4 (IL-4), tumor necrosis factor alpha (TNF alpha), lymphotoxin (LT) and interferon gamma (IFN gamma). These cytokines seem to induce histamine release from cells from AIDS patients by interaction with the cell surface immunoglobulins, since removal of the immunoglobulins prior to the exposure of the cytokines completely abolished the response to the cytokines. IL-1 alpha, IL-1 beta, IL-3, colony stimulating factor (CSF) and granulocyte-macrophage-CSF (GM-CSF) caused significant histamine release from cells from a similar number of AIDS patients and controls.

Acquired Immunodeficiency Syndrome

Ciliary activity and pollution.

The mucociliary clearance is an important part of the nonspecific defense mechanism of the human airways. Coordinated beats of cilia in the nose, trachea, and bronchi propel the mucous layer toward the pharynx, and with it inhaled microorganisms and other particles captured in the mucus. Normal function of this system depends on the efficacy of the ciliary beating and the properties of mucus. Primary ciliary dyskinesia--a congenital respiratory disease characterized by ultrastructural defects and motility disturbances of cilia--has provided us with valuable information about the role the mucociliary function plays in the protection against harmful agents in the inhaled air. Secondary ciliary dyskinesia is described in inflammatory disorders of the respiratory tract, but also some components in air pollution results in malfunction of cilia, damage of ciliated epithelium, or alteration in the mucus. This review will focus on investigations found in the literature concerning the influence of pollutants on ciliary activity. The methods applied will be evaluated.

Air Pollution

Blood transfusion and prognosis in Dukes' B and C colorectal cancer.

To evaluate the prognostic influence of blood transfusion in cancer patients, transfusion data were reviewed on 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. Data on whole blood and packed red blood cell transfusions were recorded together with a number of clinical, pathological and histochemical characteristics. The endpoint used was death with cancer. All patients were followed for 2-7 years or until time of death. Univariate statistical methods revealed a highly significant trend towards worsened prognosis with increasing volume of transfusion blood. However, this effect was insignificant when multivariate statistical methods were employed: patients receiving whole blood or packed red blood cell transfusions did no worse than expected from their clinico-pathological characteristics. It is concluded that in this series the observed association between transfusion status and prognosis is adequately explained by a multivariate prognostic model including well-established prognostic factors.

Aged

Influenza A virus potentiates bacteria-induced histamine release. Examination of normal individuals and patients allergic to bacteria.

Influenza A virus was found to enhance basophil histamine release induced by Escherichia coli, Salmonella enteritidis, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus sanguis, but did not per se release histamine. This potentiating effect of the virus was seen both when the bacteria-induced mediator release was IgE-dependent (i.e. patient allergic to bacterium) and when the bacterium caused histamine release by a non-immunological mechanism independent of IgE (putative sugar-lectin mediated). Also histamine release induced by other immunological and non-immunological stimuli, such as anti-IgE, calcium ionophore or agarose beads was enhanced in the presence of the virus. The potentiating effect of the virus on bacteria-induced mediator release might be of importance for the conversion from latent to manifest asthma in upper respiratory tract infections.

Adult

Histopathological features in stage I non-seminomatous testicular germ cell tumours correlated to relapse. Danish Testicular Cancer Study Group.

156 patients with stage I non-seminomatous testicular germ cell tumour entered a countrywide randomized study comparing the effect of postoperative irradiation of retroperitoneal lymph nodes with surveillance only. A total of 150 patients were included in this investigation of factors associated with increased risk of relapse. Thirty-four patients (23 per cent) had a relapse, i.e. 11/67 (16 per cent) in the former and 23/83 (28 per cent) in the latter group. Histopathological studies of the orchidectomy specimens were performed in order to identify features associated with relapse. Pure embryonal carcinoma and vascular involvement were significantly associated with increased risk of relapse. Thus, the relapse rate in the observation group in patients with pure embryonal carcinomas was 50 per cent (5/10) and 36 per cent (19/53) in all patients with tumours with vascular involvement.

Choriocarcinoma

Phase III trial of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) versus cisplatin, etoposide, bleomycin and prednisone (CisEBP) for the treatment of advanced non-Hodgkin's lymphoma of high grade malignancy. The Danish Lymphoma Study Group.

The trial included 85 previously untreated patients (median age 61 years) with stage III or IV non-Hodgkin's lymphoma (NHL) of the subtypes centrocytic lymphoma, diffuse centroblastic lymphoma, immunocytoma, immunoblastic lymphoma, or unclassified lymphoma of high grade malignancy. The patients were randomized to 9 monthly treatment cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CisEBP (cisplatin, bleomycin, etoposide, prednisone). Patients who had failed to achieve even a partial response (PR) after the completion of 2 cycles were switched to the alternative regimen. Complete response (CR) on primary treatment was obtained in 70% (55-83%) of CHOP-treated patients and in 25% (13-41%) of CisEBP-treated patients (p = 0.0004). Secondary CHOP treatment produced CR in 7 (30%) of 24 patients and secondary CisEBP treatment led to CR in 2 (15%) of 14 patients. The median survival was 3.4 years in the CHOP arm and 2.6 years in the CisEBP arm (p = 0.78). Hematologic toxicity was mainly leukocytopenia and anemia in both treatment arms. Non-hematological toxicity was slight, and late toxicity was insignificant. Three treatment-related deaths were noted. We conclude that CHOP induces more remissions than CisEBP in advanced lymphomas of high grade malignancy.

Adult

[Prognosis in synchronous liver metastasis from colorectal cancer. A multicenter study of patients with cancer of the rectum and cancer of the rectosigmoid colon].

A prospective investigation of 188 patients with cancer of the rectum and rectosigmoid colon with synchronous liver metastases is described. The mean survival time for 183 patients who did not receive any treatment for the liver metastases was six months and only one survived for longer than 37 months. After extirpation of the primary tumour, the most significant prognostic factors were etrahepatic metastases, enlarged liver on account of metastases and more than three liver metastases. Serum basic phosphatases had the greatest significance among a series of laboratory tests. In the sub-groups with the best possible prognoses, the mean survival time was 12 months. 25% five-year survival has been described in the literature following resection of the liver in patients with a maximum of three metastases, no other metastases and age under 70 years. Provided this holds true, liver surgery will be a therapeutic possibility in at least 100 patients per annum in Denmark with synchronous liver metastases and 25 of these will be cured. This figure requires an improved programme for the diagnosis of synchronous liver metastases than at present and the same high frequency of extirpation of the primary colorectal cancer on a national basis which was achieved in the present material.

Aged