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Biomedical subjects

J Tollemar

Publications and source records attributed to J Tollemar.

At least 73 records · Page 4Linked to original sources

Candida albicans: mannan and protein activation of cells from various human lymphoid organs.

Challenging human lymphocytes with soluble cytoplasmic Candida albicans protein antigen (CP) and cell-wall-derived C. albicans mannan (CM) induced DNA synthesis and antibody secretion measured as plaque-forming cells (PFC) in an indirect haemolytic assay. Enriched T and B lymphocytes responded poorly to CP and CM. However, when adherent cells were added, T and B cells responded well to CM, but not to CP. Peripheral blood lymphocytes responded more strongly to CP than to CM, with peak stimulation on day 7. Bone marrow cells displayed similar DNA synthetic responses as blood lymphocytes, but peak stimulation occurred on days 4 and 5 for CP and CM, respectively. Cells from the various parenchymal organs, including adenoid, tonsil, and spleen, showed peak DNA synthesis ranging from days 3 to 5 with a tendency for CM to produce an earlier response than CP. In contrast to that observed in blood and bone marrow cells, CM induced a higher DNA synthesis in cells from parenchymal organs than CP, which gave low stimulations. PFC, like DNA synthesis, in blood and bone marrow cells responded best to CP, whereas spleen cells showed the highest response to CM. In blood and bone marrow cells, only IgG PFC were induced, but in spleen cells IgA and IgM PFC were also stimulated by CM. Fetal liver cells responded poorly to these two Candida preparations. CM but not CP stimulated DNA synthesis in umbilical cord blood lymphocytes and IgG, IgA, and IgM in spleen cells, suggesting that CM is a polyclonal activator and that CP acts as an antigen.

Antibodies, Fungal↗

Tissue culture of human fetal pancreas. Effects of nicotinamide on insulin production and formation of isletlike cell clusters.

Human fetal pancreas (HFP) is a potential source of beta-cells for transplantation to insulin-dependent diabetic patients. We have previously described a method for tissue culture of HFP that results in the in vitro development of isletlike cell clusters (ICCs) containing a minority of insulin-positive cells. Recently we found that nicotinamide, an inhibitor of poly(ADP-ribose) synthetase, induces an increased islet cell DNA replication both in vivo and in vitro. In this study, this culture technique was used to evaluate the effects of addition of 10 mM nicotinamide on HFP explants cultured in RPMI-1640 medium plus 10% human serum. ICCs developed in 11 of 19 consecutive cultures with nicotinamide increased the yield of ICCs by 40%. Also, the insulin content of ICCs increased approximately 50% with nicotinamide supplementation, although measurements of DNA indicated an unchanged number of cells in each ICC. Neither the rates of insulin release in response to 16.7 mM glucose plus 5 mM theophylline nor the (pro)insulin or total protein biosynthesis rates were affected by nicotinamide addition. The combined results of this study suggest that nicotinamide is useful for stimulating the formation of ICCs from HFP.

Culture Techniques↗

Surveillance tests for the diagnosis of invasive fungal infections in bone marrow transplant recipients.

A system for serial surveillance cultures and serological tests for diagnosis of disseminated fungal infections (FI) was evaluated retrospectively in 14 bone marrow transplantation (BMT) patients with autopsy proven FI (11 with Candida albicans and 3 with Aspergillus fumigatus) and 14 control BMT patients without FI. The 2 groups did not differ with regard to clinical features. Serial cultures for candida from various sites were more often positive in the FI group than in the controls (p less than 0.001). Consistently negative cultures were never seen in the FI patients (p less than 0.05). Positive conventional blood cultures or cultures of specimens from bronchoscopy were suggestive of FI before death in 6/14 of the patients with FI. No blood cultures were positive among the controls. Sequential serum samples taken before death in 7 patients with systemic candidiasis, 3 with invasive aspergillosis, and 12 control patients, were tested retrospectively for diagnostic candida and aspergillus antibody titers and free circulating candida mannan. The serological tests gave evidence of FI in 9/10 patients with FI and in half of the controls (p less than 0.05). In 8/10 cases with FI, serological tests became positive before a positive blood culture or a clinical suspicion of FI. With a prevalence of 7.5% of FI at our clinic, the predictive values for positive and negative was 100% and 97% for the antigenemia test and 14% and 100% for the ELISA test for IgA antibody against C. albicans mannan. Our data suggest that a rational use of surveillance cultures and serological tests may aid in an earlier diagnosis of FI in BMT patients.

Adolescent↗

Fiberoptic bronchoscopy for diagnosis of opportunistic pulmonary infections after bone marrow transplantation.

As a part of the diagnostic procedure for 16 suspected pulmonary infections in 15 marrow transplant recipients fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBB) and brushing were performed. Cytomegalovirus (CMV) was the most common microorganism and CMV pneumonia was diagnosed in 8/16 (50%) episodes of pulmonary disease studied. Pneumonias were diagnosed as caused by Candida or Aspergillus species in 6 episodes and by gram-positive cocci in 2 cases. Adenovirus and Pneumocystis carinii was also isolated in 1 patient each. Three noninfectious diseases (pulmonary oedema, idiopathic pneumonia and pulmonary embolism) were diagnosed by methods other than bronchoscopy. The use of fiberoptic bronchoscopy with BAL and TBB allowed correct identification of 14/18 microorganisms involved. Brushing was less useful. Four patients' pneumonias had a multiple etiology. The bronchoscopy methods used were well tolerated even by patients whose condition was poor.

Adult↗

Variables predicting deep fungal infections in bone marrow transplant recipients.

Deep fungal infections (FI) were diagnosed in 27 out of 209 consecutive bone marrow transplantation (BMT) recipients. Autopsy verified that the incidence of deep FI was 10% and the overall incidence was 13%. Using bivariate logistic regression analysis at the time of BMT, high recipient age (p = 0.003), low bone marrow cell dose (p = 0.007), recipient cytomegalovirus (CMV) seropositivity (p = 0.009) and splenectomy (p = 0.03) were significant risk factors for deep FI. In multivariate analysis, splenectomy (p = 0.008), recipient CMV seropositivity (p = 0.01) and low bone marrow cell dose (p = 0.01) held as significant. At 30 days post-BMT anti-thymocyte globulin treatment (p = 0.0006) and graft-versus-host disease grade II-IV (p = 0.005) were significant risk variables in bivariate logistic regression analysis and Fisher's exact probability test. Patients with these risk factors are candidates for treatment with antifungal drugs when they suffer from leukopenia and unclear fever.

Adolescent↗

Pretransplant herpesvirus serology and acute graft-versus-host disease.

Logistic regression was used to analyze the influence of pretransplant herpesvirus antibodies, in both patients and donors, on the development of acute graft-versus-host disease in 111 consecutive HLA-identical bone marrow recipients. In bivariate analysis, recipient seropositivity for cytomegalovirus (P = 0.01), donor seropositivity for herpes simplex virus (P = 0.02), and low bone marrow cell dosage (P less than 0.05) were associated with a high incidence of grade II-IV acute GVHD. In multivariate analysis the P values were P less than 0.05 for a positive recipient CMV serology and P = 0.07 for a positive donor HSV serology. Positive serology for 1-2 herpes-viruses among recipients or donors both resulted in a 12% incidence of grade II-IV acute GVHD. Positive serology for 3-4 herpesviruses among patients or donors resulted in an incidence of 32% and 38% of acute GVHD, respectively (P less than 0.05). It is concluded that recipient and donor pretransplant herpesvirus immunity can be used to calculate the risk of moderate-to-severe acute GVHD.

Acute Disease↗

An increased risk of relapse in cyclosporin-treated compared with methotrexate-treated patients: long-term follow-up of a randomized trial.

Patients with haematological malignancies and HLA-identical marrow donors were randomized to treatment with cyclosporin A (CSA, n = 30) or methotrexate (MTX, n = 29) with a follow-up ranging from 32 to 70 months. The two groups were comparable regarding disease status and age. Acute graft-versus-host disease (GVHD) was similar and the cumulative incidences of chronic GVHD was 42% in both groups. The overall incidence of cytomegalovirus (CMV) infection and other late infections were also the same in the two groups. Interstitial CMV pneumonitis occurred in 13% in the CSA group compared with 32% in the MTX group (ns). The probability of relapse was 42% after 4 years among the CSA patients and was significantly higher than the probability of relapse in the MTX patients which was found to be 10% (p = 0.03). The actuarial survival after 5 years was 53% for the CSA patients and 57% for the MTX patients (ns). The relapse-free survival was 41% and 59%, respectively (ns). There were no differences between the two groups in terms of renal or hepatic function, incidence of cataracts, blood cell counts, bone marrow cellularity or Karnofsky scores at 2 and 4 years after transplantation.

Adolescent↗

Allogeneic bone marrow transplantation for leukemia: factors of importance for long-term survival and relapse.

From 1977 until June 1987, 139 patients with leukemia underwent allogeneic bone marrow transplantation at Huddinge Hospital. Among recipients of HLA identical bone marrow the survival plateau for 30 patients with acute myeloid leukemia in first remission was 71% from 3 to 7 years. Children (n = 11) had a survival of 100% compared with 52% (n = 19) in adults (p = 0.01). Among patients with acute lymphoblastic leukemia in first remission (n = 15) the actuarial 5-year survival was 73% compared with 31% for those (n = 25) in second to fourth remissions. The probability of relapse in these two groups was 9% and 45% respectively (p less than 0.05). Patients with chronic myeloid leukemia in first chronic phase (n = 27) had a survival plateau from 1 to 6 years of 65%. In Cox's multivariate regression analysis, improved survival was associated with grade 0-I acute graft-versus-host disease (GVHD) (p less than 0.0001), HLA-matched siblings (p less than 0.001), recipient age less than 17 years (p = 0.02), first remission and first chronic phase (p = 0.03), cytomegalovirus (CMV) seronegative recipients (p = 0.04) and absence of symptomatic CMV infection (p = 0.04). A decreased risk of relapse was seen in patients with first remission or first chronic phase (p less than 0.001) and in patients with asymptomatic CMV infection (p = 0.03). In multivariate analysis the p values were 0.002 and 0.09 for these two groups respectively. In these patients acute GVHD was the major obstacle to successful outcome.

Adolescent↗

Polyclonal antibody secretion during acute graft-versus-host disease.

Spontaneous plaque-forming cells (S-PFC) were followed in 67 bone marrow transplantation (BMT) recipients and 41 controls. Patients with no acute graft-versus-host disease (GVHD) had decreased IgA and IgM S-PFC up to 7 weeks after BMT compared with controls. Patients with acute GVHD had increased IgG, IgA, and IgM PFC compared with controls and patients without GVHD during the first 4 weeks after BMT. The maximum number of S-PFC increased with increasing severity of acute GVHD. However, at diagnosis of GVHD there was no difference in S-PFC in patients who resolved their GVHD or in those who developed more severe GVHD. After 6 weeks, patients with acute GVHD had significantly decreased IgA and IgM S-PFC compared with normal. No major changes in S-PFC were induced during various infections. However, a patient who developed urticaria had a dramatic increase in S-PFC. Patients studied more than a year after BMT had reduced IgM S-PFC compared with controls. It is concluded that S-PFC are reduced after BMT, but markedly enhanced during acute GVHD.

Acute Disease↗