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Biomedical subjects

B Pedersen

Publications and source records attributed to B Pedersen.

At least 19 recordsLinked to original sources
PubMed1999

Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities.

The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg) into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 15, 17, or 21, or into rat pups on postnatal day (P) 10. The principal findings were the following: (1) BrdU exposure on E11 produces profound effects on body morphology, and animals must be fed a special diet because of chronic tooth abnormalities; (2) BrdU exposure at E17 or earlier produces a change in coat spotting pattern, the precise pattern varying with age; (3) BrdU exposure on E15 or earlier produces a reduction in both brain and body weight; (4) BrdU exposure on E17 or earlier reduces cortical thickness; (5) BrdU exposure on E11-E13 and at P10 reduces cerebellar size relative to cerebral size; (6) spatial learning is significantly affected after injections of BrdU at E11-E17, but the largest effect is on E17; (7) the deficit in spatial learning may be related in part to a reduction in visual acuity; and (8) skilled forelimb ability is most disrupted after BrdU exposure at E15 but is also impaired after injections on E13 or earlier. BrdU thus has teratological effects on body, brain, and behavior that vary with the developmental age of the fetus or infant.

Abnormalities, Drug-Induced↗
PubMed1999

A single intramuscular injection with an adenovirus-expressing IL-12 protects BALB/c mice against Leishmania major infection, while treatment with an IL-4-expressing vector increases disease susceptibility in B10.D2 mice.

Experimental infection of the susceptible BALB/c (H-2d) mouse with the intracellular parasite Leishmania major induces a predominant Th2-type T cell response that eventually leads to death. In contrast, the resistant B10.D2 (H-2d) strain develops Th1 cells that control parasite replication and disease. In this study, we tested the ability of a recombinant adenovirus vector-expressing IL-12 to skew the immune response in a Th1 direction and prevent leishmaniasis in susceptible mice. We report that BALB/c mice treated with the Ad5IL-12 vector on the same day as parasitic challenge are significantly protected against leishmaniasis and acquired long-lasting immunity, because upon rechallenge with L. major parasites they were resistant to disease. The vector-derived IL-12 expression was transient and highly localized to the tissue after i.m. injection; it caused an increase in the number of Ag-specific IFN-gamma-secreting lymphocytes and enhanced NK cell activity in the draining popliteal node. In contrast, resistant B10.D2 mice given i.m. injections with a recombinant adenovirus-expressing IL-4 displayed greater susceptibility to disease, and severe lesions were produced in some of the infected animals. These results suggest the potential use of recombinant adenoviruses expressing cytokines as potent immunomodulatory agents for the generation of protective immune responses against intracellular pathogens.

Adenoviridae↗
PubMed1998

[Multidisciplinary diagnostics in acute leukemia].

Establishing the exact diagnosis of patients suspected for acute leukemia is of paramount importance not only for instituting first-line treatment, but also for prognosticating the patient and determining the status of disease, e.g. in relation to minimal residual disease. In this overview the most recent developments regarding the methods for leukaemia diagnosis (cytology, histology, immunology, cytogenetics and molecular biology) are described and their respective merits and drawbacks are discussed. Special emphasis is given to the temporal relationship for application of the methods in the course of disease in these patients.

Bone Marrow Examination↗
PubMed1998

Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia.

We have developed a multiplex reverse transcription-polymerase chain reaction (RT-PCR) reaction, which enables us to detect 29 translocations/chromosomal aberrations in patients with acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Through the construction and optimization of specific primers for each translocation, we have been able to reduce the set-up to 8 parallel multiplex PCR reactions, thus greatly decreasing the amount of work and reagents. We show the value of our set-up in a retrospective analysis on cryopreserved material from 102 AML and 62 ALL patients. The multiplex RT-PCR detected a hybrid mRNA resulting from a structural chromosomal aberration in 45 of 102 (44%) of the AML and in 28 of 62 (45%) of the pediatric ALL cases. Importantly, in 33% of AML and in 47% of the ALL cases with cytogenetic data, submicroscopic chromosomal aberrations or masked translocations were shown that were not detected in the cytogenetic analysis either for structural reasons or because of an insufficient number of metaphases obtained. This multiplex RT-PCR system, which can handle up to 10 patients with a response time of 2 working days, is thus an important tool that complements cytogenetic analysis in the up-front screening of acute leukemia patients and should provide a rapid and efficient characterization of leukemia cells, even in situations with sparse patient material.

Acute Disease↗
PubMed1998

Trisomy 10 survival: a literature review and presentation of seven new cases.

Trisomy 10 as the only chromosome aberration is a rare phenomenon in malignant and premalignant hemopoietic disorders. We describe 7 new cases and have found another 12 in the literature. It appears that, whereas adult patients have myeloid disorders (acute myeloid leukemia, myeloproliferative, or myelodysplastic syndromes), in children the diagnosis is lymphocytic leukemia or lymphoma. The median survival was 122 months in the total material. Age above 60 years proved to be a significant adverse factor (median survival only 5 months; p = 0.003). None of the other clinical, cytogenetic, or hematological variables were of demonstrable prognostic importance. In contrast with the larger trisomy 10 clones, those of limited size were associated with nonleukemic diagnoses, normal or slightly elevated leukocyte counts, and few or no circulating blasts. This may suggest that expansion of the trisomy 10 clone is associated with clinical and hematological progression.

Adult↗
PubMed1998

Blood eosinophil and monocyte counts are related to smoking and lung function.

The aim of this study was to investigate the predictive value of peripheral eosinophil and monocyte blood counts regarding lung function in smokers and non-smokers, and to investigate the influence of smoking on these cell counts. Forced expiratory volume in 1 s (FEV1) measurements and blood samples were collected from 298 non-atopic smokers and 136 never-smokers. Blood samples were repeated in 160 smokers after cessation of smoking (quitters) and 30 continuing smokers, 2, 6, 12 and 26 weeks after smoking cessation. Monocyte (P < 0.05) but not eosinophil blood counts were higher in never-smokers compared to smokers. In never-smokers, blood eosinophil counts and monocyte counts correlated inversely (P < 0.05) and directly (P < 0.01), respectively, with standardized FEV1 residuals (FEVR). In smokers, blood eosinophil (P < 0.05) and monocyte (P < 0.05) counts correlated directly with FEVR independent of smoking history. After smoking cessation, monocyte blood counts (P < 0.05) increased. Both eosinophil and monocyte blood counts showed a greater increase in quitters with decreased lung function (P < 0.05). Former heavy smokers had higher blood eosinophil (P < 0.05) but lower monocyte (P < 0.05) count increase than had former light smokers. These data suggest that smoking influences eosinophil and monocyte blood counts and that this is associated with a small negative effect on lung function. Eosinophil blood counts had an opposite relation to lung function in smokers and non-smokers. Further research should include investigations of relations between smoking and stimulatory factors for recruitment and activity of eosinophils and monocytes.

Adult↗
PubMed1998

Is the expression of classical HLA class I antigens on trophoblast of importance for human pregnancy?

PROBLEM: Human leukocyte antigen (HLA)-C and possibly also HLA-B seem to be expressed on the extravillous trophoblast. These antigens carry epitopes that function as ligands for natural killer (NK)-cell-inhibitory receptors. Antitrophoblast cytotoxicity mediated by decidual NK cells might be involved in miscarriage. We thus found it relevant to elucidate whether parental HLA-C and -Bw polymorphism play a role in recurrent miscarriage (RM). METHOD OF STUDY: HLA-C and -Bw investigations by DNA-based techniques were undertaken in 35 couples with unexplained RM and in 30 couples with normal fecundity. The number of HLA-C- and -Bw-related supertypic specificities that can bind NK-cell-inhibitory receptors was evaluated in selected couples. RESULTS: The proportions of couples with RM and control couples carrying four HLA-C alleles with the same NK-cell-inhibitory supertypic specificities were equal. In 46% of studied couples with RM, all four HLA-B alleles carried the HLA-Bw6 supertypic specificity, which was significantly higher than the corresponding frequency (17%) in the control couples (P < 0.02). CONCLUSIONS: The expression of polymorphic HLA-C on trophoblasts does not seem to play a role in RM. Assuming that HLA-B is expressed on trophoblasts, we may suggest that the revealed predominance of HLA-Bw6 expression (which excludes the presence of HLA-Bw4-protective antigens) may predispose a particular couple to the RM phenomenon.

Abortion, Habitual↗
PubMed1998

5q(-)survival: importance of gender and deleted 5q bands and survival analysis based on 324 published cases.

Survival of 5q(-)patients is known to depend on patient age, diagnosis, and acquisition of additional chromosome aberrations. The possible importance of the deleted 5q bands is unknown; nor is it known if the same or different factors are of prognostic importance in 5q(-)MDS and 5q(-)AML. In order to obtain material of sufficient size to answer these and other questions the literature was searched for 5q(-)cases with data on survival. Only MDS and AML cases with interstitial deletions were included. The results confirmed the prognostic importance of the factors mentioned above, but produced the following new data: In MDS, but not in AML, loss of the band 5q12 is an independent adverse prognostic factor; female patients survive longer in MDS while in AML men are the longer survivors; del(5)(q13q31) was found to be associated with MDS, 5q(-)as the sole aberration, and a long survival; on the other hand many del(5)(q12q32) cases showed AML, presence of additional aberrations, and short survivals. On the basis of these results the following hypotheses are proposed: 1) the female preponderance in 5q(-)MDS is due to longer female survival, and not to increased female incidence, and 2) some 5q deletions have a high diagnostic specificity, affect the rate of development of additional chromosome aberrations and thus in fact are major prognostic factors.

Chromosomes, Human, Pair 5↗
PubMed1998

Combination laser conization as treatment of microinvasive carcinoma of the uterine cervix.

During the period June 1985 to August 1992 combination laser conization was considered definite therapy in 41 patients with microinvasive carcinoma of the cervix. Selection criteria for conservative, fertility-saving therapy were: invasion 3 mm or less, no lymphovascular involvement and horizontal spread of 7 mm or less. After treatment patients were followed for 5 to 12 years, mean follow-up 81 months, and mean number of examination was 10. In one cases, adenocarcinoma in situ was diagnosed during follow-up. In all other cases persistent or recurrent disease was not diagnosed during follow-up. By thorough histopathologic evaluation and strict criteria for selection of patients, it was possible to perform conservative treatment with no observed risk of undertreatment. Combination laser conization was a useful treatment modality. A follow-up regimen based on colposcopy and cytology proved sufficient.

Adolescent↗
PubMed1997

MDS and AML with trisomy 8 as the sole chromosome aberration show different sex ratios and prognostic profiles: a study of 115 published cases.

A number of chromosome aberrations occur nonrandomly as the sole aberration in malignant and premalignant hematological disorders. They imply very different prognoses. For most of them the survival consequences have been established. For trisomy 8, which is the most frequent numerical aberration in myeloid disorders, the prognostic implications have not been investigated. In order to clarify survival in patients with trisomy 8 as the sole aberration, the literature was searched for such cases. In 115 patients survival data were available. In 103 (89.6%), a myeloid disorder had been diagnosed. Acute myeloid leukemia (AML) or a myelodysplastic syndrome (MDS) occurred in 100 cases (87.0%). The median survival was found to be 17.1 months. On multivariate survival analysis (Cox), age above 60 and a leukemic diagnosis were found to be independent adverse prognostic indicators. MDS patients survived significantly longer (median 21 months) than AML patients (median 15 months). In MDS age and in AML the trisomy 8 clonal size was an independent prognostic factor. An unexpected observation was a clear male preponderance in trisomy 8 MDS (about two-thirds of cases). In trisomy 8 AML an approximate 1:1 ratio was found. Browsing of Mitelman's catalog confirmed these ratios.

Adolescent↗
PubMed1997

The monosomy 7 clone in interphase and metaphase cell population: a combined chromosome and primed in situ labeling study.

Loss of a chromosome 7 is associated with a poor prognosis in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Some studies have shown higher frequencies of monosomy 7 (-7) in dividing than nondividing myeloid cells, which might indicate that -7 confers a proliferative advantage on the host cell. As other groups have not been able to confirm this, we compared the -7 frequencies in bone marrow metaphases as studied with conventional cytogenetics and in interphase cells using primed in situ (PRINS) labeling. We found significantly higher -7 frequencies in metaphase than in interphase cells irrespective of diagnosis and presence or absence of additional chromosome aberrations. Further, we found a significant correlation between the -7 percentages in resting and dividing cells. Finally, as our material showed a clear male preponderance, Mitelman's Catalog of Chromosome Aberrations in Cancer was searched for -7. Of 815 cases with AML or MDS, 491 (60.3%) were found to be men. To our knowledge, this is the first observation of a clear deviation from the 1:1 sex ratio in -7 patients.

Acute Disease↗
PubMed1997

Graphical interpretation of analytical data from comparison of a field method with reference method by use of difference plots.

Various viewpoints have been offered regarding the appropriate use of scatter plots or difference plots (bias plots or residual plots) in comparing analytical methods. In many of these discussions it seems the basic concepts of identity (within inherent imprecision) and acceptability based on analytical goals (analytical quality specifications) have been forgotten. With the increasing number of Reference Methods in laboratory medicine, these basic concepts are becoming more important in validation of field methods. Here we describe a simple and effective graphical test of these hypotheses (identity and acceptability) by use of difference plots. These plots display the underlying hypothesis before the measured differences are plotted and allow interpretation of the results according to specific criteria. We further describe simple but effective interpretations of the data, when the hypothesis is not fulfilled, by using two data sets drawn from comparisons of field methods for S-creatinine with a Reference Method for this analyte. The difference plot is a graphical tool with related simple statistics for comparison of a field method with a Reference Method, focusing on (a) identity within the inherent analytical imprecision or (b) acceptability within analytical quality specifications. Calculation of the standard deviation of the differences is an indispensable tool for evaluation of aberrant-sample bias (matrix effects).

Chemistry, Clinical↗
PubMed1996

[MR-scanning in complex partial epilepsy].

In a prospective investigation concerning 50 consecutive patients suffering from complex partial epilepsy who all had a normal CT investigation pathological findings were recognized in 80% using MRI. The MRI examination included volume estimation of the hippocampus. The volume estimations were compared to a reference material. In 24% a focal pathology was recognized, that was suspected of being responsible for the epileptic condition. Only 20% of the examinations were evaluated as normal. Hippocampal atrophy was recognized in 50%. In the latter group a diagnosis of hippocampal sclerosis was established in 16%. It is concluded that MRI is the investigation of choice in complex partial epilepsy and that volume estimation of the hippocampus is important.

Epilepsies, Partial↗
PubMed1996

The blood group ABO gene transcript is down-regulated in human bladder tumors and growth-stimulated urothelial cell lines.

The molecular mechanism that in human bladder tumors leads to the loss of blood group ABO glycosyltransferase activity and, thereby, the loss of ABO antigens was investigated. In 15 tumors and 3 normal biopsies from blood group AB individuals and 7 tumors and 3 normal biopsies from blood group O individuals, mRNA was detected by a reverse transcription PCR (RT-PCR) assay, and the ABO blood group structure was determined by immunohistology. The RT-PCR spanned several introns in the ABO gene to exclude DNA contamination, and the RT-PCR product was shown to reflect the ABO gene message by dideoxy sequencing. The ABO mRNA was present in normal urothelium and low-grade tumors but disappeared from high grade tumors. This correlation to tumor grade was significant (P<0.04). Immunohistochemistry with monoclonal anti-blood group antibodies showed a complete correlation between the presence of mRNA and the presence of AB carbohydrate structures on cell surfaces. In two urothelial cell lines, genotyped as A/- and A/A, growth stimulation with the cholera toxin B subunit led to a total loss of ABO mRNA, and epidermal growth factor stimulation had an identical effect on one of the cell lines. We conclude that the ABO glycosylation in normal and malignant urothelium is regulated at the mRNA level, and that a mechanism associated with cell proliferation may trigger down-regulation of ABO mRNA.

ABO Blood-Group System↗
PubMed1996

WHO-sponsored international collaborative study to evaluate methods for subtyping Listeria monocytogenes: restriction fragment length polymorphism (RFLP) analysis using ribotyping and Southern hybridization with two probes derived from L. monocytogenes chromosome.

Seven laboratories participated in a WHO-sponsored international collaborative study, to evaluate methods for subtyping Listeria monocytogenes, by performing restriction fragment length polymorph sm (RFLP) analysis-based subtyping of an international study set of 80 strains of L. monocytogenes that included 22 epidemiologically related groups. The RFLP analysis was done by Southern hybridization with one of two types of probes found in multiple copies on the chromosome of L. monocytogenes. Six laboratories performed ribotyping. These laboratories used EcoRI enzyme to restrict the L. monocytogenes DNA and ribosomal RNA or DNA as the probe for Southern hybridizations. The seventh laboratory used Ncil to restrict the DNA, and two probes, one randomly cloned and the other containing repeat sequences cloned from L. monocytogenes DNA. The overall discriminating power of ribotyping, as estimated by calculation of Simpson's index of diversity, ranged from 0.83 to 0.88 for the six laboratories. The discriminating power of the combination of two probes used by Laboratory 7 was 0.91. Ribotyping and the cloned probes used by Laboratory 7 discriminated poorly between serotype 4b strains. Neither method identified three atypical strains (identified by other subtyping methods) included in three apparently epidemiologically related groups. Ribotyping did not discriminate between strains of serotypes 4b and 4b(X) in one epidemiologically related group of strains; one cloned probe used by Laboratory 7 discriminated between these strains. Intra-laboratory reproducibilities for the seven laboratories ranged from 80.0 to 100%. as determined by their abilities to correctly identify 11 pairs of duplicate strains included in the study set. Inter-laboratory reproducibilities were generally very good considering that no attempt was made to standardize protocols used by the participants.

Bacterial Typing Techniques↗