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B Jacobsson

Publications and source records attributed to B Jacobsson.

At least 37 records · Page 2Linked to original sources

[Genetic origin of malignant hematopoiesis well defined].

It is vital to determine which cell lines are affected in haematological malignancies, since such information is important to an understanding of the biology of neoplastic stem cells and their capacity to differentiate and mature. Parallel studies of cellular morphology and of chromosomal anomalies is an approach permitting determination of lineage specificity for different haematological neoplasms. Findings in current studies suggest that acute myeloid leukaemia and myelodysplastic disorders generally involve cells of myeloid lineage only, whereas myeloproliferative disorders may also involve lymphoid cell lines. Lymphoid malignancies such as non-Hodgkin's disease or acute lymphoid leukaemia usually involve lymphoid cell lines.

Chromosome Aberrations↗

Decrease in thymidylate kinase activity in peripheral blood mononuclear cells from HIV-infected individuals.

Nucleosides and nucleoside analogs are anabolised to their triphosphates by intracellular kinases. The anti-HIV analogue zidovudine (AZT) is phosphorylated by cytosolic thymidine kinase 1 (TK1), thymidylate kinase (dTMPK), and nucleoside diphosphate kinase. It is known that dTMPK is one of the rate-limiting steps in the activation of zidovudine. The activities of TK1, dTMPK, and deoxycytidine kinase (dCK) were determined in extracts of in vitro activated peripheral blood mononuclear cells from HIV-infected patients and healthy noninfected individuals. dTMPK activity was 10-fold lower and TK1 activity was five-fold lower in extracts from infected as compared to uninfected persons. Deoxycytidine kinase activities in the extracts from both groups were very similar. Differences in in vitro activation, as determined by flow cytometry, of the peripheral lymphocytes were not responsible for the decreased TK1 and dTMPK activities. A reduced level of intracellular azido-dideoxythymidinetriphosphate in activated mononuclear cells from HIV-infected patients was also observed. The low levels of TK1 and dTMPK in lymphocytes from HIV-infected patients may be related to the anergy phenomenon observed as a result of HIV infection. This effect should also be considered in the development of new anti-HIV drugs.

Cell Cycle↗

Pronounced anti-HIV-1 activity of foscarnet in patients without cytomegalovirus infection.

Combined therapy using reverse transcriptase (RT) and protease inhibitors is the current established treatment for HIV-1 infection. Foscarnet is an RT inhibitor that is a product analogue, in contrast to the widely used nucleoside analogues. In this study, the anti-HIV-1 effect of foscarnet, 50 mg three times per day administered intravenously for 4 weeks, was evaluated in 10 patients with minor or no symptoms. Serious adverse events developed in 2 patients, although most patients experienced some side effects. The levels of HIV-1 RNA decreased from a median value of 4.7 to 2.6 10log copies/ml. The effect was sustained through 4 weeks. One week after cessation of treatment, HIV-1 RNA levels increased to baseline. In contrast, no increase in the number of CD4+ cells was observed. The anti-HIV-1 effect was considered to be a direct effect on HIV-1 replication because no patient had concomitant cytomegalovirus (CMV) infection.

AIDS-Related Complex↗

Gain of chromosome 7 marks the progression from indolent to aggressive follicle centre lymphoma and is a common finding in patients with diffuse large B-cell lymphoma: a study by FISH.

Gain of chromosome 7 represents one of the most frequent cytogenetic findings in B-cell lymphomas with a follicular growth pattern. We used fluorescence in situ hybridization (FISH) and a probe specifying chromosome 7 on lymph node imprints and/or bone marrow (BM) and peripheral blood (PB) smears from six consecutive patients with follicle centre lymphomas (FCLs) grade I or II (low-grade lymphomas), four patients with FCLs grade III and 11 patients with diffuse large B-cell lymphomas (DLBCLs) (high-grade lymphomas). We found gains of chromosome 7 in 14/18 successfully analysed cases (i.e. 2/6 FCLs grade I-II, 3/3 FLCs grade III and in 9/9 DLBCLs) using lymph node imprints. Moreover, the FISH technique demonstrated gains of chromosome 7 in 1/4 BM and 0/4 PB samples from FCLs grade I-II, in 2/4 BM and 2/4 PB specimens from FCLs grade III and in 4/9 BM and 2/9 PB samples from the DLBCLs. In contrast, morphologically recognizable lymphoma cells were seen in only 1/4 BM and 0/4 PB samples from the FCLs grade III and in 1/11 BM and 1/11 PB samples from the DLBCLs. We conclude that: (i) gain of chromosome 7 marks the progression from indolent to aggressive FCL and would appear to be a common finding in patients with FCLs grade III and in DLBCLs, (ii) clonal lymphoid cells occur frequently in BM and PB in high-grade lymphomas, making traditional staging by cytomorphology uncertain, and (iii) using gains of chromosome 7 as a marker of lymphoma cells, FISH is a useful method to detect minimal residual disease in FCLs grade III and DLBCLs.

Adult↗

Evaluation of DMSA scintigraphy and urography in assessing both acute and permanent renal damage in children.

PURPOSE: To evaluate dimercaptosuccinic acid (DMSA) scintigraphy and urography in the detection of renal involvement in children with urinary tract infection (UTI) in order to identify patients with a high risk of developing renal damage. MATERIAL AND METHODS: A total of 157 children (median age 0.4 years, range 5 days to 5.8 years) with first-time symptomatic UTI were examined scintigraphy (with an assessment of renal area involvement) and urography at the time of UTI and 1 year later. All evaluations were made blindly. RESULTS: Of the total 314 kidneys, 80 (25%) were abnormal at initial scintigraphy. Of these 80 kidneys, 44 (55%) had normalized at follow-up. Of the 234 initially normal kidneys, 29 (12%) were abnormal at follow-up. One year after UTI, abnormalities were seen in 59 children at scintigraphy and in 18 children at urography. Renal area involvement was larger and split function abnormalities more common in kidneys that were abnormal at both scintigraphy and urography than in kidneys with only scintigraphic abnormalities. CONCLUSION: Quantitation of renal area involvement and split renal function at early scintigraphy would seem to be useful in identifying patients at risk of developing renal damage. Urography at 1 year after infection identified mainly those with the most severe scintigraphic abnormalities. The clinical importance of scintigraphic abnormalities that are not confirmed by urography is not known.

Acute Disease↗

Urodynamic pattern in infants with urinary tract infection.

PURPOSE: We studied the urodynamic pattern in infants with urinary tract infection and evaluated the influence of the infection. MATERIALS AND METHODS: Cystometry was combined with voiding cystourethrography (video cystometry) in 90 male and 68 female infants admitted to the hospital with first time urinary tract infection. Evaluation was performed 1 to 30 days (mean 11) and 32 to 78 days (mean 46) after diagnosis in 93 and 65 infants, respectively. RESULTS: Bladder instability was found in two-thirds of male and female infants. Compared to older children male infants had high voiding detrusor pressure and low bladder capacity (hypercontractility). Female infants also had increased voiding pressure levels but they were significantly lower than those in male infants. The voiding detrusor pressure was even higher in both sexes when evaluation was delayed after the infection. CONCLUSIONS: Infants with urinary tract infection have bladder instability and hypercontractility compared to older children. Bladder hypercontractility was less pronounced early after infection, suggesting that the infectious agents inhibit detrusor muscle contractility. Whether hypercontractility is a normal urodynamic pattern in infancy or represents bladder dysfunction can only be addressed by urodynamic studies of healthy infants.

Bacteriuria↗

Trisomy 12 and lymphoplasmacytoid lymphocytes in chronic leukemic B-cell disorders.

BACKGROUND AND OBJECTIVE: Although the finding of trisomy 12 in B-cell malignancies has been extensively documented especially in B-CLL, little is known about the clonal involvement of different tissues and there are few sequential studies documenting the development of trisomy 12 during the course of the disease. The aim of this study was, therefore, to: 1) ascertain the prevalence of trisomy 12 by FISH; 2) correlate the findings of trisomy 12 with hematologic and clinical features; 3) study the trisomy 12 positive clone during the course of the disease, and 4) compare findings of trisomy 12 in different tissues. DESIGN AND METHODS: This a study of an unselected population of 118 patients with CLL or other B-cell disorders in leukemic phase from a defined geographic area. Trisomy 12 was detected by FISH. RESULTS: Trisomy 12 was found in 18 patients (15%). The aberration was significantly more common in morphologically atypical CLL (aCLL) (24%) and CLL/PL (67%) compared to typical CLL (2%) (p < 0.001). aCLL cases had predominantly lymphocytes with lymphoplasmacytoid features. Sequential studies of peripheral blood showed an increase in the proportion of trisomic cells during the observation time, mostly associated with disease progression. None of the initially trisomy 12 negative patients acquired the aberration during follow-up. The percentage of lymphocytes exhibiting trisomy 12 was significantly (p < 0.05) higher in the bone marrow than in peripheral blood. INTERPRETATION AND CONCLUSIONS: Trisomy 12 might define a distinct disease entity with atypical lymphocytes in chronic leukemic B-cell disorders.

Aged↗

Coxarthrosis and farm work: a case-referent study.

The purpose of this case-referent study was to analyze the association between coxarthrosis and occupation. The study was performed in a Swedish agricultural county and comprised 269 cases of radiologically verified arthrosis of osteoarthritis (< 3 mm joint space) that were compared to 538 randomly selected controls in the same region, matched for age, sex, and place of residence. Farmers and agricultural workers showed an increased risk of coxarthrosis and the observed risk increased with increasing number of years of farming. Tractor driving and milking were associated with coxarthrosis, whereas no association with other types of machine work could be demonstrated. An association between coxarthrosis and heavy physical work before the age of 16 years was also observed. The results give only limited information on the external causes of coxarthrosis, however. More detailed studies of groups of individuals with coxarthrosis in order to obtain more information about contributing and underlying factors would therefore be valuable.

Adult↗

Cystatin C and transthyretin expression in normal and neoplastic tissues of the human brain and pituitary.

The localization of cystatin C (CC) and transthyretin (TTR) synthesis was studied using Northern blot and immunohistochemical methods. Normal brain tissues from all sites studied contained CC mRNA. Immunoreactive CC was present in the choroid plexus epithelial cells, cerebral and cerebellar neurons, astrocytes, ependymal cells, macrophage-like cells of the arachnoid membrane and in neuroendocrine cells of the anterior pituitary lobe. TTR mRNA and TTR were restricted to the choroid plexus. In primary brain tumors, the transcript for CC was found in all 39 tumors examined, while the protein could only be demonstrated in 3/5 choroid plexus papillomas, 8/8 astrocytomas, 7/23 anaplastic astrocytomas and glioblastomas, 1/6 oligodendrogliomas, 1/1 oligoastrocytoma, 1/4 anaplastic oligodendrogliomas, 3/7 ependymomas, 0/1 anaplastic ependymoma, 0/5 primitive neuroectodermal tumors, 0/1 neuroblastoma, 3/11 meningiomas and 16/16 pituitary adenomas. CC cannot be used as a marker for any specific brain tumor type but the fact that the protein could be demonstrated more frequently in astrocytomas than in their more malignant counterparts suggests that the cellular production and secretion of CC changes with the malignant progression of these tumors. TTR mRNA and TTR were present only in the choroid plexus papillomas, indicating that TTR synthesis is mainly restricted to such brain neoplasms.

Blotting, Northern↗

Differences in cell lineage involvement between MDS-AML and de novo AML studied by fluorescence in situ hybridization in combination with morphology.

We have employed fluorescence in situ hybridization (FISH) in combination with standard morphology (MGG/FISH) to identify the clonal involvement of different bone marrow cell lineages in 20 AML patients (14 MDS-AML, 6 de novo AML). Even though the number of cells belonging to the abnormal clone varied between individual cases, the percentage of clonal blasts was similar in MDS-AML and de novo AML patients. The erythropoietic cells appeared to be part of the abnormal clone in 13 of 14 patients with MDS-AML, but only in 1 of 6 with de novo AML. Similarly, clonal granulocytes were detected in 13 of 14 patients with MDS-AML, compared to 2 of 6 with de novo AML. Lymphocytes consistently displayed normal, diploid karyotype. The results suggest that it is possible to distinguish between MDS-AML and de novo AML by the use of MGG/FISH; in de novo AML the abnormal chromosomal clone is generally confined to the immature myeloid cells, while in MDS-AML mature granulocytes and erythroid cells are of clonal origin. It is, however, not possible to conclude that MDS-AML is a "multipotent" type of leukaemia, since it cannot be ruled out that the chromosomally aberrant erythroid cells and granulocytes represent surviving cells from the original MDS clone.

Adult↗

Imaging and compartmental classification of solid pelvic tumours in children.

Thirty-five children aged from 1 day to 16 years (median 5 years) with solid pelvic tumours were investigated with US, CT and MR. All three methods gave similar estimates of tumour size. For defining location of the tumours, the pelvis was divided into three midline compartments (anterior, middle and posterior) and a right and left lateral compartment. CT and MR were accurate and equally reliable in determining the tumour location, US was less accurate. Evaluation of confinement to organ of origin was uncertain, regardless of imaging modality. Tissue characteristics with CT and MR did not contribute to the differentiation of the various tumour types, and contrast medium enhancement did not improve the discrimination. Compartmental localization was equally well assessed by CT and MR and, together with sex, was found to correlate with the tumour type.

Adolescent↗

Renal damage one year after first urinary tract infection: role of dimercaptosuccinic acid scintigraphy.

OBJECTIVE: The aim of this study was to determine whether age, C-reactive protein (CRP), body temperature, or results of voiding cystourethrography at diagnosis of first-time symptomatic urinary tract infection could predict the risk of renal damage as evaluated by dimercaptosuccinic acid (DMSA) scintigraphy performed 1 year after the infection. DESIGN: The study included 157 children (median age, 0.4 year, range, 5 days to 5.8 years) with first-time symptomatic urinary tract infection. In children 1 year of age or older, a body temperature of 38.5 degrees C or higher was necessary for inclusion. CRP and body temperature were measured at the time of infection, and voiding cystourethrography was performed shortly thereafter. DMSA scintigraphy was performed 1 year later in all children. RESULTS: After 1 year, 59 (38%) of the 157 children had renal damage as evaluated by DMSA scintigraphy, and of these, 28 (47%) had reflux. There was a positive correlation between renal damage and CRP, body temperature, and reflux. Children with high levels of CRP, high fever, and dilating reflux had a risk of renal damage up to 10 times higher than children with normal or slightly elevated CRP levels, no or mild fever, and no reflux. CONCLUSION: CRP concentration and body temperature at the index infection, in combination with the results of voiding cystourethrography, are useful in classifying children at high and low risk of scintigraphic renal damage 1 year after urinary tract infection.

Age Factors↗

Fluorescence in situ hybridization in combination with morphology detects minimal residual disease in remission and heralds relapse in acute leukaemia.

Fluorescence in situ hybridization in combination with morphology (MGG/FISH) was used to detect minimal residual disease (MRD) in complete remission (CR) in 12 cases of acute leukaemia (six MDS-AML, five de novo AML, one pre-B ALL) with numerical chromosomal aberrations at diagnosis. Residual leukaemic cells could be detected in the remission bone marrows by MGG/FISH in five patients, whereas the other seven showed no abnormalities. All five patients with signs of MRD at CR relapsed in the bone marrow with 2-9 months, in contrast to two of seven with a normal finding by MGG/FISH at CR. In both these patients a second MGG/FISH analysis showed that a subpopulation of leukaemic blasts had reappeared, 4 and 5 months prior to the leukaemia becoming clinically overt. One patient suffered a CNS relapse, but without any evidence of bone marrow involvement. The remaining four patients with no evidence of MRD at CR were still in haematological remission at follow-up after 4, 11, 12 and 13 months, respectively. We conclude that MGG/FISH seems to be a clinically useful method to detect MRD in acute leukaemia and to predict relapses, particularly when repeat studies are performed during CR.

Adult↗

Development of the urodynamic pattern in infants with myelomeningocele.

OBJECTIVE: To study changes in the urodynamic pattern during the first year of life in patients with myelomeningocele (MMC) and to correlate these to deleterious effects on the upper urinary tract. PATIENTS: methods Thirty-four infants with MMC were investigated using cystometry, micturating cystourethrography and urography at 1, 4 and 10 months of age. RESULTS: Detrusor contractility was characterized by an increase in activity, with hyper-reflexia in 45% initially, increasing to 65% at the 4-month investigation. During the same period, the number of infants with areflexia decreased from 25% to 12%. Between 4 and 10 months, there were only minor changes in detrusor contractility. The number of patients with poorly compliant bladders also increased between the first and fourth month. The number of patients with elevated outlet resistance increased only slightly during the first year, from 32% of all infants at the initial investigation to 40% at the 10-month follow-up. Vesico-ureteric reflux was detected in 12 of the patients during the year, with five already diagnosed at the first investigation. Almost all refluxes were cured with clean intermittent catheterization, with additional pharmacological therapy in two patients; one patient required a vesicostomy. CONCLUSIONS: This study indicates that detrusor activity, and to some extent outlet resistance, change during the first year of life in infants with MMC. The changes were mainly increases in activity and occurred mostly between the first and fourth months of age. There was a strong correlation between the occurrence of reflux and poor compliance, hypercontractility and outlet obstruction.

Humans↗

Early 99mTc dimercaptosuccinic acid (DMSA) scintigraphy in symptomatic first-time urinary tract infection.

During a 2 year period, 175 children below 6 years of age (median 0.4 year) with non-obstructive symptomatic urinary tract infection were studied by 99mTc dimercaptosuccinic acid (DMSA) scintigraphy. DMSA scintigraphy was performed at a median of 10 days after the start of treatment and was abnormal in 73 children (42%), equivocal in 29 (16%) and normal in 73 (42%). Reflux was seen in 27% of all children and in 38% of the renal units that were abnormal at DMSA scintigraphy. A decreasing frequency of abnormalities at DMSA scintigraphy was seen within the first 14 days after the start of treatment. C-reactive protein and grade of reflux correlated significantly with abnormal DMSA studies. To demonstrate renal involvement in acute urinary tract infection, DMSA scintigraphy should be performed within days after the start of treatment. It is noteworthy that reflux was seen in less than half of renal units with abnormal DMSA scintigraphy.

Acute Disease↗

Classical morphology, esterase cytochemistry, and interphase cytogenetics of peripheral blood and bone marrow smears.

We used peripheral blood (PB) and bone marrow (BM) smears in the development of two methods based on cytomorphology and esterase cytochemistry in combination with fluorescence in situ hybridization (FISH). The first method involves photodocumentation of May-Grünewald-Giemsa (MGG)-stained cells, followed by destaining in methanol-acetic acid, fixation in paraformaldehyde, and digestion with protease and RNAse before FISH using alpha-satellite probes that specify chromosomes X, 7, 8, and 17. On average, two hybridization signals were seen in 94.5% of disomic BM cells. The hybridization sensitivity was found to vary, however, both among morphologically defined hematopoietic cell lineages and among differentation levels within a lineage. In the second method, an esterase staining technique was followed by the same treatment as for MGG-stained cells. The esterases and FISH signals could be simultaneously visualized and the method was found suitable for rapid screening of in situ signals in cytochemically defined granulocytes and lymphocytes but not in monocytes. The combined methods proved very useful in elucidating the clinical significance of chromosomal abnormalities seen in two cases of leukemia.

Blood Cells↗

Clonal cell lineage involvement in myelodysplastic syndromes studied by fluorescence in situ hybridization and morphology.

We have used DNA fluorescence in situ hybridization (FISH) in combination with morphology to study cell lineage involvement in peripheral blood and bone marrow smears from 15 patients with myelodysplastic syndromes (MDS) and known numerical chromosomal aberrations. Eleven cases were investigated at diagnosis of MDS, and four at transformation to acute myeloid leukemia (MDS-AML). Using conventional cytogenetics, monosomy 7 was detected in nine cases, monosomy 17 in two, and trisomy 8 in five, either as a single aberration or as part of a complex clone. One case had both monosomy 7 and 17. Three biotinylated DNA probes directed against the pericentromeric region of chromosomes 7, 8 and 17, respectively, were used. Bone marrow smears were first stained with May-Grünewald-Giemsa (MGG) for morphologic evaluation, and regions of interest documented by photography. Later the same regions were targeted after hybridization, which allowed FISH analysis of selected bone marrow cells. In each patient between 267 and 921 cells (mean 453) were studied. In most cases a majority of the non-lymphoid bone marrow cells appeared to be of clonal origin, ie showed either monosomy or trisomy by FISH, while in contrast both lymphocytes and plasma cells generally were disomic, ie displayed two fluorescent spots for each probe. The percentages of clonal bone marrow cells differed greatly between patients, but in a single case there was a good agreement between the extent of granulocytic, monocytic and erythrocytic cell lineage involvement. In relation to the clinical stage of MDS, patients with more advanced disease had a significantly higher mean percentage of bone marrow blasts showing monosomy or trisomy, while disomic, possibly non-clonal cells were more frequent among the earlier forms of MDS. In the four cases of MDS-AML nearly all non-lymphoid bone marrow cells belonged to the abnormal clone. The FISH technique offers information regarding the distribution of clonal and non-clonal bone marrow cells in MDS, which might have prognostic and possibly, therapeutic implications.

Acute Disease↗