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Biomedical subjects

B Jacobsson

Publications and source records attributed to B Jacobsson.

At least 19 recordsLinked to original sources
PubMed2001

Deoxynucleoside anabolic enzyme levels in acute myelocytic leukemia and chronic lymphocytic leukemia cells.

The deoxynucleoside kinase reaction is often rate-limiting in the anabolism of pharmacologically active anti-cancer nucleosides. The levels of thymidine kinase (TK), deoxycytidine kinase, deoxyguanosine kinase (dGK), and thymidylate kinase were determined in leukocyte extracts from patients with chronic lymphocytic leukemia (CLL) and acute myelocytic leukemia (AML). The extracts from AML patients showed significantly higher TK activity than the ones from CLL patients. There were no differences in the levels of the other three kinases. In the case of dGK, the determinations were carried out with both an immunoblotting assay and selective enzyme activity measurements.

Blotting, Western↗
PubMed2001

Masked monosomy 7 in myelodysplastic syndromes is uncommon and of undetermined clinical significance.

Masked monosomy 7, i.e. detected by FISH but not by conventional cytogenetics, has been reported in varying frequency in MDS. To establish the prevalence and possible clinical significance of the aberration, we studied the 123 previously karyotyped MDS patients using FISH and a DNA probe specific for chromosome 7. Metaphase cytogenetics revealed ten patients (8%) with monosomy 7 (6 RAEB and 4 RAEB-t). FISH confirmed this result and detected four more cases (4%) with masked monosomy 7 (3 RA and 1 RARS). Thus, masked monosomy 7 is less common than has been suggested, and does not seem to carry the same prognostic weight as monosomy 7 diagnosed by metaphase cytogenetics.

Adult↗
PubMed2001

Association between urinary tract infection, renal damage and birth size.

UNLABELLED: The aim of this study was to investigate whether birth size is associated with permanent renal damage in children with urinary tract infection (UTI). A cohort of 1221 children under 16 y of age was diagnosed with their first symptomatic UTI between 1970 and 1979. Of these, 74 had urographic renal scarring in childhood and 57 were re-examined as adults. The birth files of 48 of these patients (35F, 13M) were available, and birthweight and birthlength in relation to gestational age were analysed and compared with a Swedish reference population. Children who had renal damage without vesicoureteric reflux were significantly smaller at birth (median weight, -0.76 SDS) compared with both children who had renal damage and reflux (median weight, -0.01 SDS) and the reference population. CONCLUSION: The demonstration of low birthweight among children with UTI and renal damage but no reflux suggests that low birthweight may be a risk factor for the development of renal damage.

Adolescent↗
PubMed2000

Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. Within MDS, 5q- syndrome constitutes a distinct clinical entity characterized by an isolated deletion of the long arm of chromosome 5 (5q-), a relatively good prognosis, and infrequent transformation to acute leukemia. The cell of origin in 5q- syndrome as well as in other 5q-deleted MDS patients has not been established, but evidence for involvement of multiple myeloid (but not lymphoid) lineages has suggested that a myeloid-restricted progenitor rather than a pluripotent (lympho-myeloid) stem cell might be the primary target in most patients. Although in 9 patients no evidence of peripheral blood T-cell and only 1 case of B-cell involvement was found, the data herein support that 5q deletions occur in hematopoietic stem cells (HSCs) with a combined lympho-myeloid potential. First, in all investigated patients a minimum of 94% of cells in the minor CD34(+)CD38(-) HSC compartment were 5q deleted as determined by fluorescence in situ hybridization. Second, in 3 of 5 patients 5q aberrations were detected in a large fraction (25% to 90%) of purified CD34(+)CD19(+) pro-B cells. Furthermore, extensive functional characterization with regard to responsiveness to early-acting cytokines, long-term culture-initiating cells, and nonobese diabetic/severe combined immunodeficiency repopulating cells supported that MDS HSCs in 5q-deleted patients are CD34(+)CD38(-), but inefficient at reconstituting hematopoiesis.

Antigens, CD34↗
PubMed2000

Detection of urographic scars in girls with pyelonephritis followed for 13-38 years.

We report the detection and progression of renal scars in girls prospectively followed from their first recognized urinary tract infection. There were 107 infection-prone subjects with a median age of 7.1 years at the first and 21.7 years at the last urography. Of 51 females who ultimately had lesions, 38 had established scars at the first urography. In 18 subjects, new scars were found in previously undamaged kidneys, 5 already with unilateral scarring. There had been a normal urography after the 5th birthday in 8 of those with later scarring. Worsening of scarring was seen in 10 of the 38 subjects with established scars. The renal damage was in most cases slight or moderate. By stepwise logistic regression analysis, grade of reflux and number of pyelonephritic attacks correlated with scarring, and number of pyelonephritic attacks with new scars and worsening of the lesions. In summary, of the females who ultimately had renal lesions, one-third developed new scars. In most of those with established scars at the first urography, the focal character of lesions suggests that most were also acquired. Since reflux and number of pyelonephritic attacks were identified as risk factors, prevention of renal deterioration should be possible.

Adolescent↗
PubMed2000

Standardized ultrasound method for assessing detrusor muscle thickness in children.

PURPOSE: We standardized transabdominal ultrasound measurement of bladder wall thickness in children and evaluated its reliability. MATERIALS AND METHODS: Using ultrasonography we measured the thickness of the low echogenic layer of the ventral and dorsal bladder walls at increasing degrees of bladder fullness in the setting of voiding cystourethrography. For assessing intra-observer variability an observer blinded to the numerical values of the measurements studied 38 patients 0.2 to 13.7 years old (median age 1. 5). Measurements were performed as pairs of replicates at well-defined sites with reference to the urachal remnant, and rectal impression and/or contour. For assessing interobserver variability 3 independent observers measured the same child. Eight children 0.3 to 10.5 years old (median age 6.4) were evaluated at 2 degrees of bladder fullness per child. RESULTS: The thickness of the low echogenic layer of the ventral and dorsal walls was 0.4 to 2.9 (median 0.9) and 0.4 to 2.8 mm. (median 1.1). The dorsal wall was slightly thicker than the ventral wall. The intra-observer and interobserver variability of measurements (standard deviation) was 0. 2 mm. for each wall part. There was a small systematic difference among observers. CONCLUSIONS: It is possible to determine the thickness of the low echogenic layer of the bladder wall with a systematic and anatomically defined method of acceptably reliable measurements. The ventral and dorsal walls should continue to be measured until more is known about their pathological appearance.

Adolescent↗
PubMed1999

Urodynamic pattern in asymptomatic infants: siblings of children with vesicoureteral reflux.

PURPOSE: We studied the urodynamic pattern in asymptomatic infants who are siblings of children with vesicoureteral reflux. MATERIALS AND METHODS: Cystometry and perineal electromyography were performed with voiding cystourethrography in 16 male and 21 female infant siblings screened for reflux at age 0.2 to 7.3 months (median 1.1). RESULTS: Vesicoureteral reflux was present in 25% of the male and 10% of the female infants. In those without vesicoureteral reflux unstable bladder contractions were noted in 8% of the male and 16% of the female subjects. In these infants median maximum voiding detrusor pressure was 127 (range 84 to 211) and 72 cm. water (range 42 to 240), respectively, and median bladder capacity was 20 ml. (range 10 to 49 and 10 to 120, respectively). Maximum voiding detrusor pressure was significantly higher in male than in female infants (p <0.01). Perineal electromyography was interpretable in 13 of the 16 male and 16 of the 21 female infants overall. All but 1 female subject had increased activity during voiding, which was also present intermittently in all subjects. CONCLUSIONS: Our study of asymptomatic siblings of children with vesicoureteral reflux has provided results that may be used as reference data for normal urodynamics in early infancy. Instability was rare. Bladder capacity was lower than expected with a predicted capacity at birth of approximately 20 ml. Maximum voiding pressure was high, especially in male subjects. The urodynamic voiding pattern suggests physiological dyscoordination, probably due to immature detrusor-sphincter function.

Female↗
PubMed1999

Gain of chromosome 7, which marks the progression from indolent to aggressive follicle centre lymphomas, is restricted to the B-lymphoid cell lineage: a study by FISH in combination with morphology and immunocytochemistry.

In a previous fluorescent in situ hybridization (FISH) study of patients with high-grade follicle centre lymphomas (FLCs), we often found additional copies of chromosome 7 in bone marrow (BM) cell nuclei even though obvious malignant tumour cells could not always be morphologically identified in the corresponding cell smears. This raised the question whether the gains of chromosome 7 are really confined to B-lymphoid tumour cells or whether other cell lineages are also of clonal origin. In the present investigation we employed FISH in combination with immunomarkers and morphological studies on BM smears and lymph node imprints from seven patients with high-grade FCLs and diffuse large B-cell lymphomas (DLBCLs). Three out of seven BM samples were found to contain clonal CD20-positive B-lymphoid cells (range 0.4-96% of the cells) and no extra copies of chromosome 7 were detected in the myelomonocytoid or erythroid cells or in the CD3-positive T lymphocytes. All seven patients showed additional copies of chromosome 7 in the lymph nodes and, again, this cytogenetic abnormality was also restricted to the CD20-positive cells (range 0.7-80% of the cells). Thus the present findings confirm that high-grade B-cell lymphomas with or without BM engagement involve the CD20-positive B-lymphoid cells exclusively and not the T lymphocytes, erythroid or myelomonocytoid cell lineages. These findings may indicate that anti-CD20 immunotherapy could be of value in high-grade B-cell lymphomas.

Bone Marrow Diseases↗
PubMed1999

Diagnosis of vesico-ureteric reflux.

The demonstration and grading of reflux is crucial in examination and follow-up of any child with upper urinary tract infection. A variety of factors can influence the occurrence of reflux, e.g. race, genetics, state of maturation of the ureterovesical valve, diuresis, infection and bladder dysfunction, including obstruction and neurogenic disorders. Even when reflux is investigated under strictly standardized conditions, two consecutive bladder fillings frequently show different grades of reflux. Voiding cystourethrography is, to date, the only method with a generally accepted, well-defined grading of reflux. It also allows detection of intrarenal reflux and anatomical and functional information about the bladder and urethra that is unobtainable by other methods. It is therefore usually considered the method of choice. Radionuclide cystography and, possibly, contrast enhanced ultrasonography can be complementary to voiding cystourethrography, but mainly for postoperative follow-up and screening of siblings.

Chelating Agents↗
PubMed1999

Imaging of abdominal neuroblastoma in children.

PURPOSE: The aims of the study were: 1) to assess the efficacy of different imaging methods for use prior to treatment; 2) to compare the surgico-histopathologically-based International Neuroblastoma Staging System (INSS) staging with the imaging results; and 3) to suggest a localisation scheme for abdominal neuroblastoma. MATERIAL AND METHODS: Thirty-one children with an abdominal neuroblastoma (median age 2 years), underwent abdominal US, CT of chest and abdomen, MR imaging of abdomen and spine, chest radiography, skeletal survey, radionuclide bone scintigraphy, MIBG scintigraphy, and bone marrow biopsy. RESULTS: In the evaluation of local disease, CT and MR were superior to US. There was no significant difference between CT and MR in assessment of the location or size of the tumour. Evaluation of invasive growth and lymphadenopathy was uncertain irrespective of imaging modality. Intraspinal extension was more distinctly demonstrated with MR. Tissue characterization with CT and MR did not contribute in the assessment of the tumours. Contrast enhancement at CT and MR examinations both improved demarcation between tumour and kidney, and was a necessity for evaluation of vessel encasement with CT. The local disease was best assessed by either CT or MR, while metastatic disease was best revealed by CT, MR, scintigraphy or bone marrow biopsy. CONCLUSION: Imaging may be a valuable basis for clinical assessment and pretreatment staging of abdominal neuroblastoma.

3-Iodobenzylguanidine↗
PubMed1999

Successful treatment with fludarabine in two cases of angioimmunoblastic lymphadenopathy with dysproteinemia.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is today recognized as a T-cell lymphoma which in most cases runs an aggressive course. The diagnosis is often difficult because of the varying clinico-pathological picture. Less than a third of the patients can be expected to have long-term remissions even after multiagent chemotherapy. Complete remissions have been reported after the use of interferon-alpha, cyclosporin A, and recently purine analogues in a few patients. We now report two cases of AILD that had unmaintained remissions for 32 and 10 months, respectively, after fludarabine therapy. In one of the patients fludarabine was used up-front and in the other after she had proved to be resistant to CHOP treatment. No severe infectious complications were noted. The use of purine analogues should be investigated further in AILD.

Aged↗
PubMed1998

[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↗
PubMed1998

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↗
PubMed1998

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↗