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Biomedical subjects

M Hellström

Publications and source records attributed to M Hellström.

At least 55 records · Page 3Linked to original sources
PubMed1998

Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli.

Kidney glomerulus mesangial cells fail to develop in mice carrying targeted null mutations in the platelet-derived growth factor (PDGF)-B or PDGF-Rbeta genes. We have examined the pattern of expression of these genes and smooth muscle markers during kidney development, to address the possible mechanisms underlying the mutant phenotypes. In wild-type embryos, PDGF-B was expressed in vascular endothelial cells, particularly in capillary endothelial cells in the developing glomeruli, whereas PDGF-Rbeta was found in perivascular mesenchymal cells in the developing renal cortex. In the course of glomerular development, small groups of PDGF-Rbeta and desmin-expressing cells collected in the 'S'-shaped and early cup-shaped vesicles, and at later stages such cells were found in the glomerular mesangium. In PDGF-B or -Rbeta null embryos, some PDGF-Rbeta/desmin or desmin-positive cells, respectively, were seen in early cup-shaped vesicles, but fewer than in the wild type, and further development of the mesangium failed. In mouse chimeras composed of PDGF-Rbeta +/+ and -/- cells, the Rbeta-/- cells failed to populate the glomerular mesangium. Our results show that while the mesangial cell lineage is specified independently of PDGF-B/Rbeta, these molecules provide critical permissive signals in mesangial cell development. We propose a model in which mesangial cells originate from PDGF-Rbeta-positive progenitors surrounding the developing glomerular afferent and efferent arterioles, and are co-recruited in response to PDGF-B during angiogenic formation of the glomerular capillary tuft.

Animals↗
PubMed1997

Neo-adjuvant GnRH therapy and radical prostatectomy: effects on tumorous and benign tissue volumes - a morphometric study.

UNLABELLED: The effect on tumour and prostate volumes of a 3-month course of neo-adjuvant hormone therapy was studied using computerised planimetry on serially sectioned specimens obtained by radical prostatectomy. Fifty-four specimens from patients not receiving pre-treatment were compared to 38 specimens from patients given the gonadotropin-releasing hormone (GnRH) analogue triptorelin for 3 months before the operation. Glandular volume and volume of the index tumour was determined. To determine the position of the index tumour within the gland, the centre of mass of the tumour was identified and the distance to the gland margin calculated. This value (M1) represents the sum of the tumour radius and the various amounts of normal tissue. The amount of surrounding tissue could be approximated by correlating M1 to the corresponding tumour volume. RESULTS: The two groups differed significantly in total gland volumes, but not in tumour volumes. M1 was strongly correlated to the tumour volume in the treatment group (r = 0.73), whereas in the control group the correlation was found to be significantly weaker (r = 0.44), indicating that there was less tissue surrounding the tumour in the pre-treated group. In a multiple regression analysis of all 92 patients, index tumour volume was found to be associated with total gland volume, DNA ploidy pattern, tumour grade but not whether or not pre-treatment was given. This study found that the volumes of the single largest tumour focus were not significantly affected by hormonal pre-treatment, and that "the prostate condenses around the tumour rather than that the tumour shrinks back into the prostate". However, the precise relationship between tumour epithelial volume and stroma with or without neo-adjuvant hormonal pre-treatment remains to be clarified.

Gonadotropin-Releasing Hormone↗
PubMed1997

Effect of androgen deprivation on epithelial and mesenchymal tissue components in localized prostate cancer.

OBJECTIVE: To measure the area distribution of epithelial and mesenchymal components in the prostate of patients with localized prostate cancer after temporary androgen deprivation. PATIENTS AND METHODS: Surgical specimens from 38 patients treated with the gonadotrophin-releasing hormone agonist triptorelin for 3 months before radical prostatectomy were examined (group I). Specimens from a second group of 54 patients who underwent the same surgical procedure with no prior therapy were used as controls (group 2). The specimens were serially step-sectioned and whole-mount tissue sections prepared. The epithelial, smooth muscle and connective tissue components were stained separately with immunohistochemical and histochemical techniques, respectively. Using colour-based image analyses, the tissue components were classified into three categories, displayed in different colours. The percentage of tumour areas occupied by cancer epithelial cells, connective tissue and smooth muscle was determined. RESULTS: In specimens from group 1, the cancer epithelium was sparse and scattered throughout the tumour area. A mean (SD) of 21 (11)% of the area was occupied by cancer cells, compared with 40 (11)% in the corresponding material from group 2 (P < 0.001). The connective tissue/smooth muscle ratio in stroma (about 1:1) was similar in both groups. CONCLUSIONS: Neoadjuvant hormone treatment of patients with localized prostate cancer was associated with a marked reduction in tumour density and thus in the total amount of cancer epithelium.

Androgen Antagonists↗
PubMed1997

Diagnostic efficacy of MnDPDP in MR imaging of the liver. A phase III multicentre study.

PURPOSE: To assess the diagnostic efficacy, safety and tolerability of mangafodipir trisodium (MnDPDP, Teslascan) in MR imaging of the liver. MATERIAL AND METHODS: Eighty-two patients from 4 centres underwent MR imaging with pre-contrast sequences including T1-weighted SE and GRE, and T2-weighted turbo SE sequences. MnDPDP at a dose of 5 mumol/kg b.w. was administered by slow i.v. infusion, and 20-60 min after infusion the T1-weighted SE and GRE sequences were repeated. Diagnostic efficacy was evaluated by counting the number of lesions and by evaluating whether more information for lesion characterisation was available in post-contrast images. Safety and tolerability were assessed by recording adverse events and infusion-related discomfort. RESULTS: Significantly more lesions were found in MnDPDP-enhanced T1-weighted SE and GRE images than in unenhanced images of the same sequences. More lesions were also found in these images compared with T2-weighted images at a level of marginal significance. More information was obtained from MnDPDP-enhanced images in 40 cases. Mild to moderate adverse events were experienced by 17% of the patients. CONCLUSION: MnDPDP-enhanced images can improve lesion detection in the liver and are helpful for lesion characterisation. To obtain optimal diagnostic information of liver lesions T2-weighted images are also valuable. MnDPDP is a safe contrast agent for MR imaging of liver lesions.

Adult↗
PubMed1997

Alveogenesis failure in PDGF-A-deficient mice is coupled to lack of distal spreading of alveolar smooth muscle cell progenitors during lung development.

PDGF-A(-/-) mice lack lung alveolar smooth muscle cells (SMC), exhibit reduced deposition of elastin fibres in the lung parenchyma, and develop lung emphysema due to complete failure of alveogenesis. We have mapped the expression of PDGF-A, PDGF receptor-alpha, tropoelastin, smooth muscle alpha-actin and desmin in developing lungs from wild type and PDGF-A(-/-) mice of pre- and postnatal ages in order to get insight into the mechanisms of PDGF-A-induced alveolar SMC formation and elastin deposition. PDGF-A was expressed by developing lung epithelium. Clusters of PDGF-Ralpha-positive (PDGF-Ralpha+) mesenchymal cells occurred at the distal epithelial branches until embryonic day (E) 15.5. Between E16.5 and E17.5, PDGF-Ralpha+ cells multiplied and spread to acquire positions as solitary cells in the terminal sac walls, where they remained until the onset of alveogenesis. In PDGF-A(-/-) lungs PDGF-Ralpha+ cells failed to multiply and spread and instead remained in prospective bronchiolar walls. Three phases of tropoelastin expression were seen in the developing lung, each phase characterized by a distinct pattern of expression. The third phase, tropoelastin expression by developing alveolar SMC in conjunction with alveogenesis, was specifically and completely absent in PDGF-A(-/-) lungs. We propose that lung PDGF-Ralpha+ cells are progenitors of the tropoelastin-positive alveolar SMC. We also propose that postnatal alveogenesis failure in PDGF-A(-/-) mice is due to a prenatal block in the distal spreading of PDGF-Ralpha+ cells along the tubular lung epithelium during the canalicular stage of lung development.

Animals↗
PubMed1996

PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.

A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.

Actins↗
PubMed1996

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↗
PubMed1996

A 3-year follow-up of patients with localized prostate cancer operated on with or without pre-treatment with the GnRH-agonist triptorelin.

OBJECTIVE: To examine the effect of pre-operative androgen deprivation on the progression rate of malignancy in patients operated on for localized prostate cancer. PATIENTS AND METHODS: A total of 53 patients received no hormone therapy (group 1) and a further 38 patients (group 2) received the generic releasing-hormone agonist triptorelin during the 3 months before surgery. The patients in group 1 had T1b-T2 tumours, whereas 12 of those in group 2 had clinical stage T3 tumours. Despite this, the surgical specimens from the patients in group 2 showed a rate of cancer invasion of the surgical margins 20% lower than those from the patients in group 1. After prostatectomy, the patients were followed for 3 years by repeated analyses of prostate-specific antigen (PSA) in serum. RESULTS: During the follow-up, the PSA level exceeded the upper threshold (0.6 ng/mL) in 16% of the patients in group 1 and in 43% of those in group 2 (P < 0.05). This difference was mainly related to the pre-treatment stage of the tumor. Some of the patients in group 1 received post-operative radiotherapy but this was not reflected in their PSA levels. Of the patients in group 1 and 2, 4% and 14% respectively (P > 0.05), developed symptoms from skeletal metastases. CONCLUSION: There was no evidence that pre-operative hormone therapy slowed the progression of prostate cancer.

Aged↗
PubMed1996

Interleukin (IL)-6 and IL-8 in children with febrile urinary tract infection and asymptomatic bacteriuria.

Urine and serum interleukin (IL)-6 and IL-8 responses were higher in children with febrile urinary tract infection (n = 61) than in those with asymptomatic bacteriuria (n = 39). By univariate analysis, cytokine levels were related to age, sex, reflux, renal scarring, urine leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and bacterial properties (P fimbriae but not hemolysin). Multivariate modeling showed that urine IL-6 responses were higher in girls than boys, increased with age, and were positively associated with CRP, ESR, serum IL-6, and urine leukocyte counts. The urine IL-8 response was not influenced by age, but it was influenced by P fimbriae and was associated with ESR, CRP, urine leukocytes, and female sex. The results show that cytokine responses to urinary tract infection vary with the severity of infection and that cytokine activation is influenced by a variety of host and bacterial variables.

Bacteriuria↗
PubMed1996

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↗