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H Haapasalo

Publications and source records attributed to H Haapasalo.

At least 55 records · Page 3Linked to original sources
PubMed1996

c-erbB-2 in astrocytomas: infrequent overexpression by immunohistochemistry and absence of gene amplification by fluorescence in situ hybridization.

Recent studies suggest that aberrations of c-erbB-2 may be involved in astrocytic brain tumours. We screened immunohistochemically c-erbB2 protein (p185) expression in 94 astrocytic grade 1-4 neoplasms of the brain. The amplification of the c-erbB-2 oncogene was investigated in protein overexpression cases by dual colour fluorescence in situ hybridisation (FISH). p185 overexpression was correlated with p53 and epidermal growth factor receptor (EGFR) expression, as well as with clinicopathological features. Only two anaplastic (grade 3) astrocytomas and one glioblastoma (grade 4) showed overexpression of p185 protein by immunohistochemistry (monoclonal MAb1 antibody TA250), whereas none of the grade 1-2 astrocytomas was positive. Interestingly, the expression of p185 was confined solely to the cytoplasm of neoplastic astrocytic cells and not to the cell membranes as found in malignancies with amplification of the c-erbB-2 oncogene. Two of the three overexpression cases were also positive by EGFR. No amplification of the c-erbB-2 gene was observed by FISH in the three tumours with immunohistochemical p185 overexpression or seven weakly positive/negative tumours. In conclusion, our results suggest that p185 overexpression is infrequent in astrocytomas, that it is of no important diagnostic or prognostic value and that c-erbB-2 oncogene amplification is not seen in the few cases in which there is overexpression.

Adolescent↗
PubMed1995

Effect of starting age of physical activity on bone mass in the dominant arm of tennis and squash players.

OBJECTIVE: To determine in female tennis and squash players the effect of biological age (that is, the starting age of playing relative to the age at menarche) at which tennis or squash playing was started on the difference in bone mineral content between the playing and non-playing arms. DESIGN: Cross-sectional study. SETTING: Finnish tennis and squash federations. PARTICIPANTS: 105 female Finnish national-level players and 50 healthy female controls. MAIN OUTCOME MEASURES: Differences in bone mineral content in playing and nonplaying (dominant to nondominant) arms (proximal humerus, humeral shaft, radial shaft, and distal radius) were compared in the players and controls and among six groups of players. Players were divided into groups according to the biological age (years before or after menarche) at which their playing careers began: more than 5 years before; 3 to 5 years before; 2 to 0 years before; 1 to 5 years after; 6 to 15 years after; and more than 15 years after. RESULTS: Compared with controls (whose mean +/- SD differences in bone mineral content were 4.6% +/- 4.6%, 3.2% +/- 2.3%, 3.2% +/- 3.8%, and 3.9% +/- 4.3% at the previously noted anatomical sites), the players had a significantly (P < 0.001) larger side-to-side difference in every measured site (15.5% +/- 8.4%, 16.2% +/- 9.8%, 8.5% +/- 6.6, and 12.5% +/- 7.1%). Among players, the group differences in bone mineral content were significant (P < 0.001 to P = 0.005), with the group means clearly decreasing with increasing starting biological age of playing. The difference was two to four times greater in the players who had started their playing careers before or at menarche (lowest mean difference in bone mineral content, 10.5% +/- 7.2%; highest difference, 23.5% +/- 7.2%) than in those who started more than 15 years after menarche (lowest difference, 2.4% +/- 4.8%; highest difference, 9.6% +/- 4.9%). Adjustment for potential confounding factors (age and height) did not change these trends. CONCLUSIONS: Bones of the playing extremity clearly benefit from active tennis and squash training, which increases their mineral mass. The benefit of playing is about two times greater if females start playing at or before menarche rather than after it. The minimal level and minimum number of years of activity necessary to produce these results, the extent to which this benefit is sustained after cessation of intensive training, and the degree to which these results can be extended to other forms of physical activity and other bone sites should be studied further.

Age Factors↗
PubMed1995

Expression of peripheral-type benzodiazepine receptor and diazepam binding inhibitor in human astrocytomas: relationship to cell proliferation.

The expression of peripheral-type benzodiazepine receptor (PBR) and diazepam binding inhibitor (DBI) were studied in human astrocytic tumors using immunocytochemistry and in situ hybridization. Both PBR and DBI were prominently expressed in neoplastic cells, whereas in normal brain their amount was low or undetectable. Immunocytochemical double staining demonstrated that PBR and DBI were present in the same cells, suggesting that DBI may act in an autocrine manner in these cells. Analysis of 86 cases showed that PBR expression was statistically significantly associated with tumor malignancy grade (P = 0.004) and the proliferative index as determined by immunocytochemistry with the MIB-1 antibody (P = 0.004). Patients having tumors with high levels of PBR-immunoreactive cells had a shorter life expectancy than patients whose tumors showed lower PBR contents (P = 0.024). In conclusion, these results show that PBR expression is higher in neoplastic cells than in normal brain tissue. They also suggest that PBR immunocytochemistry might be useful in evaluating malignancy in brain tumors.

Adolescent↗
PubMed1995

Bone mineral density in female athletes representing sports with different loading characteristics of the skeleton.

To address the hypothesis that osteogenic effect of physical loading increases with increasing strain rates and peak forces, we examined 59 competitive Finnish female athletes (representing three sports with different skeletal loading characteristics), physically active referents (they reported an average of five various types of exercise sessions per week), and sedentary referents (two sessions per week) using dual energy X-ray absorptiometry. The measured anatomic sites were at the lumbar spine, femoral neck, distal femur, patella, proximal tibia, calcaneus, and distal radius. The athlete group consisted of aerobic dancers (N = 27), squash players (N = 18), and speed skaters (N = 14). The squash players had the highest values for weight-adjusted bone mineral density (BMD) at the lumbar spine (13.8% p < 0.001 as compared with the sedentary reference group), femoral neck (16.8%, p < 0.001), proximal tibia (12.6%, p < 0.001) and calcaneus (18.5%, p < 0.001). Aerobic dancers and speed skaters also had significantly higher BMD values at the loaded sites than the sedentary reference group, the difference ranging from 5.3% to 13.5%. The physically active referents' BMD values did not differ from those of the sedentary referents at any site. The results support the concept that training, including high strain rates in versatile movements and high peak forces, is more effective in bone formation than training with a large number of low-force repetitions.

Adult↗
PubMed1995

Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia.

OBJECTIVE: To relate the expression of HIV regulatory proteins and HIV-specific mRNA in the brain cells of infected individuals with clinical neurological disease. DESIGN: Formalin-fixed postmortem brain tissue from 14 HIV-infected adult patients, with previous repeated neurological and neuroradiological examinations, was studied by immunohistochemical and molecular biological methods. Samples from non-infected brains served as controls. METHODS: Immunohistochemistry with monoclonal antibodies (MAb) was combined with in situ RNA hybridization. Target cells were identified with MAb to glial fibrillary acidic protein (GFAP; astrocytes), CD68 (activated macrophages) and Ricinus communis agglutinin (RCA-1; microglia, endothelial cells). For HIV, a panel of MAb against HIV Nef, Tat, Rev and Env proteins or probes specific for all classes of mRNA (nef), for singly or non-spliced mRNA (env) and for non-spliced mRNA (gag/pol) were used. RESULTS: Nef protein was detected in subcortical or subpial astrocytes in seven out of 14 samples, and in multinucleated giant cells in two cases. Gag/pol or env mRNA-expressing astrocytes were detected in four cases. In four out of five cases studied, HIV Rev, but not Tat, was also expressed in astrocytes. Six out of the seven patients with Nef-positive astrocytes had suffered from moderate to severe dementia. The patient with most rapidly progressing severe dementia showed extensive HIV mRNA expression together with Nef and Rev expression in astrocytes. CONCLUSION: In adult human brain, astrocytes are infected by HIV and preferentially express HIV Nef and Rev proteins but are also sometimes productively infected. Astrocyte infection is associated with moderate to severe dementia which agrees with recent knowledge on the housekeeping activities of astrocytes and their eventual role in learning and memory.

AIDS Dementia Complex↗
PubMed1995

Proliferative potential of sporadic and neurofibromatosis 2-associated schwannomas as studied by MIB-1 (Ki-67) and PCNA labeling.

Neurofibromatosis 2 (NF2), a dominantly inherited disorder, is typically manifested as bilateral vestibular Schwannomas and predisposes to other nervous system tumors. Vestibular Schwannomas also occur sporadically but the onset is usually at an older age. Surgical and histological studies have shown that vestibular Schwannomas of NF2 patients are more invasive than sporadic Schwannomas and that the two groups also have morphological differences. We compared the proliferation activity of 26 vestibular Schwannomas (19 NF2 patients) to that of 27 sporadic cases using the Ki-67 (MIB-1) and PCNA (19A2) monoclonal antibodies. In addition, proliferation was assessed in 20 spinal benign Schwannomas, 4 spinal cellular Schwannomas and 3 spinal malignant peripheral nerve sheath tumors (MPNST). We found a significant difference in the proliferation potential between NF2 and sporadic vestibular Schwannomas (MIB-1-LI: 1.72 +/- 0.93 vs 0.95 +/- 0.57, p = 0.001; and PCNA-LI: 1.40 +/- 0.75 vs 0.81 +/- 0.52, p = 0.001). Age does not explain the detected difference in proliferation, since NF2 vestibular Schwannomas also had higher MIB-1 indices than 34 age-matched sporadic tumors. In spinal tumors, MPNST had higher MIB-1 indices than cellular Schwannomas, and therefore MIB-1 staining may be useful in distinguishing between them. Although the defective NF2 gene is important in the tumorigenesis of both NF2 and sporadic Schwannomas, our results suggest that there are differences in the molecular biology of these tumors.

Adolescent↗
PubMed1995

Proliferative activity and DNA index do not significantly predict survival in primary central nervous system lymphoma.

Proliferative activity and DNA index were analyzed and correlated with histology and survival in 30 primary central nervous system lymphomas (PCNSL) in immunocompetent patients. Proliferative activity was determined using mitotic activity index and volume-corrected mitotic index, percentage of Ki-67 (MIB-1) immunopositive nuclei and flow cytometric S-phase fraction. Twenty-nine PCNSL were of B-cell origin and one of T-cell; by Kiel classification there were 23% low grade and 77% high grade and by Working Formulation there were 7%, 73% and 20% low, intermediate and high grade tumors, respectively. Mean survival time for non-survivors (n = 26) was 11.5 months and median 6.5 months. When indicators of proliferative activity were evaluated against histological grading, correlation existed only between mitotic activity index and Kiel classification. None of the proliferation markers or DNA index correlated significantly with survival, but there was a trend for patients with higher volume-corrected mitotic index to have shorter survival. In conclusion, most PCNSL have poor prognosis irrespective of their histological grade and proliferative activity. Furthermore, because at present stereotactic biopsy is recommended for establishing the diagnosis, exact histological subtyping and determination of proliferation activity in such small samples appears to be of only marginal significance.

Adult↗
PubMed1994

Magnetization transfer imaging of lumbar disc degeneration. Correlation of relaxation parameters with biochemistry.

OBJECTIVES: The authors attempted to find out if magnetization transfer (MT) imaging with magnetic resonance imaging (MRI) provides new information of disc degeneration. SUMMARY OF BACKGROUND DATA: Magnetization transfer technique improves soft-tissue contrast and characterization. It measures the cross-relaxation and chemical exchange processes between free and macromolecule-bound water protons in tissues. METHODS: The lumbar MRI and MT of four living subjects and six cadaveric spines were performed at 0.1 T. Disc water, protein, proteoglycan, and collagen contents of cadaveric samples were correlated to MT parameters. RESULTS: The rate of magnetization transfer between free-water protons and the macromolecule-bound protons was elevated in degenerated discs. A positive correlation was found between disc collagen and total protein concentration and the rate of transfer. The contrast of normal and degenerated discs on MT images was not altered much. CONCLUSIONS: More studies are needed to fully establish the importance of MT processes in the disc.

Adult↗
PubMed1994

Long-term unilateral loading and bone mineral density and content in female squash players.

We examined 19 female Finnish national level squash players and 19 healthy female controls with a dual energy x-ray absorptiometric (DXA) scanner for the determination of the association between long-term unilateral activity and bone mineral density (BMD) and content (BMC) of the upper extremities. In players, the BMDs and the BMCs were significantly higher in each bone site of the playing extremity. The side-to-side difference was largest in the proximal humerus (BMD 15.6%, BMC 17.8%) and smallest in the ulnar shaft (BMD 5.6%, BMC 7.3%). In sex-, age-, weight-, and height-matched controls, the side-to-side differences were significantly smaller, ranging from 1.6% to 4.1%. The number of training years and elbow flexion strength correlated positively with the relative BMD and BMC in the humerus of the playing arm (r = 0.632-0.685). The starting age of training in turn correlated negatively (r = -0.483 to -0.577) with these bone parameters. Significantly larger side-to-side differences (average 22%) were found in players who had started their career before or during menarche than in those who had begun the training 1 year or more after the menarche (9%). These findings suggest that the bones of the playing extremity clearly benefit from active squash playing. The benefit is largest in humerus and smaller in the bone of the forearm. The benefit of playing is stronger if the athlete has started the training at or before menarche than after it.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Sources of variation in the assessment of cell proliferation using proliferating cell nuclear antigen immunohistochemistry.

The reproducibility in quantitation of proliferation activity, determined using the monoclonal antibody 19A2 to proliferating cell nuclear antigen (PCNA), was tested in visual and computer-assisted analyses of brain tumor material. The PCNA labeling index was scored using count (PCNA-LI, visual and computer analyses) and area (PCNA-LIa, computer analysis) estimates of immunopositivity. The quality of immunostaining was the most important reason for variation in the assessment results. Other significant variation sources in the assessment were experience in selecting microscopic fields and distinguishing immunopositive nuclei from immunonegative ones. Computer-assisted analysis improved the reproducibility of quantitation between different observers (visual rPCNA-LI = 0.624 versus computer assisted rPCNA-LI = 0.904). Also, the use of PCNA-LIa improved the intraobserver and interobserver reproducibility in different stainings (observer 1:rPCNA-LI = 0.857 versus rPCNA-LIa = 0.874; observers 1 and 2: rPCNA-LI = 0.904 versus rPCNA-LIa = 0.927; observers 3 and 4: rPCNA-LI = 0.848 versus rPCNA-LIa = 0.906). PCNA-LIa by computerized image analysis improves accuracy in the evaluation of the granularly expressed PCNA level. Furthermore, the effect of tumor heterogeneity on the assessment results can be diminished with the computerized method because large tissue areas can be analyzed faster.

Astrocytoma↗
PubMed1993

Grading of superficial bladder cancer by quantitative mitotic frequency analysis.

A cohort of 270 superficial (stages Ta to T1) transitional cell bladder tumors was followed for more than 8 years. World Health Organization (WHO) grade, papillary status and 2 mitotic indexes were related to progression, recurrence-free survival and bladder cancer related survival during followup. Mitotic activity index and volume corrected mitotic index were significantly related to WHO grade and papillary status (p < 0.0001). WHO grade, papillary status and mitotic indexes were related significantly to progression in univariate analysis (p < 0.001) whereas in a multivariate analysis only volume corrected mitotic index included independent prognostic information (p < 0.001). Recurrence-free survival was related to volume corrected mitotic index in the entire cohort (p = 0.03) and in papillary tumors (p = 0.07). Bladder cancer related survival was related to WHO grade, papillary status, mitotic activity index and volume corrected mitotic index (all p < 0.0001). In papillary tumors mitotic activity index (p < 0.0001), volume corrected mitotic index (p < 0.0001) and WHO grade (p = 0.0036) predicted survival. In multivariate analysis mitotic activity index predicted independently recurrence-free survival in the entire cohort (p = 0.043) and in papillary tumors (p = 0.012). Bladder cancer survival in the entire cohort and in papillary tumors was related independently to volume corrected mitotic index (p < 0.001). The results show that superficial transitional cell bladder tumors can be efficiently categorized into prognostic groups by quantitative mitotic frequency analysis and the results provide a new classification system for superficial transitional cell bladder tumors.

Aged↗
PubMed1993

Prognostic factors in nodular transitional cell bladder tumours.

A cohort of 106 nodular transitional cell bladder cancers (TCC) were followed up for a mean of 9 years. Clinical stage, WHO grade, six morphometric nuclear factors and volume corrected mitotic index (M/V index) were correlated to progression and survival during the follow-up period. Nuclear factors were related to WHO grade with a borderline significance (p = 0.01-0.3) whereas the M/V index showed a highly significant relation to WHO grade. Neither nuclear factors nor the M/V index were related significantly to T-, N- or M-categories at the time of diagnosis. Progression in N- and M-categories was related independently to WHO grade whereas progression in T-category could not be predicted significantly by none of the variables included in this analysis. Survival was predicted by T-category (p = 0.0028), N-category (p = 0.0001), M-category (p = 0.0057) and M/V index (p = 0.010). In T1-T2N0M0 tumours survival was predicted by the Dmax (p = 0.015) and by the M/V index (p = 0.039). In multivariate survival analysis T-category (p < 0.001) had independent prognostic value. In T1-T2N0M0 tumours only the M/V index predicted survival independently (p = 0.007). The results show that only the proliferation rate in addition to T-category have prognostic significance in nodular TCC.

Aged↗
PubMed1993

Aberrant p53 expression in astrocytic neoplasms of the brain: association with proliferation.

Aberrant expression of the p53 suppressor gene was evaluated in 102 cases of astrocytic neoplasms. Immunohistochemical staining with a monoclonal antibody (DO-7) and a polyclonal antibody (CM-1) to p53 protein (both wild type and mutant) on formalin-fixed paraffin sections showed a strong correlation with malignancy grade. The staining was positive in 49% of malignant neoplasms (grades III and IV) and in 19 to 29% of grade II astrocytomas, whereas none of the grade I tumors were positive. p53 expression was significantly associated with proliferation rate determined by immunohistochemical proliferating cell nuclear antigen (PCNA)-staining (median PCNA-labeling index (%): 4.22 (DO-7-positive) versus 1.18 (DO-7-negative), P < 0.0001; 4.02 (CM-1-positive) versus 1.18 (CM-1-negative), P < 0.001). Interestingly, in the glioblastoma group (n = 44), p53-positive tumors had higher proliferation indices, suggesting that histologically similar tumors could be divided into prognostically different subgroups by immunohistochemical demonstration of aberrant p53 expression.

Analysis of Variance↗
PubMed1992

Independent clinical, histological and quantitative prognostic factors in transitional-cell bladder tumours, with special reference to mitotic frequency.

A cohort of 537 transitional-cell bladder cancers (TCC) was followed up for a mean of 9 years. Clinical stage, WHO grade, papillary status, 6 nuclear factors and volume-corrected mitotic index (M/V index) were related to progression and survival. Classic and quantitative prognostic factors were significantly interrelated (p less than 0.001). In Ta-Tl tumours M/V index predicted progression independently (p less than 0.001) and in the entire cohort progression was related independently to the M/V index (p = 0.0001) and to the WHO grade (p = 0.0022). In survival analysis, clinical stage (p less than 0.0001), M/V index (p less than 0.0001), WHO grade (p less than 0.0001), papillary status (p less than 0.0001) and nuclear factors (p less than 0.0001) were significant predictors. In papillary tumours, clinical stage (p less than 0.0001), M/V index (p less than 0.0001), WHO grade (p less than 0.0001) and nuclear factors (p = 0.0001-0.0133) were related to survival. In a multivariate analysis T-category (p less than 0.001), WHO grade (p less than 0.001), M/V index (p = 0.002) and papillary status (p = 0.034) predicted survival independently in the entire cohort whereas in papillary tumours T-category (p less than 0.001) and M/V index (p less than 0.001) were independent predictors. If tumours with pelvic lymph-node metastases or distant metastases at diagnosis were excluded from the analysis, T-category (p less than 0.001), M/V index (p less than 0.001) and WHO grade (p less than 0.001) were independent predictors. In papillary tumours T-category (p less than 0.001), M/V index (p less than 0.001) and WHO grade (p = 0.048) predicted survival. The results emphasize the importance of mitotic activity as a most important histological prognostic factor in TCC, second only to clinical stage. In Ta-TI tumours quantitative mitotic frequency analysis includes all the available independent prognostic information. Accordingly, TCC can be graded by mitotic frequency analysis in place of subjective grading systems.

Carcinoma, Transitional Cell↗
PubMed1992

Prognostic factors in WHO grade 2 transitional-cell bladder cancer (TCC); a novel two-grade classification system for TCC based on mitotic index.

A retrospective histological analysis has been carried out on 537 cases of transitional-cell bladder carcinoma, followed-up over a period of 9 years. In the first part of the study WHO grade 2 tumours were analysed and a number of independent factors predictive for survival identified. In a multivariate analysis the T category and M/V index (number of mitotic figures/mm2 neoplastic epithelium) were the most important prognostic factors. In a subsequent analysis of the whole series of 537 cases, overall the M/V index was not as important in predicting survival as the stage of the tumour. However, in superficial tumours (Ta-T1) subsequent analysis showed that the M/V index alone could be used to predict survival.

Aged↗
PubMed1992

Prediction of superficial bladder cancer by nuclear image analysis.

A cohort of 270 superficial transitional cell bladder tumours (Ta-T1) was followed-up for over 8 years. WHO grade, papillary status and six nuclear factors were related to progression, recurrence-free survival (RFS) and bladder cancer-related survival (BS) during the follow-up period. Mean nuclear area (NA), standard deviation of nuclear area (SDNA), nuclear perimetry (PE), standard deviation of nuclear perimetry (SDPE), shortest nuclear axis (Dmin) and longest nuclear axis (Dmax) were significantly related to WHO grade and papillary status (P < 0.0001). All the nuclear factors were related significantly to progression in univariate analysis (P < 0.01) whereas in a multivariate analysis WHO grade (P < 0.0001) and papillary status (P = 0.048) included independent prognostic information. RFS was related to PE (P = 0.009), SDPE (P = 0.013), Dmin (P = 0.021), Dmax (P = 0.028) and SDNA (P = 0.029). In papillary tumours SDPE (P = 0.007) and Dmin (P = 0.024) predicted RFS. BS was related to WHO grade, papillary status, NA, SDNA, PE, Dmax, Dmin (all P < 0.0001) and to SDPE (P = 0.003). In papillary tumours PE (P < 0.0001), Dmax (P = 0.0022), Dmin (P = 0.0027), WHO grade (P = 0.0036), NA (P = 0.0005), SDNA (P = 0.0355) and SDPE (P = 0.0718) predicted BS. In multivariate analysis SDPE (P = 0.029) predicted RFS and survival was related to WHO grade (P < 0.001) and PE (P = 0.014) independently. In papillary tumours only Dmax (P = 0.001) predicted survival independently. The results show that superficial papillary transitional cell bladder tumours can be efficiently categorised into prognostic groups by nuclear image analysis and the results provide a new classification system for superficial papillary bladder tumours. Tumours with high nuclear factor values should be considered for radical primary therapy and adjuvant therapy after transurethral resections.

Aged↗