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R Johansson

Publications and source records attributed to R Johansson.

At least 19 recordsLinked to original sources
PubMed2006

CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma.

We investigated the expression of CD44 and MMP-9 in primary oral squamous cell carcinoma (OSCC) and evaluated their association with each other and clinicopathological factors as well as their prognostic value during long term follow up. Histological samples from 138 OSCC patients were immunohistochemically stained for the expression of CD44 and MMP-9. The staining results were compared with conventional prognostic factors and their impacts to patients' prognosis were also studied with survival analyses. Irregular staining of CD44 in tumour cells was associated with poor tumour differentiation (p=0.003), higher clinical stage (III-IV) (p=0.049), and the presence of T3-4 tumour stage (p=0.03). Strong stromal MMP-9 staining intensity was correlated with poor tumour differentiation (p=0.03). In univariate survival analysis irregular staining of CD44 in tumour cells was related to poor disease free and overall survival (p=0.001 and p<0.001, respectively). In multivariate analysis CD44 staining was a significant independent predictor for overall (p=0.03) and disease free survival (p=0.003). MMP-9 expression showed no statistical significance in survival analyses. Strong stromal staining intensity of MMP-9 correlated with irregular staining of CD44 in tumour cells, but had no prognostic significance in the present cohort. However, irregular staining of CD44 predicted more advanced disease and shortened survival of the patients.

Adolescent↗
PubMed2006

Biological and prognostic role of acid cysteine proteinase inhibitor (ACPI, cystatin A) in non-small-cell lung cancer.

BACKGROUND: Acid cysteine protease inhibitor (ACPI) is an intracellular protein, often linked to neoplastic changes in epithelium and thought to have an inhibitory role in malignant transformation. AIM: To analyse the expression and prognostic role of ACPI in non-small-cell lung cancer (NSCLC). METHOD: Histological samples from 199 patients with resected NSCLC were stained immunohistochemically for the expression of ACPI in normal and preneoplastic bronchial epithelium, and in various types of lung carcinomas. RESULTS: A normal bronchial epithelium showed positive staining for ACPI in the basal cells, whereas the upper two-thirds of the dysplastic epithelium was ACPI positive. High staining for ACPI was found in 74% (91/123) of squamous-cell carcinomas, whereas 16% (8/49) of adenocarcinomas and 30% of (8/27) large-cell carcinomas showed the high expression of ACPI (p<0.001). Among squamous-cell carcinomas, low expression of ACPI was correlated with poor tumour differentiation (p=0.032). In the whole tissue, reduced expression of ACPI was associated with tumour recurrence (p=0.024). In overall survival (OS) and disease-free survival (DFS) analyses, the histological type of the tumour (both p<0.001) and stage of the tumour (p=0.001, p=0.013, respectively) were related to patient outcome. Low expression of ACPI in tumour cells was associated with poor OS and DFS (p<0.041, p=0.004, respectively). In multivariate analysis, ACPI did not retain its prognostic value, whereas the traditional factors were the most important prognostic factors. CONCLUSIONS: ACPI expression is linked with the malignant transformation of the bronchial epithelium and predicts a risk of tumour recurrence as well as poor rate of survival for the patients. However, ACPI does not have any independent prognostic value in NSCLC.

Adenocarcinoma↗
PubMed2005

Expression of CD 44 s, CD 44 v 3 and CD 44 v 6 in benign and malignant breast lesions: correlation and colocalization with hyaluronan.

AIMS: To examine the expression of CD 44 s, CD 44 v 3 and CD 44 v 6 in breast lesions, and to correlate it with the expression of hyaluronan (HA). METHODS AND RESULTS: CD 44 expression was studied in 75 breast tissue samples, consisting of benign, premalignant and malignant breast lesions, using immunohistochemistry. CD 44 s, but not CD 44 v 3 or CD 44 v 6, was found in the stromal cells, and it was similar in benign and malignant tumours. In benign lesions CD 4 v 6 was detected in 20-30% of the ductal epithelial cells, while C 44 v 3 and CD 44 s were not expressed. CD 44 s, CD 44 v 3 and CD 44 v 6 were all up-regulated in the in situ carcinomas and invasive carcinomas. The level of CD 44 expression in carcinoma cells did not correlate with the type or differentiation of the tumours. CD 44 and HA expression levels were not closely linked in the benign or malignant breast lesions, because HA was overexpressed later in breast cancer progression than CD 44. However, in breast carcinomas CD 44 and HA positivity was often found in the same areas of the sections, and the dual staining confirmed actual colocalization of CD 44 s and HA in the same cells. CONCLUSIONS: CD 44 s, CD 44 v 3 and CD 44 v 6 are up-regulated earlier than HA in breast carcinoma progression, and in later stages they often colocalize with cell surface HA.

Breast Neoplasms↗
PubMed2004

Balance control and adaptation during vibratory perturbations in middle-aged and elderly humans.

The objective was to investigate if healthy elderly people respond and adapt differently to postural disturbances compared to middle-aged people. Thirty middle-aged (mean age 37.8 years, range 24-56 years) and forty healthy elderly subjects (mean age 74.6 years, range 66-88 years) were tested with posturography. Body sway was evoked by applying pseudorandom vibratory stimulation to the belly of the gastrocnemius muscles of both legs simultaneously. The tests were performed both with eyes open and eyes closed. The anteroposterior body sway was measured with a force platform and analyzed with a method that considers the adaptive changes of posture and stimulation responses. The results showed that middle-aged people generally used a different postural control strategy as compared to the elderly. The elderly responded more rapidly to vibratory perturbation, used more high-frequency (>0.1 Hz) motions and the motion dynamics had a higher degree of complexity. Moreover, the elderly had diminished ability to use visual information to improve balance control. Altogether, despite having an effective postural control adaptation similar to that of middle-aged people, the elderly had more difficulty in withstanding balance perturbations. These findings suggest that the balance control deterioration associated with aging cannot be fully compensated for by postural control adaptation.

Adaptation, Physiological↗
PubMed2004

Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma.

Several malignant tumours accumulate hyaluronan (HA), a matrix component suggested to promote cancer cell growth and migration. The expression and prognostic value of HA was analysed in a cohort of 151 oral squamous cell carcinoma (SCC) patients with adequate archival tumour material and follow-up data. The tumour samples were stained using a biotinylated HA-specific probe. Normal squamous epithelium showed a strong and homogeneously distributed staining for HA. The most superficial layers were HA-negative. In moderate (n=11) and high grade (n=16) dysplasias an irregular HA staining was observed around invasive cancer. Malignant transformation in oral squamous cell epithelium changed the staining toward irregular with focal reduction of HA. The well (n=92) or moderately differentiated (n=47) carcinomas had a strong HA staining intensity. In poorly differentiated tumours (n=12) the HA staining was weaker and mainly intracellular. The stromal tissue showed usually moderate (n=69) or strong (n=67) HA staining intensity with no statistically significant correlation with the degree of tumour differentiation. At the end of the follow-up (median 52 months) 66 (43%) patients had died because of an oral SCC. A significant difference in overall survival (OS) and disease free survival (DFS) (P=0.0002 and 0.0020, respectively) was noticed between the patients with the different epithelial staining patterns for HA. The reduction of HA staining was associated with poor survival. In Cox's multivariate analysis HA staining was a significant independent predictor of OS (P=0.011) and DFS (P=0.013). These results suggest that HA is a prognostic marker in oral squamous cell carcinoma.

Adolescent↗
PubMed2003

Systemic capillary leak syndrome resulting from gemcitabine treatment in renal cell carcinoma: a case report.

In a few cases, gemcitabine (GCB) has been shown to result in systemic capillary leak syndrome (SCLS) in the treatment of non-small cell lung, pancreatic, and ovarian carcinomas. SCLS is a life-threatening condition characterized by increased capillary permeability resulting in manifest pulmonary and peripheral edema. Usually SCLS responds successfully to corticosteroid therapy and diuretics. We present a case where GCB treatment likely resulted in SCLS in a male patient with metastatic renal cell carcinoma (RCC) in the absence of predisposing cardiac, pleural, or pulmonary disease.

Biopsy, Needle↗
PubMed2002

Analysis of short- and long-term effects of adaptation in human postural control.

The short-term (i.e., days) and long-term (i.e., months) effects of adaptation to posturography examinations were investigated in 12 normal subjects who were repeatedly examined for five consecutive days and again after 90 days. The examinations were conducted both with eyes open and closed, and the perturbations were evoked by a pseudorandomly applied vibration stimulation to the calf muscles. The evoked anteroposterior responses were analyzed with a method considering adaptation in the slow changes in posture and in the stimulus-response relationship. Repetition of examinations on a daily basis revealed a gradual improvement of postural-control performance. The body sway induced by the stimulation was significantly reduced and the dynamical properties changed. Most of the improvements remained after 90 days, but some parameters such as the complexity of the control system used were increased to the initial level. The results confirm previous observations that postural control contains several partially independent adaptive processes, observed in terms of alteration of posture and as a progressive reduction of body sway induced by stimulation. The method used for the adaptation analysis in this study could be applied to analyze biological systems with multiple individual adaptive processes with different time courses or characteristics, or where the adaptation processes are related to multiple internal or external factors.

Adaptation, Physiological↗
PubMed2002

Supraglottic and glottic carcinomas. clinically and biologically distinct entities?

This study aimed to examine the clinical and biological differences in 198 patients with either T1-T2 local glottic or supraglottic squamous cell carcinomas. The patients with supraglottic cancer had a poorer prognosis, as well as more advanced and histologically aggressive tumours than the patients with glottic tumours. They also had lower levels of haemoglobin and a poorer nutritional and performance status. Expression of alpha-catenin, hyaluronan, CD44, p53, p21/WAF1 and bcl-2 in the primary tumour were not associated with the site of the laryngeal carcinoma. In supraglottic tumours, the rate of spontaneous apoptosis and mitotic indices were significantly higher than in glottic tumours. The results suggest that clinical parameters including the haemoglobin level of the patient together with the tumour cell kinetics (mitotic and apoptotic rates) may contribute to the aggressive nature of supraglottic carcinoma.

Adult↗
PubMed2002

Cardiovascular manifestations in 75 patients with Williams syndrome.

OBJECTIVE: The prevalence and types of various cardiovascular diseases in different age groups as well as the outcomes of cardiac surgery and other interventions were assessed in a population of 75 Williams syndrome (WS) patients aged 4 months to 76 years (median 22.7 years). STUDY DESIGN: The diagnosis of WS was in each case confirmed by the clinical phenotype and by a FISH test showing elastin hemizygosity. Clinical and operative data were collected from all hospitals where the patients had been treated. RESULTS: Cardiovascular symptoms were evident in 35 of 75 (47%) WS children at birth. During follow up, 44 of 75 (53%) WS patients were found to have cardiovascular defects. Among them, the definitive diagnosis was made before 1 year of age in 23 (52%) infants, between 1 year and 15 years of age in 14 (32%) children, and older than 15 years of age in 7 (16%) adults. Multiple obstructive cardiovascular diseases were found in six infants. Supravalvular aortic stenosis (SVAS) was diagnosed in 32/44 (73%), pulmonary arterial stenosis (PAS) in 18/44 (41%), aortic or mitral valve defect in 5/44 (11 %) of cases, and tetralogy of Fallot in one (2%) case. Altogether, 17/44 (39 %) underwent surgery or intervention. Surgery was most frequently performed in the infant group (6% v 21% v 0%, p=0.004). After 1 year of age, seven patients underwent SVAS relief and two cases PAS relief. Postoperatively there was no mortality (median follow up time 6.9 years). Arterial hypertension was found in 55% of adults. In three adults, arterial vasculopathy was not diagnosed until necropsy. CONCLUSIONS: Our data indicate the following in WS. Cardiac symptoms are common in neonates. Heart disease diagnosed in infancy frequently requires operation. After 1 year of age, PAS tends to improve and SVAS to progress. Life long cardiac follow up is necessary because of the risks of developing vasculopathy or arterial hypertension.

Adolescent↗
PubMed2001

Prognostic value of hyaluronan expression in non-small-cell lung cancer: Increased stromal expression indicates unfavorable outcome in patients with adenocarcinoma.

The prognostic value of hyaluronan (HA) was analyzed in a large number of patients (n = 261) with non-small-cell lung cancer (NSCLC) by staining archived tumor samples with a biotinylated HA-specific probe. The level of HA in the tumor cells and surrounding stroma was scored and compared with parallel CD44 stainings, clinicopathological factors and survival data. Adenocarcinomas were characterized by a low percentage of HA-positive cells with low staining intensity compared with squamous-cell and large-cell/anaplastic carcinomas. The HA signal in the peri-tumoral stroma was often higher than that in the uninvolved stroma in all subgroups of NSCLC. CD44 and HA associated with the cancer cells showed a strong positive correlation with each other. In the whole tumor material, dominated by squamous-cell carcinomas (n = 168), recurrences were more often found in cases showing a low percentage of cancer cell-associated HA. However, within the adenocarcinoma subgroup (n = 68), a high percentage of cell-associated HA was correlated with poor tumor differentiation. Also specific for the adenocarcinoma subgroup was the increased number of recurrences in cases with a strong stromal HA signal. In survival analysis of the whole material (n = 189), a low percentage of HA-positive cancer cells was associated with a shortened disease-free survival (DFS) together with stage and tumor type. However, in the subgroup of patients with adenocarcinoma (n = 49), a strong stromal signal for HA predicted poor DFS. The level of HA in the stroma of adenocarcinomas retained its prognostic value in Cox's multivariate analysis. These results indicate that the frequency and intensity of HA has a significant prognostic value in NSCLC, particularly when the histological subtypes are analyzed as separate entities.

Adenocarcinoma↗
PubMed2001

Comparison of denuder and impinger sampling for determination of gaseous toluene diisocyanate (TDI).

An air-sampling method employing denuders coated inside with a chemisorptive stationary phase has been evaluated for analysis of the hazardous gaseous 2,4 and 2,6 isomers of toluene diisocyanate (TDI). The denuder stationary phase consisted of polydimethylsiloxane (SE-30) to which dibutylamine (DBA) was added as a reagent for derivatization of TDI. The accuracy and precision of sampling by means of denuders were shown to differ only slightly from those of the established impinger method. The denuder method was, however, also shown to be suitable for long-term measurements (up to 8 h). The limit of determination (LOD) of the method, including LC-APCI-MS-MS analysis, was found to be 1.9 microg m(-3) and 1.2 microg m(-3) for 2,4- and 2,6-TDI, respectively, for short-term measurements (15 min). Significant lower LOD was obtained for long-term measurements. This is well below the Occupational Safety and Health Administration (OSHA) 8-h TWA (time-weighted average) exposure limit, which is 40 microg m(-3) for the sum of the TDI isomers. The denuder method was also found to be robust and easy to handle. The samplers can be prepared several days before sampling with no loss in performance. The contents of denuders should, on the other hand, be extracted immediately after sampling to prevent degradation of the isocyanate derivatives formed.

Journal Article↗
PubMed2001

Multi-stimulus multi-response posturography.

In this study a method for the analysis of simultaneous multiple measurements of kinematics and stabilizing forces related to human postural dynamics is proposed. Each subject in a group of normal subjects (n=10) was tested with eyes-open and eyes-closed with simultaneous but uncorrelated vestibular and proprioceptive stimuli in order to investigate the contributions of individual sensory feedback loops. Statistical analysis was made by means of multi-input multi-output identification of a transfer function from stimuli to stabilizing forces of the feet and the resulting body position, the transfer function being compatible with a biomechanical model formulated as a stabilized segmented inverted pendulum subject to feedback of body sway and position. Each individual model estimated is effective in predicting a subject's response to new stimuli and in describing the interacting effects of stimuli on body kinetics. The proposed methodology responds to the current needs of data analysis of multi-stimulus multi-response experiments.

Adolescent↗
PubMed2001

Characterization of thermally generated aerosols from polyurethane foam.

Isocyanates constitute a group of highly reactive chemicals used on a large scale for the production of flexible polyurethane (PUR) foam. Exposure to isocyanates is known to produce irritation of the mucous membranes and the eyes. Isocyanates also have strong sensitizing properties and may cause occupational asthma. It is therefore important to monitor isocyanate emissions at workplaces. To obtain information for the improvement of isocyanate samplers and for health risk assessments of exposure, the emitted aerosol from two types of flexible PUR foam subjected to thermal degradation was characterized. Particle size distribution and toluene diisocyanate (TDI) concentration in the emitted aerosols were measured. Thermal degradation of flexible PUR foam at temperatures from 250 to 300 degrees C produced an aerosol with a geometric mean particle diameter of 30-50 nm. Between 5% and 9% of the PUR foam was emitted as TDI, and 2% to 6% of TDI monomers were found in the particle phase under the experimental conditions used. The 2,6-TDI isomer was more abundant in the gas phase than in the particle phase.

Aerosols↗
PubMed2001

Classification of electrocardiographic P-wave morphology.

The atrial activity of the human heart is normally visible in the electrocardiogram as a P-wave. In patients with intermittent atrial fibrillation, a different P-wave morphology can sometimes be seen, indicating atrial conduction defects. The purpose of this study was to develop a method to discriminate between such P-waves and normal ones. 20 recordings of each type were used in a classification which, based on impulse response analysis of the P-wave and linear discrimination between various parameters, produced a correct classification in 37 of the 40 recordings (sensitivity 95%, specificity 90%).

Atrial Fibrillation↗
PubMed2000

Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses.

Herpes simplex virus thymidine kinase (HSV tk) gene therapy combined with ganciclovir (GCV) medication is a potential new method for the treatment of malignant glioma. We have used both retrovirus-packaging cells (PA317/tk) and adenoviruses (Adv/tk) for gene therapy for malignant glioma. Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients. As a control group, seven tumors in seven patients were transduced with lacZ marker gene 4-5 days before tumor resection. Safety and efficacy of the gene therapy were studied with clinical evaluation, blood and urine samples, MRI follow-up, and survival of the patients. Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction. Frequency of epileptic seizures increased in two patients. No other adverse events possibly related to gene therapy were detected. In the retrovirus group, all treated gliomas showed progression by MRI at the 3-month time point, whereas three of the seven patients treated with Adv/tk remained stable (p < 0.05). Mean survival times for retrovirus, adenovirus, and control groups were 7.4, 15.0, and 8. 3 months, respectively. The difference in the survival times between the adenovirus and retrovirus groups was significant (p < 0.012). It is concluded that HSV tk gene therapy is safe and well tolerated. On the basis of these results further trials are justified, especially with adenovirus vectors.

Adenoviridae↗
PubMed2000

Caspase-dependent and -independent mechanisms in apoptosis induced by hydroquinone and catechol metabolites of remoxipride in HL-60 cells.

The hydroquinone and catechol like metabolites, NCQ344 and NCQ436 respectively, of the antipsychotic remoxipride have recently been demonstrated to induce apoptosis in myeloperoxidase (MPO)-rich human bone marrow progenitor and HL-60 cells [S.M. McGuinness, R. Johansson, J. Lundstrom, D. Ross, Induction of apoptosis by remoxipride metabolites in HL-60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia, Chem. Biol. Interact. 121 (1999) 253-265]. In the present study, we determined the molecular mechanisms of apoptosis induced by these remoxipride metabolites in HL-60 cells. Our results show that apoptosis was accompanied by phosphatidylserine (PS) exposure, activation of caspases-9, -3, -7 and DNA cleavage. In HL-60 cells treated with the hydroquinone NCQ344 and catechol NCQ436, the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp. fluoromethyl ketone (Z-VAD.FMK) blocked DNA cleavage and activation of caspases-9, -3/-7. In addition, PS exposure was significantly but not completely inhibited by Z-VAD.FMK. These results demonstrate that although Z-VAD.FMK inhibitable caspases are necessary for maximal apoptosis induced by NCQ344 and NCQ436, additional caspase-independent processes may orchestrate changes leading to PS exposure during apoptosis induced by the remoxipride polyphenolic metabolites.

Amino Acid Chloromethyl Ketones↗