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Biomedical subjects

P Ekman

Publications and source records attributed to P Ekman.

At least 19 recordsLinked to original sources
PubMed2006

Nucleostemin mRNA is expressed in both normal and malignant renal tissues.

Nucleostemin (NS), a p53-binding protein, has been shown essential for stem and cancer cell proliferation and implicated in oncogenesis. To explore potential contributions of NS to the development of clear cell renal cell carcinomas (ccRCCs), we determined NS expression in ccRCC cell lines, and in paired normal and malignant renal tissues from 31 patients with ccRCC. Nucleostemin mRNA and/or protein expression was observed in all four cell lines and 27 of 31 (87%) tumour specimens. Surprisingly, 16 of 31 (52%) adjacent normal renal samples also expressed NS mRNA and its levels in four of them were comparable with those in paired tumour tissues. Three of the patients had detectable NS mRNA in their normal renal tissues whereas lacked its expression in the matched tumours. Compared to the oncogene c-MYC expression in these same samples, NS expression showed a much less specificity for ccRCC. We further demonstrated that NS mRNA expression was closely associated with cellular proliferation in normal fibroblasts or T lymphocytes and renal cell carcinoma cell lines. Collectively, NS expression widely occurs in normal and malignant renal tissues, and is likely a proliferation marker rather than a unique regulator of cell proliferation and survival in stem and cancer cells.

Adult↗
PubMed2004

The autonomic and behavioral profile of emotional dysregulation.

The authors describe a patient with focal brain atrophy and emotional lability characterized by episodes of excessive crying and laughing. The patient was selectively impaired in the production of voluntary complex facial movements and was unable to regulate her emotional behavior and autonomic reactivity. She also displayed increased behavioral and autonomic changes when explicitly trying to suppress her responses to emotional stimuli (compared with when not trying to regulate her responses). This pattern of deficits supports a selective deficit in voluntary emotional control.

Atrophy↗
PubMed2003

The role of chromosome 8p22 deletion for predicting disease progression and pathological staging in prostate cancer.

The natural course of human prostate cancer is highly variable, and we still lack reliable tools to predict the patient's outcome. Recent publications suggest that the deletion of chromosome 8p22 has an important role for tumor progression in prostate cancer. Totally, 97 patients (41 Japanese and 56 Swedish) were studied to detect the status of chromosome 8p22 deletion by the fluorescence in situ hybridization (FISH) technique. Seventy-seven underwent surgery (59 radical prostatectomies or 18 lymph node dissections), and the specimens were prepared by touch biopsy. Fine-needle aspiration biopsies (FNAB) were obtained from another non-operative 20 cases. Disease progression was evaluated in 57 patients with a median follow-up of 59 months. 8p22 deletions were detected in 58 (60 %) of all cases. The frequency of 8p22 deletion did not significantly differ between different preparations of specimens (touch biopsy vs. FNAB) as well as between different races (Japanese vs. Swedish). Cases with more than pT3 tumors had a significantly higher frequency of 8p22 deletion than those with pT2 (p < 0.01). Multivariate analysis demonstrated that 8p22 deletion was the strongest parameter to predict disease progression (hazard ratio = 5.75; p = 0.0001). Studies on chromosomal deletions of 8p22 by the FISH technique may serve as a universal genetic marker to optimize the treatment strategy in patients with prostate cancer.

Aged↗
PubMed2002

A new core-biopsy instrument with an end-cut technique provides prostate biopsies with increased tissue yield.

OBJECTIVE: To evaluate the tissue yield of a new core-biopsy needle with an end-cut mechanism when used for transrectal prostate biopsies. PATIENTS AND METHODS: The end-cut instrument has an adjustable stroke length (13, 23 or 33 mm) and an inner and an outer cannula, but no trocar. It was compared with the conventional side-notch needle (Biopty, Bard, Covington, GA, USA) with trocar and fixed stroke length (22 mm). In 60 men, octant biopsies were taken including the apex, mid-medial, mid-lateral and basal positions. At random, the left side of the prostate was biopsied with one of the instruments and the right side with the other. The length and weight of the biopsy specimens were measured. In 40 men, the stroke length of the end-cut instrument was set to 23 mm, and in 20 men it was set to 33 mm. RESULTS: The weight and the weight per length of the biopsies provided by the end-cut instrument with a stroke length of 23 mm were 18.4% and 13.7%, respectively, greater than in the biopsies from the side-notch instrument (P<0.001). In 21.9% of the attempts no tissue was obtained by the end-cut needle, compared with 1.9% with the side-notch needle. With a 33 mm stroke length, the length and weight of the end-cut biopsies were 38.4% and 33.0%, respectively, greater than in biopsies from the side-notch instrument. CONCLUSION: The end-cut instrument provided a greater tissue yield than the side-notch needle, but a significant number of biopsies were lost.

Adult↗
PubMed2002

Invasion of Salmonella into human intestinal epithelial cells is modulated by HLA-B27.

OBJECTIVE: To investigate the influence of the major histocompatibility complex (MHC) class I molecule HLA-B27 on (i) the invasion of Salmonella and Yersinia into human intestinal epithelial cells, (ii) the survival of intracellular Salmonella in these cells, and (iii) the production of certain inflammatory cytokines by the cells after Salmonella infection. METHODS: The human intestinal epithelial cell line Henle-407 was transfected with HLA-B27 DNA. These cells and HLA-B27-negative control cells were infected with Salmonella or Yersinia, and viable intracellular bacteria were determined as colony-forming units. Cytokine production was assayed with ELISA. RESULTS: Salmonella invaded HLA-B27-positive Henle cells in higher numbers than HLA-B27-negative control cells. However, HLA-B27 did not affect the invasion of Yersinia or the survival of the intracellular bacteria in these intestinal epithelial cells. Salmonella infection induced production of interleukin-8 (IL-8), IL-6 and monocyte chemotactic protein 1 (MCP-1) by Henle cells that was not affected by HLA-B27 in a specific way. CONCLUSIONS: These findings suggest that HLA-B27 enhances the invasion of Salmonella into intestinal epithelial cells. The interaction between bacteria and intestinal epithelial cells plays an important role during the early phases of ReA. HLA-B27-linked modulation of Salmonella invasion may lead to an increased load of Salmonella in intestinal tissue and thus increased susceptibility to reactive arthritis.

Cells, Cultured↗
PubMed2001

Linkages between facial expressions of anger and transient myocardial ischemia in men with coronary artery disease.

The authors examined whether facial expressions of emotion would predict changes in heart function. One hundred fifteen male patients with coronary artery disease underwent the Type A Structured Interview, during which time measures of transient myocardial ischemia (wall motion abnormality and left ventricular ejection fraction) were obtained. Facial behavior exhibited during the ischemia measurement period was videotaped and later coded by using the Facial Action Coding System (P. Ekman & W. V. Friesen, 1978). Those participants who exhibited ischemia showed significantly more anger expressions and nonenjoyment smiles than nonischemics. Cook-Medley Hostility scores did not vary with ischemic status. The findings have implications for understanding how anger and hostility differentially influence coronary heart disease risk.

Adult↗
PubMed2001

Induction of innate immune responses by Escherichia coli and purified lipopolysaccharide correlate with organ- and cell-specific expression of Toll-like receptors within the human urinary tract.

Mucosal epithelial linings function as physical barriers against microbes. In addition, they participate in the first line of host defence by production of a variety of proinflammatory mediators when exposed to microbes and microbial agents. Here, we use a human urinary tract infection model to demonstrate that organ- and cell-specific innate responses induced by lipopolysaccharides (LPS) present on Gram-negative bacteria correlates with the expression of Toll-like receptor 4 (TLR4). The presence of TLR4 on human bladder epithelial cells enables them to rapidly respond to bacterial infections in vitro and in vivo. In contrast, TLR4 is not expressed on human proximal tubule cells isolated from the renal cortex, which may explain the cortical localization of bacteria in pyelonephritis. TLR4-negative renal epithelial cells, A498, are non-responsive to purified LPS, however, they respond to viable bacteria via a mannose-sensitive attachment-mediated pathway. To identify LPS components recognised by bladder epithelial cells, a bacterial lipid A mutant and LPS of different chemotypes were tested. Full interleukin 8 induction required hexa-acylated lipid A and was decreased by between 50% and 70% in the presence of O-antigen. Taken together, we propose that multiple independent pathways, which are organ- and cell-specifically expressed, mediate bacterial recognition and determine the outcome of innate responses to infection.

Cell Line↗
PubMed2001

Relatively high risk of treatment failure after prostatectomy: tumour grade, histopathological stage and the preoperative serum PSA level are key prognosticators.

OBJECTIVE: Prostate cancer is the most common malignancy among males in Sweden. Any reduction in morbidity and mortality would require early detection of cases in which curative treatment is achievable. MATERIAL AND METHODS: From 1994 through 1998. 105 patients with clinically localized T1-T2 tumours were subjected to radical prostatectomy at our department. Three patients were lost to follow-up. We obtained clinical information from the patients' medical records and used pathologist reports to characterize the tumours with respect to grade and histopathological stage. We used serum PSA levels as a surrogate end-point, with a level equal to or above 0.6 ng/ml designated as treatment failure. Outcome was examined with respect to tumour grade, histopathological stage and preoperative PSA level. RESULTS: Altogether, 29% of the patients showed PSA failure during follow-up which varied between 2 and 6 years. No mortality due to prostate cancer was recorded during this time period. We found that tumour grade, histopathological staging and as well as the preoperative PSA level correlated with treatment failure (p<0.01). About 80% of the patients with a preoperative PSA <10 ng/ml showed no signs of treatment failure. The corresponding figure for those with PSA above 10 ng/ ml was 55%. The outcome for patients with a PSA between 10-20 did not seem to be better than that for patients with a preoperative PSA >20 ng/ml. CONCLUSION: Our study indicates, that the risk of treatment failure depends strongly on the grade of the tumour and increases when preoperative PSA value is greater than l0 ng/ml.

Follow-Up Studies↗
PubMed2001

Questioning questions about symptoms of benign prostatic hyperplasia.

OBJECTIVES: Our aim was to conduct a survey about urinary symptoms and to find out if questioning patients about symptoms is helpful for the GP to make medical decisions concerning prostate problems among middle-aged men. METHODS: Twelve hundred randomly chosen men aged 55--65 years from the general population in north-west Stockholm, Sweden were sent a questionnaire consisting of symptom questions focusing on prostate problems based on the International Prostate Symptom Score (I-PSS). A subset of 120 respondents were asked to answer the same questions again and to participate in a urological examination including urodynamics and ultrasonography. The main outcome measures were the prevalence of urinary symptoms and the relationship between the symptom score and objective measures. RESULTS: A response rate of 86% was obtained in the questionnaire study. Twenty-one per cent of the respondents stated that they had general problems related to urination. Among individual symptoms, post-void dribbling and a weak stream were most common. Among the men examined at the Urological Department, the average prostatic volume was found to be 40 cm(3). Three out of four were assessed to have infravesical obstruction. No correlation between subjective symptoms and objective measurements of either a statistical or clinical significance was found. CONCLUSIONS: Urinary symptoms are common among middle-aged men. Further, an enlarged prostate and/or infravesical obstruction is often found in the ageing man. Information obtained by asking prostate-specific symptom questions cannot, however, serve as the foundation for the GP to find those men whose problems would be solved by actions directed at the prostate.

Aged↗
PubMed2001

Deletions on chromosome 8p22 may predict disease progression as well as pathological staging in prostate cancer.

PURPOSE: A recent report demonstrated that the deletion of chromosome 8p22 could predict disease progression in stage III (capsular penetrating) prostate cancer. We studied if the status of chromosomal deletions of 8p22 could reflect pathological stage as well as patient prognosis, thereby serving as a diagnostic tool to optimize the treatment strategy in prostate cancer. EXPERIMENTAL DESIGN: A total of 97 patients (41 Japanese and 56 Swedish) were studied by the fluorescence in situ hybridization technique. Seventy-seven patients (23 pT2, 18 pT3, and 36 pN+ tumors) underwent surgery (radical prostatectomy or lymph node dissection). The specimens were prepared by touch biopsy. From another 20 cases, fine-needle aspiration biopsies were obtained. RESULTS: 8p22 deletions were detected in 47 (61%) and 11 (55%) specimens of 77 touch biopsies and 20 fine-needle aspiration biopsies, respectively. No significant difference was found in the frequency of 8p22 deletion between different preparations of specimens, as well as between different races (Japanese versus Swedish). The frequency of 8p22 deletion was statistically higher in patients with pT3 or more than in those with pT2 (P < 0.01). Disease progression was evaluated in 57 patients. The Cox proportional hazards model revealed 8p22 deletion to be the strongest parameter to predict disease progression (hazards ratio = 5.75; P = 0.0001). CONCLUSIONS: Studies on chromosomal deletions of 8p22 by fluorescence in situ hybridization technique may serve as a genetic marker to optimize the treatment strategy in patients with prostate cancer to the optimal treatment.

Aged↗
PubMed2000

Modification of disease outcome in Salmonella-infected patients by HLA-B27.

OBJECTIVE: To study whether HLA-B27 modifies the outcome of Salmonella infection in vivo. METHODS: The frequency of HLA-B27 was determined in 198 Salmonella-infected patients and 100 healthy controls by immunofluorescence and polymerase chain reaction. The excretion of Salmonella was monitored at monthly intervals. The symptoms of acute infection and possible joint involvement were evaluated using questionnaires. RESULTS: Thirty-eight of 198 Salmonella-infected patients (19.2%) and 13 of 100 healthy controls (13.0%) were HLA-B27 positive. The excretion of Salmonella did not differ significantly between HLA-B27-positive and -negative patients, or for patients with versus those without joint symptoms. As many as 35 patients (17.7%) reported Salmonella-triggered joint symptoms. Three of 14 patients (21.4%) with arthralgia, 5 of 13 patients (38.5%) with probable reactive arthritis (ReA), and 6 of 8 patients (75%) with confirmed ReA were HLA-B27 positive. The duration and severity of joint symptoms directly correlated with HLA-B27 positivity. Women reported Salmonella-induced pain and swelling of joints more frequently than men (P = 0.07 and P = 0.03, respectively). Patients with Salmonella-triggered joint symptoms reported abdominal pain and headache more frequently than patients without joint symptoms (P = 0.05 and P = 0.004, respectively). CONCLUSION: HLA-B27 did not (at least, not strongly) confer susceptibility to Salmonella infection. Salmonella excretion correlated neither with HLA-B27 positivity nor with the occurrence of joint symptoms. Joint symptoms were surprisingly common during or after Salmonella infection. HLA-B27-positive patients had a significantly increased risk of developing joint and tendon symptoms. Moreover, HLA-B27 positivity correlated with the development of more severe and prolonged joint symptoms.

Adolescent↗
PubMed2000

Optimizing the therapeutic approach of transurethral alprostadil.

OBJECTIVE: To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 microg and 500 microg, MUSE, Vivus Inc., Menlo Park, CA, USA, and Astra Läkemedel AB, Södertälje, Sweden) and the need for dose titration in a general population with erectile dysfunction. PATIENTS AND METHODS: In a 12-week randomized and open multicentre study with parallel groups, 166 patients were randomised to a starting dose of either 250 or 500 microg of MUSE and evaluated for safety. Of these patients, 142 were included in the analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 microg) was supplied and during the trial the dose could be increased or decreased step-wise until a satisfactory response was attained. The efficacy was assessed using the Erection Assessment Scale (EAS), as coitus (by diary) and the International Index of Erectile Function. RESULTS: The lowest dose of MUSE with which the patients achieved at least one EAS score of 4 or 5 was 125 microg for 1% of participants, 250 ++microg for 27%, 500 microg for 32%, 1000 microg for 6%, and finally 1000 microg plus a pubic band for 8%. Thirty-five of the 142 patients (25%) did not report an EAS of 4 or 5. Most patients (> 60%) achieved an EAS of 4 or 5 on the lower doses (125, 250 and 500 microg). Almost all patients who had an EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse at least once in course of the study. More patients reported penile pain while treated with 500 microg than with 250 microg (P < 0.05) during the first 4 weeks. However, the penile pain was severe in very few men and it was a minor problem. Hypotensive symptoms were reported six times, independently of dose level. The administration of MUSE was generally rated as comfortable. No patients reported urethral stricture, penile fibrosis, or priapism either in the clinic or at home. CONCLUSION: Recommending 500 microg as a starting dose increased the percentage of patients reporting at least one EAS of 4-5, with or without sexual intercourse, from 28% to 60%. No serious dose-related systemic effects were seen. When starting on 500 microg, patients were more likely to find directly the dose that gave sufficient response and treatment satisfaction. We suggest that the appropriate starting dose of MUSE should be 500 microg.

Adult↗
PubMed2000

Epidemiology of high-grade prostatic intraepithelial neoplasia.

This review summarizes published data dealing with the prevalence of high-grade prostatic intraepithelial neoplasia (HGPIN) in a variety of prostate tissue samples. Additionally, we have attempted to document the relationship between HGPIN and the pathological parameters of prostate cancer in autopsy and radical prostatectomy specimens. Studies reporting the prevalence of HGPIN in needle biopsies, transurethral resection specimens and radical prostatectomy specimens, and those documenting the lesion in postmortem settings are compared. We also summarize studies in which the distribution and/or extent of HGPIN was correlated with prostate cancer stage, grade and volume. There is significant variation in the reported frequency of HGPIN, particularly in needle biopsy specimens, with a range of 0.8-23.9%. The factors responsible for these discrepancies include the population studied, the limited sample size that needle biopsies represent, diagnostic inconsistencies and, possibly, tissue preparation/staining variables. Because of the important implications a diagnosis of HGPIN carries, there is a pressing need to achieve greater consistency in diagnosing and reporting the lesion. Better targeted educational efforts, including teaching courses, websites with illustrations and the possibility of teleconsultations, are among possible means to attain this goal. Better documentation of the evolution of HGPIN to cancer through clinical follow-up is also recommended.

Biopsy, Needle↗
PubMed2000

Chromosomal numerical aberrations detected by fluorescence in situ hybridization on bladder washings from patients with bladder cancer.

OBJECTIVE: Previous studies on touch biopsy specimens have determined numerical or structural changes involving many different chromosomes in bladder cancer. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) assay in bladder washings as an objective technique to detect chromosomal numerical aberrations in bladder cancer. The main advantages of bladder washings are that they can be easily collected during the clinical follow-up of patients with superficial bladder cancer and they do not contain so many degenerate cells as urine samples. METHODS: We collected specimens from 25 patients who underwent transurethral resection of bladder tumors. Double target FISH assays with centromeric labeled probes for chromosomes 7, 8, 9 and 11 were used on the bladder washings and on the touch biopsy slides. The results were compared to flow cytometry and tumor grade and stage. RESULTS: We found monosomy 9 and trisomy 7, 8, 9 and 11 in 28, 32, 36, 28 and 25% respectively of the patients. FISH analysis of bladder washing versus touch biopsy specimens were concordant in approximately 90% of the slides. Total DNA aneuploidy correlated well with numerical aberrations of chromosomes 7, 8 and 11, but not with chromosome 9. CONCLUSION: Although better hybridization efficiency was obtained on touch biopsy slides, the results in bladder washings were in high concordance. FISH analysis on bladder washing samples may become a simple tool to improve the accuracy of cytology.

Adult↗
PubMed1999

Links between genetic and environmental factors and prostate cancer risk.

BACKGROUND: Genetic polymorphisms and expression of steroid receptors may explain why some individuals are more at risk of developing prostate cancer. Some risk factors often discussed are androgen stimulation, and vitamin A and D deficiency. Long CAG-repeats in exon 1 of the androgen receptor (AR) gene on the X chromosome seem to have a protective role against androgen overstimulation. Likewise, long vitamin D receptor alleles in the poly-A tract may prevent vitamin D stimulation. METHODS: Blood samples from 59 Swedish patients with sporadic prostate cancers, 59 with hereditary prostate cancer, and 34 Japanese prostate cancer patients were compared with benign controls. Tissue specimens from 37 Swedish and 23 Japanese prostate cancer patients with matching blood samples were investigated by immunohistochemical techniques. RESULTS: The number of CAG-repeats was identical in sporadic and hereditary prostate cancer patients, but the repeats were significantly shorter than in benign controls. Benign Japanese controls were similar to Swedish controls, but Japanese prostate cancers had longer repeats than did controls. Both the vitamin D and A receptor staining was stronger in Japanese than in Swedish prostate cancer specimens. Prostate cancer occurs approximately 5 years later in Japanese compared with Swedish men. CONCLUSIONS: Varying lengths of CAG-repeats of the androgen receptor cannot fully explain racial differences in clinical prostate cancer incidence. A larger content of vitamin A and D receptors may be linked to a delayed onset of clinical prostate cancer in Japanese men.

Asian People↗