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Biomedical subjects

P Ekman

Publications and source records attributed to P Ekman.

At least 109 records · Page 6Linked to original sources

Molecular genetics and human prostatic carcinoma.

Advances in molecular genetic techniques have reached the point where clinical material can be reasonably well-characterized in detail. One area that is receiving increasing attention is the genetic abnormalities of tumors. Using the technique of restriction fragment length polymorphism analysis, it is possible today to build up a picture of the genome and to identify which regions are deleted or are rearranged in the tumor cells of an individual patient. Twenty years ago, experimental and theoretical findings suggested that loss of gene function could be an essential component in oncogenesis. Such genes have been named tumor suppressor genes. The significance of the consistent loss of specific regions of genetic information from the genomes of tumor cells of a particular histological type is now appreciated, as such areas may contain as yet unrecognized tumor suppressor genes. The characterization of regions consistently lost thus forms the first step in localizing such genes. We have applied this technology to the study of prostate cancer and our preliminary findings show consistent losses of genetic information from chromosomes 8, 10, and 16.

Alleles↗

Dephosporylation with alkaline phosphatase of histone and fibrinogen phosphorylated with protein kinase C in vitro.

Alkaline phosphatase from calf intestinal mucosa dephosphorylated histone H1 and fibrinogen that had been phosphorylated with protein kinase C. The reaction velocity was dependent on the ionic strength of the buffer; decreasing with increasing concentration. The pH optimum was around 7, which is lower than pH-optima described for other kinds of substrates. (32P) phosphorylated fibrinogen was dephosphorylated about 20 times faster than (32P)phosphohistone on a weight basis and the reaction continued linearily with time for the longest time tested (3 hs) even at 37 degrees C. As alkaline phosphatase is present in the blood the possible physiological significance of the dephosphorylation of phosphofibrinogen is discussed.

Alkaline Phosphatase↗

Recessive genetic mechanisms in the oncogenesis of prostatic carcinoma.

A detailed deletion mapping of a series of human prostatic carcinomas, using restriction fragment length polymorphism (RFLP) analysis of all chromosomes, showed allelic losses on individual chromosomes at variable frequencies. Allelic losses occurred on chromosomal arms 8p, 10pq, 16q and 18q in more than 30% of the cases. Losses of genetic information from one or two of the chromosomes 8, 10, or 16 were always present in tumors showing allelic losses, indicating that genes on these chromosomes have a central role in prostatic cancer. A more extensive study of these chromosomes was thus carried out and showed the highest frequency of allelic deletions to occur on the short arm of chromosome 8 (65%) (where the minimally deleted region was between the PLAT locus and pter). The long arm of chromosome 16 had allelic deletions in 56% of informative cases, with three different break points (the most distal being between D16S4 and D16S7). Chromosome 10 exhibited a complex deletion pattern, showing allelic losses from both the short (p) and the long (q) arms, evidence of non-reciprocal translocations of the q arm, and monosomy in some cases. Our data indicate that tumor suppressor genes involved in the oncogenesis of prostatic carcinoma may be localized between 8pter and the PLAT locus and that additional/alternative tumor suppressor gamma are likely to be localized on chromosome 10 and on the long arm of chromosome 16. More aggressive tumors were accompanied by a high or frequency of allelic losses.

Alleles↗

Carcinoma of the prostate. Serum tumour markers.

Health examination - screening: Tumour markers in serum are of minor value when used for detection of the disease in health screening protocols. Reflection of the course of disease: Tumour markers are of great value for monitoring the response to a given therapy and for early detection of relapse. In recent years, measurements of PSA has replaced PAP for this purpose. Prognostic indicator: Tumour markers in serum may also be used to indicate the biological activity of the tumour. Also for this purpose PSA appears to be a more reliable marker than PAP. General recommendation: For newly detected cases of prostatic carcinoma determination of a limited number of prognostic markers is recommended. If no treatment is instituted all these determinations may be repeated at an interval of about one year. Once treatment has been instituted assay of serum markers may be restricted to PSA alone and may be carried out at about six-monthly intervals. In protocolled clinical trials the intervals may be shortened.

Acid Phosphatase↗

Studies on the substrate specificity of cAMP-dependent protein kinase using diastereomeric peptides.

A set of six different diastereomeric hexapeptides RRASVA, each with a D-amino acid residue successively in the six positions, was synthesized and tested as substrates of protein kinase A. It was found that the peptide with D-Ser was neither a substrate, nor an inhibitor of the enzyme. The other five peptides were active as substrates with slightly lower kcat values than that of the all-L amino acid peptide. However, the apparent Km values increased by one to two orders of magnitude, especially when the second arginine or the alanine residue preceding the serine was substituted. The results are discussed.

Amino Acid Sequence↗

Influence of the nervous system on experimentally induced urethral inflammation.

We have studied the contribution of the nervous system on experimentally induced urethral inflammation in the rat. Urethral inflammation was induced by inserting latex strips into the urethra. The effects of different experimental procedures was assessed by using a 4-graded inflammation scale based on the histological findings. Attenuation of urethral inflammation was produced by administration of capsaicin at birth. A more complete attenuation was produced by sympathectomy prior to application of the latex strip. Urethral inflammation was also severe in the spontaneous hypertensive rat. Injection of morphine into the third ventricle of the brain significantly reduced the experimentally induced urethral inflammation. These data taken together indicate that the sensory and postganglionic innervation of the urethral mucosa as well as the central nervous system is critically involved in the inflammatory reaction of the urethra following exposure to latex strips.

Adrenergic Fibers↗

In vitro phosphorylation of human complement factor C3 by protein kinase A and protein kinase C. Effects on the classical and alternative pathways.

Complement factor C3, recently found to contain covalently bound phosphate, was phosphorylated in vitro by cyclic AMP-dependent protein kinase (protein kinase A) and Ca2(+)-activated, phospholipid-dependent protein kinase (protein kinase C). Both protein kinases phosphorylated the same serine residue(s) located in the C3a portion of the alpha-chain. In addition, protein kinase C phosphorylated the beta-chain to a lesser extent. Protein kinase A gave a maximal incorporation of 1 mol of phosphate/mol of C3 while that value with protein kinase C was 1.5 mol of phosphate/mol of C3. The velocity in pmol of [32P]phosphate/(min x unit kinase) was 20 times higher for protein kinase C than for protein kinase A although a 10 times lower ratio of protein kinase to C3 was used in the former case. The apparent Km for C3 was 2.6 microM when protein kinase C was used. The phosphorylated C3 was found to be more resistant to partial degradation by trypsin than unphosphorylated C3. It was also found that phosphorylation of C3 in the C3a portion of the alpha-chain inhibited both the classical and alternative complement activation pathways on an approximately stoichiometric basis.

Amino Acids↗

Pseudomonas aeruginosa: adherence to and growth on different urinary catheter coatings.

Discs of urinary catheters with different coatings were exposed to a flow of artificial urine containing cells of Pseudomonas aeruginosa. Within 10 h an adherent biofilm consisting of the bacteria and their exopolysaccharide products had developed on those discs coated with latex, teflon, and silicon. In contrast, on the silver alloy-coated catheter discs no biofilm of Pseudomonas aeruginosa had developed.

Bacterial Adhesion↗

Tumour markers as prognostic aids in prostatic carcinoma.

Of 102 patients suffering from prostatic carcinoma, complete data on the serum concentration of 7 tumour markers were available from 90 patients, together with tumour grade, local stage and the presence or absence of skeletal metastases. The serum content of prostatic acid phosphatase, prostate specific antigen, neopterin, thymidine kinase, osteocalcin, C-reactive protein and tissue polypeptide antigen was measured. By means of Cox's regression and multivariate analysis the ability of these variables to predict prognosis, i.e. death from prostatic cancer, was studied. Neopterin appeared to be the most efficient marker, followed by tumour grade, thymidine kinase and prostate specific antigen. No other variable provided information of statistical significance. In multivariate analysis thymidine kinase performed best, followed by neopterin, tumour grade and prostate specific antigen. Several serum tumour markers reflect the biological activity of human prostate cancers and their value should be further explored. They may become useful in the management of individual patients.

Antigens, Neoplasm↗

Voluntary facial action generates emotion-specific autonomic nervous system activity.

Four experiments were conducted to determine whether voluntarily produced emotional facial configurations are associated with differentiated patterns of autonomic activity, and if so, how this might be mediated. Subjects received muscle-by-muscle instructions and coaching to produce facial configurations for anger, disgust, fear, happiness, sadness, and surprise while heart rate, skin conductance, finger temperature, and somatic activity were monitored. Results indicated that voluntary facial activity produced significant levels of subjective experience of the associated emotion, and that autonomic distinctions among emotions: (a) were found both between negative and positive emotions and among negative emotions, (b) were consistent between group and individual subjects' data, (c) were found in both male and female subjects, (d) were found in both specialized (actors, scientists) and nonspecialized populations, (e) were stronger when the voluntary facial configurations most closely resembled actual emotional expressions, and (f) were stronger when experience of the associated emotion was reported. The capacity of voluntary facial activity to generate emotion-specific autonomic activity: (a) did not require subjects to see facial expressions (either in a mirror or on an experimenter's face), and (b) could not be explained by differences in the difficulty of making the expressions or by differences in concomitant somatic activity.

Adult↗

Tumor markers in human prostatic carcinoma. An optimation of reference values.

Serum concentrations of prostatic acid phosphatase, prostate-specific antigen, neopterin, osteocalcin, tissue polypeptide antigen, and CA-50 were measured before onset of treatment in 86 patients suffering from prostatic carcinoma. In an attempt to identify patients with a poor prognosis, the data were related to patient survival after 3 years. When the standard reference values, which are based on studies on healthy subjects, were used in the study on the deceased, the diagnostic sensitivity was acceptable, whereas the diagnostic specificity was low. A better relation to prognosis was obtained if higher discrimination values were employed. The increased specificity could be obtained with little loss of sensitivity. It is suggested that the discrimination value should be chosen after careful consideration of the expected performance of the test in differentiating between defined groups of patients. To indicate short-term prognosis in prostatic cancer, a higher than normally recommended discrimination value for the marker should be selected.

Aged↗

Refinements in the coating of urethral catheters reduces the incidence of catheter-associated bacteriuria. An experimental and clinical study.

The tendency to develop bacteriuria during the use of various forms of indwelling catheters was evaluated in a randomized trial in 90 patients. A silver alloy and hydrogel-coated Foley catheter (SHC) was compared to a non-coated catheter (NC) and a catheter coated only with hydrogel (HC). Three patients (10%) with SHC catheters, 10 (33%) patients with HC catheters, and 15 (50%) patients with NC catheters developed bacteriuria (greater than 10(5) organisms/ml). The difference in the rate of bacteriuria after 5 days of catheterization was statistically significant between the SHC catheter and the NC catheter (p less than 0.002). There was no significant difference between the SHC catheter and the HC catheter, nor was there a significant difference between the HC catheter and the NC catheter. The toxic effects, as estimated by the IC50 value, of the urinary catheter material used was elucidated in an experimental fibroblast model. The IC50 value for the NC catheter was 33.9%, HC catheter 72.2% and for the SHC catheter 98.1%.

Bacteriuria↗

Expression and localization of gastrin messenger RNA and peptide in spermatogenic cells.

In previous studies we have shown that the gene encoding cholecystokinin (CCK) is expressed in spermatogenic cells of several mammalian species. In the present study we show that a gene homologous to the CCK-related hormone, gastrin, is expressed in the human testis. The mRNA hybridizing to a human gastrin cDNA probe in the human testis was of the same size (0.7 kb) as gastrin mRNA in the human antrum. By in situ hybridization the gastrinlike mRNA was localized to seminiferous tubules. Immunocytochemical staining of human testis revealed gastrinlike peptides in the seminiferous tubules primarily at a position corresponding to spermatids and spermatozoa. In ejaculated spermatozoa gastrinlike immunoreactivity was localized to the acrosome. Acrosomal localization could also be shown in spermatids with electron microscopy. Extracts of the human testis contained significant amounts of progastrin, but no bioactive amidated gastrins. In contrast, ejaculated sperm contained mature carboxyamidated gastrin 34 and gastrin 17. The concentration of gastrin in ejaculated human spermatozoa varied considerably between individuals. We suggest that amidated gastrin (in humans) and CCK (in other mammals) are released during the acrosome reaction and that they may be important for fertilization.

Animals↗

Ureteroscopic manipulation of stones in the ureter: four years experience.

Our experience of 223 ureteroscopies and stone manipulations is reported. Stone removal was successful in 82% of the cases whereof the stones were pushed back into the renal pelvis and subsequently managed with percutaneous nephrolithotomy or extracorporeal shock wave lithotripsy in 24%. For distal stones the success rate was 88%. Reasons for failure were acute obstruction of the ureter and previous surgery or irradiation to the pelvis. In six cases (4%) strictures requiring treatment developed secondary to ureteroscopy. Ureteroscopy can be a tedious and difficult procedure with a considerable learning time. In experienced hands the rate of serious complications is low and the procedure is an alternative in the treatment of ureteric stones, especially in the distal part of the ureter.

Adult↗

Approach-withdrawal and cerebral asymmetry: emotional expression and brain physiology. I.

In this experiment, we combined the measurement of observable facial behavior with simultaneous measures of brain electrical activity to assess patterns of hemispheric activation in different regions during the experience of happiness and disgust. Disgust was found to be associated with right-sided activation in the frontal and anterior temporal regions compared with the happy condition. Happiness was accompanied by left-sided activation in the anterior temporal region compared with disgust. No differences in asymmetry were found between emotions in the central and parietal regions. When data aggregated across positive films were compared to aggregate negative film data, no reliable differences in brain activity were found. These findings illustrate the utility of using facial behavior to verify the presence of emotion, are consistent with the notion of emotion-specific physiological patterning, and underscore the importance of anterior cerebral asymmetries for emotions associated with approach and withdrawal.

Adolescent↗

The Duchenne smile: emotional expression and brain physiology. II.

Facial expression, EEG, and self-report of subjective emotional experience were recorded while subjects individually watched both pleasant and unpleasant films. Smiling in which the muscle that orbits the eye is active in addition to the muscle that pulls the lip corners up (the Duchenne smile) was compared with other smiling in which the muscle orbiting the eye was not active. As predicted, the Duchenne smile was related to enjoyment in terms of occurring more often during the pleasant than the unpleasant films, in measures of cerebral asymmetry, and in relation to subjective reports of positive emotions, and other smiling was not.

Adolescent↗

BPH epidemiology and risk factors.

Benign enlargement of the prostate gland is extremely common with increasing age. The incidence of gross enlargement of the gland has been reported as 40% in 70 year-old males. Microscopic foci can be found in 80%. The disease seems to be most common in blacks, Caucasians, and Jews, but less frequent in males from the Far East. Epidemiological studies are subject to many pitfalls, and the data have to be interpreted with great caution. The data from the World Health Organization indicate a marked drop in deaths from benign prostatic hyperplasia (BPH) during the last 12-year period. Increasing age and an intact androgen supply seem to be prerequisites for BPH development. Apart from that, no other risk factors have been identified uncontrovertedly.

Adult↗