Phosphopeptides are a useful tool for the investigation of phosphorylation as a reversible posttranslational modification. There is a growing interest in using mimics of phosphoamino acids involved in phosphorylation in order to study the enzymes concerned in these processes. These mimics should contain a non-hydrolysable or isoelectrically modified phosphate moiety to be used as a specific inhibitor of phosphatases and kinases. We introduce sold-phase synthesis of H- and methylphosphonopeptides as a new class of mimics of phosphotyrosyl peptides. The peptides were synthesized on solid phase using the standard fluorenyl-methyloxycarbonyl (Fmoc) strategy. Tyrosine residues were incorporated as allyl-protected derivatives, which were selectively deprotected on the resin by treatment with Pd(PPh3)4. The peptide resin carrying the side-chain unprotected tyrosine of the model peptide Gly-Gly-Tyr-Ala was phosphonylated with di-tert-butyl-N,N-diethyl-phosphoramidite in the presence of 1H-tetrazole, yielding H-phosphonopeptides after trifluoroacetic acid (TFA) cleavage. Alternatively, phosphonylation of the unprotected tyrosine with O-tert-butyl-N,N-diethyl-P-methylphosphonamidite catalysed by 1H-tetrazole and followed by oxidation led to the methyphosphonopeptides after TFA cleavage. We obtained both the H-phosphonopeptides and the methylphosphonopeptides of the tetrapeptide in high yields and purities above 90%, according to reversed-phase high-performance liquid chromatography (RP-HPLC). To investigate the general applicability of our new methodology, we synthesized phosphonopeptides up to 13 amino acids long, corresponding to recognition sequences of tyrosine kinases. After cleavage and deprotection, all phosphonopeptides were obtained in high yields and purities of about 90%, as shown by mass spectrometry. The only by-product found was the unmodified peptide.

Acylation↗

PubMedDate not supplied

Imaging diagnosis of sclerosing peritonitis and relation of radiologic signs to the extent of the disease.

BACKGROUND: Sclerosing peritonitis (SP) is a serious complication of chronic ambulatory peritoneal dialysis (CAPD) that is characterized by thickened peritoneal membranes, leading to impaired ultrafiltration and intestinal obstruction. The aim of this study was to analyze the radiographic signs of SP in symptomatic patients and to compare them with the histological severity of the disease. METHODS: In 14 patients with symptoms of intestinal obstruction related to SP, plain films of the abdomen, upper GI follow-through examinations, ultrasonography, and computed tomography were evaluated retrospectively. Imaging findings such as bowel motility, bowel wall and peritoneal thickness, and the presence of intraperitoneal fluid collections were correlated to the histological degree of the fibrosis. RESULTS: Signs of intestinal obstruction and disturbed motility were present in all cases. In addition, patients with histologically severe SP had loculated fluid collections, thickening of the bowel wall and/or peritoneum, peritoneal calcifications, and thickened peritoneal membranes, and suffered more often from postoperative complications. CONCLUSION: The detection of characteristic radiographic signs in CAPD patients presenting with symptoms of intestinal obstruction may suggest the presence of severe SP and should lead to cautious surgical interventions.

Adult↗

PubMedDate not supplied

Electrohydraulic extracorporeal non-water bath shock-wave lithotripsy of gallstones: two years' experience.

A prospective study was performed to evaluate the effectiveness of extracorporeal shockwave lithotripsy (ESWL) using a non-water bath lithotripter in combination with oral chemolitholysis on gallstone clearance. Patients were treated without general anesthesia or parenteral analgesia. We treated 74 patients selected according to the widely accepted criteria. Only 2 patients could not be sufficiently treated because of pain. After a 2 year period, 24 (32%) patients showed complete stone clearance, 35 (47%) patients had residual fragments, 5 (7%) patients underwent cholecystectomy, 2 (3%) patients were lost to follow up, and 8 (11%) patients discontinued the treatment before fragment clearance. According to the life-table estimate, 77% of our patients with successful ESWL and uncomplicated oral chemolitholysis are stonefree after 1 year. We consider the major advantage of this nonsurgical treatment of gallstone disease is that general anesthesia or parenteral analgesia has become unnecessary.

Adult↗

PubMedDate not supplied

Finasteride is the main inhibitor of 5alpha-reductase activity in microdissected dermal papillae of human hair follicles.

Explore the source record for details and available documents.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMedDate not supplied

Does multiplane transesophageal echocardiography improve the assessment of prosthetic valve regurgitation?

Assessment of prosthetic valve regurgitation by echocardiography remains difficult. To study the value of the newly introduced multiplane transesophageal technology for this purpose, prosthetic valve regurgitation was examined in 63 consecutive patients with 35 mitral and 33 aortic prostheses (23 bioprostheses and 45 mechanical prostheses). Transvalvular, paravalvular and, in mechanical valves, normal or pathologic transvalvular regurgitation were identified first with 0 degrees (transverse) and 90 degrees (longitudinal) planes combined with flexion of the echoscope tip and then additionally with multiple intermediary planes by transducer rotation. In a subgroup of 20 patients interobserver variability was evaluated. Both methods showed regurgitation in 56 of 68 valves; one additional case of regurgitation was seen by multiplane imaging only. However, 19 cases of regurgitation were not clearly classifiable by biplane transesophageal echocardiography compared with only three with multiplane transesophageal echocardiography. Grading of severity was concordant by both modalities in 66 and discordant in only two cases. Observers disagreed on severity in two of 20 cases based on biplane imaging but in none based on multiplane imaging; classification of regurgitation differed in six of 20 (biplane) and one of 20 (multiplane), respectively. Multiplane transesophageal imaging improves classification of prosthetic regurgitation but has little effect on severity grading.

Adult↗

PubMedDate not supplied

The prognosis for women after an acute myocardial infarction: recommendations for practice.

Women have different needs than men after a myocardial infarction. Therefore, nursing care for women should be based on current research rather than research based on findings using the "male model." This article examines research on the prognosis for women after a myocardial infarction and recommends practice changes for the critical care nurse based on these findings.

Critical Care↗

PubMedDate not supplied

Possible relationship of gastroesophagopharyngeal acid reflux with pathogenesis of chronic sinusitis.

UNLABELLED: Gastroesophagopharyngeal reflux (GEPR) has been suggested as a cause of pediatric sinusitis. However, its contribution to the pathogenesis of chronic sinusitis in adults has not been systematically investigated. We evaluated the prevalence of GEPR in 11 CT confirmed chronic sinusitis patients (51 +/- 4 years) who had not responded to conventional therapy, and 11 normal healthy controls (44 +/- 7 years). A 3-site ambulatory esophagopharyngeal pH monitoring technique (probe location: 2 cm proximal, 3-4 cm distal to UES and 5 cm proximal to LES high pressure zones) was used. A pharyngeal pH drop was accepted as a true reflux event only if it was coincident with or preceded by esophageal pH declines of a similar or larger magnitude. Studies were performed while subjects were on a uniform 2500 calorie diet (provided). RESULTS: Ambulatory pH monitoring documented GEPR in seven of 11 patients (1-12 episodes) and two of 11 normal volunteers (1,2 episodes) (p < 0.05). A total of 34 nonbelch related pharyngeal acid reflux events were identified in patients, but none was associated with coughing. In both groups, all pharyngeal acid events occurred in the upright position. Compared to normal controls prevalence of pharyngeal reflux of gastric acid is significantly higher in patients with chronic sinusitis unresponsive to conventional therapy and suggests a different esophagopharyngeal distribution pattern of gastric refluxate in this patient group; these findings suggest that GEPR may contribute to the pathogenesis of chronic sinusitis in some adult patients.

Adult↗

PubMedDate not supplied

Growth factors in early hair follicle morphogenesis.

Classic studies show the embryonic epidermis and mesenchyme must communicate during embryogenesis to form a hair follicle. However, the methods of communication between and within the epidermis and dermis that regulate hair follicle development are poorly understood. Potentially, the epidermis and dermis communicate by utilizing cell surface receptor expression, cell adhesion molecules, extra cellular matrix products, and chemical messaging via secreted molecules. With each product involved in cell communication, intensity, potency, time of production during hair follicle development, production duration, and spatial distribution must all be considered. The total sum of these factors must provide adequate information to cells about their respective location and role within the developing hair follicle. Here we review the potential contribution made to hair follicle embryogenesis by growth factors and their receptors.

Bone Morphogenetic Proteins↗

PubMedDate not supplied

Current understanding of androgenetic alopecia. Part II: clinical aspects and treatment.

The first signs of androgenetic alopecia (AGA) may start to develop with the onset of puberty. The prevalence of progressive AGA approaches 50% of Caucasian men and women beyond the age of 40; whereas in Asian, native American and African-American men the prevalence is lower and AGA is less severe. Only exceptionally laboratory tests or scalp biopsies are needed to confirm the diagnosis. Therefore the clinical assessment of AGA is largely a matter of common sense and practice. The loss of hair is often trivialised, but hair loss may have profound effects on a patient's well-being and quality of life. The treatment of AGA is obscured by myths. Many products or procedures are advertized for the treatment of AGA such as vitamins, trace elements, exotic herbs, amino acids, "soft laser", scalp massage, etc. Most of these techniques or substances have never been verified in sound clinical trials. Because of the psychosocial impact of hair loss, however, it is important to explain to patients what they may expect in terms of continuing hair loss, and that response to any therapy may be slow and may include hair regrowth or only retardation of further thinning. The aim of AGA treatment is to reverse or to stabilize the process of HF miniaturization and with this overview we summarize the present treatment modalities for both men and women.

5-alpha Reductase Inhibitors↗

PubMedDate not supplied

Genetic susceptibility and severity of alopecia areata in human and animal models.

Alopecia areata (AA) is a non-scarring, inflammatory form of hair loss. Human and animal model observations suggest that AA is an autoimmune mediated disease. Genetic influence has been clearly demonstrated in many other autoimmune diseases and one would expect that AA is no exception. AA in rodent models involves genetic susceptibility and it is possible to cross breed the AA phenotype to unrelated rodent strains. Segregation analysis of rodent breeding programs suggests the involvement of several dominant and secondary genes. The increased frequency of AA in genetically related individuals, suggests that human AA expression also involves genetic susceptibility. Within the general population, AA does not segregate as a Mendelian, monogenic trait. AA is a continuous trait with varying degrees of hair loss within the affected population. This suggests that human AA expression involves a complex interaction of multiple genes. AA is most likely a polygenic disease where several, potentially identifiable, major genes affect disease susceptibility and minor severity modifying genes may further affect the phenotype. Here we review the literature on humans and animal models for AA to identify data in support of AA as a polygenic, multivariate penetrance disease with a threshold level for disease onset. Genome wide allelic association screening of animal models and genetically related human sibling pairs may be a suitable approach to identifying susceptibility and severity modifying genes for AA.

Alopecia Areata↗

PubMedDate not supplied

Influence of estrogens on the androgen metabolism in different subunits of human hair follicles.

The molecular pathways involved in estrogen-mediated induction of hair growth in androgenetic alopecia are unknown. Some authors found that estradiol (E) inhibited 5alpha-reductase (5alpha-R) activity and therefore we addressed the question whether 17alpha- or 17beta-E are able to modulate the activity of 5alpha-R, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) or 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in isolated compartments of human hair follicles. For this purpose, scalp biopsies from volunteers were taken and from each biopsy root sheaths, connective tissue sheaths and dermal papillae (DP) were dissected and incubated in the presence of 3H-testosterone (T) and, in addition, either 17alpha-E, 17beta-E, progesterone or finasteride for up to 48 hrs. Thereafter high-performance liquid chromatography analysis of culture supernatants was performed to detect T-metabolites. At the tested concentrations, finasteride was found to be a major inhibitor of dihydrotestosterone (DHT) formation. Even 1 nM finasteride inhibited DHT synthesis in DP by 86% and 1 nM progesterone by 75%. Estrogens were less able to inhibit the synthesis of DHT in DP (e.g. 100 nM 17alpha-E: 20%; 100 nM 17beta-E: 60%). Whether E directly inhibits 5alpha-R in DP's or whether the effect of estrogens might be explained by an increased conversion of T to the weaker androgens such as androstendione (via 17beta-HSD), androstenediol (via 3beta-HSD) or 17beta-E (via aromatase), thereby diminishing the amount of T available for the conversion to DHT, remains to be shown.

3-Hydroxysteroid Dehydrogenases↗