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Biomedical subjects

F Petersen

Publications and source records attributed to F Petersen.

At least 55 records · Page 3Linked to original sources

3-Alkanoyl-5-hydroxymethyl tetronic acid homologues and resistomycin: new inhibitors of HIV-1 protease. I. Fermentation, isolation and biological activity.

In the course of a screening program for HIV-1 protease inhibiting activity, six new homologues of 3-alkanoyl-5-hydroxymethyl tetronic acids (1 approximately 6) and the known natural product resistomycin (7) were isolated from cultures of the Actinomycete strain DSM 7357. The substituted tetronic acids belong to a recently described structural class of secondary metabolites. The HIV-1 activity of resistomycin (7) has not been reported before.

Actinomycetaceae↗

Otobothrium penetrans (Cestoda; Trypanorhyncha) in the flesh of belonid fish from Philippine waters.

In April 1990, 488 marine fish belonging to 30 species from central Philippine waters were examined for flesh parasitic infections that may affect their consumability. One species of hemirhamphids and 3 species of belonids harboured plerocercoids of Otobothrium penetrans Linton, 1907 (Proceedings of the U.S. National Museum 33, 85-126). This is the first record of this parasite from Pacific fish species. The highest intensity of infection found was 8 in Tylosurus crocodilus. Most of the larvae were located between the dorsal spines of the vertebral column, only 32% were found in the fillets. Based on the present material we give a description of the plerocercoid stage of the species using scanning electron microscopy of the armature and morphometrical measurements. Comparison to results from earlier findings of O. penetrans by Linton (1907; 1924, Proceedings of the U.S. National Museum 64, 1-114) and to O. kurisi by Shields (1985, International Journal for Parasitology 15: 635-643) lead to the conclusion that the latter species is a synonym for O. penetrans.

Animals↗

A novel molecular variant of the neutrophil-activating peptide NAP-2 with enhanced biological activity is truncated at the C-terminus: identification by antibodies with defined epitope specificity.

The human neutrophil-activating peptide 2 (NAP-2) belongs to the so-called beta-thromboglobulin/interleukin 8-family of chemotactic and reparative host defense cytokines. NAP-2 represents one of several N-terminally truncated cleavage products that originate from platelet-derived precursor molecules through proteolytic processing. Among these homologous isoforms that are comprised as beta-thromboglobulin antigen (beta-TG Ag), NAP-2 is recognized as the major component, having the highest potential for the activation of polymorphonuclear neutrophils (PMN). We now present evidence that there exists a second molecular form of NAP-2 with even higher biological activity. This novel isoform was detected in concentrates of culture supernatants from peripheral blood mononuclear cells, and could be separated from authentic NAP-2 by several steps of column chromatography. It had an N-terminus identical to that of NAP-2 but was biochemically different as indicated by its slightly lower molecular weight and a higher isoelectric point. To examine our hypothesis that the polypeptide represented a C-terminally truncated variant of NAP-2, we prepared synthetic peptides that were used for the induction and characterization of two rabbit antibody fractions, directed against different and defined epitopes within the C-terminal alpha-helix of the NAP-2 molecule. Comparison of reactivity patterns of these antibodies in Western blots as well as in a NAP-2 biological assay (PMN degranulation assay) confirmed that the variant NAP-2 was truncated at its C-terminus by at least one and by maximally three residues. The specific activity of the truncated polypeptide was estimated to be about four-fold higher than that of authentic NAP-2, as determined in the PMN degranulation assay. Thus, proteolytic modification at the C-terminus appears to play a role in the regulation of NAP-2-biological activity.

Amino Acid Sequence↗

Germicidin, an autoregulative germination inhibitor of Streptomyces viridochromogenes NRRL B-1551.

During germination spores of Streptomyces viridochromogenes NRRL B-1551 excrete a compound, germicidin, which has an inhibitory effect on the germination of its own arthrospores at a concentration as low as 200 pM (40 pg/ml). At higher concentrations germicidin inhibits porcine Na+/K(+)-activated ATPase and retards the germination of the cress Lepidium sativum. Germicidin is the first known autoregulative inhibitor of spore germination in the genus Streptomyces and was isolated from the supernatant of germinated spores, but also from the supernatant of the submerged culture. Spectroscopic analysis and derivatization reactions revealed germicidin to be 6-(2-butyl)-3-ethyl-4-hydroxy-2-pyrone (C11H16O3). Crude isolates of germicidin from the supernatant of submerged culture, but not from the spores, contained a second, structurally very similar compound (C10H14O3), in which in contrast to germicidin a 2-propyl instead of the 2-butyl chain was bound to C-6 and which did not show any activity in the germination and ATPase assay. The germination assay was evaluated as a new screening model for specifically active compounds.

Fermentation↗

Recombinant tumor necrosis factor-alpha potentiates neutrophil degranulation in response to host defense cytokines neutrophil-activating peptide 2 and IL-8 by modulating intracellular cyclic AMP levels.

The neutrophil-activating peptide 2 (NAP-2) and IL-8 are closely related in structure and function. In order to further determine their potential biologic roles in inflammation, we studied their interaction with TNF-alpha-primed human polymorphonuclear neutrophil granulocytes at the levels of effector functions and signal transduction. After short term priming (5 min) by TNF-alpha, suspended cytochalasin B-treated PMN responded to NAP-2 or rIL-8 by substantial augmentation of the degranulation response. After priming with 3 ng/ml TNF-alpha marker release from both azurophilic and specific granules was near maximum. NAP-2 and rIL-8 cooperated with TNF-alpha in very similar ways, as indicated by the almost identical increases in release rates that were induced by equipotent doses of either secondary stimulus. At the signal transduction level, pharmacologic elevation of intracellular cAMP led to the inhibition of NAP-2- or rIL-8-induced degranulation in primed and unprimed PMN, indicating a role for this second messenger as a negative feedback signal. Direct measurement of intracellular cAMP revealed that TNF-alpha by itself did not affect its levels. Instead, TNF-alpha reduced both the scale as well as the duration of the cAMP burst generated in response to secondary stimuli NAP-2 or rIL-8. Thus, there is evidence that TNF-alpha priming of neutrophils for enhanced NAP-2- or rIL-8-promoted degranulation involves the antagonistic down-modulation of stimulus-induced rises in cAMP.

Cell Degranulation↗

A prospective study of risk for peptic ulcer disease in Seventh-Day Adventists.

Cross-sectional and prospective data were collected and analyzed to identify risk factors for the development of peptic ulcer disease in a population of 34,198 white, non-Hispanic Seventh-Day Adventists. On a life-style questionnaire administered in 1976, 3853 subjects reported ever having had a physician-diagnosed peptic ulcer for a lifetime prevalence of 13.5% for men and 11.0% for women. Odds ratios of greater than 2.0 (P less than 0.0001) were observed for use of "stronger pain relievers," current cigarette smoking, and history of rheumatism or other arthritis and coronary disease. For both sexes, lower but statistically significant odds ratios (P less than 0.05) were found for eating white bread, "snacking," ever having smoked cigarettes, low church involvement, poor dietary adherence, high blood pressure, rheumatoid arthritis, aspirin use, job frustration and dissatisfaction, having a "blue collar household," and having less education. During 3 years of follow-up, 154 incident cases of ulcer were identified. The average annual incidence was 1.7 per 1000. Multivariate adjusted relative risks were statistically significant for using stronger pain relievers (P less than 0.001), having rheumatic conditions (P = 0.006), and using aspirin (P = 0.013). These findings suggest that rheumatic disease and use of aspirin and stronger pain relievers are more important risk factors for development of peptic ulcer disease in certain populations than diet, life-style, or psychological or socioeconomic characteristics.

Adult↗

Fat and gastric acid secretion.

To evaluate the importance of the terminal carboxyl group of the oleic acid molecule in the inhibition of gastric acid secretion, 6 normal persons were stimulated twice with duodenal perfusates containing either 20 mM oleic acid or 20 mM oleyl alcohol. Oleic acid significantly inhibited the gastric acid secretion stimulated by pentagastrin (100 ng/kg/h) and increased the levels of secretin in plasma. The effect of oleyl alcohol was insignificant. It is concluded that the carboxyl group of the fat molecule has an important role in the inhibition of gastric acid secretion, and the effect could in part be attributable to the release of secretin into plasma.

Adult↗

Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data.

PURPOSE: A case-controlled study of patients who reported to the European Bone Marrow Transplant Group (EBMTG) was performed to investigate the relative roles and efficacy of allogeneic (alloBMT) and autologous bone marrow transplantation (ABMT) in non-Hodgkin's lymphoma. PATIENTS AND METHODS: Of 1,060 patients who reported to the lymphoma registry, 938 patients underwent ABMT and 122 patients underwent alloBMT. A case-controlled study was performed by matching 101 alloBMT patients with 101 ABMT patients. The case matching was performed after the selection of the main prognostic factors for progression-free survival by a multivariate analysis. RESULTS: The progression-free survival was similar in both types of transplants (49% alloBMT v 46% ABMT). The overall relapse and progression rate for the alloBMT patients was 23% compared with 38% in the ABMT patients. This difference was not significant statistically. In the lymphoblastic lymphoma subgroup, alloBMT was associated with a lower relapse rate than ABMT (24% alloBMT v 48% ABMT; P = .035). The progression-free survival, however, was not significantly different because patients with lymphoblastic lymphoma who underwent alloBMT had a higher procedure-related mortality (24% alloBMT v 10% ABMT; P = .06). A significantly lower relapse/progression rate was also observed in patients with chronic graft-versus-host disease (cGVHD) compared with those patients without (0% cGVHD v 35% no cGVHD; P = .02). Fourteen of 18 patients who had cGVHD also had lymphoblastic lymphoma. CONCLUSION: This study suggests that ABMT and alloBMT for non-Hodgkin's lymphoma are comparable, with the exception of lymphoblastic lymphoma in which a graft-versus-lymphoma effect may account for the lower relapse rate for patients who underwent alloBMT.

Adolescent↗

Rate-related left bundle branch block as a cause of non-ischemic chest pain.

A case is presented of rate-dependent left bundle branch block associated with chest pain in a patient with angiographically normal coronary arteries. Lactate extraction showed no evidence of myocardial ischemia. It appears that in this case, chest pain was associated with sudden ventricular asynergy rather than myocardial ischemia.

Bundle-Branch Block↗

Coronary sinus mapping through a persistent left superior vena cava in Wolff-Parkinson-White syndrome.

Persistent left superior vena cava is not an uncommon finding in patients undergoing evaluation for preexcitation syndromes. In such patients, this anatomical configuration might be used advantageously for mapping and ablation of a left-sided accessory pathway during electrophysiologic studies. We successfully used this mapping approach in a 16-year-old boy undergoing evaluation for Wolff-Parkinson-White syndrome. The patient was found to have a persistent left superior vena cava confluent with the coronary sinus. During electrophysiologic studies, mapping of the left-sided accessory pathway was facilitated by retrograde entry into the coronary sinus through the persistent left superior vena cava. Mapping was also performed in the conventional manner, yielding identical results and thus validating this new technique.

Journal Article↗

Cryosurgical modification of the atrioventricular node for treatment of atrioventricular junctional reentrant tachycardia.

Surgical correction of atrioventricular nodal reentrant tachycardia with preservation of atrioventricular nodal conduction in a 28-year-old woman is reported. At surgery, electrophysiologic mapping techniques were used during tachycardia to reveal and enable ablation of the appropriate site of atrial activation. Postoperative electrophysiologic studies indicated successful atrioventricular nodal modification.

Journal Article↗

Neutrophil-activating polypeptides IL-8 and NAP-2 induce identical signal transduction pathways in the regulation of lysosomal enzyme release.

Interleukin-8 (IL-8/NAP-1), the neutrophil-activating peptide 2 (NAP-2), and formyl-peptides (fMLP) have been described as potent stimulators for human neutrophils (PMN). We have compared the mechanism of signal transduction induced by these factors during neutrophil activation (elastase release), by using activators and inhibitors and by direct measurement of the enzymatic activity of kinases. Moreover, costimulation kinetics of the combined factors were analyzed. Our results show that each of these stimulators induces elevated levels of cAMP, indicating the activation of adenylate-cyclase. Further results obtained with the kinase inhibitor H-7 and the cAMP analogue dibutyryl-cAMP (dbcAMP) gave evidence that cAMP-dependent kinases are involved in the down-regulation of the activation process. Degranulation could not be prevented by the inhibitor W-7, nor did the treatment of cells with calcium ionophore (A23187) lead to elevation of intracellular calcium levels. Both phenomena exclude the participation of calcium calmodulin-dependent kinases. Further results obtained with the novel protein kinase C (PKC) inhibitor BM 41440 as well as by direct measurement of PKC enzyme activity demonstrated the involvement of PKC in fMLP-mediated stimulation but not with IL-8/NAP-1 or NAP-2. Analysis of costimulation experiments conducted with these three factors and TPA confirmed these results and gave evidence that fMLP activates two different signaling pathways, one of which is PKC dependent, while the other is not. Moreover, our data indicate that NAP-2, IL-8/NAP-1, and fMLP use identical PKC-independent transduction mechanisms.

Amino Acid Sequence↗

[Standardized treatment].

Treatment protocols have not been well-defined, and may comprise anything from mere instructions regarding simple procedures to guide-lines for the treatment of the whole course of a disease. The discussion about treatment protocols has continued on since the 70's, and the system has been introduced into the Health Service of a number of countries. Those in favour of the programmes have focused, in particular, on the economic advantages and the advantage of achieving a certain quality of treatment, while those opposing the programmes insist that clinical freedom is at stake. We have found, especially via literature studies, that little knowledge is available as to what extent treatment protocols or case management protocols are employed, e.g., in Sweden and the USA where there have been a number of advocates of these systems. We have only been able to find two evaluation studies of more comprehensive programmes. In these two studies, the total expenditure for treatment was not clearly reduced, and as there were no well-defined parameters for quality of care, it has not been possible to demonstrate any improvement in the quality itself. It is, of course, possible that the discussion in respect of treatment protocols has indirectly had an effect on clinical thought, including those countries where these systems have not been introduced.

Clinical Protocols↗

Applications of a method for setting air quality standards based on epidemiological data.

A method for setting air quality standards for long-term cumulative exposures of a population based on epidemiological studies has been developed. It uses exposure estimates interpolated from monitoring stations to zip code centroids, each month applied to zip code by month residence histories of the population. Two alternative cumulative exposure indices are used--hours in excess of a threshold, and the sum of concentrations above a threshold. The indices are then used with multiple logistic regression models for the health outcome data to form dose response curves for relative risk, adjusting for covariates. These curves are useful for determination of at what exposure amounts and threshold levels, effects which have both statistical and public health significance begin to occur. The method is applied to a ten year follow-up of a sub cohort of 7,343 members of the National Cancer Institute-funded Adventist Health Study. Up to 20 years of residence history was available. Analysis for prevalence of symptoms was conducted for four air pollutants--total oxidants, sulfur dioxide, nitrogen dioxide, and total suspended particulates. For each pollutant, cumulated exposures were calculated above each of five different thresholds. Statistically significant effects were noted for total suspended particulates, total oxidants, sulfur dioxide, past and passive smoking.

Air Pollution↗

The effect of intravesically administered Cetiprin on bladder spasms after transurethral resection of the prostate. A double-blind randomized study.

A double-blind study of the short-term effects of intravesically administered emepronium bromide (Cetiprin) versus placebo on bladder spasms after transurethral prostatectomy was done in 40 male patients. In the Cetiprin group there was a significant decline in the need for analgesia, and significantly fewer catheter problems. The use of intravesically instilled Cetiprin is recommended only in cases of severe postoperative bladder spasms.

Administration, Intravesical↗

The incidence of ureteral obstruction secondary to aorto-femoral bypass surgery. A prospective study.

Hydronephrosis is reported to be an infrequent complication of aorto-femoral bypass operations. To define the true incidence of this complication, renography (131I-Hippuran) and renal scintigraphy (99 Technetium) were performed both pre- and postoperatively on 56 asymptomatic patients following successful aortic reconstruction. No patient developed signs of ureteral obstruction. It is concluded that hydronephrosis is a rare complication to aorto-femoral bypass surgery and postoperative control is only indicated in patients with symptoms from the urinary tract.

Adult↗