Melanotropin-potentiating factor isolated from filtrate of uremic patients suffering from melanosis and carbohydrate intolerance

Summary Following the characterization of a hexadecapeptide,-endorphin, melanotropin-potentiating factor (MPF) was isolated from the filtrate of uremic patients suffering from melanosis and carbohydrate intolerance. The structure of MPF has been determined on the bases of chemical and physicochemical examinations which included HPLC, Edman sequence analysis combined analysis of the amino acid composition and FAB-MS analysis. An accumulation of MPF might be a cause of melanosis in uremic patients.Abbreviations Et₃N triethylamine - TFA trifluoroacetic acid - HF hydrogen fluoride - CH₃CN acetonitrile - DCC dicyclohexyl-carbidimide - HOBT N-hydroxybenzotriazole - OBzl benzyl ester - Boc tert-butoxycarbonyl - Z bebzyloxycarbonyl - EtOH ethanol - ECUM extracorporeal ultrafiltration method - FAB-MS fast atom bombardment spectrometry - HPLC high-performance liquid chromatography - TLC thin-layer chromatography - AcOH acetic acid - AP-M aminopeptidase-M - PTH phenylthiohydantoin     

Syntheses and effects of [Glu34]-thymopoietin II fragment 32-45 and its analogs on the impaired T-cell transformation in a patient with common variable immunodeficiency

[Glu34]-thymopoietin II fragment 32-45 and its three analogs were prepared by substitution of the amino acid residue at position 37. These peptides were synthesized by a conventional solution method, followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole in trifluoroacetic acid in the presence of m-cresol. These peptides were tested for their effects on impaired T-cell transformation by phytohemagglutinin in the common variable immunodeficiency. The relative potency of the synthetic [Glu34]-thymopoietin II fragment 32-45 was one-half of that of synthetic thymopoietin II fragment 32-45. Among these tetradecapeptide analogs, one analog in which Val37 was replaced by Ile exhibited a potent activity which was more than that of the synthetic [Glu34]-thymopoietin II fragment 32-45. The relative potencies of Thr37 and Tyr37 analogs were one-third and one-half, respectively of that of the synthetic [Glu34]-thymopoietin II fragment 32-45.     

Efficient acetic acid production by repeated fed-batch fermentation using two fermentors

Summary In acetic acid fermentation, the number of viable cells decrease as the acetic acid concentration increases to more than about 40 g/l, which means that the productivity attainable by conventional fed-batch and repeated fed-batch operations using one fermentor is limited. In this paper, based on a fed-batch experiment using Acetobacter aceti 2096, a mathematical model was developed. The optimization carried out showed the superiority of repeated fed-batch operation using two fermentors. The performance evaluation was made with respect to productivity and product concentration. It was shown to be attractive in practice to use multiple fermentors, in particular for high product concentrations. Experiments were then conducted to ascertain the simulation results. Offprint requests to: T. Kobayashi     

Clock,love and memory: Circadian and non-circadian regulation of Drosophila mating behavior by clock genes

Sleep and Biological Rhythms - Mating behavior is arguably the most important and fundamental behavior in animals. In the fruit fly, Drosophila melanogaster, both experience-dependent and...     

Identification and synthesis of a tripeptide in ECUM fluid of an upemic patient

An unidentified ninhydrin and Pauly reaction positive substance of basic nature was found in the ECUM fluid of an uremic patient. This substance was isolated from ECUM fluid by the methods of ultrafiltration method and gel-filtration, and identified as H-His-Gly-Lys-OH by amino acid analysis, manual Edman degradation method and physical constants and analytical data of synthetic tripeptide.     

Soluble Amyloid Precursor Protein 770 Is Released from Inflamed Endothelial Cells and Activated Platelets: A NOVEL BIOMARKER FOR ACUTE CORONARY SYNDROME*

Most Alzheimer disease (AD) patients show deposition of amyloid β (Aβ) peptide in blood vessels as well as the brain parenchyma. We previously found that vascular endothelial cells express amyloid β precursor protein (APP) 770, a different APP isoform from neuronal APP695, and produce Aβ. Since the soluble APP cleavage product, sAPP, is considered to be a possible marker for AD diagnosis, sAPP has been widely measured as a mixture of these variants. We hypothesized that measurement of the endothelial APP770 cleavage product in patients separately from that of neuronal APP695 would enable discrimination between endothelial and neurological dysfunctions. Using our newly developed ELISA system for sAPP770, we observed that inflammatory cytokines significantly enhanced sAPP770 secretion by endothelial cells. Furthermore, we unexpectedly found that sAPP770 was rapidly released from activated platelets. We also found that cerebrospinal fluid mainly contained sAPP695, while serum mostly contained sAPP770. Finally, to test our hypothesis that sAPP770 could be an indicator for endothelial dysfunction, we applied our APP770 ELISA to patients with acute coronary syndrome (ACS), in which endothelial injury and platelet activation lead to fibrous plaque disruption and thrombus formation. Development of a biomarker is essential to facilitate ACS diagnosis in clinical practice. The results revealed that ACS patients had significantly higher plasma sAPP770 levels. Furthermore, in myocardial infarction model rats, an increase in plasma sAPP preceded the release of cardiac enzymes, currently used markers for acute myocardial infarction. These findings raise the possibility that sAPP770 can be a useful biomarker for ACS.     

Heparanase regulates esophageal keratinocyte differentiation through nuclear translocation and heparan sulfate cleavage

Heparanase is an endo-beta-glucuronidase that specifically cleaves heparan sulfate (HS) chains. Heparanase is involved in the process of metastasis and angiogenesis through the degradation of HS chains of the extracellular matrix and cell surface. Recently, we demonstrated that heparanase was localized in the cell nucleus of normal esophageal epithelium and esophageal cancer, and that its expression was correlated with cell differentiation. However, the nuclear function of heparanase remains unknown. To elucidate the role of heparanase in esophageal epithelial differentiation, primary human esophageal cells were grown in monolayer as well as organotypic cultures, and cell differentiation was induced. Expression of heparanase, HS, involucrin, and p27 was determined by immunostaining and Western blotting. SF4, a novel pharmacological inhibitor, was used to specifically inhibit heparanase activity. Upon esophageal cell differentiation, heparanase was translocated from the cytoplasm to the nucleus. Such translocation of heparanase appeared to be associated with the degradation of HS chains in the nucleus and changes in the expression of keratinocyte differentiation markers such as p27 and involucrin, whose induction was inhibited by SF4. Furthermore, these in vitro observations agreed with the expression pattern of heparanase, HS, involucrin, cytokeratin 13, and p27 in normal esophageal epithelium. Nuclear translocation of heparanase and its catalytic cleavage of HS may play a critical role in the differentiation of esophageal epithelial cells. Our study provides a novel insight into the role of heparanase in an essential differentiation process.