Determination of isomeric acid dopamine metabolites in human cerebrospinal fluid by mass fragmentography

A method for the quantitative determination of the isomers 4-hydroxy-3-methoxyphenylacetic acid (HVA) and 3-hydroxy-4-methoxyphenylacetic acid (iso-HVA) in cerebrospinal fluid (CSF) by mass fragmentography has been developed. The heptafluorobutyryl methyl ester derivations of the two compounds could not be separated by gas chromatography. The relative intensity of the base peak (m/e 333) and the molecular ion (m/e 392) in the mass spectra were, however, quite different and allowed a separate determination. Contradictory to a previous report, it was found that the concentration of iso-HVA was less than 2% of the HVA level in the investigated 12 CSF samples from patients with different diseases.     

The primary structure of crystallizable monoclonal immunoglobulin IgG1 Kol. II. Amino acid sequence of the L-chain, gamma-type, subgroup I

The immunoglobulin Kol was the first intact antibody molecule which was characterized by high-resolution X-ray crystallography. Furthermore the complete amino-acid sequence of the heavy (H)-chain is known. Here we report the complete amino-acid sequence of the light (L)-chain of the monoclonal immunoglobulin Kol (IgG1). The polypeptide has an Mr of 22,781, consists of 216 amino acids and due to its structure is of the lambda-type. With the characteristic amino acids threonine, asparagine, threonine, glycine and lysine in positions 101, 114, 116, 154, and 165, respectively the Kol L-chain is of the Mcg isotype. With the proteins Mcg, Mot, Bur, Loc and Mem six myeloma-derived amino-acid sequences of the same isotype are known. The amino-acid sequence of the N-terminal variable part is characteristic of subgroup 1. This contribution completes the primary structure of IgG1 Kol.     

An alternative classification of trypanorhynch cestodes considering the tentacular armature as being of limited importance

Based on a light- and scanning electron microscopical study of scolex morphology, tentacles and surface structures of 31 trypanorhynch species, an alternative classification of the trypanorhynch cestodes, adults, plerocerci and postlarvae, is presented. The arrangement of the tentacular armature is no longer used as a distinguishing feature for four different superfamilies. Instead, the presence or absence of ciliated pits and prebulbular organs is used to define three superfamilies: Tentacularioidea Poche, 1926; Otobothrioidea Dollfus, 1942; and Eutetrarhynchoidea Guiart, 1927. A total of 12 families are defined by the characters: the presence/absence of blastocysts, the number of bothridia and the reduction of the rhyncheal apparatus, together with a new character, complete rows of tentacular hooks (homeoacanth and heteroacanth typica) versus rows of hooks partly reduced (heteroacanth atypica and poeciloacanth). Of the 19 families previously accepted, 10 are retained (Eutetrarhynchidae, Gilquiniidae, Lacistorhynchidae, Mixodigmatidae, Otobothriidae, Paranybeliniidae, Pterobothriidae, Shirleyrhynchidae, Sphyriocephalidae and Tentaculariidae, all sensu nov.); one family is reinstated (i.e. Aporhynchidae Poche, 1926 sensu nov.) and a new one is added (i.e. Pseudotobothriidae n. fam.). Advantages of this alternative classification of trypanorhynch cestodes are: (i) the resolution of incongruities and questions caused by the use of the tentacular armature to distinguish superfamilies; (ii) the criteria for the establishment of higher taxa, superfamilies and families are clearly defined; (iii) with the findings of new species with different character combinations, this system can be enlarged up to 4 superfamilies and 48 families without loosing its stability; and (iv) all existing genera are easily re-assigned to the superfamilies and families.     

Letter: Preliminary x-ray data from well-ordered crystals of a human immunoglobulin G molecule

Crystals of an intact immunoglobulin G molecule, which are suitable for high resolution X-ray analysis, have been grown. The space group is P3₁21 (or enantiomorph) and the crystallographic diad relates the two halves of one molecule.     

Evolution and disappearance of sympatric Coregonus albula in a changing environment—A case study of the only remaining population pair in Sweden

During the past 50 years, Fennoscandian populations of spring‐spawning Baltic cisco (Coregonus albula), sympatric to common autumn‐spawners, have declined or disappeared; for example, three out of four known spring‐spawning populations in Sweden are regarded as extinct. Over the same period, the climate has changed and populations have been subject to other anthropogenic stressors. We compared historic (1960s) and recent (1990–2000s) morphological data from the still‐existent sympatric cisco populations in Lake Fegen, Sweden. Phenotypic changes were found for spring‐spawners making them more similar to the sympatric autumn‐spawners that had remained virtually unchanged. Based on results for other salmoniform fishes, a phenotypically plastic response to increased temperature during early development appears unlikely. The recent material was also analyzed with microsatellite markers; long‐term effective population size in spring‐spawners was estimated to be about 20 times lower than autumn‐spawners, with signs of long‐term gene flow in both directions and a recent genetic bottleneck in spring‐spawners. We suggest the change toward a less distinct phenotype in spring‐spawners to reflect a recent increase in gene flow from autumn‐spawners. Time since divergence was estimated to only c. 1,900 years (95% CI: 400–5,900), but still the Fegen populations represent the most morphologically and genetically distinct sympatric populations studied. Consequently, we hypothesize that less distinct population pairs can be even younger and that spring‐spawning may have repeatedly evolved and disappeared in several lakes since the end of the last glaciation, concurrent with changed environmental conditions.     

Quantitative variability of 342 plasma proteins in a human twin population

The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood‐based biomarker studies.     

Binding Affinity,Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with ²¹¹At-Rebmab200. Here, the biodistribution of ²¹¹At-Rebmab200 was evaluated, as was the utility of ^99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that ^99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.