Über die Wechselwirkung des Katalysators und Cokatalysators mit dem Monomeren und dem Polymeren bei der kationischen Polymerisation des Isobutylens. II. Modellstudium des Polymerisations-Depolymerisations-Gleichgewichts im System Triisobutylen/AlBr3/DBr/Heptan

In the reaction of triisobutylene with AlBr₃/DBr system, backbone isomerization and formation of higher oligomers takes place, in addition to deuteration. Both reactions are explained by the cleavage of the backbone bonds of the intermediate carbonium ions. The fragments formed can react with other components of the reaction system. The possible role of these reactions in the mechanism of termination and chain transfer in the cationic polymerization of isobutylene is discussed briefly.     

Baseline levels of chromosome instability in the human lymphoblastoid cell TK6

Induced genomic instability in the human B lymphoblastoid cell line TK6 manifests itself as increases in end-to-end chromosome fusions and non-reciprocal chromosome translocations. It is not associated with elevated frequencies of specific locus mutations or other cytogenetic alterations. Previous studies on a limited number of cells and end-points suggested that induced instability in TK6 mirrors spontaneous instability in terms of the types of alterations observed. In the present study we expanded on our previous analysis to include more cells and more end-points in order to derive a more precise measure of spontaneous instability in TK6 cells. The frequency of normal growth rate thymidine kinase mutants (TK(-/-)), measured in 44 independently isolated clones, was 2.73 +/- 0.78 x 10(-6)/cell, while that for slow growth mutants was 2.39 +/- 0.52 x 10(-6)/cell. These are similar to the frequencies observed for HPRT mutants in primary human cells. There was wide variation in chromatid break frequencies, but the average break frequency, at 0.04+/-0.01 breaks/cell, was only slightly higher than that reported for primary human cells. In contrast, the dicentric frequency of 0.006/cell was more than 10-fold higher for TK6 cells than that reported for normal primary human cells. Furthermore, the dicentrics in TK6 cells are unusual in that they are the result of end-to-end chromosome fusions. TK6 cells also show much higher levels of non-reciprocal chromosome translocations than are usually observed in primary human cells. The results suggest an inherent instability in TK6 cells that differs from what is observed in primary cells in that it affects the frequency of end-to-end chromosome fusions and non-reciprocal chromosome translocations, but not TK gene mutations or other cytogenetic alterations.     

Primary manifestation of Hodgkin’s disease in the central nervous system

 A 62-year-old woman presented with loss of memory and a mild hemiparesis. Neuroradiology demonstrated a left frontoparietal tumour. Biopsy specimens of this lesion revealed intracerebral Hodgkin’s lymphoma, a diagnosis supported by immunohistochemical reactions of the tumour cells for the CD30 antigen. Additional cell cycle studies revealed a high proliferative activity of the tumour cells in association with absence of apoptosis. There was no evidence that overexpression of bcl-2 or Epstein-Barr virus infection was involved in the pathogenesis of this neoplasm. Lymphomas in the lung were detected 3 months later. Following neurosurgical excision, radiotherapy, and chemotherapy, the patient had no evidence of Hodgkin’s disease after 13 months of follow-up. Received: 8 October 1997 / Accepted: 8 December 1997     

Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system

In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-chain of cytokine receptors, are described below as well as attempts to target beta-amyloid peptide aggregation. Parts of the review are also dedicated to targeting of pathologic conditions in the brain and in other tissues with peptides as well as methods to deliver larger molecules through the "blood--brain barrier" by exploring receptor-mediated transport, or elsewhere in the body by using peptides as carriers through cellular membranes. In addition to highlighting current developments in the field, we also propose, for future drug targets, the components of the inflammasome protein complex, which is believed to initiate the activation of caspase- 1 dependent signaling events, as well as other pathways that signal inflammation. Thus we discuss the possibility of targeting inflammasome components for negative or positive modulation of an inflammatory response.     

Silver-Staining Nucleolar Organizer Region Quantification in Pituitary Adenomas

Nucleolar organizer regions (NORs) are segments of DNA, encoding for ribosomal RNA. They are associated with argyrophilic proteins and, thus, they can be localized through silver staining. A correlation has been shown between the number, the size, or the intranuclear localization of AgNORs, and the proliferative activity of cells. The aim of this study was to examine numerous features of AgNORs in pituitary adenomas and to relate them to immunohistochemical typing of tumor. Histologic slides from 32 pituitary tumors and one normal pituitary were silver-stained and analyzed with a computerized system for microscopic image analysis, supported by an AgNORmeter95 program. All the tumors were also immunocyto chemically characterized. We have found that gonadotropinomas, when compared with plurihormonal adenomas, revealed a lower proportion of nuclei with a single AgNOR and a higher percentage of marginal dots. Recurrent adenomas, when compared with primary adenomas, showed a higher proportion of nuclei with three AgNOR dots, a larger total area of dots in the nuclei, and a higher standard deviation of the AgNOR dot area in the nucleus. Adenomas immunopositive for prolactin, when compared with immunonegative ones, showed a larger mean area of the AgNOR dot, a larger area of the biggest dot in the nucleus, and a higher proportion of nuclei within a single dot. These results suggest that the estimated parameters of AgNOR dots differ according to tumor aggressiveness and to the hormone immunopositivity of pituitary adenomas.     

A founder truncating variant in GDF1 causes autosomal‐recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds

The genetic basis of congenital heart malformations associated with disruption of left–right (L–R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left–right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab‐Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left–right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.     

Identification of multidrug-resistant Streptococcus pneumoniae strains isolated in Poland by multilocus sequence typing

Multilocus sequence typing (MLST) of 35 isolates of multidrug-resistant Streptococcus pneumoniae recovered in Poland during 1995-1996 distinguished 10 different sequence types (ST). The majority of the isolates were assigned to two Polish clones of serotypes 6B and 23F, although the international clones, Spain23F-1 and Spain9V-3, were also identified. Similar results were obtained using pulsed-field gel electrophoresis (PFGE), providing a direct comparison of these two typing methods.     

Effect of the physiological state of microbial cells on cadmium sorption

Live and dead cells of several strains of bacteria as well as different microbial populations isolated from natural environments were tested for their ability to sorb cadmium (Cd) from a liquid medium (0.05M phosphate buffer, pH 7.2) containing 10 g Cd/ml. The bacterial cultures were grown in a nutrient solution without Cd, harvested, and then suspended in the buffer solution for the uptake assays. The amount of Cd sorbed by dead cells was usually higher than by live cells. Killing of bacteria by chemicals (ethanol, formaldehyde, or propylene oxide) or physical (-radiation) means had a varying effect on Cd uptake by dead cells. Various bacterial strains showed different degrees of resistance to Cd and different uptake levels of this heavy metal with no established correlation. Neither storage of the cells at 4°C for 48 hr after harvesting nor varying incubation times of the bacteria before the Cd uptake experiments had any influence on the amount of Cd sorbed.Paper No. 6609 of the Journal Series of the Agricultural Experiment Station, Pennsylvania State University, University Park, PA 16802