Copolymers with soft and hard segments based on 2,2-dimethyltrimethylene carbonate and ε-caprolactone

Thermoplastic elastomers with ABA-block structure, A representing the hard segment and B the soft segment, were prepared by ring-opening polymerization from 2,2-dimethyltrimethylene carbonate (DTC, 1 ) and ε-caprolactone (ECL, 2 ) as monomers. Typical anionic initiators, viz. the dilithium salt of hydroxytelechelic poly(ethylene oxide) 200 ( 4 ) and of polytetrahydrofuran 1000 ( 5 ) and as an insertion initiator the bis(diethylaluminium) salt of triethylene glycol were used. The soft block is formed by a sequence of random (or tapered) structure comprising equimolar amounts of the two monomers and obtained by simultaneous polymerization of DTC and ECL. The hard blocks consist of highly crystalline poly(2,2-dimethyltrimethylene carbonate) sequences. The thermal properties of the polymers depend on the sequence length, the content of heterodiads in the soft block and the thermal history of the samples. Copolymer films with short end blocks and high content of heterodiads show rubber-elastic properties at normal conditions.     

CD23 and CD21 function as adhesion molecules in homotypic aggregation of human B lymphocytes

We have previously found that interleukin-4 and CD40 monoclonal antibodies (mAb) are strong potentiatiors of homotypic B cell aggregation which is dependent on LFA-1. We show here that CD23 mAb were also able to inhibit aggregation to a similar extent as LFA-1 antibodies. This inhibition was restricted to the MHM6 epitope of CD23 and antibodies to other epitopes [Epstein-Barr virus (EBV) CS-1, EBV CS-2, EBV CS-5 and mAb 25] or occupation of the Fc-binding site by IgE had no or a slightly enhancing effect on aggregation. When testing two antibodies to CD21, the recently defined ligand for CD23, one of these (BU32) was found to be inhibitory whereas the other (THB5) had no effect. By combining antibodies to LFA-1 and CD23, aggregation was often completely inhibited. These data suggest that LFA-1/ICAM-1 and CD23/CD21 are the major molecules involved in homotypic aggregation of human B cells.     

Efficacy and safety of sublingual immunotherapy.

OBJECTIVE: To review the available published data concerning the use of sublingual immunotherapy (SLIT) in respiratory allergy to primarily evaluate the clinical efficacy and safety of the treatment and to secondarily consider the mechanisms of action and any unresolved questions. DATA SOURCES: Articles in the medical literature (starting from 1986 up to November 2003) derived from searching the MEDLINE database with the keywords sublingual immunotherapy, respiratory allergy, asthma, and rhinitis. Sources included review articles, randomized controlled clinical trials, postmarketing surveillance studies, and relevant reports from meeting proceedings. STUDY SELECTION: Articles concerning safety, efficacy, and mechanisms of SLIT published in English-language, peer-reviewed journals. RESULTS: SLIT proved effective and safe in adults and children. As with traditional subcutaneous immunotherapy, SLIT has long-lasting efficacy and a preventive effect on new sensitizations. CONCLUSION: SLIT is a viable alternative to subcutaneous immunotherapy. Its use in pediatric patients seems to be particularly promising.     

Multiplicity activation of herpes simplex virus in mouse neuroblastoma (C1300) cells

Summary The virus yields and number of infectious centres of HSV infected mouse neuroblastoma C1300 cells (clone 41 A₃) infected at different multiplicities of infection (MOI) were found to vary more than the differences of HSV concentrations of the virus suspensions used for infection of the cells. This suggested that a C1300 cell had to be infected with more than one HSV particle in order to produce progeny virus—multiplicity activation. The greater than expected enhancement of virus production of C1300 cell cultures receiving increasing MOI of HSV was probably not due to improved virus adsorption, nor influenced by non-virus factors in the virus inoculum stimulatory for HSV replication. A hypothesis, that the block in virus replication was promoted by an inhibitor of an HSV specified regulatory protein and could be overcome by the addition of HSV DNA copies in the infected cell, was supported by the results of two types of experiments. Presence of phosphonoformic acid, an inhibitor of the HSV specified DNA polymerase, in the culture medium of HSV infected permissive GMK cells resulted in non-linear relationships between virus yields and MOI. An HSV temperature sensitive mutant (ts B5), defective in a late structural protein, rescued wild type HSV in C1300 cells.With 4 Figures     

The mutational spectrum of brachydactyly type C

Growth/differentiation factor-5 (GDF5), also known as cartilage-derived morphogenetic protein-1 (CDMP-1), is a secreted signaling molecule that participates in skeletal morphogenesis. Heterozygous mutations in GDF5, which maps to human chromosome 20, occur in individuals with autosomal dominant brachydactyly type C (BDC). Here we show that BDC is locus homogeneous by reporting a GDF5 frameshift mutation segregating with the phenotype in a family whose trait was initially thought to map to human chromosome 12. We also describe heterozygous mutations in nine additional probands/families with BDC and show nonpenetrance in a mutation carrier. Finally, we show that mutant GDF5 polypeptides containing missense mutations in their active domains do not efficiently form disulfide-linked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5.     

Transition between two forms of heterochromatin at plant subtelomeres

The manner of packing of the terminal DNA loci into nucleosomes and higher order structures may strongly influence their functional interactions. Besides the structural flexibility of telomeric DNA sequences, conserved features of their chromatin including short nucleosome phasing (157 bp) and nucleosome sliding have been described previously. To gain a complementary knowledge of subtelomeres, we have analysed the chromatin structure of two subtelomeric tandem repeats from the plant Silene latifolia: X43.1 and 15Ssp. X43.1 shows two distinct nucleosome periodicities – 157 and 188 bp. Preferred positions of its two nucleosomes have been mapped at both low and high resolution and the experimental results correspond to computer-predicted positions. 15Ssp is a newly-discovered sequence showing a telomere-associated position by PCR and a subtelomeric location by pulsed-field gel electrophoresis and fluorescence in situ hybridisation. Its 159 bp sequence unit shows a tandem arrangement and the presence of micrococcal nuclease-hypersensitive sites when either naked DNA or chromatin is digested. Use of a chemical nuclease results in a regular nucleosome ladder of 157 bp periodicity. Moreover, 15Ssp mononucleosomes show instability and absence of specific positioning, features typical for telomeric chromatin. This revised version was published online in July 2006 with corrections to the Cover Date.     

Nonrandomness of D-group chromosomes involved in centric-fusion translocation

Ten members of two families with D/G translocation, three members of a family with D/D translocation, and one patient with non-familial and one with apparently non-familial D/D translocation were examined. The trdnslocation chromosomes were identified by SH-thymidine labeling and autoradio-graphy as 14q21q and 13q14q, respectively. These findings support the hypothesis of nonrandomness of D group chromosomes involved in centric-fusion translocation. The importance of the identification of Dgroup chromosomes involved in centriofusion translocation in relation to genetic counseling is discussed.     

Pituitary pathology in erdheim-chester disease

Pituitary morphologic changes in patients with Erdheim-Chester disease have not been described in detail. We report here the histologic and immunohistochemical findings in the autopsy obtained pituitary of a 35-yr-old woman with extensively disseminated Erdheim-Chester disease. The posterior lobe was completely replaced by xanthogranulomatous infiltrates, providing an explanation for the patient’s diabetes insipidus. The anterior lobe was intact and immunohistochemistry demonstrated expression of GH, TSH, FSH, LH, and alpha subunit within the normal range. A clinically observed decrease of anterior pituitary function was interpreted as hypothalamic in origin due to massive destruction of the hypophysial stalk and compression of the hypothalamus. Prolactin immunoreactive cells were numerous, consistent with the view that prolactin cell hyperplasia resulted from the loss of hypothalamic dopaminergic inhibition. Massive Crooke’s hyalinization in the ACTH-producing cells was considered unrelated to Erdheim-Chester disease and was the consequence of treatment with pharmacologic doses of glucocorticoid hormones. It can be concluded that prolactin cell hyperplasia may be the only finding in the adenohypophysis of patients with disseminated Erdheim-Chester disease. It appears that in our patient the clinically apparent anterior hypopituitarism was not due to the lack of storage but rather to insufficient release of adenohypophysial hormones caused by the defect in hypothalamic regulation.     

Über die Feinstruktur eines vom Pferd isolierten Virus der Herpesgruppe

Summary A virus isolated from horses after abortion was propagated in cultures of swine kidney cells. Shape and structure of the virus particles as seen in negatively stained preparations and changes observed in ultrathin sections of infected cells suggest that the virus belongs to the herpes group. However, most of the virus particles in the nucleus and in the cytoplasm have a structure different from that of herpes virus. Instead of the nucleoid, vesicle-like formations are arranged in the particle, so as to produce a cross-shaped light area in the center of the particle.

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