Effects of glycyrrhizic acid and steroid treatment on corticotropin releasing factor and beta-endorphin containing neurons of the hypothalamus of the rat

Corticotrophin releasing factor (CRF) and beta-endorphin (beta EP) containing neurons are shown to be present in the hypothalamus and both neurons are found at the paraventricular nucleus (PVN). Steroid hormones have been found to alter the plasma level of these neurotransmitters. Glycyrrhizic acid (GCA) is the active component of liquorice. GCA inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (11HSD) which is needed for the inactivation of the steroid pathway, so therefore would cause changes to these neurons. The aim of this study was to investigate the effects of GCA as well as deoxycorticosterone (DOC) and dexamethasone (DM) on the modulation of CRF and beta EP containing neuron at the PVN of the hypothalamus. Rats were given either DM, DOC or GCA and adrenalectomized (ADX) and given either DM or DOC. At the end of treatment rats were transfused transcardially before sacrifice and the brain were dissected for immunohistochemical analysis. We found that immunostaining of the CRF containing neurons demonstrate a reduction in the number of positive neurons in DM treated rats. DOC and GCA treated rats showed the same result as in DM rats but the reduction is less. ADX, DM, DOC and GCA treated rats did not show any changes in the number of beta EP containing neurons but naloxone increased the number of beta EP containing neurons markedly. In conclusion, GCA and DOC have similar effects on CRF and beta EP containing neurons at the PVN.     

Novel type of fimbriae encoded by the large plasmid of sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H(-)

Sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:H(-) have emerged as important causes of diarrheal diseases and the hemolytic-uremic syndrome in Germany. In this study, we characterized a 32-kb fragment of the plasmid of SF EHEC O157:H(-), pSFO157, which differs markedly from plasmid pO157 of classical non-sorbitol-fermenting EHEC O157:H7. We found a cluster of six genes, termed sfpA, sfpH, sfpC, sfpD, sfpJ, and sfpG, which mediate mannose-resistant hemagglutination and the expression of fimbriae. sfp genes are similar to the pap genes, encoding P-fimbriae of uropathogenic E. coli, but the sfp cluster lacks homologues of genes encoding subunits of a tip fibrillum as well as regulatory genes. The major pilin, SfpA, despite its similarity to PapA, does not cluster together with known PapA alleles in a phylogenetic tree but is structurally related to the PmpA pilin of Proteus mirabilis. The putative adhesin gene sfpG, responsible for the hemagglutination phenotype, shows significant homology neither to papG nor to other known sequences. Sfp fimbriae are 3 to 5 nm in diameter, in contrast to P-fimbriae, which are 7 nm in diameter. PCR analyses showed that the sfp gene cluster is a characteristic of SF EHEC O157:H(-) strains and is not present in other EHEC isolates, diarrheagenic E. coli, or other Enterobacteriaceae. The sfp gene cluster is flanked by two blocks of insertion sequences and an origin of plasmid replication, indicating that horizontal gene transfer may have contributed to the presence of Sfp fimbriae in SF EHEC O157:H(-).     

Effects of fluorodeoxyuridine on the developing inner ear of the rat

The inner ear in rats develops from the surface ectoderm on day 8 of a 22-day gestational period. Labeled thymidine incorporation studies have indicated that in the developing inner ear most of the cells undergo terminal mitosis between gestational days 13 and 15. During this period the developing inner ear would be particularly vulnerable to environmental hazards. To test this hypothesis, pregnant rats were given a single intraperitoneal injection of 5-fluoro-2'-deoxyuridine (FUdR), an antimitotic substance, on gestational days 12 to 16. The rats also received one injection of 3H-thymidine 1 h prior to the removal of the fetuses. The animals were killed after various time intervals following the treatment, and the otocysts or inner ears were prepared for morphologic observations and biochemical assays. The cells in the inner ear of rats exposed to FUdR exhibited pyknotic nuclei and chromatolytic degeneration, and they eventually died. By 4 h after the administration of FUdR, pyknotic nuclei were seen in the antiluminal zone of the otic epithelium, and there was a substantial decrease in the number of the otic cells. This decline in cell number was seen until 24 h after treatment. However, the inner ears from the fetuses exposed to FUdR during gestational days 12--15 showed complete recovery from the toxic effects of the drug when examined on day 21 of gestation. The phenomenon of programmed cell death observed in the developing inner ear of the rat indicates that more cells are produced during the earlier stages of development than are required for the definitive adult structures. This phenomenon may represent an important protective feature. The redundant production of cells perhaps allows the developing otocysts to respond to an environmental stress by subtotal destruction of cells from the pool of undifferentiated cells, resulting in relatively fewer congenital anomalies of the inner ear.     

A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1-2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52-665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors.     

Abnormalities of cholesterol metabolism in autism spectrum disorders.

Although Smith-Lemli-Opitz Syndrome (SLOS), a genetic condition of impaired cholesterol biosynthesis, is associated with autism [Tierney et al., 2001; Am J Med Genet 98:191-200.], the incidence of SLOS and other sterol disorders among individuals with autism spectrum disorders (ASD) is unknown. This study investigated (1) the incidence of biochemically diagnosed SLOS in blood samples from a cohort of subjects with ASD from families in which more than one individual had ASD and (2) the type and incidence of other sterol disorders in the same group. Using gas chromatography/mass spectrometry, cholesterol, and its precursor sterols were quantified in 100 samples from subjects with ASD obtained from the Autism Genetic Resource Exchange (AGRE) specimen repository. Although no sample had sterol levels consistent with SLOS, 19 samples had total cholesterol levels lower than 100 mg/dl, which is below the 5th centile for children over age 2 years. These findings suggest that, in addition to SLOS, there may be other disorders of sterol metabolism or homeostasis associated with ASD.     

Boleodorus similis n. sp. (Nematoda: Nothotylenchinae) from India

Summary A new species, B. similis, is described from male and female specimens collected from soil around roots of Plumeria acutifolia Poir from North India. It is distinguished by a short and robust body, a broad lateral field, a more posteriorly located vulva in female and the position of phasmid and the posterior extension of lateral field in male.With 8 Figures in the Text     

Anatomical variations in human carotid bodies.

The variations in anatomical structure and position of both carotid bodies were noted in 100 consecutive subjects who came to necropsy. Considerable variations in form were found. Although most carotid bodies (83% on the right and 86% on the left) were of the classic ovoid type, an appreciable minority was bilobed (9% on the right and 7% on the left) or double (7% on the right and 6% on the left); 1% were leaf shaped. All these anatomical variants have to be distinguished from the pathologically enlarged carotid body that may have a smooth or finely nodular surface. Anatomical variants (such as the bilobed) may themselves enlarge as a consequence of carotid body hyperplasia.     

Comparison of hepatitis C viral loads in patients with or without coinfection with different genotypes

Hepatitis C virus genotyping was assessed for 257 chronic hepatitis C patients with viral loads above 1,000 IU/ml. Twelve patients were coinfected with more than one genotype. Their median viral loads did not differ significantly from those observed for monoinfected patients, which in turn did not vary significantly among different genotypes.     

G-Trisomie bei akuter Erythroleukämie

Zusammenfassung Es wird über einen Fall akuter Erythroleukämie mit G-Trisomie berichtet und die mögliche Bedeutung hereditärer Faktoren für die Manifestation akuter Leukämien diskutiert.

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Summary The cytogenetic analyses of direct bone marrow preparations in a 53 years old male with acute erythroleukaemia of 9 months disease history, revealed persistently a G-trisomy in a dominant cell line with 47 chromosomes. The peripheral blood culture preparations with phytohaemagglutinin exhibited normal diploid cell line.The frequent occurrence of akute leukaemia in Down's syndrome tempts to implicate that leukaemia with G-Trisomy having no signs of Down's syndrome is a somatic mutation initiated by some unknown hereditary recessive genes mechanisms.

     

Synthesis and physical properties of telechelic monodispersed diols 4. Monoaddition of 10-undecenol to novel dithiols

The synthesis of novel telechelic monodispersed diols produced from the radical monoaddition of an excess of 10-undecenol with novel α, ω-dithiols, initiated by peroxides, is presented. The telechelic dithiols employed were prepared from nonconjugated dienes and a commercially available dithiol, or by esterification of adipic acid with 2-mercaptoethanol. From these dithiols, the diols were selectively obtained in high yields. Such α, ω-dihydroxylated compounds were characterized by both ¹H and ¹³C NMR spectroscopy. The diol which exhibits the ester functions shows excellent solubility in common organic solvents contrarily to the other ones. The physical properties (T_g, T_m and decomposition temperatures) of these diols were compared and it is noted that the thermostability of these monodispersed telechelic diols is much better than those of the polydispersed commercially available ones such as poly(ethylene glycol)s or poly(tetramethylene glycol)s.