Renin,ANP, ACE polymorphisms,blood pressure and age in American Samoans: Preliminary data

Molecular studies have identified numerous candidate genes that may influence interindividual variation in physiologically important endpoints. Among these are molecular variants of three proteins associated with blood pressure regulation, renin, atrial natriuretic peptide (ANP), and angiotensin-converting enzyme (ACE). These loci are polymorphic in all populations examined. The purpose of this study was to determine gene and genotype frequencies at these three loci in a sample of American Samoans and to examine associations of the various genotypes with blood pressure, hypertension, and age. Genotype frequencies of a BglI restriction fragment length polymorphisms (RFLP) at the renin locus were slightly out of Hardy-Weinberg expectations (P ⩽ 0.025). Frequencies of a BglI RFLP at the ANP locus and of the insertion/deletion polymorphism at the ACE locus approximated Hardy-Weinberg expectations (P ⩾ 0.10). These frequencies differed from those reported in “Afro-Caribbean” and “Caucasian” samples from London. Neither average blood pressures nor the frequencies of either systolic or diastolic hypertension differed significantly across genotypes at the ANP or ACE loci. However, systolic pressure was elevated among those heterozygous for the renin BglI cut site (P = 0.07). Mean age was 34.4 years among individuals heterozygous for the ANP BglI cut site, while it was 46.0 years for homozygotes without the site (P = 0.04). After dividing the sample at its median age (45 years), 31.8% of younger, but only 8.7% of older participants were ANP BglI heterozygotes (G = 9.48; P = 0.005). Am. J. Hum. Biol. 10:439–449, 1998. © 1998 Wiley-Liss, Inc.     

Bifuration coronary angioplasty using a new side branch accessible stent

Two cases of successful angioplasty of bifurcational left anterior descending and diagonal lesions treated with a new side branch accessible Jomed™ stent in the LAD are discussed. A balloon dilatation of the side branch using kissing balloon technique in the first case and stenting the side branch followed by kissing balloon dilatation in the second case are described. Cathet. Cardiovasc. Diagn. 45:92–95, 1998. © 1998 Wiley-Liss, Inc.     

Cloning,expression, and immunogenicity of the assembly protein of varicella-zoster virus and detection of the products of open reading frame 33

Herpesviruses produce assembly proteins (AP) that act as scaffolding proteins for the assembly of the viral capsids. The products of the assemblin gene, which encodes both maturational protease and AP, have been established for herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (CMV). We cloned an inframe ORF (encoding amino acids 304–605), found within the ORF 33 assemblin gene of VZV, into a yeast expression vector. The 34-kDa AP was expressed as a fusion protein with the particle-forming Ty p1 protein, resulting in high-level production of hybrid AP-virus-like particles (AP-VLPs). When AP-VLPs were injected into mice and rabbits, antibodies were produced that reacted with, but that did not neutralise, native VZV. Three of four inbred strains of mice immunised with AP-VLPs produced a VZV-specific T-cell response. The mouse and rabbit sera reacted with six bands on native VZV by Western blot analysis. The dominant bands were found at 34 and 38 kDa. Bands were also seen at 66, 63, 41, and 31 kDa. The 38-kDa protein may represent the mature AP derived from the 41-kDa precursor AP, itself the release product from the full-length 66-kDa assemblin. The 34-kDa protein probably represents the product of the inframe co-translational gene within ORF 33 encoding amino acids 304–605. The genetic organisation and proteolytic maturation of VZV assemblin are, therefore, analogous to those of other herpesviruses. J. Med. Virol. 53:332–339, 1997. © 1997 Wiley-Liss, Inc.     

Biotherapy for xenografted human central nervous system leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19)- pokeweed antiviral protein immunotoxin

The study of central nervous system (CNS) leukemia has been hampered by the lack of a suitable animal model. We report that severe combined immunodeficiency (SCID) mice invariably develop rapidly progressive fatal CNS leukemia within 3 weeks after intravenous injection of NALM-6 pre-B acute lymphoblastic leukemia (ALL) cells. Colonization of the dura mater and subarachnoid space, usually of the distal spinal cord with occasional extension into the Virchow-Robin spaces of blood vessels subjacent to the meninges, followed involvement of bone marrow in the skull, vertebrae, and, occasionally, the appendicular skeleton. Occult CNS leukemia was detectable by polymerase chain reaction amplification of human DNA as early as 8 days postinoculation of leukemia cells. We used this in vivo model of human CNS leukemia to examine the therapeutic efficacy and toxicity of intrathecally administered B43 (anti-CD19)-pokeweed antiviral protein (PAP), an anti- B-lineage ALL immunotoxin directed against the pan-B-cell antigen CD19/Bp95. Intrathecal therapy with B43 (anti-CD19)-PAP immunotoxin at nontoxic dose levels significantly improved survival of SCID mice and was superior to intrathecal methotrexate therapy.     

Normal and malignant epithelial cells with stem-like properties have an extended G2 cell cycle phase that is associated with apoptotic resistance

Background  

Subsets of cells with stem-like properties have been previously isolated from human epithelial cancers and their resistance to apoptosis-inducing stimuli has been related to carcinoma recurrence and treatment failure. The aim of this study was to investigate the mechanisms of resistance to apoptosis-inducing agents of cells with stem-like properties in both normal and malignant human epithelia.