A human amphotropic retrovirus receptor is a second member of the gibbon ape leukemia virus receptor family.

Retrovirus infection is initiated by binding of the viral envelope glycoprotein to a cell-surface receptor. The envelope proteins of type C retroviruses of mammals demonstrate similarities in structural organization and protein sequence. These similarities suggest the possibility that retroviruses from different interference groups might use related proteins as receptors, despite the absence of any relationship between retrovirus receptors isolated to date. To investigate this possibility, we have identified a human cDNA clone encoding a protein closely related to the receptor for gibbon ape leukemia virus and have found that it functions as the receptor for the amphotropic group of murine retroviruses. Expression of this protein (GLVR-2) is likely to be a requirement for infection of human cells by amphotropic retroviral vectors for purposes of gene therapy.     

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability in the Rat

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability inthe Rat. SHU, H., TEITELBAUM, T., WEBB, A. S., MARPLE, L., BRUNCK,B. DEI ROSSI, D., MURRAY, J., AND PAUSTENBACH, D. (1988). Fundam.Appl. Toxicol. 10, 335-343. 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD), an unwanted by-product formed during the manufactureof hexachlorophene and phenoxyherbicides, has been found asan environmental contaminant in many U.S. and Western Europeansites. This study examines in the rat the degree of dermal absorptionof TCDD bound to soil. Such information would assist regulatoryagencies in evaluating the degree of exposure of humans whocome in contact with TCDD-contaminated soil. Several parameterswhich may influence dermal absorption were studied, includingTCDD dose, duration of contact, presence of crankcase oil asa co-contaminant, and environmentally contaminated vs laboratory-preparedsoil. The dermal penetration of TCDD following 4 hr of contactwith skin was approximately 60% of that following 24 hr of contact(P 0.05). Following 24 hr of contact with the skin, the degreeof dermal uptake of TCDD contaminated soil was approximately1% of the administered dose. Under the conditions of the presentstudy, the degree of uptake does not appear to be influencedto any significant extent by the concentration of TCDD on soil,the presence of crankcase oil as co-contaminants, or by environmentallyvs laboratory-contaminated soil. Although a number of parametersexamined in this study did not significantly influence the degreeof dermal absorption of TCDD in the rat following 24 hr of contactwith the contaminated soil, the unqualified use of the 1% valueto estimate human exposure would overestimate human exposure,since there is general agreement among researchers that ratskin tends to be more permeable than human skin to highly lipid-solublecompounds such as TCDD.     

BCG Antibody Profiles in Tuberculoid and Lepromatous Leprosy

In sera from 12 patients with polar tuberculoid leprosy, 12 with subpolar tuberculoid leprosy, and 16 with lepromatous leprosy were demonstrated a total number of 125 anti-BCG precipitins by means of crossed immunoelectrophoresis with intermediate gel. Up to 14 different precipitins were found in individual sera, and the complexity in antibody response was higher than previously realized. The specificity of 69% of the antibodies was defined, and these antibodies were titrated in three arbitrary titer units. A highly significant difference (P < 0.002) was found in antibody response between the tuberculoid and the lepromatous group. Due to simplicity, sensitivity, and high resolution, the method used is a promising tool for providing exact data to be used as guidelines for purification of important individual mycobacterial antigens. The need for reference antisera is emphasized.     

Survival of Mycobacterium lepraemurium in C57BL mice after acquired protective immunity

The protective immune response against Mycobacterium lepraemurium (MLM) in C57BL mice has been shown to stop the increase in bacillary numbers and the dissemination of bacilli, but the acid fast bacilli are not cleared from the tissues. Persistence of viable bacilli was indicated by a significant increase in the number of acid fast bacilli in the footpad of C57BL mice that were treated with cortisone acetate several weeks after the onset of the immune response. Bacilli harvested 9 and 16 days after inoculation into immune C57BL mice showed only a marginally detectable loss of viability as determined by bacillary multiplication after transfer into susceptible C3H mice. Twenty-six weeks after being inoculated into immune C57BL mice a small proportion of the bacilli was found still to be alive. A similar finding was done 15 weeks after primary inoculation of MLM into mice that developed an apparently effective protective immune response 4 weeks after being inoculated. Sixty-seven weeks after inoculation of immunized C57BL mice with MLM, bacillary numbers in the footpad were as with patent immunity, but the bacilli were found to be fully viable, suggesting incipient reactivation of the infection. When bacillary numbers were followed over a period of 52 weeks in the organs of normal C57BL mice inoculated with a low dose of bacilli it was found that after a plateau phase bacillary numbers started to increase again. Thus, in all experiments part of the bacillary population had survived the protective immune response against MLM in C57BL mice.     

CATs and HATs: the SLC7 family of amino acid transporters

The SLC7 family is divided into two subgroups, the cationic amino acid transporters (the CAT family, SLC7A1–4) and the glycoprotein-associated amino acid transporters (the gpaAT family, SLC7A5–11), also called light chains or catalytic chains of the hetero(di)meric amino acid transporters (HAT). The associated glycoproteins (heavy chains) 4F2hc (CD98) or rBAT (D2, NBAT) form the SLC3 family. Members of the CAT family transport essentially cationic amino acids by facilitated diffusion with differential trans-stimulation by intracellular substrates. In some cells, they may regulate the rate of NO synthesis by controlling the uptake of l-arginine as the substrate for nitric oxide synthase (NOS). The heterodimeric amino acid transporters are, in contrast, quite diverse in terms of substrate selectivity and function (mostly) as obligatory exchangers. Their selectivity ranges from large neutral amino acids (system L) to small neutral amino acids (ala, ser, cys-preferring, system asc), negatively charged amino acid (system x_c^–) and cationic amino acids plus neutral amino acids (system y⁺L and b^0,+-like). Cotransport of Na⁺ is observed only for the y⁺L transporters when they carry neutral amino acids. Mutations in b^0,+-like and y⁺L transporters lead to the hereditary diseases cystinuria and lysinuric protein intolerance (LPI), respectively.     

Intergenerational instability of the CAG repeat of the gene for Machado- Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter- allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.      

Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs

In this study, we evaluated the effect of low level occupationalexposure of nurses in a medical oncology unit in Cairo, Egypt,to anticancer drugs. Twenty nurses who constantly handled thesedrugs and 20 controls, matched according to age and sex, wereexamined. Metaphase chromosomes were studied. Percentages ofmetaphases with chromosomal aberrations were significantly higher(P < 0.001) in the exposed group (6.1 ± 2.7) versusthe controls (2.6 ± 1.6). The detected chromosomal aberrationswere in the form of chromatid gaps, chromatid breaks and acentricfragments. Micronucleated peripheral blood lymphocytes werealso analyzed in cytochalasin B treated binucleated lymphocytes.There was significant increase in cells with micronuclei (P< 0.001) in nurses (10.05 ± 4.71) in comparison tothe matched control (5.42 ± 2.22) (P < 0.001). Nursesexposed to the cytotoxic drugs for     

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.      

Induction of delayed type hypersensitivity against ultrasonicated Mycobacterium lepraemurium bacilli without simultaneous local reactivity against live bacilli or protective immunity.

Delayed type hypersensitivity (DTH) was induced in C3H mice by subcutaneous immunization with Mycobacterium lepraemurium (MLM) antigens in Freund's complete (FCA) or Freund's incomplete (FIA) adjuvant. The total ultrasonicate (MLMSon-P) of MLM bacilli as well as the water soluble fraction (MLMSon-S) of this ultrasonicate was found effective. MLMSon-S was used as the test antigen. Specific DTH also developed after immunization with heat-killed MLM bacilli in FIA, but not with heat-killed bacilli in saline. Some mice were pre-treated with cyclophosphamide (CY) or splenectomized to augment the effect of immunization. In no instance was DTH to MLMSon-S accompanied by detectable local reactivity to live MLM bacilli measured as swelling of the infected footpad or by reduced multiplication or dissemination of the bacilli during the first 11 weeks after inoculation. As determined by testing in the infected footpad 8 weeks after inoculation, MLM infection did not induce DTH to MLMSon-S in non-immunized mice, and MLM infection was found to neither augment nor suppress established DTH to MLMSon-S. The experiments thus demonstrated a clear dissociation between DTH to MLMSon-S and local reactivity to live MLM bacilli, as well as between DTH to MLMSon-S and protective immunity to MLM infection.