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.      

Effects of Beta-Adrenergic Activity on T-Wave Amplitude

This study addresses the hypothesis that electrocardiographic T-wave amplitude is influenced by beta-adrenergic stimulation of the heart. Beta-adrenergic activity was manipulated both pharmacologically and through behavioral challenge. Under resting conditions, 12 healthy men underwent infusion of placebo and then the beta-agonist, isoproterenol, and the beta-blocker, propranolol, in a counterbalanced, crossover design. During infusion of placebo, subjects also underwent two behavioral challenges, a structured interview and mental arithmetic. Analysis of the resting data indicated that propranolol produced a significant increase in T-wave amplitude, and isoproterenol produced significant T-wave amplitude attenuation. As previously reported, drug effects were also in evidence for heart rate. Behaviorally-induced reduction of T-wave amplitude was observed for mental arithmetic but not structured interview, which again paralleled heart rate data. Both pharmacological and behavioral data reported in this study support the hypothesis that the T-wave is significantly affected by beta-sympathetic influence on the heart. However, a nonspecific effect of heart rate change on T-wave amplitude would also account for these results. The findings are discussed in terms of their implications for the utility of T-wave amplitude in psychophysiological research.     

Antagonistic effects upon cutaneous circulation of muscular exercise and exposure to a high ambient temperature

Measurements were made in man of heart rate (Fc), arterial blood pressure (Pa), cutaneous blood flow (Z) (by plethysmography of the hand) as well as variation sin venous volume (deltaV) in the course of muscular exercise of 70 Watts intensity corresponding from 48% to 60% of the maximal oxygen consumtion of the subjects. These exercises were carried out at ambient temperatures of 22 degrees and 29 degrees C. for 8 min. In every case, an initial lowering of the Q and deltaV followed by a progressive climb was found. The average maximal reduction in output was virtually identical at 22 degrees and 29 degrees C (4.10 +/- 2.05 and 4.00 +/- 2.31 ml/min. 100 cm3). But the average maximal fall in volume turned out to be less at 29 degrees C (0.30 +/- 0.40 ml/100 cm3) than at 22 degrees C (0.60 +/- 0.60 ml/100 cm3). The resistive sector of cutaneous circulation conserves the same vasomotor capacities at the two ambient temperatures studied; the cutaneous capacitive sector shows lower reactivity at the higher ambient temperature. This would suggest that diminished venous return may be partially responsible for poor tolerance to exercise in warm climates.     

Cell-mediated anti-tumor response in the RLmale 1 system. I. T nature, H-2Dd involvement and antigenic specificity of the effector cells.

After in vivo priming and in vitro secondary stimulation by the radio-induced RL♂ 1 lymphoma cells, syngeneic BALB/c splenic lymphocytes evidenced a specific but very weak cytolytic activity against RL♂ 1 target cells. Under the same experimental conditions, spleen cells from (B6 x BALB/c)F₁ were at least 100 times more efficient. In both cases, the effector cells were cytolytic T lymphocytes (CTL). Normal H-2D^d antigens of the tumor cell surface were involved in the effector-to-target cell interaction since anti-H-2 or anti-H-2D^d antisera abolished the RL♂ 1 cytolysis by immune syngeneic CTL, whereas anti-H-2K^d were devoid of blocking activity. The testing of a series of lymphoma cells, either virus-induced or not, belonging to different H-2 haplotypes, show that the immune CTL were highly specific for RL♂ 1 target cells. Only with the P815 mastocytoma cells was a weak cross-reactivity detected by both direct tests and competition experiments. Allogeneic (H-2^k) AKR lymphoma cells which share the X1 antigen with RL♂ 1 do not react, possibly due to an H-2 restriction of the CTL activity. The CTL-reacting antigen cannot be definitely identified, since several specificities, including the serologically defined X1 antigen, are possibly involved simultaneously. The Hh antigens which could have accounted for the F₁ anti-parent reaction, appear irrelevant.     

Studies on the mechanism of interferon action: Characterization of polysome-associated cellular RNAs modified by interferon

A recent publication indicated that certain polysome-associated RNA species are altered in interferon-treated cells. The present data show that these RNA species are poly(A)-containing mRNAs, RNAs without a poly(A)-rich region and tRNAs. In addition, we show that in polyacrylamide gels in aqueous medium as well as in nonaqueous medium (formamide) the mRNAs from interferon-treated cells migrate more slowly than do control cell mRNAs, suggesting that the interferon mRNAs are slightly larger than normal. Transfer RNAs from interferon-treated cells, on the other hand, move more slowly than control tRNAs in aqueous medium, but not in formamide, suggesting that the difference in mobility in tRNAs is associated with factors other than size.     

The emerging role of immunoregulation of fibrinogen-related procoagulant Fgl2 in the success or spontaneous abortion of early pregnancy in mice and humans.

PROBLEM: Abortion of chromosomally normal embryos in the CBA X DBA/2 mating combination is triggered by release of Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma, and interleukin [IL]-1), which cause abortion via a novel prothrombinase, Fgl2, and polymorphonuclear leukocytes. The site of activation may be maternal vascular endothelium on arteries and veins nourishing the placenta. Activation of coagulation is also prominent in spontaneous abortion of chromosomally normal human embryos. We asked where is Fgl2 up-regulated in the uterus in murine abortions, and if similar Fgl2 expression occurs in human pregnancy failure. METHODS: Control CBA X DBA/2 pregnant mice, or from mice injected with TNF-alpha + IFN-gamma on day 7.5 of gestation, were removed on day 8.5, fixed, sectioned, and subject to in situ hybridization for Fgl2. Sections were also stained for fibrin. Elective first trimester termination samples or biopsies taken early in the course of a recurrent miscarriage were similarly fixed, sectioned, and analyzed by in situ hybridization. Control and cytokine-treated mice were anticoagulated with heparin, an activator of antithrombin III, and/or the direct anti-thrombin inhibitor hirudin. RESULTS: Low level Fgl2 expression localized to basal decidua remote from the embryo was noted in control mice; cytokine treatment, which causes greater than 80% of abortions, produced a striking up-regulation in this area as well as in a band at the junction of decidua and myometrium. Trophoblast also became strikingly positive. Fgl2 expression was associated with increased fibrin staining. Anticoagulation significantly protected against abortions, but doses were limited by the complication of retroplacental hemorrhage. In tissue from normal first trimester pregnancy, minimal Fgl2 positivity was seen in some villous syncytiotrophoblast, in villous stroma, cytotrophoblast, and in some cells in decidua. In spontaneous abortion of normal embryo, striking Fgl2 positivity was seen in syncytiotrophoblast and extravillous cytotrophoblast, in association with areas of thrombus formation. CONCLUSIONS: Fgl2 appears to be physiologically expressed and may protect against the internal danger of maternal and/or fetal bleeding during pregnancy and at parturition; a role in inhibiting transplacental traffic is also possible. External dangers in the form of stress, endotoxin, and antigens eliciting Th1 cytokine responses upregulate Fgl2 prothrombinase in trophoblast as well as in decidua, which results in spontaneous abortion of immunogenetically "weaker" embryos.     

MT-4 plaque formation can distinguish cytopathic subtypes of the human immunodeficiency virus (HIV)

Using the MT-4 plaque assay, differences in the plaque-forming ability among various isolates of the human immunodeficiency virus (HIV) were observed. Kinetic studies showed that these differences reflected the enhanced ability of individual HIV to replicate rapidly in T cells and cause cytopathic changes. The plaque-forming HIV all came from patients with disease; no healthy seropositive individuals had these types of isolates. Plaque formation may be a useful assay for identifying pathogenic strains of HIV.