DNA damage from polycyclic aromatic hydrocarbons measured by benzo[a]pyrene-DNA adducts in mothers and newborns from Northern Manhattan, the World Trade Center Area, Poland, and China.

Polycyclic aromatic hydrocarbons (PAH), of which benzo[a]pyrene is a representative member, are combustion-related environmental pollutants and include known carcinogens. Laboratory animal studies indicate that the dose of PAHs to the fetus is on the order of a 10th that to the mother and that there is heightened susceptibility to PAH-induced carcinogenesis during the fetal and infancy periods. Carcinogen-DNA adducts, a measure of procarcinogenic genetic damage, are considered a biomarker of increased cancer risk. Here we compare the levels of benzo[a]pyrene-DNA adducts as a proxy for PAH-DNA damage measured in maternal blood and newborn cord blood obtained at delivery in four different populations of mothers (total of 867) and newborns (total of 822), representing a 30-fold range of exposure to ambient PAHs. The populations include residents in Northern Manhattan, participants in a study of the effects of the World Trade Center disaster, residents in Krakow, Poland, and residents in Tongliang, China. Mean adduct concentrations in both maternal and cord blood and the proportion of samples with detectable adducts, increased across the populations [Northern Manhattan < World Trade Center (WTC) < Krakow < Tongliang], consistent with the trend in estimated ambient exposure to PAHs (P < 0.001). For mothers, the means in the respective populations were Northern Manhattan (0.21 adducts per 10(8) nucleotides), WTC (0.23 adducts per 10(8) nucleotides), Krakow (0.28 adducts per 10(8) nucleotides), Tongliang (0.31 adducts per 10(8) nucleotides); the corresponding means in the newborns were Northern Manhattan (0.23), WTC (0.24), Krakow (0.29), Tongliang (0.31). The percentage of mothers with detectable levels of adducts in the respective populations were Northern Manhattan (36.8%), WTC (57.5%), Krakow (72.9%), Tongliang (73.4%); the corresponding percentages among the newborns were Northern Manhattan (42.4%), WTC (60.6%), Krakow (71.1%), Tongliang (79.5%). Despite the estimated 10-fold lower PAH dose to the fetus based on laboratory animal experiments, the adduct levels in the newborns were similar to or higher than in the mothers. This study suggests that the fetus may be 10-fold more susceptible to DNA damage than the mother and that in utero exposure to polycyclic aromatic hydrocarbons may disproportionately increase carcinogenic risk. The data support preventive policies to limit PAH exposure to pregnant women and children.     

Typing of clinical herpes simplex virus isolates with mouse monoclonal antibodies to herpes simplex virus types 1 and 2: comparison with type-specific rabbit antisera and restriction endonuclease analysis of viral DNA

A total of 122 clinical isolates of herpes simplex virus (HSV) from 107 patients were typed by using an indirect immunoperoxidase technique with commercially available type-specific rabbit antisera, recently developed mouse monoclonal antibodies to HSV types 1 and 2, and restriction endonuclease analysis of viral DNA. With the commercially available type-specific rabbit antisera, 34% of clinical HSV isolates were of indeterminate type; 63% of them were typed as HSV type 1 and 37% as HSV type 2 by using monoclonal antibody and restriction enzyme typing systems. Typing by immunofluorescence assay with the monoclonal antibodies gave identical results to those obtained by restriction enzyme analysis. Simultaneous infection with both HSV types was demonstrated by monoclonal antibody typing in five isolates from three patients. These findings were subsequently confirmed by plaque purification and restriction endonuclease analysis of viral DNA. Monoclonal antibodies were as sensitive as restriction enzyme analysis for the typing of clinical HSV isolates. Because of their simplicity, they are more amenable to use in clinical laboratories than is restriction endonuclease analysis.     

DNA and protein applications of near-infrared dyes

The near-infrared region of the spectrum (650-1100 nm) offers distinct advantages over the traditional UV/vis region for spectroscopic measurements. In the past, the lack of commercially available equipment capable of working in the near infrared limited the utility of near-infrared techniques. However, since the advent of photodiodes and semiconductor lasers, much progress has been made in the development of near-infrared techniques. This paper discusses the use of near-infrared dyes used in DNA and protein applications.     

Genetic control of natural immunity to ecotropic mouse leukemia viruses: production of endogenous immunogen.

Mice of the AKR and C57L strains naturally produced low titers of antibody against ecotropic murine leukemia viruses (MuLV). The F1 hybrid of these strains produced anti-MuLV antibody in higher titer than mice of either of the parental strains. Progeny of the genetic backcross C57L X (AKR X C57L)F1 segregated for the production of infectious ecotropic MuLV (according to the Akv-1 and Akv-2 loci) and for the production of antibody against MuLV. All mice that contained infectious MuLV produced anti-MuLV antibodies. Thus, the persistent production of high-titered MuLV in these mice did not result in immunological tolerance towards viral antigens. In contrast, mice that did not contain infectious MuLV could be separated into antibody-producing and -nonproducing classes. The absence of detectable antibody to MuLV in an individual mouse was invariably associated with a virus-free phenotype. Antibody against MuLV reacted primarily with p15 and gp70 proteins of the viral envelope. It was concluded that overt production of endogenous ecotropic MuLV served as a major immunogenic stimulus for the production of anti-MuLV antibody in these mice.     

Oncornaviruses produced by murine leukemia cells in culture.

Leukemia cells from mice of the AKR and C58 strains produced leukemia viruses (MuLV) in culture that failed to induce syncytia in the XC plaque assay (XC^?), were poorly infectious for mouse embryo fibroblasts, and yielded low levels of infectious progeny upon the establishment of infection. In host range analysis the majority of these viruses were N-ecotropic, although one leukemia cell line also produced xenotropic MuLV. Viral isolates from five different leukemia cell lines were oncogenic upon inoculation into newborn AKR mice. In contrast, viruses that occurred in high titer in the tissues and sera of normal AKR mice were not oncogenic in vivo and in culture they efficiently induced (with N-ecotropism) syncytia in the XC plaque assay (XC⁺). These findings demonstrate that the transforming agent for spontaneous leukemogenesis differs in biological properties from the endogenous MuLV that is commonly observed in mice of high leukemic strains.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Selective neutralization of ecotropic murine leukemia virus by monoclonal antibodies: localization of a site on the gp70 protein associated with ecotropism

A panel of nine monoclonal antibodies against the gp70 and p15(E) envelope proteins of MuLV were tested in parallel for their ability to bind to virus and neutralize infectivity. Although each of the antibodies bound to N-ecotropic MuLV, only antibody against the gp70^f epitope neutralized infectivity. These results were interpreted as evidence for a specific site on the gp70 protein of ecotropic MuLV, in proximity of the gp70^f epitope, which was responsible for the ecotropic-specific binding of virus to the surface of cells.     

Comminuted fracture-dislocations of the elbow treated with an AO wrist fusion plate

Comminuted fracture-dislocations of the elbow are complex injuries that can result in significant postoperative loss of motion. Rigid anatomic fixation with early range of motion is the required treatment. Because of the local anatomy of the proximal ulna, it often is difficult to achieve a rigid fixation construct. A fixation technique of a dorsally applied AO limited contact-dynamic compression wrist fusion plate contoured to fit the anatomy of the proximal ulna is presented. Advantages of the AO wrist fusion plate in comminuted olecranon fractures include the ease of contouring, a low profile, and the use of variable screw hole sizing to achieve stable fixation. The hybrid design allows for rigid 3.5-mm plate fixation distally while providing low profile 2.7-mm plate fixation over the subcutaneous olecranon. The technical and biomechanical features of this plate make it an ideal alternative for fixation of these complex injuries.     

Psychological aspects of erectile and ejaculatory dysfunction

Psychological factors play the most important role in the genesis of sexual dysfunction and the role of psychologists in the prevention, diagnosis, and treatment of these dysfunctions is therefore considerable. This article discusses some of the psychological factors that accompnay erectile ejaculatory cysfunction as well as the possible psychological mechanisms that can occur during the development of these dysfunctions.     

Normative Clinical Relationships Between Orientation and Memory: Age as an Important Moderator Variable

The present study examined the relationship between memory and orientation to time, place, and personal and general information, as moderated by age, education, and simple attentional ability. A heterogeneous sample of 312 clinical referrals was divided into four groups, according to delayed memory functioning. Patients with globally good, globally poor, poor visual, and poor auditory memory were at differential risk of being disoriented, with the globally poor memory patients having the greatest risk. Overall, poorly oriented patients were older and less educated, with worse recall of digits backward. Discriminant Function Analysis selected visual and auditory memory and age as predictors of orientation. Normative tables stratified by age and memory performance are presented.