Evidence for Neutral-Current Diffractive π

The MINERvA experiment observes an excess of events containing electromagnetic showers relative to the expectation from Monte Carlo simulations in neutral-current neutrino interactions with mean beam energy of 4.5 GeV on a hydrocarbon target. The excess is characterized and found to be consistent with neutral-current π^{0} production with a broad energy distribution peaking at 7 GeV and a total cross section of 0.26±0.02(stat.)±0.08(sys.)×10^{-39} cm^{2}. The angular distribution, electromagnetic shower energy, and spatial distribution of the energy depositions of the excess are consistent with expectations from neutrino neutral-current diffractive π^{0} production from hydrogen in the hydrocarbon target. These data comprise the first direct experimental observation and constraint for a reaction that poses an important background process in neutrino-oscillation experiments searching for ν_{µ} to ν_{e} oscillations.

Measurement of Electron Neutrino Quasielastic and Quasielasticlike Scattering on Hydrocarbon at ⟨E_{ν}⟩=3.6 GeV.

The first direct measurement of electron neutrino quasielastic and quasielasticlike scattering on hydrocarbon in the few-GeV region of incident neutrino energy has been carried out using the MINERvA detector in the NuMI beam at Fermilab. The flux-integrated differential cross sections in the electron production angle, electron energy, and Q^{2} are presented. The ratio of the quasielastic, flux-integrated differential cross section in Q^{2} for ν_{e} with that of similarly selected ν_{µ}-induced events from the same exposure is used to probe assumptions that underpin conventional treatments of charged-current ν_{e} interactions used by long-baseline neutrino oscillation experiments. The data are found to be consistent with lepton universality and are well described by the predictions of the neutrino event generator GENIE.

Periapical central giant cell granuloma: a potential endodontic misdiagnosis.

This retrospective study ascertained the incidence and clinicopathologic features of central giant cell granulomas (CGCGs) associated with teeth with necrotic pulps or teeth that had received previous endodontic treatment and determined whether periapical CGCGs can result in endodontic misdiagnosis. Clinical and histopathologic data of biopsy specimens diagnosed as CGCG were collected from the archives of the Oral Pathology Laboratory, Temple University, and were reviewed. Over the 9-year period, 16 of 79 cases (20%) of CGCG were associated with a tooth that had a history of pulp necrosis. Of those, 14 (88%) were associated with previous root canal treatment. The data from this series of 79 cases of CGCG also showed that CGCGs were less common in women, less common before age 30, and did not cross the midline of the jaw as often as previously reported. Clinical and histopathologic data were compared from (1) CGCGs associated with teeth with vital pulps or that occurred in edentulous areas; (2) CGCGs associated with teeth with necrotic pulps; and (3) 194 cases of periapical granulomas and radicular cysts. These data strongly suggest that CGCGs associated with teeth with necrotic pulps are not directly related to periapical inflammation and may be misdiagnosed as endodontic lesions. Posttreatment follow-up and routine submission of periapical surgical specimens are emphasized.

The absence of Msh2 alters abelson virus pre-B-cell transformation by influencing p53 mutation.

Defects in DNA mismatch repair predispose cells to the development of several types of malignant disease. The absence of Msh2 or Mlh1, two key molecules that mediate mismatch repair in eukaryotic cells, increases the frequency of mutation and also alters the response of some cells to apoptosis and cell cycle arrest. To understand the way these changes contribute to cancer predisposition, we examined the effects of defective mismatch repair on the multistep process of pre-B-cell transformation by Abelson murine leukemia virus. In this model, primary transformants undergo a prolonged apoptotic crisis followed by the emergence of fully transformed cell lines. The latter event is correlated to a loss of function of the p53 tumor suppressor protein and down-modulation of the p53 regulatory protein p19Arf. Analyses of primary transformants from Msh2 null mice and their wild-type littermates revealed that both types of cells undergo crisis. However, primary transformants from Msh2 null animals recover with accelerated kinetics, a phenomenon that is strongly correlated to the appearance of cells that have lost p53 function. Analysis of the kinetics with which p53 function is lost revealed that this change provides the dominant stimulus for emergence from crisis. Therefore, the absence of mismatch repair alters the molecular mechanisms involved in transformation by affecting a gene that controls apoptosis and cell cycle progression, rather than by affecting these processes directly.

p53 mediates apoptotic crisis in primary Abelson virus-transformed pre-B cells.

Transformation of pre-B cells by Abelson murine leukemia virus (Ab-MLV) involves a balance between positive, growth-stimulatory signals from the v-Abl oncoprotein and negative regulatory cues from cellular genes. This phenomenon is reflected by the clonal selection that occurs during Ab-MLV-mediated transformation in vivo and in vitro. About 50% of all Ab-MLV-transformed pre-B cells express mutant forms of p53 as they emerge from this process, suggesting that this protein may play an important role in the transformation process. Consistent with this idea, expression of p19(Arf), a protein whose function depends on the presence of a functional p53, is required for the apoptotic crisis that characterizes primary Ab-MLV transformants. To test the role of p53 in pre-B-cell transformation directly, we examined the response of Trp53(-/-) mice to Ab-MLV. The absence of p53 shortens the latency of Abelson disease induction but does not affect the frequency of cells susceptible to Ab-MLV-induced transformation. However, primary transformants derived from the null animals bypass the apoptotic crisis that characterizes the transition from primary transformant to fully malignant cell line. These effects do not require p21(Cip-1), a major downstream target of p53; however, consistent with a role of p19(Arf), transformants expressing mutant p53 and abundant p19 retain wild-type p19 sequences.

Thermafil retreatment using a new "System B" technique or a solvent.

The solid plastic carrier in the Thermafil obturation system must be removed to facilitate retreatment. The purpose of this study was to compare the efficacy and time required to retreat canals obturated with Thermafil with plastic carriers using a new technique based on the System B HeatSource or a solvent. Fifty-two extracted human mandibular premolars with single canals were instrumented and then obturated with Thermafil with plastic carriers. After 2 wk storage at 22 degrees C and 100% humidity, they were randomly divided into 2 groups of 26 teeth each. Group 1 teeth were retreated using chloroform and hand files, whereas teeth in group 2 were retreated with a new technique using the System B HeatSource. The end point of retreatment was defined as complete removal of the plastic carrier. The time required for retreatment was recorded. Then, the apical 5 mm segment of each root was sectioned horizontally at 1 mm intervals and each section digitally imaged. The total area of the canal and the area of the canal occupied by gutta-percha and sealer were measured using NIH image software. Data were analyzed using an unpaired t test. The mean time for retrieval of the plastic carrier was significantly less for the System B technique (1.8 min) than for the solvent technique (3.6 min) (p < 0.001). The difference between the two groups in the amount of filling material (carrier, gutta-percha, and sealer) removed was not significant (p > 0.05).

Evaluation of pigmented intraorifice barriers in endodontically treated teeth.

The purpose of this study was to evaluate the effectiveness of three pigmented glass ionomer cements used as intraorifice barriers to prevent coronal microleakage. One hundred ten extracted mandibular human premolars were divided into four experimental groups of 25 teeth each and two control groups of 5 teeth each. The experimental teeth were instrumented and obturated using thermoplasticized gutta-percha and AH26 sealer. Group 1 teeth received no further treatment. Teeth in groups 2 through 4 had 1 of 3 pigmented glass ionomers (Vitrebond, GC America, and Ketac-Bond) placed as an intraorifice barrier. Positive control teeth were instrumented but not obturated. The negative control teeth were instrumented, obturated, and externally sealed with epoxy resin. The coronal 3 mm of each root was sealed into the lumen of an 18-mm segment of latex surgical tubing. After the apparatus was sterilized, 2.0 ml of a 24 h growth of Proteus vulgaris in trypticase soy broth (TSB) was placed in the coronal reservoir of the tooth. The inoculated apparatus was placed into a presterilized test tube containing 1.5 ml of TSB and incubated for 90 days at 37 degrees C. The TSB in the lower reservoir was observed daily for turbidity, which would indicate leakage along the full length of the obturated root canal. To determine if differences in microbial leakage occurred among the four experimental groups, Pearson's chi 2 and Fisher's exact tests were performed. The confidence level was set at 95%. The positive and negative controls validated the microbial testing method. The teeth without an intraorifice barrier leaked significantly more than teeth with Vitrebond intraorifice barriers (p < 0.05). The difference in leakage among the experimental glass ionomer barriers was not significant (p > 0.05).

Torsional properties of nickel-titanium versus stainless steel endodontic files.

The purpose of this study was to evaluate and compare the torsional properties of stainless steel K-type .02 taper and nickel-titanium U-type .02 and .04 taper instruments. Torsion tests were performed on all three designs of instruments according to ANSI/ADA specification number 28. For each design, 20 instruments of each of three sizes (15, 25, and 35) were tested. The three parameters measured were maximum torque, torque at failure, and angular deflection. Stainless steel K-type .02 taper and nickel-titanium U-type .02 and .04 taper instruments met or exceeded specification standards for maximum torque. They also satisfied and far exceeded the standards for angular deflection at the failure point. The stainless steel instruments showed no significant difference between maximum torque and torque at failure, whereas both of the nickel-titanium instruments showed a significant differential between maximum torque and torque at failure.

Effect of two obturation techniques on the filling of lateral canals and the main canal.

The three-dimensional obturation of the root canal system is widely accepted as a key factor for successful endodontic therapy. The purpose of this study was to evaluate the obturation of lateral canals and the main canal using cold lateral condensation versus the gutta-percha coated rigid carrier. Thirty epoxy blocks with five lateral canals placed at varying angles from the main canal were used. Each experimental group was obturated by a board certified endodontist with clinical experience in the respective obturation technique. The length of gutta-percha and sealer in the lateral canals was measured under a microscope (x30, Unitron) to the nearest 0.5 mm. The blocks were sectioned with an Isomet Plus precision saw (Buehler, Lake Bluff, IL) and copious water irrigation perpendicular to the main canal at the apex, the height of contour, and at 0.8, 1.6 and 2.4 mm from the canal apex. A microscope (x100, Leitz, Switzerland) was used to determine voids. There was significantly (p < .001) more gutta-percha in the lateral canals with the gutta-percha coated rigid carrier technique. In contrast, the cold lateral condensation technique had significantly (p < .001) more sealer in the lateral canals. However, there was no significant (p < .05) difference, in gutta-percha-plus-sealer filling of the lateral canals, between the two techniques. In the apical 1 mm of the main canal there were significantly (p < .011) fewer voids with the gutta-percha coated rigid carrier technique compared to the cold lateral condensation. In the model chosen, the gutta-percha coated rigid carrier technique and the cold lateral condensation technique were equally effective in filling lateral canals. In filling the main canal, however, the coated rigid carrier technique was more effective.

Radiologic evaluation of the jaundiced patient. Diagnostic and therapeutic role of current procedures.

Radiologic evaluation of the jaundiced patient generally begins with ultrasound. Computed tomography may provide better information regarding the exact level of obstruction, but it is more expensive and time-consuming than ultrasound and carries the risk associated with intravenous contrast. It thus should be used only when ultrasound findings are likely to be inadequate. Percutaneous transhepatic cholangiography and endoscopic retrograde cholangiopancreatography are both relatively safe, reliable procedures for direct opacification of the biliary tree. The choice depends on clinical and ultrasound findings. Percutaneous transhepatic cholangiography provides a foundation for percutaneous drainage if necessary. Cholescintigraphy in the jaundiced patient provides physiologic information but poor anatomic detail. It is useful in establishing common duct functional patency.

Immunosuppression in experimental trypanosomiasis: effects of Trypanosoma equiperdum on the pathogenesis of influenza virus infection in deer mice (Peromyscus maniculatus).

The effects of Trypanosoma equiperdum infections on the immunological and pathological responses of deer mice (Peromyscus maniculatus) to influenza virus exposure were investigated. Mice carrying a 5 week trypanosome infection along with an age- and sex-matched trypanosome-free control group were simultaneously exposed to influenza Ao (WSN) virus. T. equiperdum infection significantly (P less than 0.01) converted a sub-lethal virus attack into a fatal pneumonic process in a small proportion of animals. In addition, the trypanosome caused a reduction (p less than 0.1) in virus replication on PID 1 and 2, accompanied later by a tendency towards virus persistence in the lungs of affected mice. This tendency was manifested by a log reduction in virus titres between PID 2 and 4 and PID 4 and 6 in the lungs of trypanosome-infected mice, compared to 2 log drops over the same periods in the lungs of control mice. T. equiperdum infection also significantly (p less than 0.001) depressed serum and pulmonary neutralizing antibody titres to influenza virus.

Effect of pyrimidinone treatment on lethal and immunosuppressive murine cytomegalovirus infection.

The 2-amino-5-halo-pyrimidinones, which are potent interferon inducers and antiviral agents, were found to be protective against lethal cytomegalovirus (CMV) challenge in weanling or neonatal mice when administered before virus challenge. This protection was dependent upon the dosage of pyrimidinone administered. Weanling mice infected with a sublethal challenge of CMV exhibited moderate to severe immunosuppression as measured by reduced splenic cell blastogenic responses in vitro to the mitogen concanavalin A. Treatment of mice with pyrimidinones during the course of CMV immunosuppression resulted in substantial augmentation of splenic cell blastogenic responses. The degree of augmentation appeared to be dependent on the severity of CMV-induced immunosuppression.

Cross-reactive target antigen in cell-mediated cytolysis of cells infected with a temperature-sensitive mutant of Sindbis virus.

Cytotoxic T lymphocytes (CTL) against alphavirus-infected L929 cells were generated in mice by two in vivo immunizations of one virus or by in vivo immunization followed by in vitro stimulation of splenocytes with infected peritoneal exudate cells or splenocytes. These CTL caused specific H-2-restricted cytolysis equally well with homologous, heterologous or Sindbis virus ts20 mutant-infected cells. Thus, specific CTL appear to be cross-reactive components in normal immunity to alphaviruses and the E1 glycoprotein is implicated as the target antigen.

Detection of immunologically cross-reacting capsid protein of alphaviruses on the surfaces of infected L929 cells.

Hyperimmune, but not normal immune, monospecific antiserum made to capsid protein of Sindbis virus (SIN) was found to cause cytolysis equally well of both SIN- and Semliki Forest virus-infected L929 cells in antibody-dependent, complement-mediated cytotoxicity assays. The cell surface reactivity of the hyperimmune antiserum was also demonstrated by solid-phase radioimmune assays with unfixed infected cells or infected cells fixed with low concentrations of glutaraldehyde (0.025%) before reactivity with antisera. Higher concentrations of glutaraldehyde lowered the sensitivity of detection. Purified SIN capsid protein specifically inhibited antibody-dependent, complement-mediated cytotoxicity by the monospecific anti-capsid protein serum on SIN- and Semliki Forest virus-infected target cells. That hyperimmune anti-SIN serum also cross-reacts with capsid protein on the surface of Semliki Forest virus-infected cells was suggested by the fact that capsid protein inhibited cross-cytolysis in the antibody-dependent, complement-mediated cytotoxicity assay. The latter antiserum was collected after repeated injections of purified virions over a 9-month period. The results suggest that hyperimmune monospecific antisera made to SIN capsid protein or hyperimmune antisera to SIN or Semliki Forest virions detect homologous and cross-reacting capsid protein determinants on the surface of infected cells.

Identification of immunologically cross-reactive proteins of Sindbis virus: evidence for unique conformation of E1 glycoprotein from infected cells.

Hyperimmune antisera to purified Sindbis (SIN) or Semliki Forest (SF) virus were used to identify alphavirus-specific and cross-reactive proteins in virions and infected cells. The hyperimmune sera participated in homologous and cross-cytolysis of alphavirus-infected cells, and the use of monospecific antisera to SIN structural proteins suggested that E1 and E2 could serve as target proteins in cytolysis. Proteins from purified virions or infected cells were extracted with Nonidet P-40, denatured by procedures for sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose solid supports, and reacted with hyperimmune sera and 125I-labeled protein A (immunoblotting on denatured proteins). Alternatively, native proteins extracted by mild Nonidet P-40 treatment were precipitated with hyperimmune sera before denaturation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After immunoblotting, homologous antiserum reacted with the virus structural proteins E1, E2, capsid extracted from purified virions, and the counterparts of these proteins extracted from infected cells. In addition, PE2 and a 92,000-molecular-weight protein from infected cells reacted with homologous antiserum. These proteins were also immunoprecipitated with homologous antiserum. After immunoblotting, the Sindbis capsid protein was shown to be cross-reactive whether derived from purified virions or from infected cells; no cross-reactivity was observed with PE2 or E2 from either source, and the E1 glycoprotein was shown to be cross-reactive only when obtained from virions. However, the E1 glycoprotein could be cross-immunoprecipitated from infected cells (as well as from disrupted virions), and, in addition, capsid and a 92,000-molecular-weight protein were cross-immunoprecipitated from infected cells. These results suggest that a native conformation of the cell-associated E1 glycoproteins may be required for immunological cross-reactivity (immune precipitation), whereas virion but not cell-associated E1 retains immunological cross-reactivity after denaturation (immunoblot technique). The findings extend our previously published evidence which suggested that alphavirus maturation is accompanied by a change in immunological cross-reactivity with respect to E1.

Exposure to ozone reduces influenza disease severity and alters distribution of influenza viral antigens in murine lungs.

Exposure to ambient levels of ozone (0.5 ppm) was shown to alter the pathogenesis of respiratory infection after aerosol infection of mice with influenza A virus. A semiquantitative method for determination of the sites of virus replication by direct immunofluorescence indicated that exposure to ozone reduced the involvement of respiratory epithelium in the infectious process and resulted in a less widespread infection of the alveolar parenchyma. Furthermore, the ozone-mediated alteration in viral antigen distribution was consistent with significantly reduced influenza disease mortality and prolonged survival time, but only when the oxidant was present during the course of infection. Reduced disease severity in ozone-exposed animals appeared to be independent of peak pulmonary virus titers, pulmonary interferon titers, and pulmonary and serum-neutralizing antibody titers. These studies suggested that the distribution of influenza virus in the murine lung was a key factor in disease severity.

Cross-reactive, cell-associated antigen on L929 cells infected with temperature-sensitive mutants of sindbis virus.

Temperature-sensitive (ts) mutants of Sindbis virus (SIN) were used to aid in the identification of alphavirus cross-reactive proteins on the surface of infected cells by antibody-dependent, complement-mediated cytolysis. Antisera prepared in rabbits against purified SIN or Semliki Forest viruses were highly cytotoxic for cells infected with wild-type SIN and for cells infected at the permissive temperature with maturation-defective, ts mutants of SIN belonging to several distinct complementation groups. When these SIN mutants were analyzed by antibody-dependent, complement-mediated cytolysis at the restrictive temperature only cells infected with the SIN mutant of complementation group E, ts20, participated in both homologous (with anti-SIN serum) and heterologous (with anti-Semliki Forest virus serum) antibody-dependent, complement-mediated cytolysis reactions. These data and the known defect of ts20 suggested that the cell-associated viral E1 glycoprotein was a functional target antigen for homologous and cross-immunoreactivity in alphavirus-infected cells. At the restrictive temperature there were quantitative differences in antibody-dependent, complement-mediated cytolysis reactivity of ts20- versus wild type-infected cells consistent with the suggestion that ts20-infected cells do not fully express all of the homologous or the cross-reactive antigenic determinants found in wild-type infection. Additional potential sites for antigenic determinants involved in alphavirus-immune cross-reactivity are discussed in relation to events in virus maturation.