The ATHENA HPV study underrepresents "other" high-risk HPV genotypes when compared with a diverse New York City population.

OBJECTIVE: Persistent infection with oncogenic high risk HPV (hrHPV) types causes virtually all cases of cervical cancer. HPV 16 and 18 have been targeted for individual genotyping and vaccination because of their presence in 71% of invasive cervical cancers worldwide. Montefiore Medical Center, Bronx, New York serves a population known for ethnic and racial diversity. Given this diversity it is possible that HPV genotypes not individually detected by current testing are causing significant disease. METHODS: We conducted a retrospective analysis of liquid based cervicovaginal cytology and Cobas HPV results reported between October 5, 2015 and March 30, 2016. This included 20 483 samples from patients aged 16-95 (average age 42), with racial distribution including: African-American 32.4%, Other (includes denied, unknown, mixed, Hispanic) 52.1%, Caucasian 14.5%, Asian 0.7%, American Indian/Alaskan Native 0.3%. In all, 14 938 samples (72.9%) were submitted for clinically requested COBAS 4800 HPV testing, which separately reports HPV 16, 18 and a pool of 12 other hrHPV. RESULTS: A total of 3180 (21.5%) tested hrHPV positive. The percentage of patients with cytologic diagnosis of HSIL (high-grade squamous intraepithelial lesion) that were positive only for HPV 16 was 19.4% vs 1.8% for all cytologic diagnoses. However, only one of the HSIL cases was HPV 18 positive along with other hrHPV (OHR). Surprisingly, a majority (64.5%) was positive for only OHR. CONCLUSIONS: Further evaluation is needed to determine if this pool of other hrHPV includes individual genotypes that in our population carry a higher risk of persistence and progression to cancer.

SurePath Specimens Versus ThinPrep Specimen Types on the COBAS 4800 Platform: High-Risk HPV Status and Cytology Correlation in an Ethnically Diverse Bronx Population.

OBJECTIVE: To compare the cytologic preparations of 130 cervical specimens (from women of various ethnicities at high risk for human papillomavirus [HPV] infection) using the SurePath (SP) collection system with specimens gathered using the ThinPrep (TP) system, as processed on the Cobas 4800 analyzer, to determine which collection method more accurately identifies HPV infection. METHODS: In our prospective study, specimens were collected from 130 women of various ethnicities residing in or near Bronx County, NY. The SP-collected specimen was first processed for cytologic findings; if clinical HPV testing was requested on that specimen, it was tested using Hybrid Capture II (HC2) methodology. We tested the remnant SP-collected cell concentrate using the Cobas analyzer. Then, the TP-collected and SP-collected specimens were tested in the same run on that analyzer, and the results were compared. We also compared the results with the concurrent cytologic findings. RESULTS: The results were concordant for overall HR-HPV status in 93.8% of cases. Also, a statistically significant lower cycle threshold value was observed with Cobas testing of specimen concentrates tested via the BD SurePath Pap Test (P = .001), suggesting higher sensitivity compared with specimens tested via the ThinPrep Pap Test. CONCLUSION: Cobas 4800 HPV testing of SP-collected specimen concentrates yields comparable results to TP-collected specimen concentrates. Based on the limited data that we derived, SP collection may be a more favorable methodology than TP collection for HPV testing of individuals at high risk in our ethnically diverse, urban patient population.

Persistence of metastable vortex lattice domains in MgB2 in the presence of vortex motion.

Recently, extensive vortex lattice metastability was reported in MgB2 in connection with a second-order rotational phase transition. However, the mechanism responsible for these well-ordered metastable vortex lattice phases is not well understood. Using small-angle neutron scattering, we studied the vortex lattice in MgB2 as it was driven from a metastable to the ground state through a series of small changes in the applied magnetic field. Our results show that metastable vortex lattice domains persist in the presence of substantial vortex motion and directly demonstrate that the metastability is not due to vortex pinning. Instead, we propose that it is due to the jamming of counterrotated vortex lattice domains which prevents a rotation to the ground state orientation.

Observation of well-ordered metastable vortex lattice phases in superconducting MgB2 using small-angle neutron scattering.

The vortex lattice (VL) symmetry and orientation in clean type-II superconductors depends sensitively on the host material anisotropy, vortex density and temperature, frequently leading to rich phase diagrams. Typically, a well-ordered VL is taken to imply a ground-state configuration for the vortex-vortex interaction. Using neutron scattering we studied the VL in MgB(2) for a number of field-temperature histories, discovering an unprecedented degree of metastability in connection with a known, second-order rotation transition. This allows, for the first time, structural studies of a well-ordered, nonequilibrium VL. While the mechanism responsible for the longevity of the metastable states is not resolved, we speculate it is due to a jamming of VL domains, preventing a rotation to the ground-state orientation.

A rare case of primary lung adenocarcinoma detected by routine liquid-based cervical cytology.

Cervical cytology is mainly used for the screening and detection of early cervical cancers and its precursors. Rarely, detection of malignant cells in cervical cytology specimens is the first manifestation of an extrauterine (EU) malignancy. We report a case of a 49-year-old female in which adenocarcinoma initially diagnosed on routine, liquid-based cervical cytology led to the detection of a primary lung cancer.

Identification of a mutant bovine herpesvirus-1 (BHV-1) in post-arrival outbreaks of IBR in feedlot calves and protection with conventional vaccination.

Outbreaks of infectious bovine rhinotracheitis (IBR) have recently been observed in vaccinated feedlot calves in Alberta a few months post-arrival. To investigate the cause of these outbreaks, lung and tracheal tissues were collected from calves that died of IBR during a post-arrival outbreak of disease. Bovine herpesvirus-1 (BHV-1), the causative agent of IBR, was isolated from 6 out of 15 tissues. Of these 6 isolates, 5 failed to react with a monoclonal antibody specific for one of the epitopes on glycoprotein D, one of the most important antigens of BHV-1. The ability of one of these mutant BHV-1 isolates to cause disease in calves vaccinated with a modified-live IBR vaccine was assessed in an experimental challenge study. After one vaccination, the majority of the calves developed humoral and cellular immune responses. Secondary vaccination resulted in a substantially enhanced level of immunity in all animals. Three months after the second vaccination, calves were either challenged with one of the mutant isolates or with a conventional challenge strain of BHV-1. Regardless of the type of virus used for challenge, vaccinated calves experienced significantly (P < 0.05) less weight loss and temperature rises, had lower nasal scores, and shed less virus than non-vaccinated animals. The only statistically significant (P < 0.05) difference between the 2 challenge viruses was the amount of virus shed, which was higher in non-vaccinated calves challenged with the mutant virus than in those challenged with the conventional virus. These data show that calves vaccinated with a modified-live IBR vaccine are protected from challenge with either the mutant or the conventional virus.

Esophageal carcinoma metastatic to the retina. Diagnosis of a case by cytologic examination of intraocular vitreous washings.

BACKGROUND: The most common primary tumors of the eye are melanomas in adults and retinoblastomas in children. Although generally not recognized, metastases to the eye are more frequent than primary tumors. RESULTS: Occult esophageal carcinoma metastasized to the retina in a 51-year-old woman. The cytologic diagnosis of carcinoma was established on intraocular vitreous washings. Further workup disclosed an adenocarcinoma of the esophagus, confirmed by brushings and biopsy. CONCLUSION: The cytologic features of the intraocular aspirate allowed a rapid and reliable diagnosis that led to further investigation.

Interferon augments the cytotoxicity of hydroxyurea without enhancing its activity against the M2 subunit of ribonucleotide reductase: effects in wild-type and resistant human colon cancer cells.

The effects of prolonged exposure to the ribonucleotide reductase (RR) inhibitor, hydroxyurea (HU), were assessed in the presence or absence of recombinant interferon alfa-2a (IFN) in wild-type human colon cancer cells (HT-29) and variants expressing low-level resistance to HU (R200). IFN at nontoxic concentrations decreased the IC50 of HU from 368 microM to 215 microM (P < 0.01) in wild-type cells, but not in the resistant variants. Potential cellular targets for the HU/IFN interaction were examined. In wild-type, but not resistant cells, treatment with HU at clinically achievable concentrations (1000 microM) resulted in rapid early inhibition of RR activity between 4 and 24 h after treatment with a maximal decrease of 65% at 12 h, decreases in cellular levels of dATP, dCTP and dGTP by 50-90% over the same time course, and a two- to fourfold increase in the level of mRNA for both the M1 and M2 subunits of RR, at 24, but not between 1 and 4 h, which probably represents a response to the earlier decrease in RR activity. IFN at a clinically achievable concentration (500 U/ml) failed to augment the effects of HU on RR protein, RR mRNA levels or RR enzyme activity in either the wild-type or resistant cells, suggesting that the mechanism by which IFN augments the effects of HU in the wild-type cells is independent of the effects of HU on M2.

Interaction of the erythroid transcription factor cGATA-1 with a critical auto-regulatory element.

We have performed a mutational analysis of the promoter for the chicken erythroid-specific GATA-1 transcription factor, and have investigated in detail the interaction of the factor with an upstream auto-regulatory element (ARE). We find that a single proximal GATA binding site of the ARE is required for promoter activity in primary erythroid cells; however, this minimal promoter is inappropriately active in fibroblasts. At least two molecules of GATA-1 can interact with the ARE, and sequences outside of the consensus site appear critical for the transcriptional activity of the bound protein. Finally, we provide evidence for complex protein/DNA interactions at the ARE, including the ability of GATA-1 to bend DNA.

Cytologic features of poorly differentiated "insular" carcinoma of the thyroid. A case report.

A case of poorly differentiated "insular" carcinoma of the thyroid is presented. Fine needle aspiration cytology suggested the differential diagnosis of poorly differentiated carcinoma versus anaplastic carcinoma. Histologic examination of the resected specimen confirmed the diagnosis of insular carcinoma. The cytologic features of this uncommon primary thyroid malignancy are described and discussed with reference to the literature.

Behavioral and reproductive differences in mice as a function of inbreeding.

Twenty brother-sister pairs of mice were randomly selected from a genetically heterogeneous population of mice to begin a schedule of inbreeding that lasted for six generations (F = 0 to F = .732). We examined a number of indices of reproductive behavior and found that all declined as a function of inbreeding. Specifically, there was a consistent decline in the number of fertile matings, in the number of offspring that survived to weaning, and in the weight of the pups at the time of weaning (21 days of age). We also examined a number of behaviors with the following results: there was a systematic increase in the number of trials required to learn an active avoidance task and a consistent decrease in the number of trials required to extinguish this habit. We observed a statistically significant difference in the retention of a passive avoidance habit, but these results were quite variable and not consistent across generations of inbreeding. Finally, we observed that inbreeding had little effect on measures of locomotor behavior.

Nigral 5-HT and substance P-induced enhancement of passive avoidance retention.

Peripheral, posttraining injection of substance P (SP) has been shown to facilitate the retention of aversive and appetitive learning tasks, suggesting that SP may play a role in information processing. In addition, SP may modulate the release of nigrostriatal monoamines, which have also been linked with avoidance learning. This paper examines the interaction between SP and nigrostriatal monoamines by observing the behavioral effects of neurochemical lesions on SP-induced avoidance retention, and by measuring changes in nigrostriatal monoamine activity and receptor regulation following avoidance training and SP injection. In Expt. 1, 5,7-dihydroxytryptamine lesions of the substantia nigra, but not the caudate, attenuated the retention-enhancing effects of posttraining SP injection. Further, 6-hydroxydopamine lesions of the substantia nigra produced a deficit in avoidance conditioning that was reversed by posttraining SP injection. Expts. 2 and 3 demonstrated that although passive avoidance training and posttraining SP injections did not significantly alter nigral 5-hydroxytryptamine (5-HT) activity, SP increased 5-HT1 receptor density. It was concluded that SP may affect avoidance retention by modulating nigral 5-HT activity.

The effect of substance P and its fragments on passive avoidance retention and brain monoamine activity.

It has been shown that substance P(SP), as well as its carboxy and amino terminal fragments, affects a wide range of behaviors. In order to test the CNS activity of these fragments, we measured their effects on passive avoidance learning and monoamine activity. Following one-trial passive avoidance training, mice were injected intraventricularly with either a carboxy or amino terminal SP fragment (SP-C or SP-N), SP itself or phosphate-buffered saline (PBS). SP-N enhanced avoidance retention, which was tested 24 h after training. In a second experiment, monoamine activity was measured one hour after intraventricular injection of SP, PBS or SP fragments. SP-C decreased both nigral 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) and, to a lesser extent, 3,4-dihydroxyphenylacetic acid/dopamine, while SP-N increased nigral 5-HIAA/5-HT. It was concluded that SP-N and SP-C can exert behavioral and neurochemical effects that may be independent of the parent SP molecule.

Substance P facilitation of memory: effects in an appetitively motivated learning task.

Food deprived, heterogeneous strain (HS/IBG) mice were trained on two different discrimination tasks for food reinforcement. In one experiment animals were trained to make spatial discriminations in a T maze. Immediately after training they were given subcutaneous injections of either substance P (1 ng/g) or vehicle. Twenty-four hours later the animals were given reversal training in the same maze. The results showed that substance P-treated animals took significantly longer to acquire the reversal habit than did control mice. In a second experiment, animals were trained to make visual discriminations in a T maze. Immediately after reaching acquisition criterion animals were injected with either substance P (1 ng/g) or vehicle. Different groups of mice were retrained on the same task either 1, 2, 3, or 7 days after original learning. Savings scores were calculated and, at every interval, substance P-treated mice retained the task better than control animals. One interpretation of these data is that substance P-treated mice remembered the original task significantly better than vehicle-injected control animals.

Nicotine-produced relearning deficit in C57BL/6J and DBA/2J mice.

Acute nicotine administration has been shown to influence the acquisition and retention of learning tasks. In order to investigate the many possible behavioral and pharmacological effects of nicotine, a modified 2 X 2 state-dependent learning design was used to assess nicotine's effects on active avoidance learning. Male and female mice of the C57BL/6J (C57) and DBA/2J (DBA) inbred strains were injected with a control solution or with 0.5, 1.0, or 2.0 mg/kg nicotine 5 min before the start of training and, following a 24-h period, 5 min before retraining. Nicotine had no effect on the acquisition of the learning task but, depending on strain and sex, did have an effect on relearning. Relearning in the C57 males was unaffected by nicotine injection, whereas the most prominent effect of nicotine in the C57 females and the DBA males and females was a retrieval deficit. The prevalence of a nicotine-induced retrieval deficit in the present experiment suggests that those mechanisms underlying the retrieval of previously learned information are, in part, mediated or modulated by perturbations within nicotine-sensitive areas of the central nervous system.

Substance P enhancement of passive and active avoidance conditioning in mice.

In a series of seven experiments we explored the effects of peripherally administered substance P on passive and active avoidance conditioning in mice of two genotypes. The peripheral post-trial administration of substance P significantly enhanced the retention of a single-trial passive avoidance task. This effect was dose dependent; 1 ng/g of substance P enhanced the retention of this habit, whereas higher and lower doses were either less effective or ineffective. In heterogeneous strain (HS) mice, substance P administered before training on an active avoidance task did not alter the rate at which these animals learned this habit. However, animals that had been trained with substance P were significantly more resistant to extinction than were animals that had been injected with vehicle. Similarly, C57Bl/6J mice that had been treated with substance P immediately after active avoidance training were more resistant to extinction than were mice that had been given control injections. The enhancement of retention of the passive avoidance habit with substance P was reversed in animals that had been pretreated with naltrexone. Substance P enhancement of the retention of the passive avoidance habit, and its reversal with naltrexone, was observed in both sham operated and adrenalectomized mice.

Substance p reversal of electroconvulsive shock and cycloheximide-induced retrograde amnesia.

Subcutaneous post-trial administration of the neuropeptide substance P was found to reverse the amnestic effects of both electroconvulsive shock and cycloheximide. Substance P was observed to reverse the amnestic effects of cycloheximide in both C57B1/6J and heterogeneous strain (HS) mice. Substance P was found to reverse the amnestic effects of electroconvulsive seizures in C57B1/6J animals. Peripheral injections of substance P were also found to facilitate the retention of a single-trial passive avoidance habit in animals of both genotypes, provided a weak footshock was used during training.

Effects of cycloheximide administered in conjunction with nicotine on retention of a passive avoidance task in mice.

Retention of a passive avoidance task was studied in mice given either cycloheximide or cycloheximide in combination with nicotine. Two similar experiments were conducted: In the first experiment, the effects, of these drugs were studied in inbred C57Bl/6J mice. In the second experiment, the effects of these drugs were studied in genetically heterogenous mice. Cycloheximide was found to have a deleterious effect on retention of the passive avoidance task. Larger doses of cycloheximide were found to be necessary to disrupt memory in heterogenous mice than in C57Bl/6J animals. Nicotine, when administered in conjunction with cycloheximide, abolished the memory disruptive effects of cycloheximide. The results of these experiments are discussed in terms of a time-dependent consolidation model of memory storage.

Acoustic priming and kanamycin-induced chochlear damage.

The cochleae from 3 lines of mice, selectively bred for differential susceptibility to priming-induced audiogenic seizures, were examined following acoustic priming and retest or kanamycin treatment, and the degree of cochlear damage was assessed. After 60 sec of acoustic priming, animals from the high and unselected lines which had subsequently developed audiogenic seizure susceptibility exhibited severe cochlear damage limited to the outer hair cells. Low line mice, which had been selected for resistance to acoustic priming-induced audiogenic seizures and were not seizure susceptible, exhibited no cochlear pathology following acoustic priming. Following kanamycin treatment, all 3 lines developed subsequent audiogenic seizure susceptibility. Histological examination of cochleae from mice so treated revealed a pattern of damage similar to that caused by acoustic priming, except that the cochleae of priming-induced audiogenic seizure resistant low line mice revealed a significant amount of outer hair cell damage. The results are discussed with respect to the physiological mechanism underlying a selectively bred behavioral phenotype in terms of a possible instance of damage/disuse-supersensitivity in the central nervous system.