Concurrent oral and genital infection with HPV DNA types 6 and 11 in a heterosexual male

Objective Detection of HPV DNA in oral and genital lesions of a heterosexual male. 4 months after oral and vaginal intercourse with a woman with vulvar warts. Passible modes of acquisition of oral HPV infection in the male sexual partner are discussed. Setting Genitourinary Medicine clinic. Methods Polymerase chain reaction amplification of genomic DNA from oral and genital lesions. HPV DNA typing by dot blot hybridization. Results HPV DNA types 6 and 11 were identified in a polypoid tongue lesion and in a penile wart from the male sexual partner. Conclusions The acquisition of oral HPV infection in the male sexual partner may have resulted from genital-oral HPV transfer, either by direct contact with vulvar warts or by digital self-inoculation.     

Differential subcellular distribution of the alpha 6 subunit versus the alpha 1 and beta 2/3 subunits of the GABAA/benzodiazepine receptor complex in granule cells of the cerebellar cortex.

The distribution of the alpha 6 subunit of the GABAA receptor has been established in rat cerebellum and compared to the distribution of the alpha 1 (cat) and the beta 2/3 (rat, cat) subunits, using immunocytochemistry. The synapses established by Golgi cell terminals on the dendrites of granule cells were immunoreactive for the alpha 6, alpha 1 and beta 2/3 subunits in virtually all glomeruli, indicating that two variants (alpha 1 and alpha 6) of the same subunit are co-localized at the same synapses. The somatic membranes of the granule cells, which receive no synapses, were immunopositive for the alpha 1 and beta 2/3 subunits, but not for the alpha 6 subunit. Thus, the alpha 1 and the beta 2/3 subunits are located at both synaptic and extrasynaptic sites, but the alpha 6 subunit is detectable only at synaptic sites.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

Selective blockade and recovery of cell surface alpha 2-adrenergic receptors in human erythroleukemia (HEL) cells. Studies with the irreversible antagonist benextramine

alpha 2-Adrenergic receptors are present on human erythroleukemia (HEL) cells, both on the cell surface and in a sequestered compartment. In the current study we show that benextramine, a hydrophilic irreversible antagonist, can be used to investigate alpha 2-adrenergic receptor compartmentation in these cells. In membranes prepared from HEL cells, benextramine competed for all alpha 2-adrenergic receptors ( [3H]yohimbine sites). In intact cells, at 4 degrees, benextramine exhibited a biphasic competition curve for alpha 2-adrenergic receptors, with EC50 values of approximately 10 microM and greater than 1 mM for the high and low affinity components, respectively. We propose that the alpha 2-adrenergic receptors preferentially blocked by benextramine are those on the surface of the cell, whereas those with low affinity are sequestered receptors because: 1) only epinephrine-accessible sites [i.e., cell surface sites; McKernan et al., Mol. Pharmacol. 32:258-265 (1987)] are removed by prior treatment of cells with benextramine, 2) a preparation enriched with surface membranes is also enriched in receptors with a high affinity for benextramine; and 3) after blockade of cell surface receptors (54 +/- 6% of total sites, n = 7) by benextramine, the ability of the alpha 2-adrenergic agonists epinephrine and UK-14,304 to inhibit forskolin-stimulated cAMP accumulation is lost. The latter result implies that only cell surface and not sequestered receptors are functionally coupled to adenylate cyclase. The return of receptors from the sequestered compartment to the cell surface and the recovery of alpha 2-adrenergic receptor function were measured after HEL cells were treated with benextramine (50 microM for 1 hr at 4 degrees). The recovery of receptor binding (t1/2 = 25 min) was somewhat slower than the recovery of function (t1/2 approximately 8 min). This is consistent with the existence of "spare receptors" and also suggests that the sequestered compartment of alpha 2-adrenergic receptors can rapidly exchange with those on the surface. When all alpha 2-adrenergic receptors were blocked by incubation of HEL cells with benextramine for 1 hr at 37 degrees, repopulation of surface and sequestered receptors was much slower (t1/2 = 9 hr for recovery of total receptors). Surface receptors recovered even more slowly than did total cellular receptors consistent with the idea that alpha 2-adrenergic receptors must traverse through intracellular locations before insertion into the cell surface.(ABSTRACT TRUNCATED AT 400 WORDS)     

Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype

Inhibitory neurotransmission in the brain is largely mediated by GABA(A) receptors. Potentiation of GABA receptor activation through an allosteric benzodiazepine (BZ) site produces the sedative, anxiolytic, muscle relaxant, anticonvulsant and cognition-impairing effects of clinically used BZs such as diazepam. We created genetically modified mice (alpha1 H101R) with a diazepam-insensitive alpha1 subtype and a selective BZ site ligand, L-838,417, to explore GABA(A) receptor subtypes mediating specific physiological effects. These two complimentary approaches revealed that the alpha1 subtype mediated the sedative, but not the anxiolytic effects of benzodiazepines. This finding suggests ways to improve anxiolytics and to develop drugs for other neurological disorders based on their specificity for GABA(A) receptor subtypes in distinct neuronal circuits.     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

Phenoxybenzamine partially inhibits alpha 2-adrenoceptors without affecting their presynaptic function

The turnover of alpha-adrenoceptors was assessed by administering phenoxybenzamine (PBZ) intraperitoneally to rats in order to block the receptors irreversibly. The reappearance of the binding of [3H]prazosin, [3H]clonidine and [3H]rauwolscine in membranes from cerebral cortices was then measured. Maximum inhibition of binding occurred 3 hr after administration of phenoxybenzamine. The binding of [3H]prazosin was inhibited by 95% after administration of phenoxybenzamine (2 X 4 mg/kg, i.p.), and the half life (t1/2) for the alpha 1-adrenoceptor was 1.87 days. The "turnover" of binding for the alpha 2-adrenoceptor ligands ([3H]clonidine and [3H]rauwolscine) was similar: with doses of phenoxybenzamine up to 15 mg/kg (i.p.), the binding of both ligands was inhibited to a maximum of 30%. Maximum recovery occurred 3 days after treatment with phenoxybenzamine and the alpha 2-adrenoceptor has an apparent half life for recovery of 12 hr. Since only partial blockade of alpha 2-adrenoceptors was possible with phenoxybenzamine the possibility that these blocked sites included functional presynaptic autoreceptors was investigated. Clonidine (1 microM) attenuated K+-induced release of preloaded [3H]noradrenaline from cortical synaptosomes prepared from control rats by some 35%. Clonidine inhibited this release of [3H]noradrenaline to the same extent in synaptosomes prepared from rats treated with phenoxybenzamine 3 hr prior to sacrifice. This indicates that the alpha 2-adrenoceptors which are blocked by phenoxybenzamine are not part of the functional receptor population.     

Drug-Resistant Tuberculosis in Pet Ring-Tailed Lemur,Madagascar

We diagnosed tuberculosis in an illegally wild-captured pet ring-tailed lemur manifesting lethargy, anorexia, and cervical lymphadenopathy. Whole-genome sequencing confirmed the Mycobacterium tuberculosis isolate belonged to lineage 3 and harbored streptomycin resistance. We recommend reverse zoonosis prevention and determination of whether lemurs are able to maintain M. tuberculosis infection.