GLUT1 expression in human papillomavirus-positive anogenital lesions.

BACKGROUND: GLUT1, an ubiquitous glucose transporter in the mammalian cells, is upregulated in many tumours, including human papillomavirus (HPV)-induced head and neck or cervical cancer. OBJECTIVE: To study in anogenital lesions whether or not GLUT1 expression correlates with genomic high-risk HPV integration, the first step in neoplastic transformation. METHODS: Forty-three HPV-positive biopsies positive for either low-risk or high-risk HPV were selected. Paraffin sections adjacent to those tested for the presence of HPV were processed for GLUT1 immunocytochemistry. GLUT1 expression was analysed by two histologists, blinded to HPV type and status and then compared with HPV typing results. RESULTS: Two main staining patterns were observed, either staining from the basal to the granular layer or staining of superficial layers only. The first staining pattern corresponded to lesions with high number of episomal HPV-positive nuclei. Superficial staining was observed in lesions with low number of episomal HPV nuclei or when high-risk HPV was integrated in the cell genome. CONCLUSION: Our results show that GLUT1 overexpression correlates with the number of episomally infected cells in the lesion, but not with the type (low or high risk) of HPV.

Novel SPG10 mutation associated with dysautonomia, spinal cord atrophy, and skin biopsy abnormality.

BACKGROUND: SPG10 is a rare form of autosomic dominant hereditary spastic paraplegia (HSP) caused by mutations in the KIF5A gene, which may be involved in axonal transport. METHODS: We report the characteristics of a French family with a novel missense mutation c.580 G>C in exon 7 of the KIF5A gene. RESULTS: The proband and his sister presented with an adult onset HSP, a sensory spinal cord-like syndrome, dysautonomia, and severe axonal polyneuropathy. Contrary to the proband, his sister presented a secondary improvement in spasticity and walking. In the proband, MRI findings consisted in spinal cord atrophy and symmetric cerebral demyelination, whereas the skin biopsy suggested a defect in the number of vesicles and synaptophysin density at the pre-synaptic membrane. CONCLUSION: This study extends the phenotype of SPG10 and argues for abnormalities in the axonal vesicular transport.

Vaginal keratinization during the estrous cycle in rats: a model for evaluating retinoid activity.

A model is described for evaluating the activity of a retinoid based on its effect on the keratinization of the vaginal epithelium that occurs on estrus (day 4) of a 4-day cycle in female rats. This keratinization process is dependent on the endogenous estradiol (E2) secreted between the evening of diestrus 2 (day 2) and that of proestrus (day 3). Various doses of all-transretinoic acid (tRA) were injected at different time points during the estrous cycle and the vaginal keratinization was assessed by microscope examination of unstained native or Papanicolaou-stained smear preparations. Additionally, the preovulatory E2 secretion was measured and ovaries were histologically examined. A single injection of 10 mg/kg tRA either on diestrus 2 (evening) or on proestrus (early morning) was able to induce a complete inhibition of the vaginal keratinization in more than 80% of the cases. This can be considered as a direct effect on the vaginal epithelial differentiation since neither the E2 secretion nor the ovulatory process were affected. The inhibition of vaginal keratinization can be used as a rapid and convenient in vivo model for screening retinoid candidates with antikeratinizing activity.

Induction of progestin receptors in the mediobasal hypothalamus of gonadally intact male rats primed with estrogen in relation to display of lordosis behavior.

The purpose of this study was to determine whether the effects of estrogen on lordosis behavior in the male rat were related to the number of progesterone (P) receptors in the mediobasal hypothalamus (MBH) and/or dependent on blood P concentration. Two groups of gonadally intact male rats were given five successive doses of 1.0 or 2.5 micrograms estradiol benzoate (EB) and tested for lordosis behavior with a male stimulus at the end of the treatment. One month later they were again injected with EB and sacrificed under the same temporal schedule, but they were not tested for lordosis so as to prevent any emotionally stressful effects of intermale cohabitation. The males given 2.5 micrograms EB more frequently displayed lordosis responses to male mounts than those receiving 1 microgram EB, with a parallel increase in the number of MBH P receptors. The total number of MBH P receptors also appeared to be higher in the animals that displayed lordosis responses (lordosis group) than in those which did not (no lordosis group). In contrast, the display of lordosis behavior was negatively correlated with blood P concentration. Comparing MBH P receptors and blood P values in the EB treated and in nonhormonally treated gonadally intact animals which had been selected for either ability or inability to spontaneously display lordosis behavior, we observed that (1) EB was capable of increasing the number of MBH P receptors in the male rat; and (2) in the absence of EB treatment blood P values were higher in the animals showing lordosis than in those which did not. These data are discussed with respect to observations made in castrated male rats and in ovariectomized females.

Changes in estrogen receptors in the mediobasal hypothalamus mediate the facilitory effects exerted by the male's olfactory cues and progesterone on feminine behavior in the male rat.

The purpose of this study was to determine whether facilitory effects exerted by olfactory cues on lordosis behavior in the male rat involved changes in estradiol receptors at the hypothalamic level. Male rats were orchidectomized as adults. They were given either 25 micrograms estradiol benzoate (EB) alone or 25 micrograms EB and 100 micrograms progesterone (P) sequentially and exposed or not to the odor of male urine. Some of them were tested for lordosis behavior at 8 h after P. The other ones were killed 4 h after P and used for estradiol (E2) and P receptor assay in mediobasal hypothalamus (MBH). Olfactory cues were shown to increase the number of E2 receptors in both the animals given EB or EB + P. Progesterone as such appeared to be capable of increasing the number and the rate of occupancy of E2 receptors. A population of constitutive and estrogen-inducible P receptors was detected in the MBH. Since only the animals given EB + P were shown to be sensible to the facilitory effects of male urine on lordosis behavior, it may be assumed that E2 and P on one hand and olfactory cues on the other exert cumulative effects at the level of the MBH and that both a high level and a high rate of occupancy of E2 receptors are necessary for the olfactory cues to facilitate the display of lordosis behavior in the male rat.

Hormonal control of the perception of the olfactory signals which facilitate lordosis behavior in the male rat.

This study was designed to evaluate in the male rat the hormonal requirements for the facilitation of feminine behavior by the odor of male urine. Wistar rats from the WI and WII strains in our colony were orchidectomized (ORCH) as adults. A first group was given a single dose of 75 micrograms estradiol benzoate (EB) and tested for lordosis behavior 48 hr later. Exposure to the odor of male urine by 9 +/- 1 hr before the behavioral session did not increase the number of animals showing lordosis behavior as compared to non exposed controls. A second group of WI rats was given 0.5 micrograms EB every day for 4 to 8 days. A similar number of animals displayed lordosis behavior irrespective of whether they were exposed to the odor of urine before testing. A third group of WI rats was injected with 75 micrograms EB and 1 mg progesterone (P) 39 hr apart. Exposure to the odor of urine during estrogen treatment remained ineffective but significantly increased the number of animals showing lordosis behavior when performed at the time of P injection. A last group of WII rats was given 25 micrograms EB and 100 micrograms or 150 micrograms P 39 hr apart. Although uncapable as such to facilitate lordosis behavior the dose of 100 micrograms P rendered the animals responsive to the odor of urine. It was concluded that (1) the perception by feminized males of olfactory signals from the male was dependent on P; (2) an interaction between hormonal and sensory mechanisms was involved in the facilitation of lordosis behavior in the male rat.