Relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 overexpression in Barrett metaplasia.

BACKGROUND: There is a need for molecular markers of malignant progression in Barrett metaplasia (BM). The aim of this study is to determine the relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 in BM. METHODS: Sections of esophageal biopsy specimens from 120 patients with BM were evaluated for dysplasia, p53 protein, and Glut1 expression by immunohistochemistry, and DNA ploidy by Feulgen stain and image analysis. In cases with diploid DNA histograms, the percentage cells in the G0G1 and G2M phases of the cell cycle were determined. RESULTS: Of 108 diploid cases 19 (28%) of 69 cases with G0G1 > or = 90% or G2M > or = 8.33% were p53-positive, in contrast to only 1 (3%) of 39 cases with lower G0G1 or G2M (P = 0.0008). Of 32 p53-positive cases 11 (32%) were aneuploid, in contrast to none (0%) of 88 p53-negative cases (P < 0.0001). Ten (91%) of 11 aneuploid cases were high-grade dysplasial adenocarcinoma (HGD/CA), compared with only 1 (1%) of 109 diploid cases (P < 0.0001). Five (45%) of 11 cases with HGD/CA were Glut1-positive, in contrast to none (0%) of 109 cases without HGD/CA (P < 0.0001). CONCLUSIONS: Our data strongly suggest that in BM, after oxidative DNA damage, as a result of gastroesophageal reflux, there is an increase in the percentage of cells in the G0G1 or G2M phases of the cell cycle to enable repair of damaged DNA; in some of these cases this is followed sequentially by p53 gene mutation and protein accumulation, DNA aneuploidy, HGD, and CA with or without Glut1 overexpression. These events can be detected in routinely processed biopsy samples.

Model surgery prediction for mandibular midline distraction osteogenesis.

Mandibular midline distraction osteogenesis is available as a treatment option for the correction of mandibular transverse arch deficiency. A model surgery technique is presented here through a case report that will allow the surgeon to predict the amount of transverse expansion that can be gained by this procedure. Utilizing measurements from a three-dimensional stereolithography model, the mandibular cast is mounted on a semi-adjustable articulator. The maxillary model is mounted onto the articulator using an interocclusal record. Acrylic straps are fabricated that relate the condylar elements of the articulator to the right and left mandibular dental segments. The mandibular model is sectioned at the midline, the hemi-mandibular segments are rotated laterally until the desired midline expansion is achieved and the mandibular model is luted into its new position. The post-expansion relationship of the maxillary and mandibular arches can be visualized on the articulator and provide useful information to the surgeon and orthodontist.

Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillofacial surgery.

The preparation and use of platelet gel, an autologous formulation of fibrin glue, are described. The unique features of this biologic sealant are that it is derived from autologous blood collected in the immediate preoperative period by the anesthesiologist, it contains a high concentration of platelets, and it can be used in patients who are not candidates for blood bank donation. Platelet gel has been used successfully in the area of reconstructive oral and maxillofacial surgery in conjunction with ablative surgery of the maxillofacial region, mandibular reconstruction, surgical repair of alveolar clefts and associated oral-antral/ oral-nasal fistulas, and adjunctive procedures related to the placement of osseointegrated implants.

Ovarian hormones alter the behavioral response of the medial preoptic anterior hypothalamus to arginine-vasopressin.

In Syrian hamsters (Mesocricetus auratus) arginine-vasopressin (AVP) within the medial preoptic-anterior hypothalamus (MPOA-AH) plays a critical role in the control of a hormone-dependent behavior called flank marking. The present study investigated whether ovarian hormones influence flank marking by altering the response of the MPOA-AH to AVP. The amount of flank marking stimulated by microinjection of AVP (9 microM in 200 nl saline) into the MPOA-AH varied significantly over the 4 days of the estrous cycle with the lowest levels of flank marking observed on estrus. A second experiment demonstrated that administration of progesterone significantly reduced AVP-stimulated flank marking in estradiol-treated ovariectomized hamsters. These data support the hypothesis that the changing levels of estradiol and progesterone during the estrous cycle influence flank marking by altering the sensitivity or response of the MPOA-AH to AVP.

Role of oxytocin in the hypothalamic regulation of sexual receptivity in hamsters.

Oxytocin (OXT) has been implicated in the control of a variety of social and reproductive behaviors in several species. The purpose of the present study was to test the hypothesis that OXT activity within the medial preoptic-anterior hypothalamus (MPOA-AH) and the ventromedial hypothalamus (VMH) plays a critical role in the expression of sexual receptivity in Syrian hamsters. The first 2 experiments investigated whether OXT would stimulate sexual receptivity in female hamsters in a dose-dependent manner. A 3rd experiment investigated whether sexual receptivity would be inhibited when endogenous OXT activity was blocked. Microinjection of OXT into the MPOA-AH or the VMH induced sexual receptivity in a dose-dependent manner in ovariectomized (OVX) hamsters primed with estradiol. Microinjection of a selective OXT antagonist, d(CH2)5[Tyr(Me)2Thr4,Tyr-NH29] ornithine vasotocin into the MPOA-AH or the VMH significantly reduced the levels of sexual receptivity exhibited by OVX hamsters administered estradiol and progesterone. These findings support the hypothesis that OXT activity in the MPOA-AH and the VMH plays an important role in the regulation of sexual receptivity in hamsters.

Recent advances in high-performance liquid chromatography/mass spectrometry and high-performance liquid chromatography/tandem mass spectrometry: detection of cyclosporine and metabolites in kidney and liver tissue.

Recent advances in both ionization methods and mass spectrometers have resulted in powerful new techniques for the study of drug metabolism and disposition. The interest in high-performance liquid chromatography/mass spectrometry (HPLC/MS) is the result of the lack of a sensitive universal detector for HPLC. Although it is not the ideal detector, HPLC/MS has become a reliable technique for xenobiotic analysis. The application of HPLC/MS to studies of the pharmacology and toxicology of molecules of mass < 1,500 daltons is most advantageous in three areas: development of specific methods for trace analysis, detection and characterization of metabolites, and studies of interactions between drug molecules and peptides/proteins. We have used HPLC/MS to study the deposition of cyclosporine and its metabolites in needle biopsy samples from kidney and liver in which sample size is severely limited. The limit of detection in the single-ion monitoring mode was 500 fg (450 amol), which is about a thousandfold lower than UV limits of detection.

Caffeoyltartronic acid from catnip (Nepeta cataria): A precursor for catechol in lubber grasshopper (Romalea guttata) defensive secretions.

Adults of the lubber grasshopper (Romalea guttata) secrete increased amounts of catechol from their defensive glands when fed diets containing only catnip leaves (Nepeta cataria). Model compound bioassays showed that these insects were able to sequester and biomagnify simple phenols, such as catechol and hydroquinone, in their defense gland secretions. Excessive catechol secretions from caffeic acid-fortified diets indicated metabolic pathways exist to perform efficiently more complex biochemical conversions. Reverse-phase HPLC of methanol extracts of catnip revealed only one major caffeoyl-polyphenol as a possible precursor for the observed elevated catechol secretions, when this plant is fed to lubbers. The compound was shown to be caffeoyltartronic acid (CTA). During analysis of CTA by probe-MS or gas chromatography (of its silylated derivative), CTA decomposed by loss of carbon dioxide to form caffeoylglycolic acid (CGA), making identification by these methods ambiguous. Only fast atom bombardment mass spectrometry (FAB-MS, negative mode) gave a true molecular weight. Groundivy (Glecoma hederacea), a relative of catnip, was also shown to contain CTA. The mung bean (Phaseolus radiatus=Vigna radiata), a species totally unrelated to catnip, is the only other reported plant source of CTA. Catnip leaves were found to contain about twice as much CTA as mung bean leaves.