Healing of horizontal circumferential periodontal defects following regenerative surgery in beagle dogs

Regenerative surgery of dog teeth with reduced periodontal support was undertaken to determine: if new connective tissue attachment could be predictably attained back to the level of the cemento-enamel junction; and to what extent the new attachment would be accompanied by bone regeneration, root resorption, and ankylosis. The alveolar bone around mandibular premolars was surgically reduced up to 6 mm from the cementoenamel junction. The denuded root surfaces were exposed to the oral environment during a period of 3 months without plaque control. Regenerative surgery was then carried out employing citric acid root conditioning and coronally positioned flaps. 6 months later, histologic evaluation of the midbuccal and midlingual areas of mesial and distal roots revealed new attachment over extended portions of the root surfaces. In 91 of 120 available surfaces, there was no epithelial downgrowth apical to the cemento-enamel junction. Bone regeneration varied from negligible amounts to complete reformation. However, root resorption and ankylosis were prevalent features. 2 different types of resorptions could be distinguished: those occurring near the cemento-enamel junction (cervical resorption), and those occurring more apically in areas of newly formed bone (ankylosis-associated resorption). Resorption of either or both types was noted for 92 of the 120 surfaces.     

Antimicrobial irrigation of deep pockets to supplement non-surgical periodontal therapy

106 sites with probing pocket depths 7 mm or greater from 14 patients were treated with plaque control instruction and 1 episode of root planing. Sites in each patient were either irrigated with 2% chlorhexidine or left as non-irrigated controls. Irrigation immediately followed root planing and was repeated daily, by the patient, for 24 weeks. Clinical measurements were made at 12 and 24 weeks, as were gingival washings for determining the number and % of spirochetes. Results at 24 weeks demonstrated that bleeding scores decreased from 91% to 9%; the % of spirochetes dropped from approximately 9% to less than 1%; probing pocket depths decreased from 7.5 to 4.5 mm, and probing attachment levels gained 1.1 to 1.4 mm. The chlorhexidine irrigated experimental group and the non-irrigated control group did not differ significantly in any of the studied parameters. Thus, daily patient-administered chlorhexidine irrigation of deep pockets did not augment the effects of non-surgical periodontal therapy.     

Expression of vascular endothelial growth factor induces an invasive phenotype in human squamous cell carcinomas

Inhibition of the vascular endothelial growth factor (VEGF) receptor Flk-1 has been shown to prevent invasion of experimental squamous cell carcinomas (SCC). To directly investigate the role of VEGF in tumor invasion, we stably transfected human SCC-13 cells, which are characterized by a noninvasive phenotype in vivo, with expression vectors containing murine VEGF(164) in sense (SCC/VEGF+) or antisense (SCC/VEGF-) orientation or with vector alone (SCC/vec). SCC/vec cells formed slowly growing, well-differentiated tumors with well-defined borders between tumor and stroma, after intradermal or subcutaneous injection. In contrast, SCC/VEGF+ tumors were characterized by rapid tumor growth, with small cell groups and single cells invading into the surrounding tissue, and by admixture of blood vessels and tumor cells in areas of tumor invasion. We detected an increase in tumor vessel density and size in VEGF-overexpressing tumors, resulting in a more than fourfold increase in total vascular areas. In contrast, SCC/VEGF- clones formed noninvasive, sharply circumscribed tumors with reduced vascular density. These findings demonstrate that selective VEGF overexpression was sufficient to induce tumor invasiveness, and they provide further evidence for an active role of the tumor stroma in cancer progression.     

No association between 5HT‐2A and bipolar disorder irrespective of genomic imprinting

Recent evidence that 5HT‐2A may be subjected to genomic imprinting prompted us to examine a collection of Irish family trios (an affected individual and both parents) for evidence of an association between 5HT‐2A and bipolar disorder. Family trios offer an advantage over case control studies in regard to genomic imprinting since with family trios it is possible to trace the path of alleles from the parents to the offspring. Using haplotype‐based haplotype relative risk (HHRR) and transmission/disequilibrium (TDT) analyses, no evidence was found for an association of 5HT‐2A with bipolar affective disorder under the assumption of no imprinting and of imprinting. © 2001 Wiley‐Liss, Inc.     

Regulation of ovarian cancer cell viability and sensitivity to cisplatin by progesterone receptor membrane component-1

CONTEXT: Progesterone (P4) influences ovarian cancer cells by an unknown mechanism. OBJECTIVE: The objective was to determine whether P4 acts through progesterone receptor membrane component-1 (PGRMC1) in ovarian cancers. DESIGN, SETTING AND PATIENTS: Archival tissue and cDNA provided by OriGene were used for expression studies. In vitro experiments were conducted with Ovcar-3 cells. MAIN OUTCOME MEASURES: PCR, Western blot, and immunohistochemistry were used to measure expression of PGRMC1 and nuclear progesterone receptor (PGR). PGRMC1's role in regulating the viability of ovarian cancers was assessed by overexpressing PGRMC1, depleting PGRMC1 using small interfering RNA, and attenuating PGRMC1's action with a blocking antibody. Apoptosis was determined by 4',6'-diamino-2-phenylindole staining. RESULTS: PGRMC1 mRNA increased and PGR mRNA decreased in advanced stages of ovarian cancer. Unlike PGR, PGRMC1 was expressed in virtually every cancer cell within the tumor. A similar relationship between PGRMC1 and PGR was observed in Ovcar-3 cells. In these cells P4 suppressed apoptosis induced by either serum withdrawal or cisplatin (CDDP). Moreover, in the presence of P4, the following occurs: 1) overexpression of PGRMC1 reduces the effectiveness of CDDP, 2) depletion of PGRMC1 with small interfering RNA enhances the effects of CDDP, and 3) PGRMC1 antibody treatment increases the apoptotic response to CDDP. CONCLUSIONS: These findings indicate that PGRMC1 plays an important role in promoting ovarian cancer cell viability and that attenuating PGRMC1's action makes the ovarian cancer cells more sensitive to CDDP. These data suggest that targeted depletion of PGRMC1 could be useful as an adjunct to CDDP therapy.