Practical implant dentistry--the mandibular removable overdenture prosthesis

The fully edentulous mandible presents functional, esthetic, and psychological challenges for the patient and the dentist. The mandibular overdenture supported by endosseous implants can provide a superior treatment modality, overcoming many of the difficulties inherent in the conventional denture. Advantages cited are increased denture retention, improved chewing efficiency, maintenance of bone height, replacement of lost anatomy, increased denture stability, reduction of soft tissue coverage and extension of the prosthesis, and easy access for hygiene maintenance. The major disadvantage rests with the patient's intolerance of a removable prosthetic design.     

Putrescine administration reverses cadmium-associated inhibition of liver regeneration

The liver is of central importance in the metabolism of essential and toxic metals such as cadmium. Cadmium pretreatment suppressed the liver regenerative response to partial hepatectomy, due to the inhibition of the enzymatic activity of thymidine kinase. Exogenous putrescine administration has been reported to stimulate liver regeneration in animal models of acute liver failure. The purpose of this study was to document whether the administration of this polyamine enhances the impaired regenerative capacity of hepatocytes in cadmium-pretreated partially hepatectomized rats. The intraperitoneal administration of putrescine (1 or 10 mg/kg body weight), at the time of surgery and at 4 and 8 hr postoperatively partly restored the suppressed hepatocyte deoxyribonucleic acid (DNA) biosynthesis and thymidine kinase activity in cadmium-pretreated partially hepatectomized rats. Mitotic activity and the percentage of hepatocytes positive for proliferating cell nuclear antigen nuclei were in accordance with the liver proliferative status. Our results showed that exogenous putrescine administration is able to improve diminished liver regeneration after partial hepatectomy in this animal model of acute hepatic injury.     

Induction of tolerance in experimental autoimmune myasthenia gravis with solubilized MHC class II:acetylcholine receptor peptide complexes

Stimulation of T lymphocytes through the T cell receptor in the absence of costimulatory signal(s) induces a state of unresponsiveness to subsequent antigen presentation. We have employed solubilized complexes consisting of rat class II MHC molecules containing an immunodominant peptide of the acetylcholine receptor (AChR alpha 100-116) to induce unresponsiveness in the autoreactive T lymphocytes mediating an animal model of myasthenia gravis. In vitro incubation of rat T cell lines specific for peptide AChR alpha 100-116 with solubilized complexes of MHC II and AChR alpha 100-116 (MHC II:AChR alpha 100-116) rendered the T cells unresponsive to subsequent stimulation by antigen presenting cells and the peptide. T cell lines with a broader specificity to the entire AChR protein pentamer had an 81% reduction in proliferation to AChR following a preincubation with solubilized MHC II:AChR alpha 100-116. Treatment with the solubilized MHC II:AChR alpha 100-116 induced phosphatidylinositol 4,5-bisphosphate hydrolysis, an early signalling event associated with binding to the TCR. Rats primed with AChR and injected intravenously with MHC II:AChR alpha 100-116 had reduced in vitro T cell proliferation to the AChR alpha 100-116 peptide and to whole AChR. Solubilized MHC II:AChR alpha 100-116 injected i.v. into rats exhibiting serological clinical symptoms of experimental autoimmune myasthenia gravis (EAMG) prevented death in 67% of the treated animals, compared to a 0-20% survival rate in all other control groups. These results demonstrate that solubilized MHC II complexed with an immunodominant autoantigenic peptide is tolerogenic and improves the survival rate of rats with EAMG, suggesting the basis for an antigen-specific therapy in autoimmune diseases such as MG.     

p185c-erbB-2 signal enhances cisplatin-induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair

The c-erbB-2 (HER-2/neu) protooncogene encodes an M(r) 185,000 transmembrane glycoprotein with intrinsic tyrosine kinase activity. Agonistic antibodies against p185c-erbB-2 enhance the cytotoxic effect of the DNA alkylator, cisplatin, against c-erbB-2-overexpressing human carcinoma cells (Hancock et al., Cancer Res., 51:4575-4580, 1991). We have studied the possible association between receptor signal transduction and cisplatin-mediated cytotoxicity utilizing the SKBR-3 human breast cancer cell line and the anti-p185 TAb 250 IgG1. TAb 250 induced tyrosine phosphorylation of p185 and the receptor substrate phospholipase C-gamma 1, as well as rapid association of these molecules in vivo. Simultaneously with phosphorylation, phospholipase C-gamma 1 catalytic activity measured in a [3H]phosphatidylinositol-4,5-bisphosphate hydrolysis assay was increased 61 +/- 12% above control. Preincubation of SKBR-3 cells with the tyrosine kinase inhibitor tyrphostin 50864-2 abrogated the enhancement of drug-mediated cell kill induced by TAb 250. The supraadditive drug/antibody effect was not seen in SKBR-3 cells with TAb 263, an anti-p185 IgG1 that does not induce receptor signaling or with TAb 250 in MDA-468 breast cancer cells which do not overexpress c-erbB-2. In addition, transforming growth factor-alpha increased cisplatin-induced cytotoxicity against NIH 3T3 cells overexpressing an epidermal growth factor receptor/c-erbB-2 chimera. Cellular uptake or efflux of [195mPt]cisplatin by SKBR-3 cells was not altered by TAb 250. Finally, simultaneous treatment of SKBR-3 cells with TAb 250 and cisplatin increased cisplatin/DNA intrastrand adduct formation and delayed the rate of adduct decay. Taken together these data support a direct association between p185c-erbB-2 signal transduction and inhibition of cisplatin-induced DNA repair.     

Automatic internal cardioverter-defibrillator patch erosion into the upper airway presenting as a cavitary lesion

Erosion of an automatic internal cardioverter-defibrillator (AICD) patch into the lingular bronchus occurred 4 years after implantation; the erosion presented as a cavitary mass associated with hemoptysis and weight loss. On bronchoscopy to evaluate for suspected carcinoma, a cavity was entered through a bronchial defect and the AICD patch clearly identified. The complication was successfully treated with patch removal and fistula closure.     

Differential expression of MARCKS and other calmodulin-binding protein kinase C substrates in cultured neuroblastoma and glioma cells

Expression of the protein kinase C substrate MARCKS and other heat-stable myristoylated proteins have been studied in four cultured neural cell lines. Amounts of MARCKS protein, measured by [3H]myristate labeling and western blotting, were severalfold higher in rat C6 glioma and human HTB-11 (SK-N-SH) neuroblastoma cells than in HTB-10 (SK-N-MC) or mouse N1E-115 neuroblastoma cells. Higher levels of MARCKS mRNA were also detected in the former cell lines by S1 nuclease protection assay. At least two additional 3H-myristoylated proteins of 50 and 40-45 kDa were observed in cell extracts heated to > 80 degrees C or treated with perchloric acid. The 50-kDa protein, which bound to calmodulin in the presence of Ca2+, was more prominent in cells (N1E-115 and HTB-10) with less MARCKS, whereas neuromodulin (GAP-43) was detected in N1E-115 and HTB-11 cells only. Heating resulted in a fourfold increase in the detection of MARCKS by western blotting; this was not paralleled by a similar increase in [3H]myristate-labeled MARCKS and may be due to a conformational change affecting the C-terminal epitope or enhanced rechange of the protein on nitrocellulose. Addition of beta-12-O-tetradecanoylphorbol 13-acetate resulted in three- to fourfold increased phosphorylation of MARCKS in HTB-11 cells, with little increase noted in HTB-10 cells. These results indicate that MARCKS, neuromodulin, and other calmodulin-binding protein kinase C substrates exhibit distinct levels of expression in cultured neurotumor cell lines. Of these proteins, only MARCKS appears to be correlated with phorbol ester stimulation of phosphatidylcholine turnover in these cells.     

Seroprotective groups among isolates of Borrelia burgdorferi

We demonstrated that different seroprotective groups exist among isolates of Borrelia burgdorferi and Borrelia garinii. The major group was composed of isolates 297, B31, S-1-10, MMTI, IPT, and ATCC 35211 and 21 isolates obtained from California, Illinois, New York, Texas, and Wisconsin. A second group was composed of European isolates PBi and G25. A third group was composed of a single isolate, C-1-11. These groupings were supported by Western immunoblot findings. In addition, the seroprotective groups were confirmed by passive transfer of immune sera and challenge of recipient hamsters with the homologous isolate or other isolates of B. burgdorferi or B. garinii. These studies demonstrate that a monovalent vaccine will not provide complete protection against infection with all isolates of B. burgdorferi.