ABSTRACT
Cochlear recently released the Nucleus Freedom System which has been based on the Nucleus Research Platform 8. Both systems make use of the same implant, the CI24RE, which includes expanded total stimulation rates up to 32 kHz. In this study the performance of the ACE strategy at 500, 1200 and 3500 pps/channel was investigated using an ABC-CBA design. At the end of each period speech tests were performed. In the CBA phase the patients completed a comparative questionnaire to determine the subjective rate preference. Preliminary results in 13 recipients indicate no differences in for the ACE strategy at rates ranging from 500 pps to 3500 pps/channel.
Subject(s)
Choice Behavior , Cochlear Implants , Hearing Loss, Sensorineural/therapy , Acoustic Stimulation/instrumentation , Adult , Aged , Female , Hearing Loss, Sensorineural/diagnosis , Humans , Male , Middle Aged , Prosthesis Design , Severity of Illness Index , Speech PerceptionABSTRACT
Mutations in the human GJB3 gene that codes for Connexin31 (Cx31), a protein subunit of gap junction channels, have recently been reported to cause deafness and the skin disorder erythrokeratodermia variabilis. To study the function of this gene in mice, we generated animals with targeted replacement of the Cx31 gene (Gjb3) by a lacZ reporter gene. Although homozygous Cx31-deficient adult mice (Gjb3(-/-)) were found among the offspring of heterozygous Cx31-deficient parents (Gjb3(+/-)), 60% of the animals expected according to Mendelian inheritance were lost between ED 10.5 and 13.5. Placentas of Gjb3(-/-) embryos at ED 9.5 were smaller than controls as a result of severely reduced labyrinth and spongiotrophoblast size. From ED 10.5 onward, placentas of surviving Gjb3(-/-) embryos recovered progressively and reached normal size and morphology by ED 18.5. This corresponds to a time period in which another connexin isoform, Connexin43, is upregulated in spongiotrophoblast cells of Cx31-deficient and control placentas. No morphological or functional defects of skin or inner ear were observed in surviving adult Gjb3(-/-) mice. We conclude that Cx31 is essential for early placentation but can be compensated for by other connexins in the embryo proper and adult mouse.
Subject(s)
Connexins/genetics , Connexins/physiology , Hearing/genetics , Placenta/abnormalities , Skin/cytology , Alleles , Animals , Audiometry , Blotting, Northern , Blotting, Southern , Blotting, Western , Cell Differentiation/genetics , Cell Division , Connexin 43/biosynthesis , Connexin 43/genetics , Connexin 43/physiology , Connexins/biosynthesis , Crosses, Genetic , Cytoplasm/metabolism , Ear/physiology , Embryo, Mammalian/cytology , Epidermis/metabolism , Female , Genes, Reporter , Genotype , Immunohistochemistry , Lac Operon , Male , Mice , Mice, Knockout , Microscopy, Fluorescence , Protein Isoforms , Skin/metabolism , Stem Cells/metabolism , Testis/metabolism , Time FactorsABSTRACT
The paper describes finite element related procedures for inverse localization of multiple sources in realistically shaped head models. Dipole sources are modeled by placing proper monopole sources on neighboring nodes. Lead field operators are established for dipole sources. Two different strategies for the solution of inverse problems, namely combinatorial optimization techniques and regularization methods are discussed and applied to visually evoked potentials, for which exemplary results are shown. Most of the procedures described are fully automatic and require only proper input preparation. The overall work for the example presented (from EEG recording to visual inspection of the results) can be performed in roughly a week, most of which is waiting time for the computation of the lead field matrix or inverse calculations on a standard and affordable engineering workstation.
Subject(s)
Cerebral Cortex/physiology , Evoked Potentials, Visual/physiology , Head/physiology , Electroencephalography , Humans , Models, NeurologicalABSTRACT
The electric conductivities of different tissues are important parameters of the head model and their precise knowledge appears to be a prerequisite for the localization of electric sources within the brain. To estimate the error in source localization due to errors in assumed conductivity values, parameter variations on skull conductivities are examined. The skull conductivity was varied in a wide range and, in a second part of this paper, the effect of a nonhomogeneous skull conductivity was examined. An error in conductivity of lower than 20% appears to be acceptable for fine finite element head models with average discretization errors down to 3 mm. Nonhomogeneous skull conductivities, e.g., sutures, yield important mislocalizations especially in the vincinty of electrodes and should be modeled.
Subject(s)
Brain/physiology , Head/physiology , Models, Biological , Models, Neurological , Skull/physiology , Electric Conductivity , Electroencephalography , HumansABSTRACT
Interleukin 2 (IL-2) and interleukin 4 (IL-4) secreted by activated but not by resting mature T cells are pleiotropic cytokines affecting growth and differentiation of diverse cell types, such as T cells, B cells, and mast cells. There is little information about the molecular basis for the constitutive repression of IL-2 and IL-4 gene expression in unstimulated T cells. We investigated the possibility that wild-type (wt) p53, a nuclear tumor suppressor protein, might serve to repress IL-2 and IL-4 gene expression in murine E14 T lymphoma and in human Jurkat cells. We transiently cotransfected these cells with constitutive simian virus 40 (SV 40) early promoter expression plasmids overproducing wt or mutant murine p53 and with appropriate luciferase (luc) reporter plasmids containing the promoter elements of murine IL-2 and IL-4 genes to evaluate the effect of various p53 species on these promoters. Murine wt p53 derived from pSG5p53cD strongly repressed the IL-2 and IL-4 promoters in both cell lines induced by the phorbol ester TPA and the Ca2+ ionophore ionomycin but not, however, in uninduced cells. In similar transient transfection experiments with lymphoma cells, overexpression of deletion mutant species of murine p53 revealed that the N-terminal and C-terminal domains are crucial for inhibition of both IL-2 and IL-4 gene expression. These parts of p53 comprise the transactivation domain at the amino terminal side, which has previously also been shown to interact with the TATA-box binding-protein TBP and the carboxy-terminal oligomerization domain. Additionally, it was shown that a previously described inhibitory protein, the high-mobility-group protein HMG-I/Y, does not functionally interact with p53. Cotransfection of expression plasmids for both p53 and HMG-I/Y did not alter the extent of inhibition by the individual proteins. These data suggest that p53 can downmodulate both IL-2 and IL-4 gene expression and that both the transactivation and oligomerization domains of the tumor suppressor protein are essential for this transcriptional repression.
Subject(s)
Gene Expression Regulation, Neoplastic/drug effects , Interleukin-2/genetics , Interleukin-4/genetics , Promoter Regions, Genetic , Transcription, Genetic/drug effects , Tumor Suppressor Protein p53/pharmacology , Animals , Genes, p53 , HMGA1a Protein , High Mobility Group Proteins/genetics , High Mobility Group Proteins/physiology , Humans , Interleukin-2/biosynthesis , Interleukin-4/biosynthesis , Ionomycin/pharmacology , Ionophores/pharmacology , Leukemia-Lymphoma, Adult T-Cell/genetics , Leukemia-Lymphoma, Adult T-Cell/pathology , Lymphoma, T-Cell/genetics , Lymphoma, T-Cell/pathology , Mice , Recombinant Fusion Proteins/metabolism , Sequence Deletion , Tetradecanoylphorbol Acetate/pharmacology , Transcription Factors/metabolism , Transfection , Tumor Cells, CulturedABSTRACT
The onset of DNA replication is an important step within the life cycle of the human neurotropic polyomavirus JC. In this report, evidence that both the human and the murine tumor suppressor protein p53 strongly inhibit JCV DNA replication in vivo is presented. This inhibition is dose-dependent and not a secondary effect of a decreased expression of JCV large T-antigen in response to p53. Using deletion mutants of murine p53 and tumor-derived point mutations of human p53, the basis of the suppression of JCV DNA replication by p53 was dissected. Deletion of either the amino- or the carboxy-terminal domain of murine p53 did not interfere with the repression of JCV DNA replication. However, deletion of the highly conserved central region of p53 abolished the inhibitory effect on replication. The tumor-derived human mutant p53(His273) inhibited JCV DNA replication significantly, whereas another tumorigenic mutant, p53(His175), had no inhibitory effect Concomitantly, a direct protein-protein interaction between p53 and JCV large T-antigen was lost in mutants which did not affect JCV DNA replication. These results strongly suggest that p53 inhibits JCV DNA replication by interacting with JCV large T-antigen.
Subject(s)
Antigens, Polyomavirus Transforming/immunology , DNA, Viral/biosynthesis , JC Virus/genetics , Tumor Suppressor Protein p53/physiology , Animals , Antigens, Polyomavirus Transforming/genetics , Base Sequence , Binding Sites , DNA, Complementary , Humans , JC Virus/immunology , JC Virus/physiology , Mice , Molecular Sequence Data , Sequence Deletion , Spodoptera/cytology , Tumor Cells, Cultured , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/immunology , Virus ReplicationABSTRACT
Three manual suture techniques (double-layer inverting, single-layer end-to-end, and continuous suture of the submucosa) were compared with anastomoses performed by stapling instruments (EEA, KZ 28) on the canine colon. The two manual techniques with exact end-to-end apposition led to primary wound-healing during the early postoperative period (3-20 days). There was no significant stenosis at the site of anastomosis five and ten months postoperatively. Inverting sutures as well as stapled anastomoses, however, showed delayed healing with considerable inflammatory reaction, resulting in marked stenosis after five to ten months.
Subject(s)
Colon/surgery , Suture Techniques , Wound Healing , Animals , Colon/pathology , Dogs , Intestinal Mucosa/pathology , Intestinal Mucosa/surgery , Surgical Staplers , Surgical Wound Dehiscence/pathologyABSTRACT
Postoperative parenteral nutrition can only be optimally effective if the characteristics of post-traumatic metabolism are taken into account. Two main possibilities are discussed for the carbohydrate component of parenteral nutrition during this phase: glucose with high doses of insulin or non-glucose carbohydrates (sugar substitutes) possibly in a suitable combination with glucose. The risks as well as the technical and organisational problems involved in the use of them are discussed and the authors prefer the second of the two alternatives. Possible side effects of non-glucose carbohydrates are pointed out and it is shown how these can be avoided by observing dose guidelines. So far a combination of frucose : glucose : xylitol in a ratio of 2 : 1 :1 with a total dose of 0.50 g/kg/hour has been studied most thoroughly. This combination normalises the fat metabolism and improves glucose tolerance without requiring exogenous insulin. Experiences with this combination as well as individual non-glucose carbohydrates on operated patients have been given continuously for up to 7 days and in some cases even for several weeks. No side effects, no deviations from a steady state and no abnormal changes of the laboratory values occurred. The authors are of the opinion that non glucose carbohydrates are necessary if the facilities for frequent blood sugar controls are not available.