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J Davidson

Publications and source records attributed to J Davidson.

At least 91 records · Page 5Linked to original sources

The free flap and plate in oromandibular reconstruction: long-term review and indications.

The purpose of this study was to define the role of reconstruction plates as bone replacement in oromandibular reconstruction. From 1987 through 1991, 71 consecutive oral cancer patients underwent composite resection and reconstruction and were entered into one of two studies. In the first study of 31 patients, 15 underwent oromandibular reconstruction using a radial forearm osteocutaneous flap, while the remainder (16) received a radial forearm fasciocutaneous flap together with a mandibular reconstruction plate. The second study involved 40 subsequent patients, all receiving the latter form of reconstruction. Twenty-one of the plates were stainless steel, and the remaining 19 were of the titanium hollow screw (THORP) type. We followed the patients prospectively. We defined success as a reconstruction that we did not have to remove. Additionally, since the patients had limited life expectancy, we developed the idea of days of life lost and incorporated it into our definition of a successful outcome. Vascularized autogenous bone proved to be more successful than metallic plates used alone in terms both of reconstruction survival and of minimizing days of life lost. The overall success rate of mandibular plate reconstruction was 78.9 percent, but analysis by defect type revealed a failure rate of 35 percent when the defects were anterior and only 5 percent when they were lateral. THORP plates demonstrated a trend towards more durability. We would now recommend plate reconstruction only in lateral defects in patients with a poor prognosis.

Bone Plates↗

Lack of influence of non-inherited maternal HLA-DR alleles on susceptibility to rheumatoid arthritis.

OBJECTIVE: To reproduce findings from previous reports that non-inherited maternal HLA class II antigens might contribute to rheumatoid arthritis (RA) susceptibility in the offspring. METHODS: Families were recruited from the Arthritis and Rheumatism Council's National Repository of RA families and HLA-DRB1 alleles were examined in these individuals and their first degree relatives using DNA typing methods. RESULTS: There was no evidence of an increase in either non-inherited maternal HLA-DR4 or the HLA-DRB1 shared epitope as a whole compared with the frequency expected using the non-inherited paternal antigens as controls. CONCLUSIONS: The numbers of probands who were shared epitope negative were small, but we are unable to confirm in these families the findings that non-inherited maternal HLA contributes an additional susceptibility factor to rheumatoid arthritis.

Alleles↗

Wound healing.

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Growth Substances↗

Desensitization of gonadotropin-releasing hormone action in the gonadotrope-derived alpha T3-1 cell line.

Sustained exposure of gonadotropes to GnRH causes a pronounced desensitization of GnRH-stimulated gonadotropin release, but the mechanisms involved are poorly understood. Recent studies have suggested, however, that GnRH-stimulated phosphoinositidase C (PIC) activity does not undergo rapid ( < 5 min) homologous desensitization in alpha T3-1 cells, and we have, therefore, used this cell line to address the question of whether desensitization occurs distal to PIC activity and/or in an intermediate time frame. We show that GnRH stimulates a rapid increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3; maximum at 10-20 sec with a modest reduction thereafter] and that the GnRH-stimulated accumulation of [3H]IPs (in cells stimulated in the presence of LiCl) increases linearly over 5-300 sec. This clearly indicates that desensitization of PIC does not occur within this period and that the dramatic reduction in the rate of Ins(1,4,5)P3 accumulation (10-30 sec) is due to its metabolism, rather than to a reduction in Ins(1,4,5)P3 generation. Pretreatment for 60 min with 10(-7)M GnRH reduced cell surface GnRH receptor number by 48% (without measurably altering Kd). The pretreatment also reduced maximal GnRH-stimulated [3H]IP accumulation (to 66% of the control) and increased the EC50 for GnRH-stimulated [3H]IP accumulation approximately 3-fold, demonstrating that desensitization of GnRH-stimulated [3H]IP accumulation can, indeed, occur within 60 min, but that this may be attributable to receptor loss (without appreciable uncoupling of residual receptors from their immediate effector system). Pretreatment for 60 min with GnRH also caused a dose-dependent reduction in both spike and plateau phases of the GnRH effect on cytosolic Ca2+. This effect could not be overcome by stimulation with high concentrations of GnRH and appears, therefore, to reflect not only receptor loss, but, also, an additional inability of agonist-occupied GnRH receptors to elevate cytosolic Ca2+. The effect of KCl on cytosolic Ca2+ was similarly reduced by GnRH pretreatment, suggesting that desensitization of voltage-operated Ca2+ channels mediates desensitization of the plateau phase Ca2+ response to GnRH. Such a mechanism could not, however, explain desensitization of the spike phase of the Ca2+ response to GnRH seen in normal or Ca2+ -free medium. Accordingly, the data reveal a novel mechanism for homologous desensitization to GnRH in which agonist-occupied GnRH receptors are rendered unable to mobilize intracellular Ca2+ and imply that desensitization of GnRH-stimulated Ins(1,4,5)P3 production and/or action occurs.

Buserelin↗

Multisite oligonucleotide-mediated mutagenesis: application to the conversion of a mitochondrial gene to universal genetic code.

Using multisite oligonucleotide-mediated mutagenesis in conjunction with a mutagenesis selection procedure and rapid screening by allele-specific oligonucleotide hybridization has allowed us to develop a reliable protocol that enables a large number of base changes to be introduced rapidly into a piece of DNA, with the minimum number of manipulations. We have applied this protocol to generate synthetic versions of four mouse mitochondrial genes capable of being expressed in the nucleus/cytosol.

Amino Acid Sequence↗

The clinically negative neck in patients with early oral cavity carcinoma: a decision-analysis approach to management.

Despite improvements in both diagnostic and therapeutic techniques in recent decades, the prognosis for oral cavity squamous cell carcinoma has not improved. Patients presenting with overt regional metastases necessarily undergo therapeutic intervention directed to both the primary site and the neck. However, controversy persists regarding the best management for patients without clinical evidence of nodal disease. Would these patients best be managed with elective treatment of the neck, with no neck treatment unless overt nodal metastases are detected, or would some diagnostic test be beneficial in determining which patients are at highest risk of having occult nodal disease and, therefore, most likely to benefit from elective treatment? We performed a decision analysis to address this question. Baseline probability assumptions were made based on the evidence available in the literature for the parameters of interest. A decision tree was constructed and analyzed. In the final analysis, two options, elective functional neck dissection for all patients and a supraomohyoid neck dissection, were equally beneficial and were significantly better than the remaining options tested. Either of these surgical treatment strategies shifted the survival distribution curve significantly to the right.

Biopsy↗

Meeting of minds in psychiatry and homeopathy: an example in social phobia.

Communication between homeopaths and the biomedical community can be enhanced by an interpretation of the homeopathic repertory in light of current medical diagnostic terminology. This report reviews the current, conventional symptom formulation for social phobia, the third most common psychiatric diagnosis in the US community. Eighty-three rubrics in the homeopathic materia medica corresponding to symptoms of social phobia were identified and then used in a computerized repertorizing program to identify potential homeopathic remedies for social phobia. Although Kent's Repertory describes many symptoms of social phobia, the terminology should be updated, and there is a surprising lack of information about some key rubrics. Clinical judgment is always needed to interpret the significance of symptoms that could be caused by more than one pathogenic mechanism. Although many of the remedies traditionally thought to be useful in treating patients with social phobia do indeed appear in the computerized Repertory search, additional remedies emerged, including both polycrests and small remedies, which may have a place in treating this disorder.

Homeopathy↗

Tissue ablation by a free-electron laser tuned to the amide II band.

Efforts to ablate soft tissue with conventional lasers have been limited by collateral damage and by concern over potential photochemical effects. Motivated by the thermal-confinement model, past infrared investigations targeted the OH-stretch mode of water with fast pulses from lasers emitting near 3,000 nm (refs 1, 7-9). What does a free-electron laser offer for the investigation of tissue ablation? Operating at non-photochemical single-photon energies, these infrared sources can produce trains of picosecond pulses tunable to the vibrational modes of proteins, lipids and/or water. We report here that targeting free-electron laser radiation to the amide II band of proteins leads to tissue ablation characterized by minimal collateral damage while maintaining a substantial ablation rate. To account for these observations we propose a novel ablation mechanism based on compromising tissue through resonant denaturation of structural proteins.

Amides↗

The role of surgery following radiotherapy failure for advanced laryngopharyngeal cancer. A prospective study.

BACKGROUND: To comment on the use of surgery following radiotherapy failure for advanced laryngopharyngeal cancer. METHODS: Of 212 participants, 88 underwent potentially curative surgical salvage following radiotherapy failure. These 88 patients were followed up prospectively for a median of 4.4 years following surgery; complications, recurrences, tumor measures, and survival were documented to facilitate a critical analysis. RESULTS: Surgical complications developed in 48% of the patients, were most prevalent following pharyngectomy (P = .03), and were not influenced by the addition of a neck dissection (P = .76). Postsurgical survival was statistically associated with the TNM stage of the recurrent tumor and the site of recurrence (local or regional vs both), but was not associated with the TNM stage of the original tumor, time to recurrence, age, sex, or primary site. The overall 5-year postsurgical survival for this cohort was 35%. Utilizing a policy of primary radiotherapy, reserving surgery for radiotherapy failures, 41% of our patients retained functional larynges without reducing their overall survival. CONCLUSIONS: We suggest that recurrent tumors be restaged, as the measures of the recurrent tumor, not the tumor at original presentation, correlate best with survival following surgical intervention for tumor recurrence.

Aged↗

"Homozygosity" for the HLA-DR shared epitope contributes the highest risk for rheumatoid arthritis concordance in identical twins.

OBJECTIVE: To assess the contribution of HLA-DRB1 alleles in determining rheumatoid arthritis (RA) concordance in monozygotic twins. METHODS: Ninety-one monozygotic twins pairs in which at least 1 twin was affected were typed for HLA-DRB1 using both serologic methods and polymerase chain reaction amplification with sequence-specific oligonucleotide hybridization. The role of DR4 and of the shared epitope in disease concordance was investigated. Relative risks (RR) with 95% confidence intervals were determined. RESULTS: Increased concordance for RA was observed in both DR4 positive and shared epitope positive pairs (RR 3.4 and 3.7, respectively). A 5-fold risk for RA concordance was seen in twins who were "homozygous" for the shared epitope, compared with those negative for the shared epitope. CONCLUSION: In the absence of the shared epitope, RA concordance in monozygotic twins is rare. In contrast, "homozygosity" for the shared epitope is the most important factor in determining RA concordance.

Arthritis, Rheumatoid↗

The cytoplasmic domain mediates localization of furin to the trans-Golgi network en route to the endosomal/lysosomal system.

To investigate the mechanisms of membrane protein localization to the Golgi complex, we have examined the intracellular trafficking of epitope-tagged forms of the mammalian endopeptidase, furin, in stably transformed rat basophilic leukemia cells. Our studies show that furin is predominantly localized to the trans-Golgi network (TGN) at steady state, with smaller amounts present in intracellular vesicles. Biochemical and morphological analyses reveal that furin is progressively delivered to a lysosomal compartment, where it is degraded. Analyses of furin deletion mutants and chimeric proteins show that the cytoplasmic domain is both necessary and sufficient for localization to the TGN in various cell types. Interestingly, deletion of most of the cytoplasmic domain of furin results in a molecule that is predominantly localized to intracellular vesicles, some of which display characteristics of lysosomes. To a lesser extent, the cytoplasmically deleted molecule is also localized to the plasma membrane. These observations suggest the existence of an additional determinant for targeting to the endosomal/lysosomal system within the lumenal and/or transmembrane domains of furin. Thus, the overall pattern of trafficking and steady state localization of furin are determined by targeting information contained within more than one region of the molecule.

Amino Acid Sequence↗