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Biomedical subjects

J Davidson

Publications and source records attributed to J Davidson.

At least 109 records · Page 6Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

"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↗
PubMed1994

Promotion of responsible drinking in hotels.

This study reports on an intervention programme to promote responsible drinking in hotels. The licensees of eight hotels agreed to participate in a trial of measures designed to assist patrons to avoid drink-driving, and seven other hotels were used as controls. The interventions acceptable to licensees comprised commercial-quality promotional material with the theme "0.05 Know Your Limits", and a breath analysis machine and poster on its use. Patrons leaving the hotels on Thursday, Friday and Saturday nights were interviewed and breath-tested. Although the intervention material had been seen by one-third of patrons in the intervention hotels, there was no significant difference between them and control hotel patrons in either median BAC or the proportion who were going to drive with BAC over the legal limit. There was poor compliance by hotels with the intervention procedures, indicating that a major impediment to the implementation and evaluation of programmes to promote responsible drinking is a lack of motivation by many licensees, despite support by some licensees and the Australian Hotels Association.

Journal Article↗
PubMed1994

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↗
PubMed1994

Low levels of ATP synthase and cytochrome c oxidase subunit peptide from hearts of copper-deficient rats are not altered by the administration of dimethyl sulfoxide.

This study determined if reported decreases in the delta subunit of ATP synthase and nuclear-encoded cytochrome c oxidase subunits in hearts of copper-deficient rats were secondary to the heart disease pathology or due to lack of the trace element. Male weanling Long-Evans rats were randomly divided into six groups: rats fed a copper-adequate or copper-deficient diet (with free access) with or without 5% dimethyl sulfoxide (DMSO) in the drinking water and rats pair-fed the copper-adequate or copper-deficient diet without DMSO treatment. After 4 wk, rats in the groups fed the copper-deficient diet had lower liver superoxide dismutase and heart cytochrome c oxidase activities compared with groups fed the copper-adequate diet. Administration of DMSO, an antioxidant, and energy restriction (pair-feeding) partially blocked cardiac hypertrophy in rats fed the copper-deficient diet. Greater mitochondrial volume density and mitochondrial:myofibrillar ratio and disrupted myofibrils and basal laminae were observed in the hearts from rats fed the copper-deficient diet and not treated with DMSO compared with hearts from groups fed the copper-adequate diet. The DMSO-treated rats fed the copper-deficient diet had hearts with intact structure but enlarged mitochondria compared with other groups fed the copper-deficient diet. The delta subunit of ATP synthase and the nuclear-encoded cytochrome c oxidase subunits IV and V were depressed in rats fed a copper-deficient diet regardless of antioxidant treatment and pair-feeding. These data suggest that the effects of copper deficiency upon ATP synthase and cytochrome c oxidase proteins are not due to the cardiac pathology.

Animals↗
PubMed1994

Lipid metabolism.

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Lipid Metabolism↗
PubMed1994

Long-term safety and clinical acceptability of venlafaxine and imipramine in outpatients with major depression.

The antidepressant efficacy and safety of venlafaxine was shown previously in 6-week, placebo-controlled trials. We evaluated the long-term safety and clinical acceptability of venlafaxine and imipramine in a double-blind, parallel-group, comparative study. Two hundred ninety depressed outpatients were treated with venlafaxine, and an additional 91 received imipramine for as long as clinically necessary, up to 1 year. The total daily dose of each drug could vary from 75 to 225 mg. The Clinical Global Impressions Scale and a therapeutic response rate that was based on Clinical Global Impressions Scale-Improvement and incorporated discontinuation information were used to evaluate efficacy. Safety determinations and patient subjective ratings were used to evaluate safety and clinical acceptability. During the study, the adverse events were generally mild to moderate and most subsided with continued treatment; the most frequent were nausea for venlafaxine and dry mouth for imipramine. The anticholinergic side effect burden was significantly higher in the imipramine group than in the venlafaxine group. Venlafaxine was judged significantly more acceptable than imipramine, on the basis of the subjective ratings by patients. Fewer venlafaxine-treated patients than imipramine-treated patients withdrew because of adverse events and unsatisfactory response. There was a consistent trend in the therapeutic response rates in favor of venlafaxine that reached statistical significance at months 2, 6, and 12. In this long-term study, patient acceptability was greater for venlafaxine than for imipramine, suggesting therapeutic advantages for venlafaxine in the long-term treatment of depression. Additional studies with other active comparators are underway to confirm and extend these encouraging results.

Adult↗
PubMed1994

Cell cycle dependent regulation of the protein kinase TTK.

TTK is a novel protein kinase detectable in all proliferating human cells and tissues. Expression of the TTK gene is markedly reduced or absent in resting cells and in tissues with a low proliferative index. In view of the apparent association between TTK gene expression and cell proliferation, we examined the regulation of this protein kinase during transit of the cell cycle. We found very low levels of TTK mRNA and protein in starved cells. When cells are induced to enter the cell cycle, levels of TTK mRNA, protein and kinase activity increase at the G1/S phase of the cell cycle and peak in G2/M. TTK mRNA levels, as well as kinase activity, drop sharply in early G1, whereas protein levels are largely maintained. TTK may play a role in cell cycle control.

Cell Cycle↗
PubMed1993

Submaximal, aerobic exercise training exacerbates the cardiomyopathy of postweanling Cu-depleted rats.

To determine the dual effect of exercise training and copper depletion on myocardial function and ultrastructure, postweanling rats were either trained or sedentary while fed copper-adequate or copper-deficient diets for 8 wk. Rats developed characteristic myocardial subcellular degeneration and increased cardiac mitochondrial volume density when copper depleted, despite lack of overt cardiac hypertrophy, hypertension, or anemia. Training combined with copper depletion induced mild left ventricular hypertrophy. Basal laminae appeared fractionated in areas at capillary-myocyte interface, with focal pericapillary and interstitial collagen accumulation, whereas overt fibrosis was absent or minimal. Electrocardiograms revealed increased QRS wave and QT duration and notching of QRS complex with copper depletion, consistent with intraventricular conductance disturbances. The oxidative capacity of soleus muscle increased with training in copper-adequate rats, but was reduced with progressive copper depletion. These data suggest that copper depletion and training are synergistic in effecting focal accumulation of collagen, with deleterious effect on exercise capacity.

Aerobiosis↗