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Biomedical subjects

J Davidson

Publications and source records attributed to J Davidson.

At least 235 records · Page 13Linked to original sources

Selection for mutants altered in the expression or export of outer membrane porin OmpF.

Strains in which the lacZ gene (which specifies beta-galactosidase) is fused to a gene encoding an envelope protein often exhibit a phenotype termed overproduction lethality. In such strains, high-level synthesis of the cognate hybrid protein interferes with the process of protein export, and this leads ultimately to cell death. A variation of this phenomenon has been discovered with lacZ fusions to the gene specifying the major outer membrane porin protein OmpF. In this case, we find that lambda transducing phage carrying an ompF-lacZ fusion will not grow on a host strain that constitutively overexpresses ompF. We have exploited this observation to develop a selection for ompF mutants. Using this protocol, we have isolated mutants altered in ompF expression and have identified mutations that block OmpF export. Our results suggest that it should be possible to adapt this selection for use with other genes specifying exported proteins.

Bacterial Outer Membrane Proteins↗

A diagnostic and family study of posttraumatic stress disorder.

A family history study of 36 patients with chronic posttraumatic stress disorder revealed a positive history of familial psychopathology in 66% of the patients. Alcoholism, depression, and anxiety disorders were the disorders most commonly found. The patients also had a higher prevalence of alcoholic siblings than did a retrospectively derived control group of depressed and anxious male patients. With respect to the proportion of familial anxiety to familial depression, the probands with posttraumatic stress disorder more closely resembled probands with generalized anxiety than probands with depression. Every patient had experienced at least one significant psychiatric illness during his lifetime, most commonly alcohol abuse or depression.

Adult↗

Platelet MAO activity in posttraumatic stress disorder.

Platelet monoamine oxidase (MAO) activity was assessed in 23 patients with posttraumatic stress disorder and 19 age-matched male control subjects. An overall significantly lower MAO activity was observed in the posttraumatic stress disorder group. When the group was divided into those with and those without a history of alcohol abuse, only the former group differed significantly from control subjects. The heuristic importance of these findings is discussed.

Adult↗

Isolation of influenza viral proteins by size-exclusion and ion-exchange high-performance liquid chromatography: the influence of conditions on separation.

Constituent proteins of influenza virus and of vaccines containing whole virus or viral antigens (surface antigen vaccines) have been separated by size-exclusion high-performance liquid chromatography. Preparations of whole virus have also been examined by high-performance anion-exchange chromatography. The separations are influenced by the conditions employed and, in particular, by the nature of detergent used to disrupt the virus and that incorporated in the eluting solvent. Individual proteins are recovered with retention of immunological activity. The method is applicable to small portions of a single human dose of vaccine.

Chromatography, High Pressure Liquid↗

Studies on allergens of mammalian origin.

Cat and dog saliva and extracts obtained from cat and dog hair have been examined by high-performance liquid chromatography (HPLC) to identify the likely allergenic molecules. Separation of the materials by size exclusion HPLC showed that several components in the range of apparent molecular weight from 35,000 to 200,000 had inhibitory activity in the radioallergosorbent test (RAST) when tested against pooled serum from donors hypersensitive to dogs and cats. One of these components active in our test system was identified as albumin. Despite differences in gross composition of the extracts no significant difference in the position of the active fractions was observed between cat hair and saliva, between dog hair and saliva or between hair extracts from different breeds of dog. Fractionation by anion-exchange HPLC, although promising, was complicated by problems of sensitivity.

Allergens↗

Comparative diagnostic criteria for melancholia and endogenous depression.

Five scales were evaluated for the diagnosis of melancholia or endogenous depression. Of 21 total items, none appeared in all five scales, but four items occurred in four of the scales: autonomy of mood, prevasive anhedonia, psychomotor change, and guilt. Vegetative changes were represented inconsistently, with anorexia and weight loss in three scales, as was distinct quality of mood. Thereafter, item agreement between the scales fell off. Scale performance was tested in 50 depressive patients. Major differences were found in frequency of melancholia and scale orientation toward inpatients and outpatients. A number of old controversies remain dormant in these scales. Unresolved are the relationship between melancholia and severity of depression; the relevance of precipitating events, previous depressive episodes, type of onset, and adequacy of personality; and whether to classify by category or continuum. The merits of statistically and consensually derived scales also need to be evaluated.

Adult↗

Treatment of painful diabetic polyneuropathy with mixed gangliosides.

We studied 18 patients with painful diabetic neuropathy in a double-blind study of 40 mg per day of mixed gangliosides. Diabetes control was maintained throughout by analysis of serum glucose and glycosylated hemoglobin levels. Median motor and sensory, and peroneal motor conductions we evaluated in placebo and treated groups before and after a treatment period of three months. All conductions were performed by one technician on a TECA-4 EMG machine with surface temperature controlled at 37 degrees C. There was a definite improvement in nerve conductions in the treated group, particularly noted in the median sensory conductions. We have demonstrated a difference between right and left-sided conductions in the same patients confirming that this illness, at least from an electrophysiological point of view is asymmetric. Clinical improvement was variable but when present was dramatic. Side effects of this drug were minimal. Half of the patient complained of a transient increase in pain during the first two weeks of treatment. No patient stopped the drug because of this complaint. We conclude that in this three-month study mixed gangliosides caused a significant improvement in some nerve conductions without significant side effects. Further studies seem warranted to determine the nature and extent of this effect.

Adult↗

An evaluation of two doses of isocarboxazid in depression.

Two fixed doses of isocarboxazid were studied over a 4-week period in depressed in-patients. Thirty-five patients completed treatment, 20 of whom received 30 mg isocarboxazid per day, and 15 of whom received 50 mg isocarboxazid per day. No overall difference between the two doses was observed. When patients were subdivided into melancholia/endogenous depression or non-melancholia/non-endogenous depression, the higher dose exerted significantly greater antidepressant effects in the latter groups. Diagnostic type is considered to be an important variable in studies of dose-effect relationships with antidepressant drugs. The side effects of isocarboxazid at the two doses studied did not differ materially, although there was a suggestion of greater anticholinergic effect at 50 mg.

Adult↗

The Newcastle Endogenous Depression Diagnostic Index: validity and reliability.

The newcastle Endogenous Depression Diagnostic Index of Carney et al. was studied for reliability and validity. Good inter-rater reliability was obtained for diagnostic category and for item scores in 36 patients. The scale showed construct validity with reference to the Hamilton and Montgomery-Asberg rating scales. Concurrent validity was shown relative to other diagnostic scales of endogenous depression. Predictive validity was demonstrated in that endogenous and nonendogenous depressive responded differently to isocarboxazid. The continued use of 5 as the point of separation between endogenous and nonendogenous depression is questionable.

Depressive Disorder↗

Use of phenelzine in continuation therapy.

In 18 depressed patients, phenelzine had proved to be a beneficial drug during treatment of the acute illness. Following 4 weeks' remission induced by either 45 or 60 mg/day, patients were assigned to take part in a double-blind study in which the dose either remained fixed at the original dose, or was decreased by 15 mg/month and eventually replaced by placebo. 15 patients completed the study. Patients who remained at the same dose did significantly better on measures of anxiety and depression. The dropout rate ('relapse' rate) also differed significantly between the two dose groups. It is concluded that in this group of patients, maintenance of the full dose of phenelzine is recommended for at least 6 months.

Depressive Disorder↗

Role of pleural mesothelial cells in the production of the submesothelial connective tissue matrix of lung.

The pleura is comprised of a single layer of mesothelial cells resting on a complex layer of connective tissue. The ability of mesothelial cells to produce the components of this connective tissue was investigated using cultured rat mesothelial cells. These cells produced several components of extracellular matrix, including 6.8 +/- 0.2 X 10(5) collagen pro-alpha-chains per cell per hour, which represented 3.09 +/- 0.05% of all proteins synthesized by these cells. Chemical and immunologic criteria were used to demonstrate that these collagen chains included those of collagen types I, III, and IV. In addition, these cells produced elastin, as well as the connective tissue glycoproteins laminin and fibronectin. Moreover, electron microscopic studies revealed that lung mesothelial cells were capable of organizing these components into complex structures that resembled components of the extracellular matrix (thick collagen fibers, the amorphous component of elastic fibers, and basement membranelike structures), and restricted the formation of these structures to the basal region below the cells in culture. Thus, pleural mesothelial cells are active sources of a variety of connective tissue macromolecules found beneath mesothelial cells in situ, and can assemble these components into structures resembling the pleural extracellular matrix.

Animals↗

Validation of four definitions of melancholia by the dexamethasone suppression test.

The authors evaluated four sets of diagnostic criteria, the Newcastle Index, DSM-III, RDC, and the Michigan Diagnostic Index, for the diagnosis of melancholia. Forty-nine depressed inpatients, all of whom met RDC for major depression, also received consensus diagnostic assessment for melancholia. The dexamethasone suppression test (DST) was administered before drug treatment began. Results showed that the sensitivity of the DST ranged from 39% to 48%, specificity from 80% to 100%, and diagnostic confidence from 66% to 100%. All four scales received validation, but DSM-III showed the lowest specificity and predictive value.

Adult↗

Total hip arthroplasty with a low-modulus porous-coated femoral component.

Fifty-seven patients had sixty-three total hip replacements, performed using a femoral stem with a soft, low-modulus porous coating of Proplast and a conventional acrylic-cemented acetabular component. Forty-seven of the hips were followed for an average of thirty-seven months. Seventeen (36 per cent) of the forty-seven hips were judged to be clinical failures, and five of the failures were revised by inserting a new femoral component and fixing it with acrylic cement. The prostheses were thought to have failed because they had inadequate support, due to deficiencies in the design of the stem and in the fit of the implant in the femur. The five retrieved prostheses were found to have fibrous-tissue ingrowth into the coating, which had failed by shear within its substance. Therefore, we concluded that the coating had insufficient strength to withstand normal weight-bearing loads. To improve performance, a more stable prosthesis with a stronger porous coating is needed. In addition, a posterior surgical approach through a transtrochanteric osteotomy may give better exposure of the femoral canal and facilitate the use of longer-stem (140 to 153-millimeter) designs, which are less likely to be inserted in a varus position.

Biocompatible Materials↗

MAO inhibitor therapy in trichotillomania associated with depression: case report.

Trichotillomania may sometimes be an atypical variant of depressive illness. A case is reported in which the MAO inhibitor isocarboxazid was successfully used to treat both depression and associated trichotillomania. The symptoms recurred upon discontinuation of the drug and were ameliorated by reintroduction of isocarboxazid .

Adult↗

The importance of dose in isocarboxazid therapy.

Little information is available on the effectiveness and safety of particular doses of isocarboxazid. In a study using isocarboxazid doses of 30 and 50 mg/day in depressed inpatients, the higher dose was well tolerated and did not result in any greater toxicity than the 30 mg dose. Significantly greater elevation of plasma serotonin (Week 2) and platelet MAO inhibition were seen with 50 mg/day. In nonmelancholic depressions, 50 mg proved to be more effective than 30 mg in symptoms of depression and anxiety. However, this did not apply to the vegetative-physiologic symptoms of depression.

Anxiety Disorders↗

Classification of depressive disorders: a multiaxial approach.

Classification of depressive disorders can be performed following the Linnaean binomial nomenclature model by defining depression as a genus and the subtypes as species. A medical classification of depressive disorders would need to be jointly inclusive and mutually exclusive between subtypes, and to provide time of onset, severity of illness, pathological process, prognosis, and treatment indications. Etiologic, phenomenologic (clinical, descriptive), statistical, and biological approaches have been used to classify depression. A convergence of these various systems in different combinations has evolved, and a consensus approach using the multiaxial system, such as DSM-III, has advanced psychiatric nomenclature to provide clinical relevance and heuristic possibilities.

Arousal↗

Patient compliance with MAO inhibitor therapy.

Exaggerated fears of monoamine oxidase inhibitors (MAOIs) and of their interactions with foods often restrict their use. A review of the literature reveals seven food items most likely to produce a hypertensive crisis in combination with MAOI administration: aged cheeses, smoked or pickled fish, beef or chicken liver, dry fermented sausage, pods of broad beans, brewer's yeast products, and certain alcoholic beverages. Improved understanding of the dietary restrictions, benefits, and mechanism of action of the MAOIs can enhance cooperation with the prescribed treatment program.

Alcoholic Beverages↗

Practical aspects of MAO inhibitor therapy.

Instructions for patients regarding the observation of dietary and medication restrictions during MAOI therapy are presented. Principles of physician management of MAOI therapy, including avoidance and management of hypertensive crises and the potential for drug-drug interactions, are briefly reviewed.

Anesthetics↗