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Biomedical subjects

D A Johnson

Publications and source records attributed to D A Johnson.

At least 289 records · Page 16Linked to original sources

The use of benzodiazepines in depression.

In clinical practice the benzodiazepines are prescribed almost as frequently as the tricyclic antidepressants for the treatment of depression. The therapeutic effects of the benzodiazepines and tricyclic antidepressants in depression have been compared in only 29 double-blind studies. The antidepressants proved overwhelmingly superior with only one study (alprazolam) even suggesting a possible parity of action. A symptom response analysis failed to show any true antidepressant action for the benzodiazepines. No clear indication for the use of a combination of drugs was revealed, although certain symptoms may show a more rapid response initially with combination therapy.

Anti-Anxiety Agents↗

Social adjustment and interaction after severe head injury.

The social adjustment of 11 severely head injured patients was assessed using the KATZ adjustment scale. The result suggested that the group had poor social adjustment, and on many dimensions was similar to a psychiatric population. The head-injured patients also had social interaction difficulties as assessed by a range of observational and self-report measures. When compared to an out-patient and non-clinical group they had poor social performance, high social anxiety and low self-esteem. The implications of this for rehabilitation are discussed.

Adolescent↗

Use of nonfat dry milk to block nonspecific nuclear and membrane staining by avidin conjugates.

The use of fluorescein-avidin or rhodamine-avidin conjugates in conjunction with biotinylated secondary antibodies for indirect immunohistology frequently results in pronounced nonspecific nuclear staining in kidney sections. This nonspecific nuclear staining can be effectively blocked by using 5% (w/v) nonfat dry milk in buffered saline as the diluent for the avidin conjugates. In contrast, 5% (w/v) bovine serum albumin, a commonly used blocking agent, has only a modest effect. Nonfat dry milk is also effective as a blocking agent and carrier when used in fluorescence-activated cell sorter (FACS) analysis. These results emphasize the broad usefulness of milk-based blocking reagents.

Animals↗

Antipsychotic medication: clinical guidelines for maintenance therapy.

In neuroleptic maintenance therapy, first-illness schizophrenic patients should be prescribed continuing medication for at least one year. In the management of chronic schizophrenic patients following relapse, neuroleptic medication in standard oral doses or depot injections is recommended for periods in excess of 5 years to reduce the risk of relapse. Results are summarized from studies regarding drug therapy in conjunction with psychotherapeutic factors and family environment, the efficacy of lower dosage, benefit/risk ratios, and the advantages of long-term neuroleptic maintenance. The relationships of neuroleptic dose to plasma level and to therapeutic response are considered, as well as the implications of polypharmacy (e.g., use of anticholinergic drugs with neuroleptics).

Administration, Oral↗

Crohn's disease and systemic lupus erythematosus.

A 28-year-old man with inflammatory bowel disease with complex extraintestinal involvement was found to have diagnostic features of both systemic lupus erythematosus and Crohn's disease. Although some of the systemic complications of these diseases may overlap, both diseases may occur as primary disorders. Coexistence of systemic lupus erythematosus should be considered in patients with inflammatory bowel disease and complex extraintestinal manifestations.

Adult↗

Human lung tryptase. Purification and characterization.

Human lung tryptase, a mast cell-derived trypsin-like serine protease, has been isolated from whole human lung tissue obtained at autopsy. Increased yields from this purification process have allowed extensive characterization of the enzyme. One of the critical steps in the purification scheme is the use of a linear heparin gradient to elute active material from cellulose phosphate. Gel filtration studies in 1.0 M NaCl yielded an apparent Mr = 135,000, and subsequent electrophoresis on sodium dodecyl sulfate-polyacrylamide gels demonstrated the presence of two active species with apparent Mr = 30,900 and 31,600. Enzymatic activity was sensitive to NaCl concentrations above 0.05 M and was only 50% in 0.15 M NaCl, decreasing to 18% in 0.6 M NaCl. The effects of synthetic and natural inhibitors have also been studied, confirming the enzyme's trypsin-like characteristics and demonstrating that naturally occurring serum inhibitors are incapable of diminishing its activity. A complete amino acid analysis showed a high tryptophan content. Lastly, antisera to human lung tryptase have been generated, and the immunological identity of active fractions has been investigated as well as the localization of the enzyme to the mast cell granule by immunohistochemical staining.

Amino Acids↗

Fluorescence energy transfer between cobra alpha-toxin molecules bound to the acetylcholine receptor.

An approach was developed with steady state fluorescence energy transfer measurements to examine the spatial relationship between the two alpha-toxins bound to the acetylcholine receptor. By taking advantage of the slow dissociation rates of alpha-toxins (Naja naja siamensis 3) from the receptor and of the equal probability with which alpha-toxins bind to the two alpha-toxin-binding sites, we derived an equation which allows prediction of a "true" efficiency of transfer based on the relationship between fractional site occupancy and the observed transfer efficiency ascertained from donor quenching. Using this approach, we examined the efficiency of energy transfer between two fluorescently labeled alpha-toxins, N epsilon-fluorescein isothiocyanate lysine 23 alpha-toxin and monolabeled tetramethylrhodamine isothiocyanate alpha-toxin bound to the receptor from the Torpedo californica electric organ. Significantly greater (32 versus 14%) energy transfer was observed with the membrane-associated than with the solubilized receptor, suggesting that transfer between fluorophores on separate receptor molecules is greater than that occurring intramolecularly between the two sites on the receptor. The magnitude of the distances calculated from the intrareceptor energy transfer efficiency combined with the considerable inter-receptor energy transfer indicate that the fluorophores would reside on the outer perimeter of the receptor molecule rather than near the central axis perpendicular to the plane of the membrane.

Animals↗

Changes in rat parotid salivary proteins associated with liquid diet-induced gland atrophy and isoproterenol-induced gland enlargement.

The composition of secretory proteins in the parotid saliva of untreated rats, fed a stock pelleted diet (CON), was compared to that of rats maintained on a liquefied diet (LIQ), so as to reduce gland secretory activity, and to rats treated chronically with isoproterenol (ISO), so as to enhance activity. Each experimental treatment resulted in marked changes in protein composition. In CON rats, the basic and acidic proline-rich proteins accounted for 25 per cent of all secretory protein. In LIQ rats, the proportion was 13 per cent. Several basic proline-rich proteins were absent and the major acidic proline-rich protein was markedly reduced. Amylase was reduced whereas DNase and a leucine-rich protein (fraction I) were increased. The proportion of cystine-rich protein (fraction V) was not different from CON rats. The changes observed in the saliva of ISO rats were in marked contrast to these findings. Basic and acidic proline-rich proteins were increased and accounted for 90 per cent of all secretory protein, amylase was responsible for the remaining 10 per cent. Thus the composition of secretory proteins in the parotid saliva of rats can be altered by experimental conditions which affect gland secretory activity. The mechanisms by which these changes occur is not known.

Amino Acids↗

Synthesis of F-pilin polypeptide in the absence of F traJ product.

The products of a lambda transducing phage (ED lambda 101) which carries a segment of the F tra operon expressing F traA , traL , and traE activity from the lambda leftward promoter were examined using a uv-irradiated host system. After infection of an F- host, products of traE (19,500 Da) and traA (14,000 Da) were detectable among the lambda early proteins synthesized. Infection of an Flac host altered the pattern of polypeptides synthesized by the phage in that the 14,000-Da traA product became barely detectable and was replaced by a polypeptide which migrated at 7000 Da. A derivative of ED lambda 101 carrying the traA1 amber mutation was unable to synthesize either the 14,000-Da polypeptide in F- cells or the 7000-Da polypeptide in Flac cells. The 7000-Da polypeptide derived from ED lambda 101 was synthesized in the absence of traJ product in F- cells coinfected with a second transducing phage which carried a tra operon segment including traQ . It was also a product of ED lambda 134 which expresses genes traA through traH . The 7000-Da polypeptide, like F-pilin, associated primarily with the inner membrane, and could be immunoprecipitated with antiserum prepared against purified F-pili. Analysis of membranes from F- cells infected with ED lambda 101 indicated that the 14,000-Da traA product synthesized under these conditions accumulated in the inner membrane. These results show that both the 14,000-Da traA product might be processed to F-pilin in a traQ -dependent reaction which occurs in or on the inner membrane of the Escherichia coli host. However, the possibility that traQ encodes a regulatory product which affects expression of the traA sequence has not been excluded.

Bacterial Proteins↗

Kinetics of interaction of N epsilon-fluorescein isothiocyanate-lysine-23-cobra alpha-toxin with the acetylcholine receptor.

We have studied the kinetics of N epsilon-fluorescein isothiocyanate-lysine-23 cobra alpha-toxin (FITC-toxin) binding to the membrane-associated acetylcholine receptor from the Torpedo californica electric organ. The fluorescent toxin not only enabled us to monitor the binding reaction continuously but also to examine simultaneously the enhancement of ligand fluorescence and the increase in steady state polarization of fluorescence associated with binding of the alpha-toxin. Over the range of concentrations employed, both parameters yielded identical kinetic constants, suggesting that the enhancement of fluorescence of fluorescein and its immobilization are occurring in the same time frame. Both an initial rate analysis and the integrated rate expression showed association to be a simple, reversible bimolecular process. The apparent second-order association rate constant derived from the integrated rate analysis was constant within a factor of 2 over a 40-fold concentration range (6.7 +/- 1.7 X 10(3) M-1 S-1). The unimolecular dissociation rate constant was found to be 3.3 +/- 0.5 X 10(-5) S-1.

Animals↗

Zinc deficiency-induced changes in rat parotid salivary proteins.

This study was undertaken to determine the effects of zinc deficiency on rat parotid salivary proteins. Male rats were fed a pelleted diet containing either 40 ppm Zn (ad libitum- and pair-fed control groups) or 0.9 ppm Zn (zinc-deficient group) for a period of 4 weeks. At the time they were killed, stimulated parotid saliva was collected and analyzed for concentration and composition of secretory protein. In addition, gland specimens were examined ultrastructurally, and liver and serum samples were assayed for zinc concentration. The zinc-deficient group exhibited retarded body growth, decreased appetite and significantly lower serum and liver zinc concentrations. The most significant finding in the saliva of the deficient animals was the marked reduction in acidic proline-rich proteins. Parotid gland secretory activity also seemed reduced. Morphologically, distinctive secretory granules were observed in the acini of the deficient animals. The altered composition of salivary secretory proteins coupled with a diminished flow rate may, in part, be responsible for the increased susceptibility to dental caries in zinc-deficient rats.

Animals↗

Bacillus cereus-induced myonecrosis.

A patient with an incomplete amputation due to a crush injury to his arm developed a myonecrosis with Gram-positive rods noted on muscle and wound aspirates. The patient was treated for a probable Clostridium perfringens infection but culture results proved the organism to be Bacillus cereus. In light of the reported resistance of Bacillus cereus to penicillin, this case serves to emphasize the importance of expanded empiric coverage with high-dose penicillin and an aminoglycoside pending the return of culture and sensitivity results.

Adult↗

Legionnaires' disease with rhabdomyolysis and acute reversible myoglobinuric renal failure.

We have described a patient with rhabdomyolysis, myoglobinuria, and acute reversible renal failure. Serologic studies were diagnostic for legionnaires' disease and were negative for other viruses associated with rhabdomyolysis. Bacteriologic cultures were also negative, and other nontraumatic causes of rhabdomyolysis were ruled out. No other causes of acute reversible renal failure were found. With a clinical picture of pneumonia, rhabdomyolysis, myoglobinuria, and acute renal failure, legionnaires' disease should be considered in the differential diagnosis and appropriate antibiotic therapy instituted.

Acute Kidney Injury↗