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Biomedical subjects

D Gregory

Publications and source records attributed to D Gregory.

At least 37 records · Page 2Linked to original sources

A cooperative taxonomic study of mycobacteria isolated from armadillos infected with Mycobacterium leprae.

Seventeen strains of mycobacteria, recovered from six armadillos experimentally infected with Mycobacterium leprae, were examined in ten different laboratories. This collaborative study included use of conventional bacteriological tests, lipid analyses, determination of mycobactins and peptidoglycans, characterization by Py-MS, and immunological, metabolic, pathological and DNA studies. These armadillo-derived mycobacteria (ADM) formed five homogeneous groups (numbered ADM 1 to 5) on the basis of phenetic analyses. However, DNA studies revealed only four homogeneous groups since group ADM 1 and one of the two strains in group ADM 3 showed a high level of DNA relatedness. The phenetic and DNA studies confirmed that the ADM strains differed from all other known mycobacteria. Cultural, biochemical, metabolic and pathogenic properties as well as DNA-DNA hybridizations clearly differentiated these ADM from M. leprae.

Amino Acids

Genetic causes of chronic musculoskeletal disease in childhood are common.

We surveyed admissions to a pediatric orthopedics hospital for calender years 1957 (polio era) and 1982 (post-polio era). The relative importance of genetic causes of musculoskeletal disease increased after poliomyelitis immunization became universal. Admissions for musculoskeletal disease with a genetic cause (chromosomal, Mendelian, multifactorial, and familial) accounted for 45% of the total in 1957 and 57% in 1982 (p less than 0.02); non-genetic causes were 44% in 1957 and 28% in 1982 (p less than 0.001). The high probability of recurrent disease in the families of these patients implies that genetics has an important place in the provision of services and in the education of staff in pediatric orthopedic hospitals.

Bone Diseases

Commentary on the utility of experimental social and learning models of alcoholism.

This chapter reviews the status of models in scientific research generally and in alcohol research in particular. The reader's attention is drawn to both advantages and disadvantages of models. The authors concur with others that models should be judged primarily by a criterion of usefulness rather than that of truthfulness . The commentary then examines what animal models of alcoholism have purported to model and the variety of criteria offered to evaluate such models. The authors agree in part with Cicero that there is not now and perhaps never will be a "true animal model of alcoholism." Indeed, when the variety of expression of alcoholism in humans is considered, the utility of any single, comprehensive model of alcoholism (animal or human) is questionable. However, the authors note that models of alcohol-relevant phenomena need not replicate or map all the characteristics thought to be present in the human alcoholic. Finally, the authors review several examples of models of alcohol-related phenomena (presented in Chapters 1-4), noting that although such models may be limited, they appear useful in advancing our understanding of this complex and pressing problem area. The authors conclude that an effective strategy for alcohol investigators would be to develop parallel models for both animals and humans and to engage in collaborative research based on such models.

Alcohol Drinking

Group A meningococcal disease in skid rows: epidemiology and implications for control.

Interviews conducted during outbreaks of group A meningococcal disease in skid row communities suggested that heavy alcohol use was associated with increased risk of disease. Frequent moving within skid row and from one skid row to another was characteristic of a subpopulation with increased risk of disease and may have facilitated spread within and between skid rows. The observations discussed herein have important implications for control of communicable diseases in and near skid rows.

Adult

Forskolin lowers intraocular pressure by reducing aqueous inflow.

Forskolin is a diterpene derivative of the plant Coleus forskohlii that stimulates adenylate cyclase activity without interacting with cell surface receptors. Forskolin lowers the intraocular pressure of rabbits, monkeys, and humans. In rabbits, net aqueous humor inflow decreases, outflow facility remains unchanged, and ciliary blood flow increases. Tolerance to the intraocular pressure lowering effect did not occur in rabbits after topical doses given every 6 hr for 15 days. In vitro forskolin activates adenylate cyclase of crude particulate homogenates prepared from cultured human ciliary epithelia or from dissected ciliary epithelial processes of rabbit or human eyes. This activation is not blocked by timolol. The stimulation of adenylate cyclase by isoproterenol in vitro is potentiated in the presence of forskolin. Forskolin represents a potentially useful class of antiglaucoma agents differing in molecular mechanism of action from previously used drugs.

Adenylyl Cyclases

Fine structural studies of ciliary processes after treatment with cholera toxin or its B subunit.

Delivery of 2 micrograms of cholera toxin (CT), a specific, irreversible activator of adenyl cyclase, via the blood causes dilation of capillaries and stromal edema of the ciliary processes. These morphologic changes occur within 3 h, are maximal at 12 to 24 h, then gradually return to normal by 72 h. In the late phase of hypotony, ultrastructural changes in the ciliary epithelia, similar to Greeff vesicles, are due to a "paracentesis effect" from hypotony, caused by decreased aqueous flow through the eye. Delivery of 2 micrograms of the B subunit of CT (Sub-B) causes very mild capillary dilation and stromal edema of ciliary processes. These changes reach their peak at 3 h, then return to normal at 24 h. No significant damage occurred to the pigmented or non-pigmented epithelium with either agent. No hemorrhage, invasion of inflammatory cells or appearance of fibrin exudates in the ciliary processes could be detected.

Animals

Ultracytochemistry of cholera-toxin binding sites in ciliary processes.

Cholera toxin reduces the rate of aqueous humor in concentrations (10-11M) that do not disturb the morphology of the aqueous-humor forming epithelial cells of the ciliary processes of the rabbit eye. The search for an endogenous mediator of aqueous-humor formation comparable to cholera toxin in its mode of operation prompted us to map the distribution of cell surface receptors for cholera toxin in the ciliary processes of the eyes of rabbits. Cytochemical studies were carried out with the use of conjugates of cholera toxin to fluorescein isothiocyanate (CT-FITC) and to horseradish peroxidase (CT-HRP), and of the B subunit of cholera toxin to horseradish peroxidase (B-HRP). Multiple fluorescent CT-FITC binding sites were observed on the outer nonpigmented epithelial layer near the crests of the processes. Processes incubated with CT-HRP in vitro showed surface staining of 30-40% of the nonpigmented epithelial cells. A prominent reaction product was observed along the basal and lateral plasma membranes of these cells. In vivo studies carried out after arterial infusion of B-HRP showed a reproducible dense reaction product between the apical surfaces of the pigmented epithelium (PE) and of the nonpigmented epithelium (NPE) facing each other. Aggregations of reaction product were observed with the electron microscope in the extracellular space between the apices of PE and NPE. The apical plasma membrane of the endothelium of the blood vessels near the crests of the ciliary processes was stained after either in vivo or in vitro exposure to peroxidase conjugates. These findings indicate that the cell-surface receptors which mediate the action of cholera toxin on aqueous humor formation are very likely localized in the apical plasma membranes of the epithelium of the ciliary processes.

Animals

N-acetyl-beta-glucosaminidase, beta-glucuronidase and acid phosphatase in Mycobacterium leprae.

N-Acetyl-beta-glucosaminidase, beta-glucuronidase and acid phosphatase activities were detected in cell-free extracts of Mycobacterium leprae (from armadillo liver). Extracts of bacteria which had been treated with 7-diazonaphthalene-1,3-disulphonic acid to inactivate surface enzymes retained 30-45% of the activity of the glycosidases and 15% of the activity of the acid phosphatase. When intact bacteria were treated with 1 M-NaOH, the corresponding activity in the extracts was 4--9% for the glycosidases and 7% for the acid phosphatase. Inhibition studies with lactones and the use of concanavalin A-agarose showed differences between the glycosidases in extracts of M. leprae and those of armadillo liver. Inhibition studies with vanadate using extracts from NaOH-treated bacteria and extracts of armadillo liver showed differences between the acid phosphatases. Enzymes removed from the surface of M. leprae could have been adsorbed to the surface from host tissue (i.e. lysosomal enzymes) or they could have been extracellular enzymes or associated with the bacterial membrane.

Acetylglucosaminidase

Intraocular pressure and aqueous flow are decreased by cholera toxin.

Delivery of 2.1 microgram of cholera toxin, a specific, irreversible activator of adenylate cyclase, via the blood lowers IOP from 17.4 to 11.2 mm Hg in 81/2 hr. decreases net aqueous flow by about 50% in 8 hr, and doubles blood flow to the anterior uvea at 8 to 13 hr. Intravitreal injection of 0.26 microgram of cholera toxin lowered IOP from 15.0 to 9.6 mm Hg, but heat-inactivated toxin had no effect on IOP. The toxin activates adenylate cyclase from ciliary processes 2.2-fold and stimulates cyclic AMP production by ciliary processes 7.4 times. Absence of aqueous flare, normal protein concentrations in the aqueous, and histologic examination all confirmed the functional and structural integrity of the blood-aqueous barrier after cholera toxin infusion. The data point to an important role for ciliary process adenylate cyclase in regulation of aqueous flow and maintenance of IOP.

Adenylyl Cyclases

A model for service delivery research and evaluation: management implications for alcohol, drug abuse and mental health organizations.

Public alcohol, drug and mental health organizations have failed to adequately demonstrate their impact. Historically, the justification for these programs have relied more on good intentions and good faith to support their efforts than on their documented efficacy. This lack of documentation has contributed, in part, to recent federal and state mandates for better management, control, and evaluation of publicly financed mental health, alcohol and drug abuse care. This paper presents a model of applied research and evaluation designed to enhance the capabilities of public mental health, drug and alcohol programs in demonstrating their clinical and rehabilitative results.

Alcoholism

Feasibility of an alcoholism health insurance benefit.

The present study examined the impact of alcoholism treatment upon the subsequent utilization of health care services. Information gathered on a sample of 2,362 alcoholic clients at time of admission and six months later, was utilized to compare the savings in medical care expenses with the costs of alcoholism treatment. For the first year following treatment, costs exceeded savings by an average of $263 per client (benefit-cost ratio = 0.63:1). However, if the savings were sustained, the benefits would exceed costs within two years of the treatment period. These findings support the notion that alcoholism treatment produces a reduction in medical costs and provides some economic justification for an alcoholism insurance benefit.

Adult

Superoxide dismutase, peroxidatic activity and catalase in Mycobacterium leprae purified from armadillo liver.

Superoxide dismutase has been identified and peroxidatic activity demonstrated in Mycobacterium leprae. The superoxide dismutase, shown indirectly to be a manganese-containing enzyme, was present at low activity in the cell-free extract. Peroxidatic activity was detected in a haemoprotein on polyacrylamide gels, but quantitative assay was not possible. Catalase, although present in a cell-free extract, appeared to be a host-derived enzyme, thus emphasizing the importance of establishing the authenticity of enzyme activities in host-derived M. leprae. The implications for the growth of M. leprae in vivo and its non-cultivability are discussed in the light of these findings.

Animals

Improving psychiatric care for prisoners.

While psychiatry has been ambivalent about treating mentally ill offenders, recent mandates for better mental health care for prisoners will require the profession's intervention. The authors, whose study of mental health care needs of inmates in Oklahoma is reported in the article following this one, believe that because the prison is a community, a community-mental-health-like system offering a continuum of services is indicated. Some of the services they propose for prisons include outpatient and partial hospital services, an acute inpatient unit, a residential tertiary care unit, and an intermediate living unit. They also believe that mental health professionals should help improve the environment of prisons, and can do so by sharing lessons learned in their own institutional settings about the effects of a therapeutic community and a legitimate patient government.

Health Services Needs and Demand

Psychiatric morbidity in prisons.

Faced with the recommendation by an outside consultant to construct a large hospital for the criminally insane, the Oklahoma legislature approved a proposal by the state mental health department to study the mental health treatment needs of the prison population. Through a variety of assessment techniques, the authors found the inmates had a spectrum of disorders needing different treatment approaches. Approximately 78 per cent of the inmates are diagnosable. Thirty-five per cent require treatment other than brief intervention, and 10 per cent are seriously ill. It is estimated that 20 per cent may be resistive and may require involuntary treatment.

Adult

Antimicrobial prophylaxis of recurrent urinary tract infections: a double-blind, placebo-controlled trial.

To study once-daily antimicrobial prophylaxis of urinary tract infections, we gave trimethoprim-sulfamethoxazole (40 mg/200 mg), trimethoprim (100 mg), nitrofurantoin macrocrystals (100 mg), or placebo to 60 women for 6 months. During prophylaxis, infections per patient year were comparable in the groups receiving trimethoprim (0.0), nitrofurantoin (0.14), or trimethoprim-sulfamethoxazole (0.15) and occurred less frequently than in patients receiving placebo (2.8; P less than 0.001, placebo versus each drug regimen). The effectiveness of prophylaxis was limited to the 6 months that antimicrobials were given, and infections were more likely to develop after prophylaxis in women who had three or more infections in the year before prophylaxis (P less than 0.005). Further, women whose preprophylaxis infection was positive for antibody-coated bacteria were more likely to have same-strain relapse when infections recurred (P = 0.001). Emergence of trimethoprim-resistant Escherichia coli was rare, but non-E. coli infections occurred more often after prophylaxis (P less than 0.05). Prophylaxis with these drugs is effective, well tolerated, and did not produce emergence of resistant E. coli but may predispose to non-E. coli urinary tract infections after its discontinuation.

Adolescent