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Biomedical subjects

R M Adams

Publications and source records attributed to R M Adams.

At least 19 recordsLinked to original sources

Electrophilic 18F from a Siemens 11 MeV proton-only cyclotron.

Because more and more PET centres are using small proton cyclotrons there is a renewed interest in methods for the production of electrophilic 18F by proton irradiation of [18O]O2. A method for the routine production of clinically useful quantities of [18F]F2 having a specific activity of 35 Ci/mmol has been developed and implemented using an 11 MeV proton cyclotron and [18O]O2. Based on the yield, purity, reproducibility, and specific activity of [18F]F2 this is the most efficient method reported thus far.

Cyclotrons

Concomitant positive patch test results with standard screening tray in North America 1985-1989.

Responses to patch test substances may occur contemporaneously. Such simultaneous reactions may reflect concomitant sensitization to 2 dissimilar allergens to which concurrent exposure has taken place (e.g., ethylenediamine dihydrochloride and neomycin). It may occur when the individual has been exposed to only 1 of the substances and exhibits a response to other substances of similar chemical structure (i.e., cross-sensitization such as between para-phenylenediamine and benzocaine). Such simultaneous responses may also be chance occurrences, reflecting multiple sensitization or the result of altered response due to the "angry back syndrome". This investigation established that such concurrence of response is not uncommon and adds further documentation to the literature of these associations in patch test responses.

Adult

Infection by retroviral vectors outside of their host range in the presence of replication-defective adenovirus.

Retrovirus infection is normally limited to cells within a specific host range which express a cognate receptor that is recognized by the product of the env gene. We describe retrovirus infection of cells outside of their normal host range when the infection is performed in the presence of a replication-defective adenovirus (dl312). In the presence of adenovirus, several different ecotropic vectors are shown to infect human cell lines (HeLa and PLC/PRF), and a xenotropic vector is shown to infect murine cells (NIH 3T3). Infectivity is demonstrated by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining, selection with G418 for neomycin resistance, and PCR identification of the provirus in infected cells. Infectivity is quantitatively dependent upon both the concentration of adenovirus (10(6) to 10(8) PFU/ml) and the concentration of retrovirus. Infection requires the simultaneous presence of adenovirus in the retrovirus infection medium and is not stimulated by preincubation and removal of adenovirus from the cells before retrovirus infection. The presence of adenovirus is shown to enhance the uptake of fluorescently labeled retrovirus particles into cells outside of their normal host range, demonstrating that the adenovirus enhances viral entry into cells in the absence of the recognized cognate receptor. This observation suggests new opportunities for developing safe retroviral vectors for gene therapy and new mechanisms for the pathogenesis of retroviral disease.

3T3 Cells

Gene transfer into human thyroid follicular cells.

The authors established a means of effective gene transfer into human thyroid follicular cells via retroviral-mediated mechanisms. Using specific harvest and culture techniques, we investigated the selection of human thyroid cells in serum-free media. Normal adult human thyroid tissue was obtained after thyroidectomy from fresh specimens sent for frozen-section analysis. Follicular cells were harvested and grown in hormonally defined, serum-free media to prevent fibroblast growth with selection for differentiated function assessed by immunohistochemical staining for thyroglobulin. The efficiency of gene transfer into human thyroid cells was compared between the zen-beta-gal and LNL6 retroviral vectors. The zen-beta-gal retrovirus encodes the product beta-galactosidase, and gene expression was demonstrated by histochemical staining in 0.1% to 1% of the cells. An improved efficiency of 2% to 3% transduction was demonstrated using the LNL6 vector which carries the gene for neomycin resistance (NEO-R). Polymerase chain reaction (PCR) identification of the integrated proviral sequence (NEO-R gene) with Southern blot confirmation was used to quantitate LNL6 transductions and compare confluent versus actively dividing cell cultures. Follicular cell gene therapy has significant potential for treating congenital or acquired diseases of the thyroid as well as disorders of circulating proteins such as diabetes, hypopituitarism, and hemophilia. The ability to culture human follicular cells and perform effective gene transfer is paramount in the eventual realization of thyroid gene therapy.

Cells, Cultured

The dermatologist and workers' compensation. Theory and practice.

Workers' compensation law is poorly understood by many physicians, including dermatologists. The tenets of this law throughout the country are basic and fairly straight forward, and the most important of them are nearly the same for all of the states. By understanding how the law operates and what is required of physicians, helping patients with their work-related dermatoses can be a gratifying experience.

Adult

Transduction of primary human hepatocytes with amphotropic and xenotropic retroviral vectors.

Experiments in animal models suggest that it is feasible to consider hepatic gene therapy using a strategy in which hepatocytes would be isolated by partial hepatectomy, transduced with recombinant retroviral vectors containing genes of therapeutic importance, and then transplanted back into the patient by autologous hepatocellular transplantation. The application of this strategy in clinical trials will require adapting these methods to human cells. We describe the transduction of primary human hepatocytes with two forms of retroviral vectors: amphotropic vectors, which have been used previously in clinical trials, and xenotropic vectors, which have a different host range. Human hepatocytes were harvested from organs preserved in Belzer's solution and were cultivated in a serum-free, tyrosine-free, hormonally defined medium. These cells proliferated for 3-5 days in culture, exhibited characteristic hepatocyte morphology, and expressed liver-specific functions, including phenylalanine hydroxylase, alpha 1-antitrypsin, and glutamine synthase. Transduction with an amphotropic LNL6 retroviral vector resulted in stable incorporation of the provirus into 1% of the cells as estimated by semiquantitative PCR. Consistently higher transduction efficiencies (as much as 10% of the cells) were observed with a xenotropic N2 vector. These data support the feasibility of using LNL6 as a marker gene in clinical trials of hepatocellular transplantation. These data also suggest that the efficiency of transducing hepatocytes with amphotropic vectors in animal models may not accurately reflect the utility of these vectors for human applications. Consideration should be given to the use of xenotropic vectors for optimizing the efficiency of transduction for human applications.

Animals

Methylchloroisothiazolinone-methylisothiazolinone reactions in patients screened for vehicle and preservative hypersensitivity.

More than 1100 patients were tested with methylchloroisothiazolinone-methylisothiazolinone, 100 ppm, in aqueous and petrolatum-based patch test materials from 1985 to 1987 by members of the North American Contact Dermatitis Group. Thirteen reactions to the aqueous materials and 10 to the petrolatum-based materials were observed. Irritant reactions were infrequent, and about half the reactions were deemed relevant. From 1984 to 1985, patch tests with this substance at a concentration of 250 ppm in petrolatum were conducted. Thirteen persons were identified as allergic, but three others were sensitized by the patch test procedure. Sensitization as not observed in tests with aqueous or petrolatum-based substance at a concentration of 100 ppm, and this concentration appears to be the best compromise between safety and sensitive detection of allergy. Use tests are helpful but not infallible as a guide in establishing relevance with methylchloroisothiazolinone-methylisothiazolinone. Wash-off products are frequently well tolerated by patients with positive reactions to this substance.

Adult

Depressive symptoms by self-report in adolescence: phase I of the development of a questionnaire for depression by self-report.

As the first step in validating a criteria-based, self-report depression questionnaire specifically for children and adolescents and to determine the prevalence of self-reported depressive symptoms, we studied 3,294 high school students of mixed ethnic background in a large urban school district. They completed the Weinberg Screening Affective Scale. The 21-item Beck Depression Inventory was also completed to allow comparison with a previous study. The prevalence of clinically significant depressive symptoms suggesting depression by self-report ranged from 18% on the Beck Depression Inventory to 13% on the Weinberg Screening Affective Scale. Hispanic females had the highest scores, while white males had the lowest. Being behind in school, female, and nonwhite predicted more self-reported depressive symptoms.

Adolescent

Reactions to thimerosal in hepatitis B vaccines.

Hypersensitivity to thimerosal in vaccines has been reported to induce persistent local reactions, urticarial and generalized exanthematic eruptions, and, in the case of the hepatitis B vaccine, urticaria with asthma. The authors describe two cases of extensive reactions, one in a patient who did not form antibodies to the principal vaccine antigen. Although not all thimerosal-sensitive patients develop adverse reactions to vaccines containing this material, there is a potential risk, and the reactions can be very long lasting.

Adult

Alstroemeria. A new and potent allergen for florists.

Alstroemeria (Peruvian or Inca lily) has found particular favor because of its beauty and durability. However, it may induce a dermatitis so severe that workers have to change jobs. The dermatitis is chronic, with fissuring at the tips of the fingers bilaterally. Itching is often a less prominent symptom. Preventative measures are of little benefit, and many floral shops are vanishing the plant.

Adult

Mycosis fungoides in relation to environmental exposures and immune response: a case-control study.

Mycosis fungoides is a cutaneous T-cell lymphoma of unknown etiology, thought to be a rare sequela of chronic antigenic stimulation that may occur, for example, with exposure to contact allergens. To explore this possibility, we interviewed 174 patients with mycosis fungoides and 294 randomly selected control subjects in the San Francisco, Los Angeles, and Seattle areas concerning their lifetime histories of employment, chemical exposures, allergy, atopy, and certain medical conditions. Patients reported higher prevalence of cancers other than the non-Hodgkin's lymphomas and skin cancers (relative risk = 3.3, P less than .001) and were more likely than controls to burn when exposed to the sun (for nonblacks, relative risk = 1.7, P = .01). The latter difference may reflect a manifestation rather than a precursor of the disease. We found no consistent or biologically plausible differences between patients and controls with respect to types of jobs held, or to occupational or vocational exposures to chemicals. These findings do not support the hypothesis that persistent antigenic stimulation by contact allergens is etiologically important in the pathogenesis of mycosis fungoides.

Case-Control Studies

Prevalence and relevance of allergic reactions in patients patch tested in North America--1984 to 1985.

Between Jan. 1, 1984, and May 1, 1985, 1199 patients with suspected allergic contact dermatitis were patch tested with 32 "standard" allergens, 707 patients with 19 "vehicle and preservative" allergens, and 613 patients with 10 "special study" allergens. Ten dermatologists representing nine geographic centers collected and analyzed data with the use of the American Academy of Dermatology's mainframe computer in Evanston, Illinois. The most common sensitizers identified were nickel, p-phenylenediamine, quaternium-15, neomycin, thimerosal, formaldehyde, cinnamic aldehyde, ethylenediamine, potassium dichromate, and thiuram mix. Each positive reaction was assessed for its clinical relevance.

Adult

Panels of allergens for specific occupations.

It is important to have available panels of materials for patch testing patients working in specific occupations. Although it is not essential in every case to test with each substance listed on a given panel, careful consideration of the patient's work environment should suggest the specific test items that will provide the highest diagnostic yield in cases of allergic contact dermatitis.

Allergens

Contact allergic dermatitis to dicyclohexylcarbodiimide used in protein synthesis.

Dicyclohexylcarbodiimide is a commonly used coupling agent found in protein synthesis. It is a potent allergic sensitizer found especially in the emerging industries involved in recombinant DNA synthesis. Chemists who work in research and development of this industry are especially at risk of development of contact dermatitis, unless they are careful and avoid skin contact. This report describes two chemists with allergic contact dermatitis from repeated contact with this compound in their work as research and development chemists. An appropriate concentration for patch testing is suggested.

Adult