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Biomedical subjects

H C King

Publications and source records attributed to H C King.

At least 19 recordsLinked to original sources
PubMed2001

Gene expression profile analysis by DNA microarrays: promise and pitfalls.

DNA microarrays represent a technological intersection between biology and computers that enables gene expression analysis in human tissues on a genome-wide scale. This application can be expected to prove extremely valuable for the study of the genetic basis of complex diseases. Despite the enormous promise of this revolutionary technology, there are several issues and possible pitfalls that may undermine the authority of the microarray platform. We discuss some of the conceptual, practical, statistical, and logistical issues surrounding the use of microarrays for gene expression profiling. These issues include the imprecise definition of normal in expression comparisons; the cellular and subcellular heterogeneity of the tissues being studied; the difficulty in establishing the statistically valid comparability of arrays; the logistical logjam in analysis, presentation, and archiving of the vast quantities of data generated; and the need for confirmational studies that address the functional relevance of findings. Although several complicated issues must be resolved, the potential payoff remains large.

Gene Expression Profiling↗
PubMed2000

Stimulus-specific assembly of enhancer complexes on the tumor necrosis factor alpha gene promoter.

The human tumor necrosis factor alpha (TNF-alpha) gene is rapidly activated in response to multiple signals of stress and inflammation. We have identified transcription factors present in the TNF-alpha enhancer complex in vivo following ionophore stimulation (ATF-2/Jun and NFAT) and virus infection (ATF-2/Jun, NFAT, and Sp1), demonstrating a novel role for NFAT and Sp1 in virus induction of gene expression. We show that virus infection results in calcium flux and calcineurin-dependent NFAT dephosphorylation; however, relatively lower levels of NFAT are present in the nucleus following virus infection as compared to ionophore stimulation. Strikingly, Sp1 functionally synergizes with NFAT and ATF-2/c-jun in the activation of TNF-alpha gene transcription and selectively associates with the TNF-alpha promoter upon virus infection but not upon ionophore stimulation in vivo. We conclude that the specificity of TNF-alpha transcriptional activation is achieved through the assembly of stimulus-specific enhancer complexes and through synergistic interactions among the distinct activators within these enhancer complexes.

DNA-Binding Proteins↗
PubMed1998

Alternatives in the diagnosis and treatment of food allergies.

The diagnosis of food allergy remains a difficult and often inexact proposition, with the treatment being equally cumbersome and complex. For this reason a variety of approaches have been developed, varying in acceptance and approval. Although many approaches represent alternative medicine, today's alternative may be tomorrow's standard.

Administration, Oral↗
PubMed1994

Exploring the maze of adverse reactions to foods.

Nowhere in medicine is a test or battery of tests more needed than in the diagnosis of adverse reactions to foods. Such tests are not at present a reality. Research produces tests that individually appear to show validity, but when challenged with the entire range of possible adverse reactions and their results, the tests fall short. Considering the range of mechanisms involved in adverse reactions to foods, this is to be expected. There is a tendency to discount positive test results when they fail to cover all of the parameters desired. The inherent weakness in any test is that all available formats explore a single or limited reaction route. The reality is the presence of multiple routes, multiple target organs, and multiple external variables not subject to programming into a single test. Considering the range of possibilities, it is amazing that any existing tests show any clinical validity at all. We as scientists should not denigrate any study that shows a significant degree of reliability, even within a limited range. This simply halts progress. An encouraging study should be used as a stepping stone to a more comprehensive format for evaluating the overall range of adverse reactions and providing us with at least some inroads in coping with this most difficult problem. To quote Sir Peter Medawer on receiving the Nobel Prize in Science: "Nothing must be said or written that diminishes the likelihood that someone else will get at the truth."

Allergens↗
PubMed1992

Mast cell stabilizers.

The precise mode of action of the well-studied cromolyn sodium and the newer nedocromil sodium has not been completely elucidated. Because the drugs do not pass the cell membrane and enter the cell, they are virtually not metabolized, do not exert a systemic action, and therefore are associated with only minimal systemic toxicity. To be effective either drug must be applied topically and directly to the nasal mucosa. Proper contact with the nasal mucosa is essential for efficacy; in patients with nasal congestion and secretions, vasoconstrictors or saline lavages are indicated before cromolyn or nedocromil use. Both products are highly effective in patients who have IgE-mediated allergic rhinitis but must be administered prophylactically before exposure to an allergen to prevent development of the allergic event. Neither drug is effective in vasomotor rhinitis, exercise-induced rhinitis, or in the management of nasal polyps. Correct diagnosis is essential before therapy.

Administration, Intranasal↗
PubMed1992

Skin endpoint titration. Still the standard?

Skin endpoint titration, being both quantitative and calibrated in accordance with the patient's own reactivity, may still be considered the most sophisticated means of identifying an allergenic offender. Other forms of skin testing, simpler to perform, are rapidly becoming more uniform and quantitative. Laboratory tests provide more specific information and improved convenience. All occupy important positions in allergy diagnosis.

History, 20th Century↗
PubMed1990

Allergy testing by primary care physicians.

Primary care physicians will treat allergy to some degree purely because of supply and demand. The effectiveness of treatment depends on their interest and involvement. A thorough history and physical examination are essential. Physicians should not depend on a remote, computerized plan for diagnosis and treatment. Various diagnostic tests are available, some appropriate to nearly all levels of interest. Primary care physicians must choose between referral, pharmacotherapy, or more extensive involvement in allergy care. Immunotherapy involves some risk and a better possibility of pure result, but it requires additional training. Food allergy cannot be diagnosed by in vitro tests. Elimination and challenge with subsequent long-term elimination of offending foods is the only practical course for primary care physicians.

Enzyme-Linked Immunosorbent Assay↗
PubMed1990

The evolution of otolaryngic allergy practices.

We review the evolution of the allergy diagnosis and treatment techniques endorsed by the American Academy of Otolaryngic Allergy. These endorsements were made only after careful consideration of supporting data accumulated during their evolution.

Food Hypersensitivity↗
PubMed1985

Endpoint titration and immunotherapy.

Inhalant allergy, or "atopy" as it is now termed, is the best understood form of allergy today. In some circles, it is the only recognized form of allergy. While an overall picture of its effects on the body and a reasonable approach to its treatment now exist, many problems remain to be solved and much improvement in its treatment will probably occur within the next several years. Many new approaches to treatment of aeroallergens are now available; however, all are compared with the skin test, which is and has been the baseline for testing and treatment. Endpoint titration provides a quantitative means for undertaking treatment of aeroallergen sensitivity. In no other way does it differ from the forms of skin testing that have been widely used for generations. The practitioners of endpoint titration feel that this difference is highly significant in simplifying, validating, and shortening the necessary period of therapy. While the concept of endpoint titration is not difficult, it is by definition a quantitative form of testing and requires a degree of expertise in performing it correctly. While a good understanding of the method may be gained from the literature, adequate hands-on experience should be obtained by any physician prior to instituting the technique as a treatment modality. Once mastered, it becomes a reliable baseline for all forms of inhalant allergy care.

Allergens↗
PubMed1983

Plasmid-encoded trimethoprim resistance in salmonellas isolated in Britain between 1970 and 1981.

Trimethoprim resistance was plasmid-encoded in all trimethoprim-resistant Salmonella typhimurium and in the majority of trimethoprim-resistant salmonellas of other serotypes isolated since 1970 from humans and food animals in Britain. In S. typhimurium, non-autotransferring plasmids of compatibility group 3 and autotransferring plasmids of group H2 predominated. The predominance of these plasmid types has resulted from the spread of clones of trimethoprim-resistant strains of phage types 18, 170 and 204c. In other salmonellas, a variety of plasmid compatibility groups have been identified. Almost all plasmids which conferred resistance to trimethoprim also coded for sulphonamide resistance.

Anti-Bacterial Agents↗
PubMed1983

Effect of the nature and amount of dietary energy on lipid composition of rat gingival tissue.

1. The effect of the nature and amount of dietary energy on the lipid composition of rat gingival tissue was studied. Male weanling rats were given one of three iso-energetic diets: high-carbohydrate, high-protein and extremely high-protein, or a fourth high-fat diet, for 49 d. 2. The high-carbohydrate, extremely high-protein and high-fat diets caused significant increases in the gingival levels of total lipids compared with the normal-protein diet. These increases in total lipids were due primarily to increases in the levels of triglycerides and cholesterol esters. There were no significant differences in the fatty acid composition of either non-polar or polar lipids among rats given the high-carbohydrate diet and those given the high-protein diet. 3. A composition of the fatty acid composition of lipids of rats given the extremely high-protein diet and the other two iso-energetic diets revealed that the proportion of palmitic acid was higher and the proportion of oleic acid was lower to animals given the extremely high-protein diet than in animals given the other two diets. Compared with the three iso-energetic low-fat diets, the high-fat diet caused decreases in the proportion of palmitic and palmitoleic acids and increases in the proportion of linoleic, arachidonic and docosapentaenoic acids in total fatty acids of both no-polar and polar lipids. It should be noted that the high-fat diet contained a high proportion of linoleic acid and it is expected that this diet would raise the 18:2 fatty acid content of the lipids and also would raise the 20:4 and 22:5 levels as 18:2 is an essential fatty acid and will, with its metabolites, be directly incorporated into tissue lipids.

Animals↗
PubMed1982

Early clinical evaluation after aortic valve replacement with the St. Jude Medical valve in patients with a small aortic root.

Forty-three patients, nine men and 34 women, mean age 60 years (range 23-81 years), who had small aortic roots underwent aortic valve replacement with a St. Jude Medical valve. Preoperatively, five patients were in New York Heart Association (NYHA) class I, 19 were in class II, 15 were in class III and four were in class IV. In 30 of 36 patients with aortic stenosis, the mean gradient was 102 mm Hg (range 52-175 mm Hg; in six patients with aortic stenosis, the gradient was not measured. Seven patients underwent surgery for aortic regurgitation. Ten patients received a 19-mm valve, 29 a 21-mm valve and nine a 23-mm valve. Two patients (4.6%) died in the hospital, one immediately postoperatively and the other from low cardiac output 9 days postoperatively. There are 670 patient-months of follow-up (mean 17 months). Thirty-six patients are NYHA class I and two patients are in class II. There have been no thromboembolic episodes in 605 months of follow-up for patients maintained on warfarin. There was one partial valve thrombosis among eight patients being managed without warfarin. No mechanical valve failures have occurred. The St. Jude Medical valve provides a satisfactory early result when used to replace the aortic valve of patients who have a small aortic root.

Adult↗