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Biomedical subjects

J K Hunter

Publications and source records attributed to J K Hunter.

At least 19 recordsLinked to original sources
PubMed2001

Malnutrition, urocanic acid, and sun may interact to suppress immunity in sojourners to high altitude.

Irradiation of skin by ultraviolet radiation in mice and humans leads to a suppression of cell-mediated immunity. This process is initiated when one of the photoreceptors in skin, trans-urocanic acid, is photoisomerized to cis-urocanic acid, an immunomodulator. High levels of L-histidine, histamine, and trans-urocanic acid are found in humans and animals when they are protein malnourished. Mice fed on an elevated L-histidine diet have more trans-urocanic acid in the skin and are more susceptible to UV-induced immune suppression. Sojourners to high altitudes are malnourished, suffer protein catabolism, are exposed to sun, and often acquire infectious diseases. There is evidence that sunscreens may not adequately protect the immune system. Furthermore, UV intensity increases with altitude. We propose a testable hypothesis: UV radiation causes photoimmune suppression in sojourners to high altitude and this allows infectious diseases to develop. The mechanism we propose includes protein malnutrition, high levels of trans-urocanic acid, ultraviolet radiation, formation of cis-urocanic acid, immune suppression, and infection.

Altitude↗
PubMed1999

The degradation of L-histidine and trans- and cis-urocanic acid by bacteria from skin and the role of bacterial cis-urocanic acid isomerase.

UV-B radiation suppresses cell-mediated immunity. Histidine forms trans-urocanic acid (trans-UCA) enzymatically in the stratum corneum. Photoisomerization of trans-UCA to cis-urocanic acid (cis-UCA) has been proposed for the initiation of an immunosuppressive process. Many microorganisms described in the literature metabolize histidine and/or trans-UCA. Our enrichment cultures of soil and sewage contain organisms that can degrade cis-UCA. We have tested microorganisms for degradation of cis-UCA, trans-UCA, or L-histidine when they are incorporated at 0.2% in nutrient broth. Six out of 10 selected genera isolated by our clinical microbiology laboratory degrade one or more of the imidazole substrates. We have cultured over 60 aerobic isolates from human skin. Of these, 33 degrade one or more of the three imidazole substrates and 12 degrade cis-UCA. Isolates from BALB/c mice are also active on cis-UCA. We have identified a cis-UCA-degrading bacterium as Micrococcus luteus. Four ATCC strains of M. luteus have been tested and three are active on histidine or trans-UCA; two are active on cis-UCA. Micrococci that degrade cis-UCA contain a new enzyme, cis-UCA isomerase, which converts the substrate to the trans-isomer. This enzyme provides access to the classical L-histidine degradation pathway. We hypothesize that an epidermal microflora that degrades L-histidine, trans-UCA, or cis-UCA influences the concentration of urocanic acids on the skin and, thus, affects immune suppression.

Adult↗
PubMed1998

The potential role for urocanic acid and sunlight in the immune suppression associated with protein malnutrition.

Irradiation of skin by sunlight or ultraviolet B (UVB, 290-320 nm) brings about a downregulation of cell-mediated immunity. An action spectrum for photoimmune suppression in mice indicates that trans-urocanic acid absorbs UV photons and is isomerized to the cis-isomer in the stratum corneum. Cis-urocanic acid is subsequently shown to suppress cellular immunity in mice. When histidine is elevated in a mouse diet, a higher level of urocanic acid is detected in mouse skin. These mice are more susceptible to photoimmune suppression. There is evidence that humans and animals experiencing protein malnutrition have very high levels of urocanic acid and/or histidine. Urocanic acid is formed by deamination of histidine in one enzymatic step. We discuss the protein malnutrition of kwashiorkor patients. They experience suppressed immunity and disturbed histidine metabolism. Here, we present a testable hypothesis: one cause of the immune deficiency observed in humans with protein malnutrition is the photoconversion by UVB of increased levels of trans-urocanic acid in skin to cis-urocanic acid, which suppresses the cellular immune system.

Animals↗
PubMed1994

Adventitious interconversion of cis- and trans-urocanic acid by laboratory light.

Urocanic acid (UCA) is a chromophore in the stratum corneum. Ultraviolet radiation (ultraviolet B) has been shown to suppress mammalian cell-mediated immunity. The photoisomerization of trans-UCA to cis-UCA was proposed as the initiator of the suppression process. Cis-urocanic acid has been demonstrated to suppress immunity by a variety of experiments. Investigators should be aware that laboratory illumination may be capable of interconverting trans-UCA and cis-UCA during experimental manipulations. This possible inadvertent contamination of one isomer by the other may influence results. We demonstrated that fluorescent lamps, daylight, sunlight and incandescent lamps were able to bring about isomerization. Window glass and container materials of plastic and clear glass did not filter out effective wavelengths, but three commercial plastic diffusers on fluorescent fixtures prevented the isomerization. Because the molar extinction coefficient (epsilon) for cis-UCA is less than that of trans-UCA, we have exposed 0.1 mM trans-UCA to ambient light and monitored the change in absorbance. A method is given to calculate the percentage of trans and cis isomers from the absorbance at 277 nm when the initial purity and absorbance are known. Using this procedure, we validated the molar extinction coefficient of cis-UCA.

Animals↗
PubMed1991

Photomodulation of enzymes.

The photomodulation of enzymes involves the activation and inactivation of enzyme reactions by UV and visible light. Enzymes or their reactions may be affected directly or indirectly. Direct effects involve photoproduction of a substrate, photodissociation of an inhibitor, photochemistry of protein amino acids, irradiation of a chromophore and irradiation of an enzyme substrate. Indirect effects involve gene expression, phytochrome and other photoreceptors which are not part of the enzyme, protein synthesis, membranes and photosynthesis. Photoactivation of enzymes is related to photocarcinogenesis, photomorphogenesis of plants, primary effects or side effects of phototherapy, deoxyribose nucleic acid (DNA) repair and many other aspects of biology and medicine. Model systems may contribute to the knowledge of protein chemistry and medicinal chemistry.

Animals↗