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.

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.

Cost analysis of a nursing center for the homeless.

Single women and children now make up a third of the vulnerable U.S. homeless population who tend to seek health care only when their symptoms can no longer be ignored. The school of nursing at SUNY was one of the programs funded by HHS Division of Nursing to develop and implement a nursing center that would provide primary health services to the homeless. The cost of providing nursing services to homeless clients in nurse-managed centers was compared to costs for alternatives in the community including emergency department visits or care at the county supported nurse-run outpatient clinics. The four sites that served the homeless donated space for the SUNY project nurses to see patients. This enhanced accessibility, earlier intervention in health care problems, and decreased client cost (and time) for transportation to other service providers. The potential for earlier and less costly interventions confirmed the value of this humanistic nurse-run service for the homeless.

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.

Factors limiting evaluation of health care programs for the homeless.

The problem of homelessness and the need for health care by homeless people does not seem to be subsiding. All indications are that current legislation to implement dramatic welfare reform will eventually increase the number of homeless persons. Evaluation to guide, monitor, and select the most effective approaches in the provision of health care will remain a key element in health care delivery. Although barriers regarding evaluation of homeless health care have been reported by previous researchers as similar, the results in this study document findings elicited from administrators in the field. The administrators have the expertise to address some of the more common barriers and reduce them. Ways to approach this endeavor and to support staff in participating in and successfully integrating evaluation activities into health care provision will require attention of funding agencies, program administrators, and inclusion of staff and clients in planning. As the era of managed care becomes the focus of how health care is delivered, evaluation of existing programs will be essential to their survival. The descriptive information obtained in this exploratory study provides useful instruction for considering issues that need to be addressed in planning and implementing evaluation of health care to homeless persons.

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.

Homeless children and families: clinical and research issues.

The rapid increase in the number of homeless children and families has focused attention on understanding the health and related needs of this vulnerable group. This paper describes challenges associated with providing health care to homeless children and evaluation of those services. Data are presented from the Nursing Center for the Homeless of the School of Nursing at the State University of New York at Buffalo. Health services provided to homeless children and families (N = 470) documented that more than half (56%) were covered by health insurance and had received age-appropriate preventive health care. Of the children seen, 50% were considered well and 30% were diagnosed as having upper respiratory infections, skin problems, and/or gastrointestinal disorders. Health teaching for parents was the most frequent nursing intervention (50%), while 20% of the children were referred to community agencies. Factors that impede data collection and provision of health services for the homeless population are discussed, including suggestions for treatment and research approaches.

A national survey to identify evaluation criteria for programs of health care for homeless.

We know that programs to deliver health care to the homeless are springing up all over the nation, but are they effective? Hunter, Crosby, Ventura and Warkentin attempt to get a sense of what data is being collected. In doing so, they identify the difficulties in collecting data on this transient population.

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.

Specific inhibition of bacterial and bovine urocanases by glycylglycine.

Urocanase (EC 4.2.1.49) purified from Pseudomonas putida was unexpectedly inhibited by the dipeptide glycylglycine. Using a spectrophotometric assay for urocanase activity, we characterized the inhibition. The inhibition was temperature-, concentration-, and time-dependent; 0.1, 0.5 and 1.0 mM glycylglycine inhibited the enzyme by 20%, 50% and 78%, respectively, in 60 min at 30 degrees C. Dithiothreitol and reduced glutathione did not prevent the process. The inhibition was a pseudo first-order reaction. Three ligands that bind to the active site, urocanate, imidazole-propionate (a competitive inhibitor) and sulfite, protected the enzyme from glycylglycine inhibition. The inhibition was very specific for glycylglycine, because fifteen related biochemicals, including glycine, triglycine, and tetraglycine, were not effective. Ethylenediaminetetraacetic acid and other chelators did not inhibit urocanase. Bovine liver urocanase was also inhibited by this peptide. The characteristics of this inhibition suggest that glycylglycine acts at the active site, does not function by metal binding and that minor alterations in the glycylglycine molecule preclude the inhibition. A specific inhibition of urocanases by glycylglycine has been observed.