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Biomedical subjects

D Tobin

Publications and source records attributed to D Tobin.

15 recordsLinked to original sources
PubMed1996

Ras-independent activation of Rel-family transcription factors by UVB and TPA in cultured keratinocytes.

UV irradiation of mammalian cells results in the activation of transcription factors which mediate induction of early response genes designed to repair and minimise the damage sustained by the cell. Evidence from studies in HeLa cells suggest that UVC regulates NF-kappa B activity via tyrosine kinases and activation of Ras and Raf kinase. In this study we have used a previously characterized TPA-responsive element (VLTRE) that binds Rel/NF-kappa B proteins and a Ras-responsive element (B10 RRE) to analyse the signalling pathway in UVB-stimulated gene transcription in cultured keratinocytes. We demonstrate that the tumour promoters TPA and UVB use different signalling intermediates to activate different sets of Rel/NF-kappa B proteins. UVB transactivation is independent of PKC activity but dependent on tyrosine kinase activity where was TPA stimulation requires PKC but not tyrosine kinase activity. Furthermore, neither UVB- nor TPA-transactivation is mediated through p21 Ras but both stimuli are dependent on a functional Raf protein. A constitutively active Raf-1 kinase however, was unable to induce transactivation through VLTRE. Thus, Raf has an essential but permissive role in UVB activation of Rel proteins. These findings demonstrate that keratinocytes contain a novel Ras-independent pathway for induction of Rel mediated transcription.

Animals↗
PubMed1994

Candida carriage in the alimentary tract of liver transplant candidates.

Thirty randomly selected patients with advanced chronic liver disease, which had been evaluated for possible liver transplantation, were sampled endoscopically at 7 alimentary tract locations to assess the frequency and amount of Candida carriage. Eighty-one percent (127/156) of the samples obtained contained Candida and 53% (82/156) yielded high counts (> 300 CFU/ml). The most predominant Candida species isolated at each site was Candida albicans, which accounted for 103 (64%) of the 160 fungal isolates. The other Candida species isolated included C tropicalis 30 (19%), C krusei 16 (10%), and C glabrata 11 (7%). Although the number of sites at which yeast was present and the quantities of yeast at each site varied widely among the patients studied, 100% of the patients had Candida in at least one site of the gastrointestinal tract. Eighty-six percent (24/28) of the duodenal aspirates contained Candida and 50% (14/28) of the duodenal samples contained greater than 300 CFU/ml. A positive culture from the stomach was a reliable predictor of the presence of Candida in the duodenum (P = 0.0001), but a positive culture at no other site readily predicted the presence of Candida at yet another site. Importantly, there was no correlation between the presence or absence of Candida in either oral or rectal swabs and colonization at other anatomic sites within the gastrointestinal tract. These findings are important in liver transplantation, particularly in those cases in which the bowel has been opened to create a choledochojejunostomy anastomosis. The operative attempts to reduce gastrointestinal fungal carriage using oral antifungal agents may be justified before liver transplantation in an effort to lower the risk of posttransplantation fungal infections, particularly in those patients expected to have a Roux-en-Y choledochojejunostomy biliary reconstruction.

Body Fluids↗
PubMed1994

The superoxide anion may mediate short- but not long-term effects of ultraviolet radiation on melanogenesis.

The present study was carried out to examine the role of reactive oxygen species in mediating the melanogenic effects of UVR. B16 mouse melanoma cells responded to a single dose of UVR by showing increases in their melanin content. Although there was a small increase in melanin at 48-72 hours, which was associated with a rise in tyrosinase activity at 48 h, the greatest change occurred at 3 h and this was not associated with an increase in tyrosinase activity. This short-term response, unlike the more delayed melanogenic response, was reduced by superoxide dismutase (SOD). Xanthine oxidase (XO), which generates the superoxide anion (O2-), also increased the melanin content of B16 melanoma cells with effects at 3 h and 48 h. As with UVR, the delayed response was accompanied by an increase in tyrosinase activity but no such association was evident at 3 h. In addition, the short-term effect, like that seen with UVR, was reduced with SOD and to a lesser extent with catalase. In contrast to the effects found with XO, glucose oxidase, which generates hydrogen peroxide, had no effect on the melanin content or tyrosinase activity of the B16 cells. These results confirm previous observations that UVR is able to act directly on cells to bring about delayed increases in melanogenesis. They further demonstrate that UVR also stimulates melanogenesis through a more rapid action that is not associated with an activation of tyrosinase. This effect could be mediated by the O2- which, rather than activating tyrosinase, could act by serving as a substrate for the enzyme.

Animals↗
PubMed1994

The presence of tyrosinase and related proteins in human epidermis and their relationship to melanin type.

The present study was carried out to investigate the abundance of tyrosinase and related proteins (TRP-1 and TRP-2) in human epidermis and their relationship to melanin type. Positive immunocytochemical staining was seen for all three proteins in epidermal melanocytes. For each protein the numbers of positively stained melanocytes were similar in all subjects studied irrespective of skin type. Following 5 daily suberythemal doses of UVB the melanocytes were larger, more dendritic, and increased in number. With TRP-1 and TRP-2 the increase in number in response to UVB was unrelated to skin type and, hence, with melanin type but with tyrosinase there was a much greater increase in skin types III and IV than in skin type I and II. The enhanced numbers of tyrosinase-positive melanocytes were accompanied by increased staining intensity, suggesting a greater expression of tyrosinase in the melanocytes from skin types III and IV compared with skin types I and II. This increase in tyrosinase could be related to the greater levels of eumelanin found in skin types III and IV, and this is in keeping with the view that higher levels of tyrosinase are associated with the production of eumelanin than phaeomelanin.

Adult↗
PubMed1994

Preparations for AIDS vaccine trials. An automated version of the Risk Assessment Battery (RAB): enhancing the assessment of risk behaviors.

Our primary objective during this pilot work has been to determine if the computerized RAB can be used in place of the paper-and-pencil version with an IDU population. As stated, reliability estimates in the form of correlations of risk scores between the two versions ranged from .82 to .94, and percentages of exact agreement of the scoreable items ranged from 88% to 100%. These correlations indicate that the C-RAB is comparable to the RAB in its psychometric properties. Further, subjects' positive ratings of the computer program and perceptions that it would better protect confidentiality indicate that this population would participate in assessments involving computer interactions. While these self-reports may be biased on clients' desire to be cooperative and the novelty of the assessment approach, the high level of approval ratings suggest that a majority of participants do prefer completing assessments on the computer. Similarly, participants' demonstrated ability to use the computer and their rating of the program as easy to use suggest that the C-RAB has potential to be a reliable and efficient tool in assessing risk behaviors among IDUs enrolled in HIV vaccine trials.

AIDS Vaccines↗
PubMed1993

Epitopes of human immunodeficiency virus regulatory proteins tat, nef and rev are expressed in skin in atopic dermatitis.

We extend our previous documentation that epitopes of HIV regulatory proteins tat, rev, and nef are expressed in tissue from uninfected individuals by the immunohistochemical analysis of normal skin (n = 10) and skin in some selected inflammatory dermatoses including urticaria (n = 6), systemic lupus erythematosus (n = 6), and atopic dermatitis (affected skin, n = 10, and after epicutaneous patch test for allergens, n = 8). A rabbit antibody to HIV-2 tat did not show immunolabeling of skin. Blood vessel endothelium was immunolabeled by one of two antibodies applied to HIV-1 tat, by an antibody to HIV-1 rev, and by two antibodies to HIV-1 nef. In addition one of the anti-nef antibodies labeled Langerhans cells. The anti-rev antibody labeled Langerhans cells and melanocytes in the epidermis, and dendritic cells in the dermis. The labeling of these skin components did not differ in prevalence between controls and groups of dermatosis. For other components, diseased skin conditions especially atopic dermatitis showed additional labeling. In affected skin, keratinocytes were labeled by antibodies to rev and one of two antibodies to nef. Skin after epicutaneous allergen patch testing also showed a statistically significantly increased prevalence of immunolabeling of dendritic cells and Langerhans cells by one of the anti-tat antibodies. We conclude that skin components show expression of epitopes recognized by antibodies to HIV-1 tat, rev, and nef; this expression is more extensive in atopic dermatitis than in normal skin, and can be further increased after epicutaneous allergen patch testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Increased number of immunoreactive nerve fibers in atopic dermatitis.

The presence of immunologic markers for neurofilaments, neuropeptides of sensory nerve fibers (Calcitonin gene-related peptide and substance P), for noradrenergic innervation (neuropeptide Y and Tyrosine hydroxylase), and Neuron-specific protein 9.5 was evaluated in frozen tissue sections from normal skin (n = 34) and from skin biopsies manifesting urticaria (n = 6), leukocytoclastic vasculitis (n = 4), systemic lupus erythematosus (n = 23), and atopic dermatitis (n = 40, of which 16 were from lesions induced by epicutaneous atopic allergen patch tests). In some normal skin specimens immunoreactive nerve fibers expressing Neuron-specific protein 9.5 were observed in the epidermis, dermis, and around blood vessels. For the other markers, immunolabeling was mainly observed in the dermis around blood vessels. Neurofilaments, which are scarce in normal skin epidermis, were present in higher density in the epidermis of affected skin in all disease conditions. Biopsies from urticaria and systemic lupus erythematosus showed a decrease in density of fibers immunolabeled for neuropeptides substance P and Calcitonin gene-related peptide and for Neuropeptide Y. In biopsies from skin with atopic dermatitis, an increased density of fibers was observed for all markers except Neuropeptide Y and Tyrosine hydroxylase. In this group, biopsies from positive atopic allergen patch tests showed an enhanced density of fibers labeled by antibody to Neuron-specific protein 9.5 and a lower density in labeling for Tyrosine hydroxylase. The data indicate a potential role of innervation and neuropeptides in dermatoses like atopic dermatitis.

Adolescent↗
PubMed1989

Prevalence and clinical characteristics of borderline patients in an eating-disordered population.

Ninety-four consecutive patients seeking treatment for eating disorders were evaluated for eating attitudes and behaviors, weight history, psychiatric symptoms, psychosocial stressors, social adaptation, family environment, and the presence of borderline personality organization. The patients were divided into borderline and nonborderline groups and were compared on the above dimensions, with 46% of the patients showing borderline personality features. The borderline patients and the nonborderline patients had relatively few differences in the severity of their symptomatic eating behaviors and attitudes. The borderline patients, however, were significantly more disturbed on a number of relevant dimensions, including general psychiatric symptoms, psychosocial adaptation, family environment, self-destructive behavior, and treatment history. The authors suggest, on the basis of their findings and the findings of previous studies, that about one third of eating-disordered patients have marked borderline characteristics. They recommend that research studies in the future control for the eating-disordered patients' character pathologies. They also recommend that clinicians use a combination of long-term relationship-oriented treatment and psychopharmacological treatment with eating-disordered patients who have borderline personality disorder.

Adolescent↗
PubMed1977

Detection of presymptomatic carriers of Huntington's chorea.

Laterality of thumb opposition and handedness were determined in three groups of subjects: patients with Huntington's chorea (n = 18), asymptomatic offspring of patients (n = 40), and asymptomatic siblings of patients over 50 years of age termed 'escapees' (n = 17). 100% of patients and 55% of young at-risk offspring had crossed laterality of thumb opposition and handedness. Only 2 (11.8%) of the 'escapees' had crossed laterality. Crossed laterality may be associated with symptomatic presymptomatic Huntington's chorea.

Adolescent↗