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Biomedical subjects

Stephen K Tyring

Publications and source records attributed to Stephen K Tyring.

At least 37 records · Page 2Linked to original sources
PubMed2005

Regulation of adrenal glucocorticoid synthesis by interleukin-10: a preponderance of IL-10 receptor in the adrenal zona fasciculata.

Several lines of evidence indicate that cytokines can affect adrenal function. To date most of these cytokines have been shown to be pro-inflammatory, such as interleukin (IL)-1, tumor necrosis factor (TNFalpha), and IL-6. However, we have previously shown that IL-10-/- (IL-10 knockout) mice have higher serum corticosterone levels than IL-10+/+ (wild type) mice following acute immune and physiologic stress, implying that IL-10, an anti-inflammatory cytokine, regulates glucocorticoid synthesis in a negative manner. Here, we show that IL-10 knockout mice produce more corticosterone under basal conditions as well (shown by ELISA). We further support this contention by showing that in Y-1 adrenocortical cells IL-10 inhibits steroid production (StAR) (measured by the production of the corticosterone precursor, progesterone), the expression of steroidogenic acute regulatory protein (semi-quantitative RT-PCR), as well as the activity of the proximal steroidogenic enzymes P450scc and/or 3beta-hydroxysteroid dehydrogenase (3beta-HSD) (measured by progesterone production in 22(R)-hydroxycholesterol-treated cells). Interestingly, all of the above-mentioned effects of IL-10 occur through its inhibition of ACTH effects, but not by IL-10 alone. Furthermore, immunocytochemistry data shows that the region of the adrenal gland responsible for the vast majority of corticosterone synthesis, the zona fasciculata, predominantly expresses the IL-10 receptor 1 (IL-10R1), with little expression in the zona glomerulosa and reticularis. These data demonstrate that IL-10 could play an important role in the regulation of glucocorticoid biosynthesis and in maintenance of homeostasis and immunity during periods of stress.

3-Hydroxysteroid Dehydrogenases↗
PubMed2005

A randomized controlled trial of a replication defective (gH deletion) herpes simplex virus vaccine for the treatment of recurrent genital herpes among immunocompetent subjects.

BACKGROUND: A replication incompetent herpes virus lacking the glycoprotein H gene has been developed as a potential therapeutic vaccine for genital herpes. GOAL: To determine vaccine efficacy on reducing HSV reactivation and clinical disease among immunocompetent persons with recurrent genital HSV-2 infection. STUDY DESIGN: Randomized multicenter placebo-controlled trial. Healthy volunteers who had six or more recurrences of genital herpes per year were randomized to receive injections of vaccine at 0 and 8 or 0, 4, and 8 or 0, 2, 4, and 8 weeks or placebo and were followed for subsequent recurrences for 1 year. RESULTS: The median times to first recurrence of genital herpes (40 days versus 30 days versus 37 days versus 42 days, respectively), mean number of recurrences (3 versus 3 versus 2.4 versus 1.9, respectively), and time to lesion healing of the first recurrence (8 days versus 7.8 days versus 7.4 days versus 7.5 days, respectively), were similar for all treatment groups. Asymptomatic viral shedding was detected by PCR in 61/74 (82%) persons performing daily sample collection following completion of the vaccination series. No differences were noted in the proportion of days with shedding between treatment groups (11.9% versus 17.2% versus 13.1% versus 16.4%, respectively). CONCLUSION: This replication incompetent HSV-2 vaccine lacking the glycoprotein H gene was safe but had no clinical or virologic benefit in the amelioration of genital HSV-2 disease among immunocompetent men and women.

Adolescent↗
PubMed2005

Expression of calpastatin, minopontin, NIPSNAP1, rabaptin-5 and neuronatin in the phenylketonuria (PKU) mouse brain: possible role on cognitive defect seen in PKU.

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. Phenylalanine hydroxylase (PAH) deficiency results in accumulation of phenylalanine (Phe) in the brain and leads to pathophysiological abnormalities including cognitive defect, if Phe diet is not restricted. Neuronatin and 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) reportedly have role in memory. Therefore, gene expression was examined in the brain of mouse model for PKU. Microarray expression analysis revealed reduced expression of calpastatin, NIPSNAP 1, rabaptin-5 and minopontin genes and overexpression of neuronatin gene in the PKU mouse brain. Altered expression of these genes was further confirmed by one-step real time RT-PCR analysis. Western blot analysis of the mouse brain showed reduced levels of calpastatin and rabaptin-5 and higher amount of neuronatin in PKU compared to the wild type. These observations in the PKU mouse brain suggest that altered expression of these genes resulting in abnormal proteome. These changes in the PKU mouse brain are likely to contribute cognitive impairment seen in the PKU mouse, if documented also in patients with PKU.

Animals↗
PubMed2005

Altered expression of myocilin in the brain of a mouse model for phenylketonuria (PKU).

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. Phenylalanine hydroxylase (PAH) mutations resulting reduced enzyme levels lead to accumulation of phenylalanine (Phe) in brain, if Phe diet is not restricted. Patients with PKU show neurophysiological abnormalities including demyelination and cognitive defect. How PAH defect causes events seen in PKU is not obvious. Therefore, expression analysis was performed in the brain of a mouse model for PKU. Microarray expression profile of the brain showed lower expression of myocilin (Myoc) in the PKU mouse. Reduced expression of Myoc was further confirmed by one-step real-time RT-PCR. Western blotting analysis of the brain using equal quantities of protein showed a thin band in PKU compared to a prominent band in the wild type brain. In addition, expression of genes associated with transcription was found to be altered in the PKU mouse brain as observed by microarray analysis. These data suggest that PAH defect alters other genes expression likely to contribute neurophysiological abnormalities seen in the mouse, if documented also in patients with PKU.

Animals↗
PubMed2005

Safety and immunogenicity of glycoprotein D-adjuvant genital herpes vaccine.

BACKGROUND: Two previous trials have suggested that a herpes simplex virus (HSV) type 2 glycoprotein D (gD) vaccine combined with the adjuvants alum and 3'-O-deacylated-monophosphoryl lipid A (MPL) is well tolerated and provides protection against genital herpes disease in women with no preexisting HSV antibody. METHODS: The safety and immunogenicity of this vaccine were evaluated in a large, multicenter, double-blind, randomized, placebo-controlled trial. The effects of sex and preexisting HSV immunity were sought. RESULTS: When solicited symptoms that continued after the initial 4 days of observation were excluded, the incidence of unsolicited symptoms occurring during the 7 months after vaccination (the primary analysis period) was 22.1% in vaccine recipients and 21.9% in placebo recipients. Significant increases in the number of local and systemic symptoms were found in vaccine recipients within 4 days after vaccination. However, most symptoms were mild to moderate in severity and were short lived. Women reported symptoms more frequently than did men, but preexisting immunity had little effect. The vaccine induced higher titers of HSV gD antibody on enzyme-linked immunosorbent assays than did natural infection with HSV. CONCLUSION: The vaccine was generally safe, well tolerated, and immunogenic.

Adjuvants, Immunologic↗
PubMed2005

Molecular diagnosis of cutaneous diseases.

OBJECTIVES: To provide an update on the molecular procedures used increasingly in the study and diagnosis of a variety of dermatologic malignancies and inflammatory disorders and to explore the potential use of these techniques in clinical dermatology. Herein, we review assays such as G-banding, fluorescence in situ hybridization, comparative genomic hybridization, and spectral karyotyping in conjunction with the polymerase chain reaction and DNA microarrays. DATA SOURCES: PubMed was searched for published articles on molecular diagnosis and dermatologic diseases. STUDY SELECTION: All English-language studies were selected if they provided useful methodologic information or highlighted the usefulness of molecular techniques. DATA EXTRACTION: Only methodologic and qualitative information was extracted. DATA SYNTHESIS: The information was synthesized into 2 sections: one describing the principles of different molecular diagnostic techniques, and the other highlighting the contributions of molecular diagnostic techniques to the understanding and diagnosis of several dermatologic diseases. CONCLUSIONS: A basic understanding of the principles of molecular diagnostic techniques is crucial for the practicing dermatologist to benefit from the increasing number of molecular diagnostic articles appearing in the literature and potentially to apply these methods in clinical practice.

Cytogenetic Analysis↗
PubMed2005

Human papillomavirus infection and P53 codon 72 genotypes in a Hispanic population at high-risk for cervical cancer.

Cervical cancer mortality is high in Texas, especially among Hispanic women living in south Texas and adjacent Mexico. Though human papillomavirus (HPV) infection has a causal role in the development of cervical cancer, there are no published data on the prevalence of HPV genotypes in this underscreened region. We studied 398 Hispanic women on both sides of the border along the lower Rio Grande River to determine the prevalence of HPV genotypes and risk factors for cervical cancer. Using a nested PCR system HPV was detected in 62% of cervical specimens, including all the known high-risk HPV genotypes, with HPV16 and HPV18 the most frequent (30.6% and 23.0%, respectively). Multiple infections were common (29.4% of the infected specimens), and where this occurred we were more likely to find high-risk HPV genotypes. We examined host p53 codon 72 genotype frequencies and found that patients with cervical abnormalities and women with HPV16 and HPV18 infections had a lower genotype frequency of the homozygous (AA) previously reported to be associated with cervical cancer, than uninfected women with no abnormalities. In this US/Mexico border population high rates of potentially oncogenic HPV viruses and multiple infections are consistent with observed elevated cervical cancer rates. These data are further evidence that in this underserved population HPV infections are associated with high rates of malignancy, but that host p53 genotypic variations are unlikely to be primary factors in oncogenesis.

Adolescent↗
PubMed2005

Rickettsial infections around the world, part 1: pathophysiology and the spotted fever group.

BACKGROUND: The rickettsial diseases are an important group of infectious agents that have dermatological manifestations. These diseases are important to consider in endemic areas, but in certain suspicious cases, possible acts of bioterrorism should warrant prompt notification of the appropriate authorities. OBJECTIVE: In this two part review article, we review these diverse diseases by examining established and up-to-date information about the pathophysiology, epidemiology, clinical manifestations, and treatment of the ricksettsiae. METHODS: Using PubMed to search for relevant articles, we browsed over 500 articles to compose a clinically based review article. RESULTS: Part one focuses on pathophysiology of the rickettsial diseases and the clinical aspects of the spotted fever group. CONCLUSIONS: At the completion of part one of this learning activity, participants should be able to discuss all of the clinical manifestations and treatments of the sported fever group. Participants should also be familiar with the pathophysiology of the rickettsial diseases.

Animals↗
PubMed2005

Cytokine regulation of tryptophan metabolism in the hypothalamic-pituitary-adrenal (HPA) axis: implications for protective and toxic consequences in neuroendocrine regulation.

AIM: Indoleamine 2,3-dioxygenase (IDO) catalyzation of tryptophan is the first rate-limiting step of the kynurenine pathway in the majority of tissues. The kynurenine pathway produces neurotoxic metabolites such as 3-hydroxykinurenine and quinolinic acid. IDO is inducible by the cytokine interferon-gamma (IFN-gamma) and has been proposed to mediate the sickness behavior of patients with infectious or other inflammatory diseases.To better understand the neuroendocrine component of cytokine induced sickness behavior we determined the effects of the pro-inflammatory cytokine IFN-gamma and the anti-inflammatory cytokine IL-10 on IDO expression in cells derived from the hypothalamic-pituitary-adrenal axis (HPA): GT1-7 hypothalamic, AtT-20 pituitary, and Y-1 adrenal cells. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to check the IDO expression from IFN-gamma and IL-10 treated cells such as GT1-7, AtT-20 and Y-1 cells. RESULTS: We found that IFN-gamma induces IDO expression after 4 h treatment in GT1-7 and AtT-20 cells. IL-10 was also able to suppress IFN-gamma induced IDO expression in these cells. In Y-1 adrenal cells, IFN-gamma treatment had no effect on IDO expression. CONCLUSIONS: Our results indicate that cytokines such as IFN-gamma and IL-10 are able to regulate IDO expression in cells of hypothalamic and pituitary origin. The ability of IL-10 to suppress IFN-gamma induced IDO expression implies that IL-10 has a putative neuroprotective role in the HPA axis. It can act at two levels, systemically by inhibiting sickness behavior-related Th1 cytokine synthesis and more centrally by inhibiting the kynurenine pathway.

Animals↗
PubMed2005

Incidence of infection during efalizumab therapy for psoriasis: analysis of the clinical trial experience.

BACKGROUND: Because many therapies for psoriasis disrupt the normal inflammatory cascade and could theoretically impair the body's ability to respond to external pathogens, a possible increase in the incidence of infection is a concern with any new psoriasis therapy that affects the immune system. Efalizumab is a biologic therapy targeted to inhibit T cells. Its efficacy has been shown in clinical trials encompassing >3500 patients with psoriasis. OBJECTIVES: The aims of this article were to review the incidence of infection observed in efalizumab-treated patients during 12-week, Phase III clinical trials, compare the incidence rate with that in patients receiving placebo, and evaluate the incidence of infection observed in patients with extended (>12-week) efalizumab use. METHODS: Adverse events (AEs) of infection were tabulated from a pooled data set of 2335 patients enrolled to receive 12 weeks of subcutaneous (SC) efalizumab 1 or 2 mg/kg . wk or placebo in 4 randomized, double-blind, placebo-controlled, Phase III efalizumab clinical studies. The incidence of infection was further evaluated using pooled data from 1115 patients who received up to 24 weeks of efalizumab therapy during 5 clinical trials with treatment extension arms and from 170 patients who received up to 108 weeks (27 months) of continuous therapy in an open-label, Phase III efalizumab trial of 36 months' total duration. RESULTS: The incidence and severity of AEs of infection during 12 weeks of efalizumab therapy were comparable to those observed in patients receiving placebo (overall, 28.6% vs 26.3%). Infections did not appear to increase with extended therapy of up to 27 months. Serious infections requiring hospitalization occurred in 1.1% of efalizumab-treated patients. CONCLUSION: The present review of the available Phase III clinical trial suggests that efalizumab is not associated with an increased risk for infection in patients receiving initial or long-term (27-month) treatment for moderate to severe chronic plaque psoriasis.

Adolescent↗
PubMed2005

Advances in antiviral therapy.

Infections with five of the herpesviruses (herpes simplex virus 1 [HSV-1], HSV-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus) are treated with topical or systemic antiviral therapies. There are more than 100 genotypes of human papillomaviruses (HPVs), which may manifest as warts, skin cancers, cervical cancer, anogenital cancers, and upper digestive tract cancers. Molluscum contagiosum (MC) is a common, benign viral infection of the skin. Immunomodulating agents, such as imiquimod, act on HPV and MC indirectly by inducing host immune responses, such as cytokines and cell-mediated immunity, and thereby reduce recurrences. There are multiple vaccines available for certain viral diseases and others in development for HSV-2 and HPV.

Antiviral Agents↗
PubMed2005

Molecular diagnosis of infectious diseases in dermatology.

UNLABELLED: The molecular diagnosis of infectious disease has been growing considerably over the past decade. Nucleic acid amplification techniques, such as polymerase chain reaction, ligase chain reaction, transcription-mediated amplification, and nucleic acid sequence-based amplification, provide highly accurate diagnosis of numerous bacterial, viral, fungal, and parasitic infections involved in a variety of dermatologic diseases. In addition, signal amplification with hybrid capture, branched-DNA assays, and in situ hybridization have been used to detect numerous viral pathogens with high degrees of sensitivity and specificity. New technology that involves the use of DNA and protein microarrays has also enabled the detection of a variety of genes and gene mutations. With time, these diagnostic assays are decreasing in cost, gaining approval of the U.S. Food and Drug Administration, and becoming easier and more efficient to use. In the future, these assays will be able to deliver rapid and accurate diagnosis of infectious diseases within a single clinic visit. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be familiar with molecular diagnosis of infectious diseases in dermatology.

Bacteria↗
PubMed2005

Tropical dermatology: fungal tropical diseases.

UNLABELLED: Fungal infections are common in tropical countries and can have an important impact on public health. Lobomycosis is a common fungal infection in the tropical rain forest of South America, and paracoccidioidomycosis (South American blastomycosis) is a widespread and sometimes severe illness. Penicilliosis marneffei is an opportunistic infection of AIDS patients in southeast Asia. Chromoblastomycosis and mycetomas are causes of morbidity around the world. Sporotrichosis is a worldwide subcutaneous mycosis with a high incidence in tropical countries and is an important illness in immunocompromised patients. Rhinosporidiosis was classed as a fungal infection but is now considered a protistan parasite that belongs to the class Mesomycetozoea. It is included in this review because of its historical classification. In the past, most of these mycoses were restricted to specific geographic areas and natural reservoirs. There are, however, situations in which people from other regions come in contact with the pathogen. A common situation involves an accidental contamination of a traveler or worker who has contact with a tropical mycosis. Even minor trauma to the skin surface or inhalation of the fungal conidia can infect the patient. Thus recognition of the clinical symptoms and the dermatologic findings of the diseases, as well as the geographic distribution of the pathogens, can be critical in diagnosis of the tropical mycoses. This review discusses some of the more common tropical subcutaneous and systemic mycoses, as well as their signs, symptoms, methods of diagnosis, and therapies. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be able to recognize the clinical and histologic presentations of tropical fungal diseases with cutaneous manifestations and be familiar with the appropriate therapies.

Animals↗
PubMed2005

Aspartoacylase gene knockout results in severe vacuolation in the white matter and gray matter of the spinal cord in the mouse.

Canavan disease (CD) is a neurodegenerative disorder characterized by the spongy degeneration of the white matter of the brain. Aspartoacylase (ASPA) gene mutation resulting enzyme deficiency is the basic cause of CD. Whether the ASPA defect in CD affects the spinal cord has been investigated using the ASPA gene knockout mouse. Luxol fast blue-hematoxylin and eosin staining in the spinal cord of the knockout mouse showed vacuolation in both white matter and gray matter areas of cervical, thoracic, lumbar, and sacral segments of the spinal cord. However, more vacuoles were seen in the gray matter than the white matter of the spinal cord. ASPA activity in the cervical, thoracic, lumbar, and sacrococcygeal regions of the spinal cord was significantly lower in the knockout mouse compared to the wild type. The enzyme defect in the knockout mouse was also confirmed using the Western blot method. These observations suggest that the ASPA gene defect in the mouse leads to spinal cord pathology, and that these changes may be partly involved in the cause of the physiological/behavioral abnormalities seen in the knockout mouse, if documented also in patients with CD.

Amidohydrolases↗
PubMed2005

HLA-DQB1 and cervical cancer in Venezuelan women.

BACKGROUND: Cervical cancer represents a major health problem in Venezuela as well as in other Latin American countries. High-risk human papillomavirus (HR-HPV) infection is known as the major risk factor of cervical cancer. However, whether or not a HR-HPV-infected woman progresses to cervical cancer may depend on the immune system effectors induced by viral antigens presented by her specific human leukocyte antigens (HLA) alleles. The role of the HLA system in presenting peptides to antigen-specific T-cells may be critical for genetic susceptibility and genetic resistance to cervical carcinoma. OBJECTIVE: We aimed to investigate the relationship between HLA-DQB1, HPV infection, and cervical cancer in Venezuelan women. METHODS: Blood samples and cervical swabs were obtained from 36 patients and 79 healthy controls; additional cervical biopsies were obtained from all the patients. HPV DNA was detected by PCR and HLA-DQB1 genotyping was performed using a PCR-SSP protocol. RESULTS.: A positive association with cervical cancer was observed for HLA-DQB1*0201-0202 and *0402 alleles, however after Bonferroni correction only HLA-DQB1*0402 remained statistically significant (P value = 0.004, RR = 5.067). CONCLUSION: This is the first report of HLA-DQB1 alleles associated with cervical carcinoma in Venezuelan women. Larger studies are needed to assess whether these HLA-DQB1*0201-0202 and *0402 alleles have a direct effect on disease susceptibility.

Adult↗
PubMed2005

Demographic, behavioral, and knowledge factors associated with herpes simplex virus type 2 infection among men whose current female partner has genital herpes.

OBJECTIVE/GOAL: The objective of this study was to evaluate risk factors for herpes simplex virus type 2 (HSV-2) infection among men whose female partners have genital herpes (GH). STUDY: Between 1998 and 2001, 717 men in heterosexual monogamous relationships, without a history of GH, completed a cross-sectional questionnaire on demographic, behavioral, and knowledge factors for GH. Their female partners were symptomatic and HSV-2-seropositive. Risk factors for HSV-2 seropositivity were assessed using logistic regression. RESULTS: On laboratory confirmation, 25% of the men were HSV-2-seropositive. Factors significantly (P<0.01) associated with HSV-2 infection included: never using condoms (adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.15-2.95), prior sexually transmitted disease (STD) (aOR, 1.80; CI, 1.27-2.58), vaginal intercourse during symptomatic episodes (aOR, 1.77; CI, 1.19-2.62), longer partnership (for each additional year aOR, 1.07; CI, 1.03-1.09), and lower knowledge of GH (aOR, 1.14; CI, 1.05-1.23). CONCLUSION: Potentially modifiable risk factors for HSV-2 infection included engaging in vaginal sex during symptomatic episodes, never using condoms, and lower knowledge of GH.

Adult↗
PubMed2005

Clinical, histopathological and virological findings in patients with focal epithelial hyperplasia from Colombia.

BACKGROUND: Focal epithelial hyperplasia (FEH) is a rare oral HPV-related disease, highly prevalent in certain ethnic communities. A previous study found 7.5% prevalence among school children from the Indian community Embera-Chami in Colombia. OBJECTIVE: To determine the prevalence and Human Papillomavirus (HPVs)-type in children with FEH. MATERIALS AND METHODS: One hundred and thirty-eight students were screened. All FEH samples were HPV-tested by two PCR-based systems. RESULTS: We identified 18 FEH cases. beta-globin amplification was obtained in 15 cases and nine were HPV-55-positive by the HPV-PCR-hybridization method. Nine cases (50%) were HPV-13-positive by the GP5+/GP6+-based method. Twelve cases (80%) were HPV-positive by one or the other method. Forty-four percent and 88% of interviewed parents reported family histories of FEH and toothbrush sharing, respectively. CONCLUSIONS: Human Papillomavirus-DNA was identified in the majority of FEH cases and HPV-13 was the only genotype involved. Frequent familiar infection suggests interfamiliar transmission, genetic predisposition or infection susceptibility among family members.

Adolescent↗