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Biomedical subjects

S K Tyring

Publications and source records attributed to S K Tyring.

At least 109 records · Page 6Linked to original sources
PubMed1997

Effects of eosinophil granule proteins on human corneal epithelial cell viability and morphology.

PURPOSE: There is mounting evidence that eosinophil granule proteins may cause tissue injury during allergic inflammation of the eye. Therefore, the authors investigated the in vitro effects of human eosinophil major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN) on cultured human corneal epithelial cell viability and morphology. METHODS: Confluent primary human corneal epithelial cell cultures were exposed to each of the four human eosinophil cationic granule proteins at concentrations ranging from 0 to 100 micrograms/ml (0, 12.5, 25, 50, and 100 micrograms/ml) for up to 48 hours in serum-free media. Morphologic changes were assessed by light microscopy at 1, 6, 24, and 48 hours; cell viability was measured using the MTT cell viability assay at 24 hours. RESULTS: Cells treated with MBP and ECP induced a dose-dependent gradual increase in morphologic changes; in contrast, EPO and EDN induced minimal changes in cell morphology. At 24 hours, both MBP and ECP induced statistically significant (P < 0.05) decreases in cell viability at a concentration of 100 micrograms/ml; EPO induced a significant (P < 0.05) decrease in cell viability at all concentrations tested, and EDN showed no significant reduction of cell viability at any of the concentrations tested. CONCLUSIONS: The current study suggests that the human eosinophil granule proteins MBP and ECP affect human corneal epithelial cell viability and morphology in vitro, whereas the protein EPO affects cell viability only. EDN had no significant effect on cell viability or morphology. Hence, MBP, ECP, and EPO perturb the corneal epithelium differentially and may contribute to keratopathy associated with severe ocular allergy.

Blood Proteins↗
PubMed1997

Successful treatment of a generalized human papillomavirus infection with granulocyte-macrophage colony-stimulating factor and interferon gamma immunotherapy in a patient with a primary immunodeficiency and cyclic neutropenia.

BACKGROUND: We describe a patient with generalized verrucosis secondary to human papillomavirus (HPV) type 2 infection and a primary immunodeficiency and cyclic neutropenia. Treatment, which was well tolerated, included granulocyte-macrophage colony-stimulating factor and interferon gamma (IFN-gamma). In vitro assays to assess responses of T lymphocytes to mitogens (ie, proliferation assay and IFN-gamma enzyme-linked immunosorbent assay) were performed. In situ hybridization and polymerase chain reaction were used to detect HPV DNA in skin biopsy specimens. OBSERVATIONS: The T lymphocytes of the patient showed a significant (P < .05, unpaired Student t test) defect in IFN-gamma production (the basis for initiating IFN-gamma therapy). The response to immunotherapy was confirmed by using molecular methods. Six months after the completion of immunotherapy, HPV DNA was undetectable in skin samples from clinically regressed warts (according to the results of in situ hybridization and polymerase chain reaction). CONCLUSIONS: Our patient had treatment-resistant generalized verrucosis for 13 years. Treatment with granulocyte-macrophage colony-stimulating factor and IFN-gamma may have reconstituted an immune response against HPV, resulting in the dramatic regression of her widespread warts.

Adolescent↗
PubMed1997

Cutaneous squamous cell carcinoma in human immunodeficiency virus-infected patients. A study of epidemiologic risk factors, human papillomavirus, and p53 expression.

OBJECTIVE: To examine risk factors for the development of cutaneous squamous cell carcinoma (SCC) in a group of human immunodeficiency virus (HIV)-infected patients, including evaluation and detection of epidemiologic risk factors of human papillomavirus (HPV) and p53 expression. DESIGN: Case-control study during a 3-year period. SETTING: Dermatologic referral center. PATIENTS: Thirty-three HIV-infected patients who had 97 SCCs were compared with 24 HIV-infected patients who had 70 basal cell carcinomas (BCCs). MAIN OUTCOME MEASURES: Age, skin type, amount of sun exposure, actinic damage, family history of skin cancer and history of smoking and warts. Specimens of SCC and BCC were examined for HPV using polymerase chain reaction. Presence of p53 was examined using immunohistochemical analysis. Specimens from tumor-free, non-sun-exposed areas from these same patients were used as controls. RESULTS: Risk factors for the development of both types of carcinoma included fair skin type and excessive sun exposure (> 6 h/d during the previous 10 years). The HIV-infected patients with SCCs tended to have outdoor occupations. The location of SCCs favored the head and neck; BCCs were located on the trunk. Patients with SCCs had later-stage HIV disease than did patients with BCCs. Half of the patients with SCC had a history of genital or nongenital warts. Seventy-one percent (17/24) had a smoking history. No statistical difference existed between patients with SCCs and BCCs for history of smoking or warts. Human papillomavirus was not found in most of our SCC, BCC, or control specimens. However, 92% (22/24) of the SCC specimens and 90% (18/20) of the BCC specimens stained for p53. Control specimens from non-sun-exposed skin of HIV-infected patients did not stain for p53. Epidermal staining was present in 95% (17/20) of tissue adjacent to SCCs and 47% (7/15) of tissue adjacent to BCCs. A significantly positive correlation existed between the amount of sun exposure and the amount of p53 staining seen in adjacent epidermal tissue (r = 0.07; P = .01). CONCLUSIONS: Risk factors for the development of SCCs and BCCs in HIV-infected patients are similar: fair skin type and excessive sun exposure. Our study does not support that HPV is an oncogenic factor in the development of these cutaneous tumors but provides evidence that p53 overexpression may play a role.

Adult↗
PubMed1997

The impact of the human immunodeficiency virus on the human papillomavirus epidemic.

OBJECTIVE: To examine how human immunodeficiency virus (HIV) infections affect human papillomavirus (HPV) infections. DATA SOURCE: MEDLINE was searched for relevant publications. STUDY SELECTION: All studies dealing with both HIV and HPV infections were reviewed. DATA EXTRACTION: Publications with clinically relevant data were included in the present analysis. DATA SYNTHESIS: A critical analysis of the data described in these articles was performed without formal statistical calculations. CONCLUSIONS: Results revealed that immunocompromised individuals have an increase prevalence of HPV-associated lesions and neoplasia. Immunosuppressed patients (eg, those who have undergone transplantation or those who have been treated with chemotherapy and/or radiation therapy) have a higher rate of HPV infections. Human papillomavirus and HIV appear to be important cofactors for developing cervical and anal dysplasia and carcinoma. Individuals who are seropositive for HIV have an increased prevalence of HPV infections, a more rapid progression of the disease, and a higher number of invasive carcinomas. The presence of HPV DNA, extent of disease, and potential for malignant transformation also appear to correlate with the degree of immunosuppression. Individuals with a CD4 cell count under 0.20 x 10(9)/L (< 200/microliters) are at greatest risk. Treatment options for immunocompromised individuals remain similar to those for normal hosts; however, immunocompromised individuals have a much higher rate of recurrence. Improved immunostimulant and/or antiviral therapy is needed for HIV-seropositive individuals with widespread genital involvement. Control of both the HPV and the HIV epidemics involves at least 3 levels of intervention: better antiviral drugs, frequent monitoring for disease progression in infected persons, and better education to reduce spread of the disease.

Forecasting↗
PubMed1997

Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus-infected patients treated with cidofovir.

BACKGROUND: Molluscum contagiosum virus (MCV) causes cutaneous skin growths that mainly affect children, sexually active adults, and immunocompromised individuals. Lesions of MCV in patients infected with human immunodeficiency virus can be large and numerous, and response to available treatments is often unsatisfactory. OBSERVATIONS: We describe 3 men infected with human immunodeficiency virus who presented with extensive MCV lesions that were not responsive to various treatments. Patient 1 demonstrated dramatic clearing of his MCV lesions when intravenous cidofovir therapy was started for his treatment-resistant bilateral CMV retinitis and because of cidofovir's possible activity against MCV. In case 2, cidofovir was compounded as a 3% cream in a combination vehicle (Dermovan) for extensive facial involvement, and complete resolution of MCV was seen after 1 month of therapy. In case 3, intravenous cidofovir therapy was started both for CMV retinitis and in an attempt to clear 90% facial MCV involvement; after 1 month of treatment, all clinical evidence of MCV had resolved. All 3 patients remain clear of recurrence. CONCLUSIONS: Cidofovir, a nucleotide analog of deoxycytidine monophosphate, appears to have contributed to clearing of advanced MCV lesions in these 3 patients, thus providing suggestive evidence of clinical activity against MCV. Controlled trials of cidofovir therapy for MCV in persons infected with human immunodeficiency virus are warranted.

Adult↗
PubMed1997

Human herpesvirus 8 DNA sequences in blistering skin from patients with pemphigus.

BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in Kaposi sarcoma (KS) and other lesions in patients both seropositive and seronegative for the human immunodeficiency virus (HIV). Kaposi sarcoma has been reported to develop in a disproportionate number of patients with pemphigus. Since HHV-8 is so strongly associated with KS, we wondered whether HHV-8 is present in pemphigus lesions from patients without KS or HIV infection. Pemphigus lesions and skin from healthy individuals were coded in a blinded fashion. Tissue-extracted DNA was tested using polymerase chain reaction, Southern blot hybridization, and automated sequencing of the polymerase chain reaction products for the presence of HHV-8 DNA. Six patients had pemphigus foliaceus, 6 had pemphigus vulgaris, and 2 had KS; 10 healthy individuals were used as controls. All 24 patients were HIV seronegative. OBSERVATION: Lesional skin from 4 of the 6 patients with pemphigus vulgaris, all 6 of the patients with pemphigus foliaceus, and both positive controls (KS) tested positive for HHV-8 DNA. Furthermore, the HHV-8 DNA sequences for KS330(233) differed between all 6 DNA specimens from pemphigus foliaceus, while 3 of the 4 DNA specimens from pemphigus vulgaris were identical. However, HHV-8 DNA was absent in all normal human skin analyzed. CONCLUSIONS: This report expands the spectrum of lesions found to contain HHV-8 DNA sequences and suggests that HHV-8 might have trophism for pemphigus lesions.

Adult↗
PubMed1996

Induction of iNOS mRNA by interferon-gamma in epithelial cells is associated with growth arrest and differentiation.

Induction of inducible nitric oxide synthase (iNOS) mRNA by interferon-gamma (IFNgamma) is well established in various cell types. We observed earlier that this induction is differentiation-dependent in human keratinocytes. Since IFNgamma-mediated growth arrest and differentiation are separable but interrelated processes in keratinocytes, iNOS might play a role in their regulation. We conducted a series of in vitro experiments on normal and transformed epithelial cells with different tissue origins. We found that immortalization and transformation can influence the IFNgamma-mediated iNOS inducibility, but this process is tissue-specific as the induction correlates with the ability of the cells to differentiate.

Antineoplastic Agents↗
PubMed1996

Induction of blister-causing antibodies by a recombinant full-length, but not the extracellular, domain of the pemphigus vulgaris antigen (desmoglein 3).

Pemphigus vulgaris (PV) is mediated by autoantibodies to desmoglein 3, the pemphigus vulgaris antigen (PVA). PVA and an extracellular domain of PVA-Ig fusion protein (PV-Ig) can completely adsorb the blister-causing Abs from PV patient sera, suggesting that the extracellular segment of PVA might be sufficient to induce pathogenic Abs. To test this, we immunized rabbits with either PVA or its extracellular domain (EPVA) expressed in insect cells in our laboratory. When Igs were passively transferred from these rabbits into neonatal mice, anti-PVA, but not the anti-EPVA, induced blisters. To understand the basis for their differential pathogenic effects, we examined the properties of these sera. Both sera showed comparable ELISA titers and indirect immunofluorescence reactivity against monkey esophagus, a source of native PVA. Moreover, EPVA, like PVA adsorbed blister-causing Abs from sera of PV patients and rabbits immunized with PVA. In contrast, when IgG preparations were incubated with fura-2-AM (acetyloxymethyl ester)-loaded human keratinocytes in culture, only IgG from anti-PVA serum induced intracellular calcium mobilization. These data showed that PVA but not EPVA can elicit Abs that induced blisters in neonatal mice and mediate intracellular signaling through calcium mobilization.

Amino Acid Sequence↗
PubMed1996

Early treatment of herpes zoster.

Although varicella virus vaccine may eventually decrease the incidence of herpes zoster, the disease will continue to plague patients and physicians for at least the next several decades. Recognition of shingles early in its vesicular stage is important, since that is when antiviral treatment is effective. Moreover, a variety of agents are now available for symptomatic relief of postherpetic neuralgia.

Aged↗
PubMed1996

Regulation of inducible nitric oxide synthase mRNA levels by differentiation and cytokines in human keratinocytes.

Inducible nitric oxide synthase (iNOS) transcription is regulated by cytokines and immune stimuli in various cell types. However, there are few data available on iNOS expression and regulation in keratinocytes, even though it can play a role in keratinocyte proliferation during inflammation following wound healing. Our studies demonstrated a differentiation-dependent regulation of iNOS transcription in human keratinocytes from epidermis but not in buccal mucosal cells, which are less differentiated. Different interferon (IFN) types (alpha and gamma) regulated skin keratinocyte iNOS mRNA levels in different ways, predominantly in a differentiation-dependent manner. TGFbeta1 and IFNalpha can antagonize IFNgamma related iNOS induction. However, the antagonistic effects of IFNalpha on IFNgamma differ from those of TGFbeta1. Our studies demonstrate: (a) the presence of iNOS mRNA in human keratinocytes; (b) inducibility of iNOS mRNA by different cytokines; and (c) antagonism between certain cytokines in induction of iNOS mRNA. Further studies are needed to determine biological and therapeutical relevance of our findings.

Cell Differentiation↗
PubMed1996

Famciclovir: review of clinical efficacy and safety.

Famciclovir is the well-absorbed oral form of penciclovir, an antiviral agent with potent activity against varicella-zoster virus (VZV) and herpes simplex virus (HSV-1) and 2 (HSV-2). After oral administration, famciclovir is rapidly converted to penciclovir with a bioavailability of 77%. penciclovir is efficiently phosphorylated to the active metabolite, penciclovir-triphosphate, and has a prolonged intracellular half-life of approximately 9-10 h in VZV-infected cells, and 10 and 20 h in cells infected with HSV-1 and HSV-2, respectively. Two multicenter clinical trials have shown that famciclovir given during the acute zoster phase accelerated healing of cutaneous lesions. More importantly, in a placebo-controlled study, famciclovir reduced the duration of postherpetic neuralgia (PHN), particularly in elderly patients. Famciclovir has also been proven effective in treating recurrent genital herpes, as demonstrated by a reduction in times to cessation of viral shedding, complete healing, and loss of all symptoms. One study showed that suppressive therapy with famciclovir was effective in reducing genital herpes episodes in patients with frequent recurrences. A promising new area of investigation for famciclovir is controlling virus replication in patients with chronic hepatitis B virus (HBV) or HBV reinfections after liver transplant. Results from a double-blind, placebo-controlled, pilot study and several case reports have shown that famciclovir, alone or in combination with other agents, decreased HBV-DNA levels and was tolerated with long-term treatment. Available clinical data indicate that famciclovir is an effective agent for treating herpes and holds significant promise for the treatment of chronic HBV infection HBV reinfection after liver transplantation.

2-Aminopurine↗
PubMed1996

Response to interferon treatment decreases with epidermal dedifferentiation in condylomas.

After interferon (IFN) treatment of patients with condyloma acuminatum, groups clinically proven to be responders or nonresponders were selected, and cellular parameters that might influence the clinical response were studied in pretreatment biopsies by reverse transcription polymerase chain reaction (RT-PCR). The nonresponders were found to express higher amounts of cellular proliferative markers, such as proliferating cell nuclear antigen (PCNA), cyclin A, and cdc 2 kinase, but lower levels of growth suppressor genes (TGF-beta 1, TGF-beta 2 and p53) before IFN treatment. The responders retained the epidermal keratinization, except for some signs of hyperproliferation (K6, K16 cytokeratins). In addition, the nonresponders showed a shift in the keratinization pattern to a mucosal or fetal type, as evidenced by high expression of the K18, K6, K16 and K13 cytokeratins but decreased K5, K14 and K10 levels before treatment. The expression of the human papillomavirus (HPV) genes is consistent with these differentiation patterns. The crucial conclusion to be drawn from this study is that those condylomas whose pretreatment phenotype most closely resembles that of normal epidermis respond to IFN treatment, whereas those more akin to nonkeratinizing epithelia fail to respond, i.e. the resistance of condylomas to IFN treatment is correlated with dedifferentiation.

Base Sequence↗
PubMed1996

Immortalization of differentiated human keratinocytes by human papillomavirus (HPV) 16 DNA.

Human papillomavirus (HPV) 16 is strongly implicated as having an etiologic role in cervical carcinoma. Human basal keratinocytes have been used in most HPV transformation studies, and transformed cells have exhibited undifferentiated characteristics. However, tumor cells in cervical squamous cell carcinoma are differentiated to certain degrees. Therefore, we hypothesize that HPV may transform not only basal cells but also differentiated keratinocytes. Human keratinocytes isolated from neonatal foreskin were induced to differentiate by treatment with 2 mM Ca2+ for various times (24, 48, 72 and 96 h) and were transfected with HPV 16 DNA. After G418 selection and repeated subculture, HPV 16-transformed cells were derived from each group of the Ca(2+)-treated and untreated cells. HPV DNA was detected in the transformed cells by polymerase chain reaction (PCR). Southern analysis and two-dimensional gel results indicated that HPV 16 DNA had been integrated into the chromosomes. The HPV 16-transformed cells exhibited an indefinite lifespan and were not tumorigenic in nude mice. They also showed the morphology and expressed the markers of differentiated keratinocytes. This study showed that differentiated human keratinocytes could be immortalized by HPV 16, and this may be a better model for cervical carcinomas in humans.

Animals↗
PubMed1996

Activation of local cell-mediated immunity in interferon-responsive patients with human papillomavirus-associated lesions.

Successful immune response to viral infection, such as human papillomavirus (HPV) infection, involves presentation of viral antigens to the immune system, recruitment of T cells and macrophages, and activation of a diverse array of cytokines. Interferons (IFN) are known to exert immunomodulatory functions via activating these pathways. However, the presence of HPV can interact with this process. We employed a reverse transcription-polymerase chain reaction (RT-PCR)-based method to study this phenomenon in biopsies of patients responding well or poorly to IFN treatment. We found that responders show a delayed-type hypersensitivity (DTH) reaction after IFN treatment, in which TH1 cells (interleukin-2, IL-2, IFN-gamma) and macrophages/NK cells (CD16) predominate. Antigen presentation capability (e.g., upregulation of MHC molecules, cytokines) is also enhanced after IFN treatment in responders. The lack of upregulation of MHC molecules (HLA-DR, beta 2-microglobulin) and certain cytokines (IL-1 alpha, IL-2, IFN-gamma) in nonresponders may be due to the overexpression of HPV early (E7) gene in contrast to responders, where HPV late (L1) gene expression predominates. We concluded that differential HPV expression in infected cells can be responsible for an inappropriate IFN-mediated immune response.

Antibody Formation↗
PubMed1996

Recombinant desmoglein 3 has the necessary epitopes to adsorb and induce blister-causing antibodies.

The development of an animal model for studying the pathogenesis of pemphigus vulgaris (PV) has been hampered by the unavailability of the purified full-length autoantigen desmoglein 3 (Dsg 3).Therefore, we expressed Dsg 3 using a baculovirus expressed system. The expressed protein was identified as Dgs 3 by its reactivity with a pan-cadherin anti-serum, an anti-serum to a Dsg 3 synthetic peptide, or patient serum, and by amino-terminal sequencing. Carbohydrate analysis showed that recombinant Dsg 3 was glycosylated. While a majority of the recombinant protein was cell associated, by immunoprecipitation, some Dsg 3 was demonstrated in the medium. The Dgs 3 could adsorb out blister-causing antibodies from patient sera. Rabbit anti- Dsg 3 antibodies induced by the recombinant Dsg 3 showed specific binding to intercellular spaces of monkeys esophagus by indirect immunofluorescence. Moreover, these antibodies induced PV-like blisters in neonatal mice and weakly bound perilesional epidermis. Availability of large quantities of relatively pure Dsg 3 should now facilitate studies aimed at understanding Dsg 3 structure and pathogenesis of PV, with implications for developing specific immunotherapies.

Animals↗
PubMed1996

Human immunodeficiency virus envelope glycoprotein 120 alters sleep and induces cytokine mRNA expression in rats [published errata appear in Am J Physiol 1996 Aug;271(2 Pt 2):section R following table of contents and 1996 Dec;271(6 Pt 3):section R following table of contents].

Sleep is altered during the course of viral infection, including that in which the human immunodeficiency virus (HIV) is the etiologic agent. Alterations in the sleep of HIV-infected individuals occur early in the course of infection, prior to the onset of AIDS. The mechanisms for such alterations in sleep are not known. The HIV envelope glycoprotein 120 (gp120) induces the synthesis and secretion of cytokines that enhance [e.g., interleukin (IL)-1 and tumor necrosis factor] and suppress (e.g., IL-10 and IL-1 receptor antagonist) sleep. We used a well-defined rat model to test the hypothesis that the HIV gp120 alters sleep. Recombinant HIV-1IIIB gp120 was injected intracerebroventricularly (20- 500 ng) into rats prior to dark onset. Sleep-wake behavior was not altered after the 20-ng dose, whereas both non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) were initially enhanced and subsequently suppressed after the 100-ng dose. NREMS was enhanced for 8 h after the 500-ng dose; REMS was not affected by this dose. Brain temperature was not altered by any of the gp120 doses used in this study. In addition, mRNA expression for IL-1 beta and IL-10 was induced in the hypothalamus by gp120; this brain region is crucial for the regulation of sleep. These new data support the hypothesis that altered cytokine concentrations within the central nervous system play a pivotal role in the complex alterations in sleep observed during HIV infection.

Animals↗