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Biomedical subjects

S K Tyring

Publications and source records attributed to S K Tyring.

At least 145 records · Page 8Linked to original sources
PubMed1995

Skin-associated lymphoid tissue in human immunodeficiency virus-1, human papillomavirus, and herpes simplex virus infections.

The skin-associated lymphoid tissue is composed of keratinocytes, Langerhans cells, skin trophic T cells, and lymphatic endothelial cells of the skin. The epidermis, which is involved in many viral infections, contains all of the components needed for an effective immune response: antigen-presenting Langerhans cells, T cells, and cytokines from leukocytes and keratinocytes. There have been some recent advances in the study of the cutaneous immunology involved in infections with the human immunodeficiency virus (HIV), human papillomavirus (HPV), and herpes simplex virus (HSV). In general, viral diseases with cutaneous manifestations lead to a decline in epidermal Langerhans cell numbers, which probably reflects Langerhans cell emigration out of the epidermis and entry into regional lymph nodes, leading to Langerhans cell activation and antigen presentation to T cells. In HSV, there is a subsequent T-cell infiltration of the epidermis, composed of CD4+ cells that have both immune modulatory action and direct cytotoxic action. In HIV, where there is a systemic depletion of CD4+ cells, the epidermis is left with reduced numbers of T cells. Intradermal injection of interleukin-2, however, leads to an epidermal cellular infiltration in HIV+ individuals. In HPV-induced condyloma, intralesional interferon increases Langerhans cells and CD4+ and CD8+ cells in the skin, as well as transforming growth factor beta 1, tumor necrosis factor-alpha, pRB, and p53. Therefore, viral infections involving the epidermal immune system have certain similar characteristics, whereas other factors are unique to the infecting virus.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Antiviral agents in dermatology: current status and future prospects.

The majority of current antiviral agents have become available only during the past decade. The above mentioned antiviral drugs, especially the viral-TK-specific agents have attempted to bring antiviral therapy on par with antimicrobial therapy. The fact, that cells infected with viruses can be selected against the relatively low toxicity to the patient, highlights the present state of antiviral therapy. Since viral infection can be viewed as an integral component of the self (i.e., a condition that cannot simply be surgically eliminated), the science of medicine is turning to the components of the self to overcome such conditions. By administering immune-system-derived agents (e.g., interferons) or compounds that stimulate the immune system (e.g., adjuvants like imiquimod), previously unmanageable conditions become manageable. The future of antiviral therapy will undoubtedly be at the molecular level. With greater understanding of the virus and the immune system with which it interacts, more specific and efficacious antiviral agents will be added to the arsenal of the clinician.

Antiviral Agents↗
PubMed1995

Cutaneous manifestations of HIV-1 infection.

Infection with the human immunodeficiency virus (HIV) leads to a chronic disarmament of the immune system. The process is progressive, having different manifestations as the status of the immune system slowly deteriorates. Some of the most common manifestations of HIV infection are cutaneous in origin, and they can have infectious, neoplastic, or noninfectious or non-neoplastic etiologies. A brief history of HIV is given, and the most common cutaneous presentations of the virus infection of interest to podiatrists are outlined.

HIV Infections↗
PubMed1995

Development of human papillomavirus type 16 associated squamous cell carcinoma of the scrotum in a patient with Darier's disease treated with systemic isotretinoin.

In contrast to squamous cell carcinoma of the penis, scrotal carcinoma has historically been associated with exposure to environmental or industrial carcinogens and has only rarely been correlated with human papillomavirus. We report on a patient with squamous cell carcinoma of the scrotum in which human papillomavirus type 16 was integrated into the tumor cell genome, suggesting a causal role of human papillomavirus in the development of squamous cell carcinoma of the scrotum. Other unique features of our case include the presence of Darier's disease, an uncommon genodermatosis, and treatment with oral retinoids, which have prophylactic value in the prevention of cutaneous malignancies.

Amino Acid Sequence↗
PubMed1994

Occurrence of human papillomavirus and p53 gene mutations in Kaposi's sarcoma.

Epidemiological evidence indicates that a sexually transmitted agent might be involved in the etiopathogenesis of Kaposi's sarcoma (KS). The prevalence of human papillomaviruses (HPV) in KS has been the focus of several investigations that have reported conflicting data. In addition, mutations of the p53 gene, which are the most frequent genetic changes found in human tumors, are absent in HPV-positive cervical carcinomas leading to the hypothesis that the function of p53 in HPV-positive tumors is inactivated through binding to the E6 viral gene product. Thus, the present study was designed to investigate the presence of HPV and p53 gene mutations in 17 formalin-fixed, paraffin-embedded KS [7 acquired immunodeficiency syndrome-KS (AIDS-KS) and 10 classic KS] specimens. HPV 6 DNA was detected in an AIDS-KS specimen, and HPV 16 DNA was found in 3 classic KS specimens. Heterozygous mutations of the p53 gene were detected in five (24%) KS samples. No p53 mutations were detected in HPV-positive KS. The p53 mutations were mainly transversions (four of five). These data indicate that HPV may contribute to the pathogenesis of some cases of KS and that p53 alteration may represent a key event in the progression of the malignancy.

DNA, Viral↗
PubMed1994

Cytokines modulate terminal differentiation and the expression of predesquamin in cultured keratinocytes.

Predesquamin is a glycoprotein that we have isolated from human epidermis. Its monospecific polyclonal antibody immunolocalizes to the lower stratum corneum. We have previously found that it is not expressed in primary keratinocyte cultures unless both interferon-gamma and serum are added to the culture media. We now show similar results with interleukin-1 alpha substituted for interferon-gamma (but not with retinoic acid). Predesquamin is expressed in media supplemented with both cytokines (with or without serum), accompanied by the observation of larger outer squames and a more mature pattern of desquamation. As both cytokines are naturally present in the epidermis, this suggests that they contribute to desquamation in vivo. The predesquamin expression is demonstrated by Western blots of cell extracts with the specific antibody. Corresponding morphological changes are illustrated by phase-contrast microscopy.

Blotting, Western↗
PubMed1994

Evidence for the production and action of interleukin-10 in pituitary cells.

1. Interleukin-10 (IL-10) has a wide range of activities in the immune system such as modulation of interferon-gamma (IFN-gamma) and antibody production. The neuropeptide hormone corticotropin (ACTH) has similar activities, suggesting that a bidirectional communication mechanism operates between the immune and the neuroendocrine system involving these two substances. 2. Murine pituitary tumor cells (AtT-20) were found to produce up to 3 ng/ml of IL-10. 3. Pituitary cell corticotropin production was enhanced by IL-10 treatment. 4. IL-10 induced the production of ACTH in mouse splenocytes. 5. Authenticity of pituitary-derived IL-10 was shown by the demonstration of identical nucleic acid sequences of reverse-transcribed, polymerase chain reaction amplified fragments of cDNA obtained from murine splenocytes, a murine pituitary tumor cell line, and freshly isolated murine pituitaries.

Adrenocorticotropic Hormone↗
PubMed1994

Interferon treatment enhances the expression of underphosphorylated (biologically-active) retinoblastoma protein in human papilloma virus-infected cells through the inhibitory TGF beta 1/IFN beta cytokine pathway.

Interferons (IFN) regulate transcription of certain genes playing a role in cell proliferation. Targets of IFN action may include tumor suppressor genes such as the retinoblastoma (RB) gene and cytokines such as transforming growth factor beta 1 (TGF beta 1) and IFN beta which are inhibitors of epithelial cell proliferation. Using reverse transcription followed by PCR amplification, an increase of those growth inhibitory gene mRNA levels (TGF beta 1, IFN beta and RB) were found after interferon treatment in condylomas harboring non-oncogenic human papilloma virus (HPV 6/11) types, in an oncogenic HPV 16-containing cell line, and in a HPV negative, epidermoid carcinoma cell line. In addition, immunodetection by Western blot demonstrated a higher proportion of underphosphorylated (active form) retinoblastoma gene protein (pRB) after IFN treatment due to the decrease in the phosphorylating cdc2 kinase levels. Changes in the phosphorylation pattern of pRB together with the increased expression of those inhibitory genes represent a growth inhibited state in those cells as demonstrated by diminished c-myc expression. Since the extent of c-myc inhibition was significantly lower in the case of oncogenic HPV infection, a role of viral oncoproteins in abrogation of the antiproliferative effect of IFN therapy could be considered. These results demonstrate a new mechanism via which IFNs exert their antiproliferative effect on HPV-infected cells by affecting the expression and phosphorylation of the RB tumor suppressor gene, through the inhibitory TGF beta 1/IFN beta cytokine pathway.

Blotting, Western↗
PubMed1994

Interferons in human papillomavirus infections.

Human papillomavirus (HPV) infections usually present as benign warts (e.g., condyloma acuminatum, CA) but can also be responsible for dysplasia and carcinoma. Therapeutic options include chemotherapeutic agents, cryotherapy and surgery, but all these treatments are anti-tumor, not anti-viral. Interferons (IFNs) are the only anti-viral drugs approved for the therapy of benign HPV-related lesions. While IFN-alpha, IFN-beta and IFN-gamma have all been tested against CA, most information is available on IFN-alpha which appears efficacious via a number of routes of administration, schedules and dosages with an acceptable safety profile. The highest rate of success with IFN-alpha therapy, in terms of reduced recurrence rates of CA was reported from studies in which all visible lesions were surgically removed with subsequent administration of subcutaneous local IFN-alpha. Less data is available on the efficacy of IFNs in the treatment of HPV-related dysplasia and carcinoma, but combination therapy (e.g., IFN-alpha plus retinoids for cervical carcinoma) appears promising. Future advances in control of HPV-related lesions are expected to continue to involve IFN combined with non-antiviral therapies as well as the use of exogenous inducers of IFNs and other cytokines.

Clinical Trials as Topic↗
PubMed1994

Analysis of multiple molecular changes in human endocrine tumours.

To define the molecular changes occurring in endocrine tumours, we have analysed three human endocrine tumours established in our laboratory: BON, a functioning carcinoid tumour from the pancreas; SIM, a nonfunctioning carcinoid of the ileum; and STAN, a pheochromocytoma. A homozygous point mutation of the N-ras gene was identified at codon 61 in BON cells in conjunction with overexpression of N-ras mRNA and protein. BON cells also exhibited increased expression of c-myc and cdc2 kinase mRNA and protein; TGF-beta 1, p53 and retinoblastoma (RB) mRNA and protein levels were decreased. In addition, increased expression of the mdm2 oncogene and both the truncated and the wild-type RB protein were noted in BON. SIM cells exhibited moderately increased N-ras and c-myc mRNA levels along with decreased levels of RB mRNA and protein. Similar to BON and SIM, analysis of STAN showed increased N-ras and c-myc levels. Our data show multiple molecular changes in the three human endocrine tumours with the BON cell line exhibiting the most dramatic changes. Furthermore, our data suggest the existence of different molecular pathways in the pathogenesis of endocrine tumours. These cell lines will provide unique in vitro models to further analyse the significance of these molecular alterations.

Aged↗
PubMed1994

Distinction of mouse interferon-alpha subtypes by polymerase chain reaction utilizing consensus primers and type-specific oligonucleotide probes.

We have developed a novel method to study the subtype-specific expression of interferon-alpha (IFN-alpha) in the mouse system: we synthesized and used consensus oligonucleotide primers to allow simultaneous polymerase chain reaction (PCR) amplification of multiple murine IFN-alpha gene sequences. In addition, a set of subtype-specific oligomer probes were designed and used to distinguish between IFN-alpha genes that differ by only a few bases. The consensus primers, corresponding to two regions highly conserved among murine IFN-alpha subtypes, were used in reverse transcription and PCR amplification of total cellular RNA, isolated from IFN-gamma-treated murine L-929 cells, to yield a fragment of the anticipated approximately 520-bp size. Southern analysis of the amplified product using an internal consensus oligomer probe confirmed specific amplification of murine IFN-alpha gene(s). Subtype-specific oligonucleotide probes indicate that IFNs-alpha 1, -alpha 2, and -alpha 5 are present following IFN-gamma treatment, whereas IFN-alpha 4 remains virtually absent. Our results indicate that the expression of specific IFN-alpha subtypes may be subject to complex regulation, dependent upon inducing agents and cell types involved, and countless other factors. The procedure described here represents a novel method for studying the subtleties of the murine IFN-alpha mRNA expression.

Animals↗
PubMed1994

Paramyxovirus-like inclusions in an intradermal nevus from a healthy woman.

A healthy 52-year-old woman had an intradermal nevus removed from the right preauricular region. Histopathologic examination disclosed intranuclear and intracytoplasmic inclusions in many of the nevus cells. A basal-cell carcinoma, an additional intradermal nevus, and a fibrous papule of the nose were also excised, however, none of these lesions showed histologically similar inclusions within the lesions. Electron microscopic studies showed inclusions that were similar to those observed in cases of subacute sclerosing panencephalitis. Immunoperoxidase and polymerase chain reaction studies for the measles virus were performed, with negative results. The patient remains in good health 2 years after excision of the skin lesions.

Basal Cell Carcinoma↗
PubMed1994

Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene.

OBJECTIVE: This study determined whether genomic amplification of HER-2/neu or mutations of the p53 and ras genes were present in gastrinomas. SUMMARY BACKGROUND DATA: Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto-oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. METHODS: The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. RESULTS: Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. CONCLUSIONS: Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.

Base Sequence↗
PubMed1994

Crusted (Norwegian) scabies in patients with AIDS: the range of clinical presentations.

Crusted (Norwegian) scabies in AIDS patients can be manifested in both typical and atypical forms. Although the classic, hyperkeratotic, nonpruritic lesions are most common, reported cases have ranged in spectrum from crusting with pruritus to a pruritic, papular dermatitis to those resembling Darier's disease or psoriasis. We report two additional cases of crusted scabies in AIDS patients, one with typical crusted, hyperkeratotic though pruritic lesions and one with severe pruritus and rare papules, initially misdiagnosed as "pruritus of AIDS." Because of the extremely contagious nature of crusted scabies, as well as its potential for complete cure with appropriate therapy, a high degree of suspicion for this disorder should be maintained in AIDS patients, even when the lesions do not have the classical appearance. The discovery of crusted scabies, whether in its common or its atypical form should prompt testing for the human immunodeficiency virus (HIV).

Acquired Immunodeficiency Syndrome↗