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Biomedical subjects

A F Nikkels

Publications and source records attributed to A F Nikkels.

At least 55 records · Page 3Linked to original sources
PubMed1996

Factor XIIIa-positive dendrocytes and proliferative activity of cutaneous cancers.

Factor XIIIa-positive dendrocytes present at the periphery and inside epithelial neoplasms are an heterogeneous group of cells. They are subsets of mesenchymal cells, cancer-associated macrophages and antigen-presenting cells. Factor XIIIa, other tissue transglutaminases, alpha 2-macroglobulin and tumour necrosis factor-alpha represent a complex network of mediators influencing tumour progression in the skin. In the present study we searched for the presence of dendrocytes and alpha 2-macroglobulin deposits inside and in the vicinity of cutaneous carcinomas (90 basal cell carcinomas and 46 squamous cell carcinomas) and malignant melanomas (69 primary and 28 metastatic tumours). We also studied the proliferation of the same neoplasms by Ki-67 immunohistochemistry. Dendrocytes were numerous, abutting on and infiltrating most basal cell carcinomas and thin malignant melanomas. In contrast, they were present in only low numbers or even absent in thick primary malignant melanomas and in their metastases. They appeared unmodified around squamous cell carcinomas compared with the surrounding skin. Extracellular deposits of alpha 2-macroglobulin were often found in locations where dermal dendrocytes were numerous. No correlation was found between the Ki-67 indices of carcinomas and the density of peritumoral dendrocytes. In contrast, negative relationships were found between the Ki-67 indices and the number of dendrocytes present inside basal cell carcinomas and thin malignant melanomas. This study has yielded circumstantial evidence to link the density of factor XIIIa-positive dendritic cells and a low proliferative rate of neoplastic cells in basal cell carcinomas and malignant melanomas.

Basal Cell Carcinoma↗
PubMed1996

Distribution of varicella zoster virus and herpes simplex virus in disseminated fatal infections.

AIMS: To study the cutaneous and visceral distribution of herpes simplex virus (HSV) and varicella zoster virus (VZV) in fatal infections. METHODS: Standard histology, immunohistochemistry (monoclonal antibodies VL8 and VL2 and polyclonal antibody IE63 directed against VZV; monoclonal antibodies IBD4 and HH2 and polyclonal antibodies directed against HSVI and HSVII) and in situ hybridisation (anti-HSV and anti-VZV probes) were applied to formalin fixed, paraffin wax sections. RESULTS: On histological examination, Herpesviridae infection was evident in various organs including the lungs, liver and skin. In addition, immunohistochemistry and in situ hybridisation revealed the presence of HSV and VZV antigens and nucleic acids in several cell types and tissues showing no cytopathological alterations suggestive of Herpesviridae infection. The organs with histological evidence of infection also contained VZV or HSV antigens and their genes. CONCLUSIONS: These findings suggest that organ failure in disseminated VZV and HSV infections is primarily caused by HSV or VZV induced cell damage and lysis. They also indicate that immunohistochemistry and in situ hybridisation can provide an accurate, type-specific diagnosis on formalin fixed, paraffin wax embedded tissue even when classic histological and cytological characteristics are lacking.

Adult↗
PubMed1995

Distribution of varicella-zoster virus gpI and gpII and corresponding genome sequences in the skin.

In the course of varicella-zoster virus (VZV) infection, some viral capsid antigens are found in the epidermis and dermis. The aim of this study was to investigate the localisation of two major VZV glycoproteins (gpI and gpII) and of their respective genes in the skin. The distribution of VZV gpI and II in 27 formalin fixed paraffin embedded skin biopsies from herpes zoster eruptions were compared by immunohistochemistry. Double immunostaining was carried our to identify infected cells. The presence of viral nucleic acids coding for gpI and gpII was examined by in situ hybridisation. The distribution of gpI and gpII and their corresponding genome sequences was similar in the epidermis. gpI and gpII were also detected in dermal FXIIIa positive dendrocytes, in Mac 387 and CD68 positive macrophages, and in perineural and endothelial cells. However, the corresponding viral nucleic acids were rarely and barely detected in these cells of the dermis. It is concluded that VZV infection of epithelial cells follows a different course than in dermal cells.

Adult↗
PubMed1995

Immunohistochemical identification of varicella-zoster virus gene 63-encoded protein (IE63) and late (gE) protein on smears and cutaneous biopsies: implications for diagnostic use.

Early and specific recognition of varicella zoster virus (VZV) infection is of vital concern in immunocompromised patients. The aim of this study was to compare the diagnostic accuracy of histochemical and immunohistochemical identification of the VZV ORF63 encoded protein (IE63) and of the VZV late protein gE on smears and formalin-fixed paraffin-embedded skin sections taken from lesions clinically diagnosed as varicella (n = 15) and herpes zoster (n = 51). Microscopic examinations of Tzanck smears and skin sections yielded a diagnostic accuracy of Herpesviridae infections in 66.7% (10/15) and 92.3% (12/13) of varicella, and 74.4% (29/39) and 87.8% (43/49) of herpes zoster, respectively. Immunohistochemistry applied to varicella provided a type-specific virus diagnostic accuracy of 86.7% (13/15; IE63) and 100% (15/15; gE) on smears, and of 92.3% for both VZV proteins on skin sections. In herpes zoster, the diagnostic accuracy of immunohistochemistry reached 92.3% (36/39; IE63) and 94.9% (37/39; gE) on smears, and 91.7% (44/48; IE63) and 91.8% (45/49; gE) on skin sections. These findings indicate that the immunohistochemical detection of IE63 and gE on both smears and skin sections yields a higher specificity and sensitivity than standard microscopic assessments.

Adolescent↗
PubMed1995

Inverse modulation of intraepithelial Langerhans' cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix.

Ninety-four cervical biopsies from normal tissue to high-grade squamous intraepithelial lesion (SILs) were examined for the presence of intraepithelial Langerhans' cells and subpopulations of stromal macrophages/dendrocytes by immunohistochemistry using anti-S100, -L1, -CD68 and -factor XIIIa antibodies. Human papillomavirus (HPV) detection was performed in all cases by using first a mixture of DNA probes for 14 HPV types commonly found in anogenital biopsies at low stringency conditions (Tm -40 degrees C) and by reanalyzing the tissues at high stringency (Tm -10 degrees C) with HPV 6/11, 16/18 and 31/33/35 biotinylated probe cocktails and individual digoxigenin-labelled probes. SILs and metaplastic tissues were significantly associated with a depletion of S100-positive intraepithelial Langerhans' cells when compared with normal epithelium. In contrast, there was a significant increase in L1-positive stromal macrophages in SIL biopsies compared with normal or metaplastic cervix. A significantly higher density of CD68-positive macrophages was also observed in high-grade SILs compared with normal or metaplastic biopsies and with low-grade SILs. The density of factor XIIIa-positive dendrocytes was found to be higher in SILs compared with metaplastic tissues and in high-grade SILs when compared with normal cervical biopsies. No specific relationship was found between the densities of these cells and the HPV type detected in SILs separated into low grade and high grade. The significance of this inverse modulation of intraepithelial Langerhans' cells and stromal macrophages/dendrocytes in normal and SIL biopsies is discussed in relation to HPV infection and malignant transformation.

Biomarkers↗
PubMed1995

Varicella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency.

Varicella-zoster virus (VZV) gene 63 encodes a protein with a predicted molecular mass of 30.5 kDa which has amino acid similarities with the immediate-early (IE) protein 22 (ICP-22) of herpes simplex virus type 1. In order to study the expression of this protein during lytic and latent infection, gene 63 was cloned in frame and downstream from the glutathione-S-transferase gene, expressed as a fusion protein, and purified. In VZV-infected Vero cells, antibodies directed against this protein detect two polypeptides of 45 and 38 kDa which are localized both in the cytoplasm and in the nucleus. Using a sequential combination of transcription and protein synthesis inhibitors (actinomycin D and cycloheximide, respectively), we demonstrated the immediate-early nature of this protein, which can thus be named IE63. Using a rat model of VZV latency, we showed that IE63 is heavily expressed, essentially in neurons, during latency. IE63 can also be detected in the skin of patients showing early herpes zoster symptoms.

Animals↗
PubMed1995

Acquired persistent atypical lentigines as a failure of 5-methoxypsoralen-containing sunscreens in the photochemoprotection from ultraviolet-radiation-induced damage.

Acquired persistent atypical lentigines are pigmentary lesions that are unusual both clinically and microscopically. They occur in young adults with photosensitive skin using 5-methoxypsoralen-containing sunscreens during sunbathing. Their biologic behavior is benign, but there are grounds for concern regarding the carcinogenic risk in these patients.

5-Methoxypsoralen↗
PubMed1995

Epithelioid cell histiocytoma: a report of two cases.

Epithelioid cell histiocytoma is a rarely reported tumor derived from factor-XIIIa-positive dermal dendrocytes. Two additional cases are presented including their clinical, histologic and immunohistochemical features.

Adult↗
PubMed1995

Localization of varicella-zoster virus nucleic acids and proteins in human skin.

The pathogenic mechanisms involved in varicella-zoster virus (VZV) infections remain elusive. The pattern of cutaneous distribution of the IE63 protein and of the gpI (gE) and gpII glycoproteins with their corresponding genome sequences during VZV infections was studied by immunohistochemistry and in situ hybridization. Skin biopsy specimens were obtained from immunocompetent and immunocompromised patients with varicella, herpes zoster, or atypical VZV lesions. The first evidence for VZV infection consisted of the presence of IE63 in keratinocytes. In the vesicles and pustules, the viral transcripts gpI, gpII, and IE63 and the corresponding nucleic acids for gpI and gpII were identified in keratinocytes, sebocytes, Langerhans cells, dermal dendrocytes, monocytes/macrophages, and endothelial cells. The gpI and gpII glycorpoteins were essentially located on the cellular membranes while IE63 expression was generally restricted to the nuclei. In three biopsies of early herpes zoster, viral proteins were disclosed in dermal nerves and in perineurial type I dendrocytes. This was never encountered in varicella. Vasculitic changes and endothelial cell involvement were more prominent in varicella than in herpes zoster. It is concluded that the secondary viremia in varicella that affects the dermal endothelial cells is followed by a cell-to-cell spread to keratinocytes. In herpes zoster, the viral progression through cutaneous nerves primarily extends to the pilosebaceous units with a secondary involvement of epidermal keratinocytes, followed by a further spread to dermal cells.

DNA, Viral↗
PubMed1994

[Kaposi's disease in a female patient with acquired HIV-negative immunodeficiency].

A 79-year-old woman of Mediterranean ascent suffered from corticosteroid-dependent chronic obstructive lung disease, hypogammaglobulinemia (IgG 1 and 2), decreased CD16 natural killer cell function and non-HIV related CD4 and CD8 lymphopenia. Such immunodeficiency could be either a variant of common variable immunodeficiency or an early stage of the idiopathic CD4 + T lymphocytopenia syndrome. She developed bilateral lesions of Kaposi's sarcoma on the lower extremities resembling the classic European type of the disease. The tumors contained both CD34 + and Factor XIIIa + cells. The HLA-DR5 haplotype was not found. Weekly low intravenous dosages of vinblastine improved the lesions but the patient died from pontic infarction.

Aged↗
PubMed1994

Viral glycoproteins in herpesviridae granulomas.

Granulomatous reactions after varicella zoster virus (VZV) and herpes simplex virus (HSV) infections are rare, and their pathogenesis remains unclear. We studied by immunohistochemistry and in situ hybridization early granulomatous reactions after VZV and HSV infections. In the five cases studied, the VZV glycoproteins gp I and gp II were present in cells abutted to altered vessels, but the corresponding genome sequences were disclosed in similar locations in only one of these cases. In an immunocompromised patient with diffuse HSV eruption, HSV I antigens were present in cells of the reticular dermis, while viral nucleic acids were not evident. Immunophenotyping of the granulomas showed strong Mac 387 and CD68 positive labelings of macrophages/monocytes, without any involvement of Factor XIIIa-positive cells. These findings suggest that the major viral envelope glycoproteins, rather than complete viral particles could trigger granuloma formation following HSV and VZV skin infections.

Adolescent↗
PubMed1994

Vimentinoma, an unusual neoplasm of the skin.

We report an unusual benign neoplasm that developed in a child. Tumoral cells were filled with vimentin intermediate filaments. No other features of differentiation were found by immunohistochemistry and electron microscopy. 'Vimentinoma' appears to be the most appropriate name for this neoplasm.

Child↗
PubMed1994

Recognition and treatment of shingles.

Varicella zoster virus (VZV) is responsible for a primary infection (varicella) followed by a latency, eventually resulting in herpes zoster (shingles). The replication cycle of VZV is normally interrupted after varicella. Consequently, VZV remains dormant in the organism. Reactivation occurs after viraemia, and the development of tissue alterations (skin and viscera) depends on the immunological status of the patient. Diagnosis of herpes zoster relies on clinical recognition and cytological and histological evaluations combined with immunohistochemistry and molecular biology techniques. Treatment of herpes zoster primarily relies upon antiviral drugs and incidentally on immunomodulating agents, specific immunoglobulins, antimicrobial agents, antiviral enzymes and corticosteroids. Drugs with a clinically relevant activity against varicella zoster virus infections include aciclovir, adenosine monophosphate, bromodeoxyuridine, desciclovir, fiacitabine, idoxuridine, interferon-alpha and vidarabine. Among them, aciclovir appears to be a first-line agent. Its efficacy has been well established by many clinical studies. Promising drugs for the future include famciclovir, penciclovir, valaciclovir and other molecules currently under investigation. Recent and promising improvements in antiviral drug development may increase patient compliance, cost-benefit ratios and therapeutic efficacy.

Acyclovir↗
PubMed1994

[Lethal varicella. Immunohistochemistry and in situ hybridization].

We report a case of lethal varicella developed in an immunocompromised man in his seventies. A study by immunohistochemistry and in situ hybridization was conducted revealing the presence of the glycoprotein gpI specific for VZV and its corresponding nucleic acids found in multiple foci of most tissues and organs, except in the brain and paravertebral sympathetic ganglia.

Aged↗