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Biomedical subjects

H Gollnick

Publications and source records attributed to H Gollnick.

At least 37 records · Page 2Linked to original sources
PubMed2001

Suprabasal overexpression of the hsRPB7 gene in psoriatic epidermis as identified by a reverse transcriptase-polymerase chain reaction differential display model comparing psoriasis plaque tissue with peritonsillar mucosa.

In psoriasis an etiopathogenetic vicious circle is nowadays hypothesized that the disease is triggered by skin-specific autoantigen structures, the expression and accessibility of which are positively correlated with the intensity of the hyperproliferation and inflammation in the epidermopapillary compartment driven by autoreactive T cells. Despite the close microanatomical relation between skin and mucosa, clinicians have always been intrigued by the observation that psoriatic affection of the mucosa, if at all existing, is only seen as very rare events in the lips and tongue sparing buccopharyngeal sites. This prompted us to establish an experimental model system comparing psoriatic-involved skin and peritonsillar mucosa from tonsillectomies by a reverse transcriptase-polymerase chain reaction/differential display strategy. Among more than 60 cDNA species to be displayed in psoriasis, but missing in peritonsillar mucosa, one species was identified as coding for the RNA polymerase IIA seventh subunit (hsRPB7 gene) as a most critical factor for DNA to RNA transcription. Immunohistochemistry showed a hitherto unknown, distinctive pattern of hsRPB7 expression that was 1) tissue type-dependent with a surplus in skin keratinocytes and a near absence in peritonsillar mucosa, 2) tightly regulated by the keratinocyte differentiation process with a sharp suprabasal up-regulation in contrast to a basal down-regulation, and 3) substantially augmented in psoriatic-involved skin as compared to normal and psoriatic uninvolved skin. Keratinocytes of actinic keratoses also showed a strong hsRPB7 expression that however did not strictly spare the basal cell layer presumably reflecting the disturbed intraepidermal stratification because of the premalignant status of these precancerous lesions.

Base Sequence↗
PubMed2001

Lipid analysis of follicular casts from cyanoacrylate strips as a new method for studying therapeutic effects of antiacne agents.

BACKGROUND: The cyanoacrylate follicular biopsy is an established method for the examination of the horny layer and quantitative assessment of microcomedones. We have optimized the method by separating follicular casts mechanically from the cyanoacrylate strips. OBJECTIVES: To use this method to analyse topical therapy-induced changes of the lipid composition in the sebaceous follicular infundibulum. METHODS: Both the follicular casts and the residual skin surface strip, the last representing a mixture of stratum corneum and surface lipids, were extracted twice with n-hexane-ethanol under ultrasonication, evaporated, redissolved in chloroform-methanol and separated by high-performance thin layer chromatography, using cholesterol sulphate, cerebroside, ceramide types 3 and 4, cholesterol, oleic acid, triolein, cholesterol oleate and squalene as standards. Identification was performed by computer-assisted densitometric analysis. Six patient groups receiving adapalene 0.1%, tretinoin 0.025%, clindamycin 1%, clindamycin 1% + tretinoin 0.025%, benzoyl peroxide 5% or benzoyl peroxide 5% + erythromycin 2% were investigated before and 12 weeks after application. RESULTS: A significant decrease in free fatty acid proportions combined with an increase in triglycerides was observed in the groups receiving antimicrobial therapy, supporting the hypothesis of lipolysis due to microbial colonization. The groups treated with topical retinoids showed an additional significant increase in ceramide subfractions, most probably reflecting their influence on epidermal keratinization. CONCLUSIONS: Our method proved suitable for the detection of quantitative and qualitative changes in lipid profiles of both infundibulum cast content and surface lipids. It enabled simple, non-invasive and objective assessment of the most relevant lipid classes in the sebaceous infundibulum, and efficient monitoring of drug effects on the follicular infundibulum.

Acne Vulgaris↗
PubMed2001

Perforin hyperreleasability and depletion in cytotoxic T cells from patients with exacerbated atopic dermatitis and asymptomatic rhinoconjunctivitis allergica.

BACKGROUND: As a plasma membrane pore-forming protein, perforin is essential for T-cell cytotoxicity mediated by lytic granules. Recent studies on the immune system of perforin knockout mice demonstrated striking similarities to the immunopathology of atopic diseases. OBJECTIVE: We sought to investigate the perforin system of atopic patients. METHODS: Monoclonal antibodies were used to characterize perforin-positive PBMCs of patients with exacerbated atopic dermatitis (AD) and asymptomatic rhinoconjunctivitis allergica (RCA) by means of immunoflow cytometry. In addition, a perforin release assay was developed to quantify the velocity of ionomycin and phorbol 12-myristate 13-acetate-induced secretion of lytic granules. RESULTS: In atopic patients significantly fewer lymphocytes contained perforin-positive lytic granules compared with those of healthy control subjects (patients with AD: 14% +/- 5%, n = 13, P <.0001; patients with RCA: 24% +/- 5%, n = 9, P <.01; healthy control subjects: 33% +/- 11%, n = 13). Of all CD8(hi+) cytotoxic T lymphocytes (CTLs), only 18% +/- 9% and 17% +/- 12% were perforin-positive in patients with AD and RCA, respectively, compared with 44% +/- 13% in control subjects (P <.0001). In addition, perforin-positive CD8(hi+) CTLs of atopic patients released their perforin twice as fast and more completely than control CTLs. This means that 50% of initially perforin-positive CD8(hi+) CTLs from patients with AD and RCA released their perforin completely within 32 +/- 16 and 36 +/- 19 minutes, respectively, and an over 85% release was reached within 113 +/- 41 and 118 +/- 60 minutes, respectively. In CTLs of healthy control subjects, however, it took 64 +/- 40 minutes to achieve a 50% release of lytic granules, and an 85% depletion was not reached in 60% of healthy control subjects, even after 180 minutes. CONCLUSION: The perforin hyperreleasability explains, at least in part, the decreased percentage of perforin-positive CD8(hi+) CTLs in atopic patients. These distortions in the system of lytic granules of atopic patients may contribute to the functional defects observed in T-cell cytotoxicity in vivo and in vitro in patients with AD and RCA.

Antibodies, Monoclonal↗
PubMed2001

Safety and efficacy of imiquimod 5% cream in the treatment of penile genital warts in uncircumcised men when applied three times weekly or once per day.

This dose-escalation study was performed to evaluate safety and efficacy of imiquimod 5% cream in the treatment of uncircumcised men with penile warts associated with the foreskin. The cream was applied 3 times/week (n=34) or once per day (n=30) over 8+/-2 h. Imiquimod 5% cream was safe in both treatment groups. However, the 3 times/week regimen was better tolerated with a lower incidence of local skin reactions. In both groups, the 2 most frequently reported local skin reactions were erythema and erosion; they were more severe with the once-daily dosing. The most frequently reported application site reactions were burning, pruritus and irritation or pain (once-daily patients only). Total clearance was achieved in 62% of the patients in the 3 times/week group and by 57% in the once-daily group. Thus, imiquimod 5% cream administered 3 times/week was the optimal dosing regimen in the treatment of penile warts in uncircumcised men.

Administration, Topical↗
PubMed2001

[Disseminated actinic keratoses. Comparison of topical photodynamic therapy with 5-aminolevulinic acid and topical 5% imiquimod cream].

We report on a 75-year-old woman with skin type I suffering for 20 years from multiple actinic keratoses of areas exposed to the sun. The skin of her forearms was treated on one side with imiquimod 5% cream over 4 weeks and on the contralateral side with photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA). Both sides showed good clinical response after 3-months follow-up, suggesting that these modalities can be effectively used for treating widespread multiple actinic keratoses.

Adjuvants, Immunologic↗
PubMed2000

A delta opioid receptor lacking the third cytoplasmic loop is generated by atypical mRNA processing in human malignomas.

delta Opioid receptors were identified in human melanomas by RT-PCR and radioligand binding. In all tumors an additional PCR amplificate was detected in which 144 bp within the third exon were deleted. This fragment corresponded to the third cytoplasmic domain of the receptor protein. The short variant resulted from atypical mRNA processing. There were no common splice recognition sequences around the deleted fragment; instead its excision resembled the removal of a transposon. The deletion was not detected in normal human melanocytes nor in human or rat brain. However, it was present in a human neuroblastoma cell line (SH-SY5Y). Thus, it appears that the occurrence of the short delta opioid receptor is correlated to malignancy.

Animals↗
PubMed2000

DNA synthesis in cultured human keratinocytes and HaCaT keratinocytes is reduced by specific inhibition of dipeptidyl peptidase IV (CD26) enzymatic activity.

The ectopeptidase dipeptidyl peptidase IV (DP IV, CD26, EC 3.4.14.5) is present on most mammalian cells. Using specific inhibitors of DP IV, it has been shown that this enzyme is involved in the regulation of DNA synthesis and in production of various cytokines in lymphocytes. The aim of the present work was to investigate the expression of DP IV/CD26 on human keratinocytes and to answer the question, whether the proliferation (DNA synthesis) of human keratinocytes is influenced by inhibition of the enzymatic activity of DP IV. Using flow cytometry, RT-PCR, and specific enzymatic activity assays, expression of DP IV-mRNA and CD26 antigen were shown on primary keratinocyte strains and on the HaCaT keratinocyte cell line. The synthetic DP IV inhibitors Lys[Z(NO2)]-thiazolidide and -pyrrolidide suppress the DNA-synthesis of these cells in a dose-dependent manner. These data demonstrate that CD26 is also involved in the regulation of DNA synthesis of keratinocytes and that the enzymatic activity is required for mediating these effects.

Adult↗
PubMed2000

Epidermolysis bullosa acquisita with ultraviolet radiationsensitivity.

A 37-year-old male patient developed a bullous eruption and erythematous plaques mainly in exposed areas following prolonged sun exposure. In addition, blisters were noted on oral and nasal mucous membranes. Histopathological examination of a lesional skin biopsy revealed a subepidermal blister. Linear deposition of IgG and C3 at the epidermal basement membrane zone was revealed by direct immunofluorescence microscopy of a perilesional skin biopsy. Indirect immunofluorescence on 1 mol/L salt-split skin showed binding of autoantibodies to the dermal side of the split. Immunoblot analysis of dermal extracts demonstrated that the patient's serum contained IgG antibodies against type VII collagen, whereas no reaction was seen with epidermal extracts or by enzyme-linked immunosorbent assay using a recombinant form of bullous pemphigoid 180. Standardized ultraviolet (UV) radiation provocation induced blistering with both UVA (13.5 J/cm2) and UVB (0. 04 J/cm2) within 24 h clinically and histologically. External and systemic UV-protective medication and nine cycles of high dosage immunoglobulins given intravenously (1.2 g/kg body weight over 2-3 days every 4 weeks) resulted in the cessation of blister formation. To the best of our knowledge, this is the first report of a case of epidermolysis bullosa acquisita with sensitivity to UV.

Adult↗
PubMed2000

Successful treatment of angiosarcoma of the scalp by intralesional cytokine therapy and surface irradiation.

An 88-year-old woman presented to us with angiosarcoma of the scalp that had developed over a 6-month period following previous trauma. Despite explicit information concerning the extremely malignant potential of the tumour the patient refused any surgical intervention. However, she agreed to receive local, intralesional interferon alpha-2b and interleukin-2 therapy. After partial remission of the tumour, the intralesional cytokine injections were combined with surface radiotherapy. This combination therapy led to a 2-year remission of both the tumour and sonographically suspicious cervical lymph nodes. Apart from the typical, moderate side-effects of interferon alpha-2b and interleukin-2 the therapy was well tolerated. In conclusion, in our limited experience intralesional cytokine therapy--alone as well as in combination with surface irradiation--seems to be an alternative therapeutic option for patients who is not a candidate for surgery.

Aged↗
PubMed2000

A sensitive gas chromatography-mass spectrometry assay reveals increased levels of monohydroxyeicosatetraenoic acid isomers in human plasma after extracorporeal photoimmunotherapy and under in vitro ultraviolet A exposure.

Extracorporeal photoimmunotherapy (photopheresis) is a highly effective therapy in the treatment of various disorders. Although extracorporeal photoimmunotherapy has been successfully used for more than 10 y, its mechanism of action is still unclear. The formation of reactive oxygen species have been implicated in extracorporeal photoimmunotherapy, but malonyl dialdehyde as a marker of systemic lipid peroxidation did not increase significantly during treatment. To investigate further the involvement of reactive oxygen species in extracorporeal photoimmunotherapy, we have introduced a highly sensitive negative ion gas chromatography-mass spectrometry based method for quantitating oxygenated arachidonic acid isomers (hydroxyeicosatetraenoic acids) in plasma samples of patients treated with extracorporeal photoimmunotherapy. In the plasma of healthy volunteers pmole amounts of 2-, 3-, 5-, 8-12-, and 15-hydroxyeicosatetraenoic acid were detected and we observed a dose-dependent augmentation in these metabolites when the blood was irradiated with increasing doses of ultraviolet A in the presence of the photosensitizer 8-methoxypsoralen. Analysis of plasma samples obtained from patients before and after extracorporeal photoimmunotherapy revealed a characteristic increase in total hydroxyeicosatetraenoic acid levels, particularly of 5-hydroxyeicosatetraenoic acid which contributed 80% to the sum of all hydroxyeicosatetraenoic acid isomers. Chiral phase high-performance liquid chromatography indicated almost equal amounts of 5S- and 5R-hydroxyeicosatetraenoic acid suggesting that the majority of lipid peroxidation products are formed via nonenzymatic oxidation reactions.

Gas Chromatography-Mass Spectrometry↗
PubMed2000

Coincidence of multiple, disseminated, tardive-eruptive blue nevi with cutis marmorata teleangiectatica congenita.

A 71-year-old woman reported a slow progression of multiple bluish dark asymptomatic macules and papules on the pretibial region of both lower legs for over 30 years. At birth a left-sided hypoplasia of the leg including the buttock accompanied by a connatal vascular nevus had been diagnosed. The ipsilateral deep veins of the pelvis and leg had a normal anlage. Histopathological examination revealed multiple blue nevi of the common type. The association of multiple blue nevi and cutis marmorata teleangiectatica congenita with limb hypoplasia has not previously been reported and is discussed in this paper. One could speculate whether these symptoms represent a new syndrome, because by thorough examination the NAME syndrome could be ruled out.

Aged↗
PubMed2000

Investigation of annexin V binding to lymphocytes after extracorporeal photoimmunotherapy as an early marker of apoptosis.

BACKGROUND: Induction of programmed cell death is assumed to be a possible effect of extracorporeal photoimmunotherapy (ECPI). OBJECTIVE: In the present study lymphocytes of patients with cutaneous T cell lymphoma undergoing ECPI were investigated for early apoptotic events. METHODS: Annexin V, known for its selective affinity to phospholipids, was used to detect early phases of apoptosis. Simultaneous staining with propidium iodide binding to DNA allowed detection of late apoptotic/necrotic cells. RESULTS: At 1 h after ECPI, an increase in early apoptotic cells was found indicating a direct effect of ECPI. At 20 h after each ECPI session, a delayed increase in the number of apoptotic lymphocytes was observed in early apoptotic annexin-stained cells and in late apoptotic cells, whereas in nonirradiated cells no remarkable changes were found. Apoptosis was confirmed by altered light scattering properties and DNA fragmentation. CONCLUSION: The apoptotic cell death of reinfused lymphocytes is supposed to be a therapeutic effect of ECPI.

Aged↗
PubMed2000

Extensive haemorrhagic-bullous skin manifestation of systemic AA-amyloidosis associated with IgGlambda-myeloma.

In an 86-year-old woman with a multiple myeloma of the IgG lambda subtype a coinciding systemic amyloidosis manifested as a macroglossia, diffuse alopecia and generalized cutaneous involvement. The skin was affected by milium-like papules, petechial haemorrhages and an increased tissue fragility with subsequent blister formation. The typical histology and immunohistology pattern revealed large intradermal amyloid masses, reacting positively with anti-amyloid A antibodies, which surrounded cuff-like dilatated blood capillaries. The abundance of these amyloid deposits led to significant deflexibilization and fragility of the capillaries and the dermal matrix eventually resulting in the haemorrhagic-bullous eruptions. The peculiar feature of the present case is the intensity of bullous-haemorrhagic skin damage due to amyloid A deposition without any detection of cutaneous IgGl as the myeloma-derived paraprotein assumed to be causative for the development of systemic AA amyloidosis.

Aged↗
PubMed2000

Systemic drugs with antipruritic potency.

Despite the predominance of itch as a leading and distressing symptom in most of the dermatological and several systemic diseases, there is relatively little progress in understanding its pathophysiology. This is most likely the main reason for the limited number of satisfactory anti-itch treatments and the fact that even today various therapies have empirical but not evidence-based character. There are no specific antipruritic drugs on the market, but there are a high number of case reports and experimental investigations describing medications with antipruritic potency. It is therefore the aim of this article to briefly review the major systemic antipruritic drugs and give a short overview on the different types of pruritus and their possible systemic therapy.

Antipruritics↗