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Biomedical subjects

C U Brand

Publications and source records attributed to C U Brand.

At least 37 records · Page 2Linked to original sources
PubMed1999

The HECA-452 epitope is highly expressed on lymph cells derived from human skin.

The cutaneous lymphocyte-associated antigen (CLA), recognized by the monoclonal antibody HECA-452, is a cell surface glycoprotein that binds specifically to E-selectin. CLA is present on most T cells at sites of cutaneous immune response and has been shown to be important in lymphocyte homing to the skin. It is expressed only by a minor subset of peripheral T cells and is absent on thymocytes. We have analysed (using a FACScan flow cytometer) the expression of CLA on human lymph cells derived from normal skin, from ultraviolet (UV)-irradiated skin and from allergic contact dermatitis. Whereas in the peripheral blood CLA was expressed on < 20% of CD4 +, CD8 + and CD56 + cells (natural killer cells), > 60% of CD4 +, CD8 + and CD56 + cells isolated from skin-derived lymph expressed CLA. Furthermore, > 90% of CD1a + dendritic lymph cells were positive for CLA. UV irradiation of the skin and induction of an allergic contact dermatitis did not change CLA expression on lymph cells, although lymph flow and cell output increased. These results provide further evidence for an important role of CLA in cell homing to the skin.

Adult↗
PubMed1999

Awareness and early detection of cutaneous melanoma: an analysis of factors related to delay in treatment.

Factors associated with the detection of cutaneous melanomas and reasons for delay in diagnosis were investigated in 429 patients with histologically proven melanoma operated on between January 1993 and June 1996. Patients were interviewed using a standardized questionnaire. In 25% of patients, treatment was delayed for more than 1 year from the time they first noticed a suspicious pigmented lesion. Melanoma was detected by the patients themselves in 67% of women and 45% of men. The three predominant clinical symptoms of melanoma were change in colour (darker), increase in size and increase in elevation of a pigmented lesion. The role of sun exposure and of naevi as risk factors for melanoma, as well as the potential benefit of early treatment, were known by 87%, 66% and 82% of the patients, respectively. However, melanoma awareness had no impact on the time period between first observation of skin changes and treatment. Among the factors associated with delay in melanoma diagnosis, an initial incorrect diagnosis as a benign lesion by the physician first visited (in 18% of all cases) had the highest significance. Patients detecting their lesions themselves were treated significantly later than patients in whom others had remarked on changes in a naevus. Furthermore, melanomas of the head and neck were treated later than melanomas at other body sites. Further efforts to educate both the public and the medical profession are essential to ensure earlier treatment for cutaneous melanomas.

Adult↗
PubMed1999

Cutaneous nocardiosis caused by Nocardia brasiliensis after an insect bite.

We report the case of a primary lymphocutaneous nocardiosis occurring on the right calf of a healthy 56-year-old man after an insect bite. Analysis of the purulent exudate obtained from the nodule revealed Nocardia brasiliensis. The initial therapy with trimethoprim-sulfamethoxazole had to be stopped due to a drug eruption. However, with minocycline treatment the patient recovered within 5 weeks. Superficial (sporotrichoid) infections and a history of outdoor injury should be considered suspicious for cutaneous nocardiosis.

Humans↗
PubMed1998

Interleukin-12 expression in human afferent lymph derived from the induction phase of allergic contact dermatitis.

Recent reports suggest that production of interleukin-12 (IL-12) by dendritic cells and keratinocytes may play an important part in contact hypersensitivity reactions. In the present study we investigated mRNA and protein expression of IL-12 in human skin lymph derived from normal untreated skin (n = 5) and from the induction phase of allergic contact dermatitis (CD) (n = 5). mRNA levels were determined at various time points in the lymph cells by a nested reverse transcriptase-polymerase chain reaction method. Time course analysis reproducibly revealed a constitutive expression of both IL-12 p40 and p35 mRNA in the migrating lymph cells in all volunteers. However, no enhancement of the IL-12 mRNA signal was found during the induction phase of allergic CD. Furthermore, as determined by a sensitive ELISA technique, IL-12 protein was not detectable in 60 lymph samples derived from normal untreated skin or in 68 lymph samples obtained during the induction phase of allergic CD at any time point of the lymph cannulation. In conclusion, our findings indicate that no significant protein levels of IL-12 are washed out from the skin into the afferent lymph or are produced and released by migrating lymph cells during the induction phase of allergic CD in vivo.

Adult↗
PubMed1998

Expression of interleukin-12 is increased in psoriatic skin.

Although the precise underlying pathomechanisms of psoriasis have not been fully elucidated, previous reports suggest that T helper 1-type cytokines are critically involved in the pathogenesis of this disease. Interleukin-12 (IL-12), a heterodimeric cytokine, has been suggested to play a major role in the development of T helper 1 cell responses. In this study, the presence of IL-12 mRNA and protein was investigated in normal human skin as well as nonlesional and lesional psoriatic skin. Messenger RNA levels were determined in biopsy specimens by a standard and a nested reverse transcriptase-polymerase chain reaction method. Additionally, IL-12 protein expression was analyzed in situ by immunohistochemistry using an antibody recognizing IL-12 p70. Whereas specific transcripts for IL-12 p35 were reproducibly detected without any significant differences in all samples, enhanced IL-12 p40 mRNA signals were only found in lesional psoriatic skin as compared with normal and nonlesional psoriatic skin. Furthermore, immunoreactivity for IL-12 p70 was markedly increased in the psoriatic skin lesions and was predominantly expressed on mononuclear cells in the dermis. In conclusion, our data suggest a critical role for IL-12 in promoting and maintaining T cell activation and inducing T helper 1-type cytokines such as interferon-gamma in psoriasis. We speculate that IL-12 might be a key cytokine in the pathogenesis of psoriasis.

Adult↗
PubMed1998

Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo.

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-alpha and IFN-gamma) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.

Adolescent↗
PubMed1998

Application of argon plasma coagulation in skin surgery.

BACKGROUND: Argon plasma coagulation (APC) is a noncontact electrosurgical technique which has been used in open surgery for about 20 years and in endoscopy for about 5 years. OBJECTIVE: The aim of the present study was to provide preliminary results on the effect of this method in skin surgery. METHODS: The effects of variations in gas flow, output power and coagulation times on the extent of the resulting skin coagulation zone were tested in a pig skin model. Furthermore, preliminary results were obtained from 48 patients. RESULTS: The depth of the coagulation zone, which depends on the output power of the high-frequency (HF) generator and the application time, was examined clinically and histologically in 150 different pig skin coagulations. The maximum depth of the coagulation zone was 4 mm. Coagulation zones below 4 mm can be maintained by controlling the output power of the HF generator and/or the duration of application. Variations of argon flow did not influence the depth of the coagulation zone significantly. In preliminary clinical tests, 48 patients with common warts, senile hemangiomas and actinic keratoses were treated with APC. In all cases, APC was highly effective and easy to perform. No severe problems or complications were observed. The skin lesions were destroyed with minimal or no scarring and without damaging the surrounding tissue. CONCLUSION: In the present preliminary study, APC proved to be an effective treatment with well-controlled tissue destruction. Further clinical studies are required to evaluate the suitability and the indications of this method in the treatment of cutaneous lesions.

Animals↗
PubMed1997

Prolonged survival of 2 years or longer for patients with disseminated melanoma. An analysis of related prognostic factors.

BACKGROUND: Once melanoma has metastasized to distant sites, the prognosis is usually poor, showing an overall median survival of 6-8 months. Long term survival is extremely rare, and there is still controversy concerning the prognostic significance of therapeutic modalities. The aim of the current study was to identify important prognostic factors associated with Stage IV melanoma. METHODS: The current study was based on data for 3258 melanoma patients, for whom clinical, pathologic, and long term follow-up information was recorded during the period 1976-1996 at the Eberhard-Karls-University in Tuebingen. Germany. The attainment of 2 years' or longer survival time by patients with disseminated melanoma was addressed, and a multivariate analysis of related prognostic factors was performed by logistic regression. RESULTS: Four hundred forty-two patients (13.6%) developed distant metastasis. The median survival time was 7 months, and the 2-year, 5-year, and 10-year survival rates were 11.9%, 6.7%, and 4.7%, respectively. Forty-five patients had prolonged survival of 2 years or longer. Significantly more females belonged to the group of long term survivors (P = 0.0186). Of the modalities of therapy given, only surgery was associated with prolonged survival (P < 0.0001). Primary metastasis to the skin (P = 0.006), the brain (P = 0.015), more than a single metastatic site (P = 0.002), and Karnofsky performance status of less than 80 (P = 0.0035) were significantly related to short term survival. In addition, subsequent development of two or more new metastatic sites was also associated with short term survival (P = 0.0025). CONCLUSIONS: In the current analysis, prolonged survival of 2 years or longer for patients with disseminated melanoma was shown to depend on gender, site of primary metastasis, number of metastatic sites, and Karnofsky performance status. Of the modalities of therapy given, only surgery significantly influenced survival. However, in a small percentage of patients, long term complete remission was achieved with chemotherapy alone or in combination with surgery, suggesting that such regimens might be curative in selected cases.

Adult↗
PubMed1997

sICAM-1, sE-selectin and sVCAM-1 are constitutively present in human skin lymph and increased in allergic contact dermatitis.

The expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin is important for the regulation of the leucocyte traffic into and in inflammatory dermatoses. ICAM-1, VCAM-1 and E-selectin were initially identified as cell-surface proteins, but recent evidence suggests that they also exist in a soluble form. The collection of human afferent lymph exclusively deriving from a selected skin area allows insight into local pathomechanisms as well as signal transmission in skin disorders. In the present study we measured the concentrations of the soluble adhesion molecules (sAM) sICAM-1, sVCAM-1 and sE-selectin in human skin lymph derived from normal untreated skin, irritant contact dermatitis (CD) and the induction and elicitation phases of allergic CD. The strong elicitation reactions of allergic CD produced an increase in sAM output to about three times the baseline values but in the weaker irritant CD we observed no increase at all. In the induction phase of allergic CD the concentrations during the first 9 days of the experiment remained unchanged, as in the lymph derived from normal untreated skin, but were slightly increased thereafter. To our knowledge, no in vivo data exist on the local involvement of sAM in irritant and allergic CD in humans. Our results provide evidence of increased concentrations of sAM mainly in strong allergic CD.

Adult↗
PubMed1997

Human skin lymph derived from irritant and allergic contact dermatitis: interleukin 10 is increased selectively in elicitation reactions.

BACKGROUND: Recent reports suggested an immunomodulatory role for interleukin 10 (IL-10) in contact hypersensitivity. OBJECTIVE: To investigate if IL-10 is important in the regulation of irritant and allergic contact dermatitis (CD), IL-10 and interferon gamma (IFN-gamma) protein levels were measured in normal skin lymph, in lymph derived from irritant and allergic (primary sensitization and elicitation) CD and in skin blister fluid from an elicitation reaction. METHODS: A superficial lymph vessel was cannulated microsurgically on the lower leg of 18 healthy volunteers. Lymph was collected twice daily. Protein levels of IL-10 and IFN-gamma were determined using commercially available ELISA kits and messenger RNA was estimated by a reverse-transcriptase polymerase chain reaction (PCR) method. RESULTS: Whereas the IL-10 levels in lymph derived from irritant CD and primary sensitization of allergic CD, similarly to those obtained from normal untreated skin, remained below 4.4 pg/ml, the IL-10 levels increased manifold both in the primary allergic reaction (928.5 pg/ml) and the elicitation of allergic CD (124 pg/ml). The levels of IFN-gamma also increased in all volunteers exhibiting an eczematous skin reaction and showed a tendency to be inversely correlated with IL-10. Using a reverse-transcriptase PCR, the expression of IL-10 and IFN-gamma in cells from lymph and from blister fluid was examined. While signals for IFN-gamma were not found, specific transcripts for IL-10 were detected in all samples examined, indicating that cells circulating in the lymph may also contribute to the IL-10 production measured. The IL-10 mRNA signal, however, was markedly stronger in lymph and epidermal blister cells from the elicitation reactions as compared to the signal in lymph cells derived from normal skin and from the primary sensitization of allergic CD. CONCLUSION: IL-10 may limit and down-regulate elicitation reactions by inhibiting cytokine and antigen-presenting cell functions in the skin and in the skin-associated lymphoid tissue.

Adjuvants, Immunologic↗
PubMed1996

IL-12 gene expression in human skin-derived CD1a+ dendritic lymph cells.

Recent reports point to a role for interleukin-12 (IL-12) in regulating T- and NK-cell function, macrophage activation and initiation of Th1-type cell responses. We sought to determine whether CD1a+ dendritic cells of the skin, as major antigen-presenting cells, are a source of IL-12 and therefore important in the initiation of Th1-type cell responses. To investigate this hypothesis, we cannulated microsurgically a skin-draining lymph vessel in the lower legs of five healthy volunteers. Altogether, ten different samples, each consisting of 1 x 10(6) lymph cells, were investigated. In four of the ten samples. CD1a+ dendritic lymph cells were isolated and purified by positive selection using mouse anti-CD1a monoclonal antibodies and sheep anti-mouse antibody-coated Dynabeads. Messenger RNA levels were estimated using a nested reverse transcriptase polymerase chain reaction (nRT-PCR) method. Total RNA was extracted from the cells, reverse transcribed to cDNA and amplified using specific primers for the target gene. Amplified products were sized by electrophoresis and visualized by ethidium bromide. Expression of IL-12 p40 and p35 mRNA was detected in all samples, both whole lymph samples and the highly enriched CD1a+ dendritic cell population. Our findings demonstrate that human skin-derived CD1a+ dendritic lymph cells produce IL-12 mRNA and may therefore be an important source of IL-12. Thus one might speculate that these CD1a+ dendritic cells, through their IL-12-producing capacity, might significantly influence the balance of Th1 versus Th2 reactions ultimately occurring.

Adult↗
PubMed1996

GM-CSF mRNA and protein in human skin-derived lymph.

GM-CSF together with IL-1 beta and TNF-alpha has been shown to play a key role in the maturation of LC in vitro. To investigate the presence of GM-CSF, IL-1 beta and TNF-alpha in human skin-derived lymph, we cannulated microsurgically a superficial lymph vessel on the lower leg of six healthy volunteers. Messenger RNA levels were estimated by a reverse transcriptase polymerase chain reaction (RT-PCR) method. From a total of 20 different samples, each consisting of 10(6) lymph cells, total RNA was extracted, reverse transcribed to cDNA and amplified using specific primers for the target gene. Amplified products were sized by electrophoresis and visualized by ethidium bromide. Specific transcripts for GM-CSF were detected in all lymph samples, indicating that circulating human skin-derived lymph cells express GM-CSF mRNA. A mean level of 11.5 +/- 2.1 pg/ml GM-CSF was detected in the lymph samples examined, as determined by a sensitive ELISA. In contrast to GM-CSF, occasional weak mRNA signals together with a mean level of 2.7 +/- 2.2 pg/ml were found for IL-1 beta, and neither specific transcripts nor protein were detected for TNF-alpha. Thus, our results demonstrate that afferent skin lymph cells constitutively express GM-CSF.

Adult↗
PubMed1996

Constitutive expression of both subunits of interleukin-12 in human keratinocytes.

Interleukin-12 (IL-12), a heterodimeric molecule consisting of disulfide-linked 35- and 40-kDa chains, is secreted by a variety of cells including macrophages and B cells. While keratinocytes have recently been demonstrated to produce IL-12 after stimulation with phorbol-12,13-dibutyrate as well as trinitrochlorobenzene, the constitutive expression of the two IL-12 subunits has remained controversial. In this study, we investigate if cultured keratinocytes derived from human epidermis and the follicle outer root sheath constitutively express IL-12. Total RNA was reverse transcribed to cDNA and amplified using a highly sensitive nested reverse transcriptase polymerase chain reaction. Both IL-12 p40 and p35 transcripts were detected in keratinocyte cultures. Moreover, low levels of the IL-12 p70 heterodimer were detected in the culture supernatants, as determined by a sensitive enzyme-linked immunosorbent assay. Since IL-12 is known to play an important role in the development of Th1 cells, the constitutive expression of mRNA for IL-12 in keratinocytes together with its secretion adds further evidence for a role of keratinocytes in immunological processes within the skin such as in contact hypersensitivity.

Base Sequence↗
PubMed1996

IL-1 beta protein in human skin lymph does not discriminate allergic from irritant contact dermatitis.

Recent data suggest a key rôle for IL-1 beta in the induction phase of allergic contact dermatitis. In the present study, the protein levels of IL-1 beta were measured in skin lymph derived from normal untreated skin as well as from irritant and allergic (induction and elicitation phase) contact dermatitis. IL-1 beta increased in the course of both types of contact dermatitis, displaying the highest levels in irritant CD. Using a reverse transcriptase-polymerase chain reaction, low signal strength of IL-1 beta mRNA was demonstrated in lymph cells derived from normal skin and allergic CD. In lymph cells collected 2 x daily during the induction phase of allergic contact dermatitis, no upregulation of the IL-1 beta mRNA signal was found. Isolated CD1a+ lymph cells derived from normal skin as well as from the induction and elicitation phase of allergic contact dermatitis did not express IL-1 beta mRNA. Our results demonstrate that in human skin lymph, the IL-1 beta profiles do not discriminate between irritant and allergic contact dermatitis and that besides resident epidermal and dermal cells, circulating lymph cells may also contribute to IL-1 beta protein production.

Adult↗
PubMed1996

Sporadic hypomelanosis of Ito with focal hypertrichosis in a 16-month-old girl.

We report the case of a 16-month-old girl with hypomelanosis of Ito, a relatively rare phenotype associated with neurocutaneous manifestations. The characteristic hypopigmented streaks along the Blaschko lines were associated with hypertrichosis of the genitals and shins, as well as musculoskeletal and dental anomalies. An underlying endocrinologic disorder of the hypertrichosis could be excluded. This presumes focal hypertrichosis as another phenotypic expression of mosaicism in this disease.

Diagnosis, Differential↗