[Sarcoidal allergic contact dermatitis due to palladium following ear piercing]. / Sarkoidale allergische Kontaktdermatitis auf Palladium nach Ohrpiercing.

Granulomatous tissue reactions due to jewelry made of gold, silver, nickel and palladium are rare but nevertheless have been known for a long time. A female patient developed nodular infiltrates after having been pierced with ear stickers containing palladium. A contact allergic reaction could be demonstrated as the underlying cause by inducing similar histological changes following patch testing with palladium.

[Sporotrichosis as the cause of a leg ulcer]. / Sporotrichose als Ursache eines Ulcus cruris.

A young man presented at Lugala Lutheran Hospital (Tanzania) with an ulcer on his lower leg which had developed over the past 9 weeks. Subcutaneous nodules and plaques were found all the way up to his groin; this observation prompted a strong suspicion that the patient had the lymphocutaneous form of sporotrichosis which had not been seen at this hospital before. The diagnosis was confirmed histopathologically. The patient was then treated with saturated solution of potassium iodide.

[Anetoderma Schwenninger-Buzzi in a dark-skinned patient]. / Anetodermie Schwenninger-Buzzi auf dunkler Haut.

A 10-year-old boy in Uganda developed primary anetoderma (Schwenninger-Buzzi). It is important not to confuse anetoderma with BL leprosy in spite of some superficial resemblance of the two diseases. Primary anetoderma is probably extremely rare in patients with dark skin although this may partly be due to a lack of dermatologists in Africa who could diagnose the disease.

[Cutaneous manifestation of cysticercosis]. / Kutane Manifestation der Zystizerkose.

Cysticercosis, an infection with the larva of Taenia solium, is caused by the accidental ingestion of the parasite's eggs. In many countries of the Third World, cysticercosis, and especially neurocysticercosis, is a widespread problem. A patient from Northern Malawi presented not only with cysticercosis but also with BT leprosy and pityriasis versicolor. Dermatologists should be familiar with the clinical picture of cysticercosis in order to make an early diagnosis in patients from at-risk areas.

Differential regulation of intestinal and liver fatty acid-binding proteins in human intestinal cell line (Caco-2): role of collagen.

Fatty acid-binding proteins (FABP) are small cytosolic proteins which are thought to play a key role in fatty acid metabolism. The intestine contains the intestinal (I-FABP) and the liver (L-FABP) isoforms, but their regulation is still poorly documented. In order to find suitable conditions for studying the regulation of the two FABP isoforms in Caco-2 cells, we investigated the effects of the presence of collagen during cell proliferation or differentiation. When collagen was present only during cell proliferation on culture dishes, I-FABP expression was enhanced, whereas sucrase-isomaltase was unaffected and L-FABP expression was merely accelerated. In contrast, when collagen was present during cell differentiation on filter inserts, both I-FABP and sucrase-isomaltase were strongly reduced, but L-FABP was not affected. Under the former conditions (the more suitable for studying FABP regulation), the peroxysome proliferator-activated receptor (PPAR) activators, clofibrate and alpha-bromopalmitate, enhanced the two isoforms. This study, which is the first one providing a quantitative protein analysis of I-FABP and L-FABP in Caco-2 cells, demonstrates different time courses of expression of these proteins during cell differentiation. It also shows that I-FABP is specifically regulated by collagen and that, under conditions optimal for their expression, both isoforms are modulated by metabolic factors.

Removal of endogenous leptin from the circulation by the kidney.

OBJECTIVE: This study was performed to test the hypothesis that the kidneys play a primary role in the clearance of endogenous leptin from the circulation of obese rats. DESIGN: Zucker (fa/fa) obese rats were anaesthetized and subjected to various surgical manipulations of the kidneys. One hour after surgery arterial blood samples were taken at 1 h intervals for times upto 8 h. Plasma leptin concentrations were determined by radioimmunoassay. RESULTS: Bilateral nephrectomy induced a rapid increase in plasma leptin concentrations above control values. In contrast, continuous intravenous re-injection of voided urine did not increase circulating leptin concentrations, indicating that leptin is not present in the urine in large quantities. This conclusion was confirmed by the very low levels of detectable leptin in urine. Leptin is not metabolized across the renal circulation and is extracted intact by the kidney. Simultaneous measurement of renal plasma flow established renal leptin extraction at approximately 59 ng/ min for both kidneys. Following intravenous infusion of leptin, renal clearance and whole body clearance were equal. This finding indicates that the kidneys alone are responsible for the systemic elimination of leptin in Zucker rats. Seven hours after bilateral ureteral ligation, a procedure which lowers glomerular filtration, plasma leptin concentrations were elevated. The renal extraction of leptin did not change over a wide range of plasma leptin concentrations suggesting that renal leptin extraction is a high capacity, non-saturable process most probably glomerular filtration. CONCLUSION: Endogenous leptin is rapidly cleared from the circulation by the kidney by glomerular filtration followed by metabolic degradation in the renal tubules.

Expression of NM23 protein in acquired melanocytic nevi, malignant melanoma and metastases of malignant melanoma: an immunohistological assessment in human skin.

BACKGROUND: It has been suggested that nm23 may exert metastasis suppressor function in human tumors. OBJECTIVE: We have analyzed expression of nm23 polypeptide in acquired melanocytic nevi (n = 19), dysplastic nevi (n = 19), malignant melanomas (n = 22) and metastases of malignant melanomas (n = 47) in situ. METHODS: Nm23 protein was detected immunohistochemically on paraffin sections using the highly sensitive labeled avidin-biotin technique. RESULTS: We found that (1) nm23 polypeptide is predominantly expressed in the cytoplasmic but also in nuclear and membrane compartments of melanocytic human cells, (2) expression of nm23 protein does not correlate with benign or malignant phenotype in melanocytic tumors of human skin. CONCLUSION: Our study challenges the hypothesis that nm23 may function in malignant melanomas as a tumor suppressor gene.

Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin.

BACKGROUND: The biologically active vitamin D analog calcipotriol is effective and safe in the topical treatment of psoriasis, but its exact mechanism of action is unknown. OBJECTIVE: We investigated expression of 1,25-dihydroxyvitamin D3 receptors, markers for inflammation (CD1a, CD4, CD8, CD11b, CD15; NAP-1/interleukin-8; 55 kd tumor necrosis factor-receptor; intercellular adhesion molecule-1; HLA-DR), proliferation (proliferating cell nuclear antigen, Ki-67), and differentiation (transglutaminase K; involucrin; cytokeratin 16) in psoriatic skin during topical calcipotriol treatment. METHODS: For immunohistochemical staining we used the labeled avidin-biotin technique on cryostat-cut sections. RESULTS: We found a significant increase of 1,25-dihydroxyvitamin D3 receptor expression in epidermal basal keratinocytes of lesional psoriatic skin during calcipotriol treatment. In all patients analyzed, effects on proliferation and differentiation of epidermal keratinocytes were stronger than effects on dermal inflammation. Effects on inflammation were more pronounced in the epidermal than in the dermal compartment. CONCLUSION: Our findings indicate that analogs of 1,25-dihydroxyvitamin D3 upregulate their corresponding receptor in human keratinocytes in vivo. This mechanism may be important in the therapeutic efficacy of vitamin D analogs in psoriasis. The differential therapeutic effects in the epidermal and dermal skin compartments may be due to a reduced bioavailability of calcipotriol in the dermal compartment.

Mechanism of leptin removal from the circulation by the kidney.

This study was performed to test the hypothesis that the kidneys play a primary role in the clearance of endogenous leptin from the circulation. Lean male Sprague-Dawley rats were anesthetized and subjected to various surgical manipulations of the kidneys. Sixty minutes after surgery arterial blood samples were taken at 1-h intervals for up to 8 h. Plasma leptin levels were determined by radioimmunoassay. Bilateral nephrectomy induced a rapid increase in plasma leptin concentrations above control values, indicating that the kidneys are important for the elimination of leptin from the circulation. Leptin was not metabolized across the renal circulation and was extracted intact by the kidney. Simultaneous measurement of renal plasma flow established renal leptin extraction at approximately 6.5 ng/min for both kidneys. Compared with the quantities extracted from the plasma, leptin was only present in the urine in small quantities, indicating extensive metabolic degradation in the renal tubules. High plasma leptin levels were not maintained after binephrectomy indicating that pathways other than the kidneys are also responsible for leptin clearance. Seven hours after bilateral ureteral ligation, a procedure which lowers glomerular filtration, plasma leptin levels were slightly elevated. The renal extraction of leptin did not change over a wide range of plasma leptin concentrations suggesting that renal leptin extraction is a high capacity, non-saturable process most probably glomerular filtration. Endogenous leptin is rapidly cleared from the circulation by glomerular filtration followed by metabolic degradation in the renal tubules.

Leptin is a physiologically important regulator of food intake.

OBJECTIVE: These studies were designed to test the hypothesis that endogenous leptin, acting within the brain plays a physiologically important role in the control of food intake in lean rats. DESIGN: Antibodies directed against mouse leptin were raised in rabbits. The purified IgG fractions prepared from pre-immune and immune sera were injected into the right lateral ventricle of lean Sprague-Dawley rats and obese Zucker fatty fa/fa rats. Changes in food intake were measured over the following 20 h period. RESULTS: The anti-leptin antibodies recognized a major epitope in the C-terminal region of the leptin molecule. The antibodies bound both mouse and rat leptin with high affinity, but did not bind human leptin, or a selected range of other hormones and neurotransmitters known to affect food intake. In competition studies, the binding of mouse, but not human leptin to the human Ob-Rb receptor was prevented by the antibodies. This indicates that the antibodies can block the action of leptin by preventing its binding to the ob-Rb receptor. Injection of the anti-leptin antibodies into the brain of lean rats led to an increase in food intake during the first hour after injection which was not compensated during the following 19 h period. Injection of the anti-leptin antibodies did not affect food intake in Zucker fatty fa/fa rats which express an abnormal ob-Rb receptor. CONCLUSION: Endogenous leptin acting within the brain plays a physiologically important role in the control of food intake in lean rats.

Leptin is cleared from the circulation primarily by the kidney.

OBJECTIVE: This study was performed to determine the pharmakocinetics of recombinant leptin in lean rats and to test the hypothesis that the kidneys play an important role in the clearance of leptin from the circulation. DESIGN: 126I-leptin was administered by bolus intravenous injection. Blood samples were taken at various time points ranging from 1-180 min after administration and assayed for leptin. Pharmacokinetic parameters were determined in normal animals and after either bilateral nephrectomy or bilateral ureteral ligation. RESULTS: Leptin was eliminated from the circulation following a three compartment model. The importance of the kidneys to the systemic clearance of leptin was studied by administrating leptin to binephrectomized rats. The systemic clearance of leptin in anephric rats was only 19% of that calculated for control animals. In order to assess the role of glomerular filtration, both ureters were ligated 5 h before leptin administration. Ureteral ligation reduced the systemic clearance of leptin by 30%. CONCLUSION: These findings demonstrate that the short half life of leptin in the circulation is mainly determined by efficient renal clearance which is mediated in part by glomerular filtration.

Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade.

BACKGROUND: Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF. METHODS AND RESULTS: Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals). CONCLUSIONS: We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

Contact stomatitis due to palladium and platinum in dental alloys.

We report a patient with contact stomatitis due to combined sensitization to palladium and platinum. Patch testing showed strong and persistent allergic patch test reactions to palladium chloride (1% pet.), ammonium tetrachloroplatinate (0.25% pet.), and a palladium metal plate. A platinum metal plate showed a weaker reaction. Histological examination of a biopsy from the test site of palladium chloride (1% pet.) at D3 showed both eczematous and lichenoid changes.

Rapid and unbiased estimation of the volume of cutaneous malignant melanoma using Cavalieri's principle.

The Cavalieri volume estimator has been employed to determine the macroscopic tumor volume of 34 cutaneous malignant melanomas. With this rapid and unbiased method using histological specimens from slabs of known thickness, tumor volumes between 3.9 mm3 and 841.5 mm3 were found. The coefficient of error (CE) for tumor volumes ranged between 0.028 and 0.141, with a combined group CE of 0.043. There was a remarkably good correlation between tumor volume and maximal vertical tumor thickness estimated according to Breslow, with a correlation coefficient of r = 0.86 for all tumors, and of r = 0.82, if the one extremely big tumor is omitted. Both inter- and intraobserver variability was very low, with only approximately 1-2% difference. Thus, the method described allows for the reproducible, rapid, and unbiased estimation of tumor volume independent of the shape of the tumor.

Expression of CD44 isoforms in basal cell carcinomas.

The expression of CD44 isoforms (CD44std, CD44v6, CD44v10) was investigated by an immunohistochemical technique in 42 basal cell carcinomas (BCC) of the superficial and nodular variety. All BCCs studied displayed very low amounts of CD44std, a receptor for hyaluronic acid. Except for single CD44std-positive cells located preferentially in the central parts of the BCC nests, the bulk of the tumour formations were CD44std-negative. CD44v6 showed a heterogeneous distribution pattern accentuated in the peripheral palisading tumour cells. In superficial BCCs, the labelling intensity for CD44v6 increased with the size of the tumour nests. CD44v10 was not detectable in BCCs. Our findings support the notion that CD44v6 is not linked to the metastatic proclivity of tumours originating from keratinocytes. We suggest that the very low expression of the receptor for hyaluronic acid (CD44std) may be one of the factors which block the formation of metastases from BCCs.

Integrin molecules: a clue to the non-metastasizing behaviour of basal cell carcinomas?

Does the integrin profile of basal cell carcinomas explain their non-metastasizing behaviour? Immunohistochemical Investigation of nodular (n = 31) and superficial (n = 17) tumours yielded a strong expression of alpha 2, alpha 3, alpha 6, beta 1, and beta 3 subunits and a weak expression of alpha 4 subunits by the epithelial tumour component. alpha 5 subunits were focally detected in superficial basal cell carcinomas but not in the nodular type. Tumour cells were nearly devoid of alpha v subunits. The integrin profile of basal cell carcinomas does not differ essentially from that of metastasizing tumour varieties and cannot be regarded as a major reason for the non-metastasizing phenotype of basal cell carcinomas.

Differential expression of heat shock protein 70 in well healing and chronic human wound tissue.

Heat shock protein 70 (hsp 70) is an important member of the heat shock protein family, which is induced by different forms of stress. We attempted to find out if hsp 70 is also involved in wound healing, which likewise resembles a stress situation for cells too. Therefore we collected tissue samples from well healing and chronic human wound tissue. We used Northern- and Western-blot analysis to study the expression of hsp 70. At the protein level we found a strong correlation between well healing wounds and high expression of hsp 70, whereas chronic wounds showed no or weak expression. Interestingly hsp 70 mRNA did not show this significant correlation, displaying a variant expression pattern in the same kind of wound tissue, possibly due to unknown posttranscriptional regulating step, which has to be investigated in further studies. To localize hsp 70 mRNA and protein was used insitu hybridization and immunohistochemistry. Both displayed an overexpression in endothelial cells of capillary vessels.