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Biomedical subjects

L Weber

Publications and source records attributed to L Weber.

At least 37 records · Page 2Linked to original sources
PubMed2002

Childhood epidermolysis bullosa acquisita: a novel variant with reactivity to all three structural domains of type VII collagen.

Most patients with epidermolysis bullosa acquisita develop an autoimmune response to the non-collagenous (NC) 1 domain of type VII collagen. We report a 4-year-old girl of white European descent presenting with widespread blistering disease involving the face, hands, genital area and oral mucosa. Histopathology revealed subepidermal blisters, and linear deposits of IgG and C3 were seen along the dermal-epidermal junction on direct immunofluorescence (IF) microscopy of a perilesional skin biopsy. On indirect IF microscopy, circulating autoantibodies exclusively stained the dermal side of 1 mol L-1 NaCl-split skin. The patient's IgG autoantibodies labelled a 290-kDa protein on Western blotting of dermal extracts, and reacted with the NC1, NC2 and triple helical domains of type VII collagen on immunoblotting of recombinant and cell-derived fragments obtained by pepsin and collagenase digestion of the full-length protein. Oral methylprednisolone and dapsone led to clearance of lesions, which healed with mild scarring and milia formation. Treatment was discontinued after 1 year and the patient has now been in remission for more than 3 years.

Autoantibodies↗
PubMed2001

Reactivity of the inversely polarized phosphaalkenes RP=C(NMe2)2 (R = tBu, Me3Si, H) towards arylcarbene complexes [(CO)5M=C(oEt)Ar] (Ar= Ph, M = Cr, W; Ar = 2-MeC6H4, 2-MeOC6H4, M = W).

The reaction of the arylated Fischer carbene complexes [(CO)5M=C(OEt)Ar] (Ar=Ph; M = Cr, W; 2-MeC6H4; 2-MeOC6H; M = W) with the phosphaalkenes RP=C(NMe2), (R=tBu, SiMe3) afforded the novel phosphaalkene complexes [[RP=C(OEt)Ar]M(CO)5] in addition to the compounds [(RP=C(NMe2)2]M(CO)5]. Only in the case of the R = SiMe3 (E/Z) mixtures of the metathesis products were obtained. The bis(dimethylamino)methylene unit of the phosphaalkene precursor was incorporated in olefins of the type (Me2N)2C=C(OEt)(Ar). Treatment of [(CO)5W=C(OEt)(2-MeOC6H4)] with HP=C(NMe2)2 gave rise to the formation of an E/Z mixture of [[(Me2N)2CH-P=C(OEt)(2-MeOC6H4)]W(CO)5] the organophosphorus ligand of which formally results from a combination of the carbene ligand and the phosphanediyl [P-CH(NMe2)2]. The reactions reported here strongly depend on an inverse distribution of alpha-electron density in the phosphaalkene precursors (Pdelta Cdelta+), which renders these molecules powerfu] nucleophiles.

Journal Article↗
PubMed2001

Efficacy of ultrasound B-scan compared with physical examination in follow-up of melanoma patients.

BACKGROUND: The value of ultrasound B-scan for routine follow-up of melanoma patients still is not generally accepted. Therefore, the authors compared the efficacy of physical examination (PE) with ultrasound B-scan (UBS) for detection of regional tumor recurrence in melanoma patients. The aim of the current study was to evaluate whether early detection of metastases improves relapse-free and overall survival. METHODS: For a period of 4 years, 829 consecutive melanoma patients were followed prospectively. Physical examination of 3011 patients and concomitant UBS of in-transit routes and regional lymph node basins were performed. Suspicious lesions were diagnosed by fine-needle aspiration cytology and pathology. RESULTS: During the study period, 242 (90.6%) of 267 patients with melanoma recurrences were first recognized by PE or UBS within the routine follow-up program. The sensitivities of both methods differed significantly (P = 0.001). Metastases were detected by PE in only 61 of 242 recurrences (25.2%, 95% confidence interval [CI]: 19.9-31.2%), whereas UBS revealed 240 recurrences (99.2%, 95% CI: 97.3-99.6%). The specificity was 98.4% (95% CI: 97.8-98.8%) and 98.3% (95% CI: 97.7-98.7%), respectively. Survival of 103 patients who presented with a first nodal melanoma recurrence was followed and analyzed by multiple Cox regression. Overall survival was affected by the diameter of the largest metastasis (P = 0.001) and the number of metastatic lesions (P = 0.012). CONCLUSION: The study found that ultrasound B-scan was highly effective in the early detection of regional melanoma metastases compared with physical examination. Earlier detection of such metastases seemed to result in improved overall survival.

Adolescent↗
PubMed2001

Interferon-gamma in 5 patients with cutaneous radiation syndrome after radiation therapy.

BACKGROUND: Irradiation can cause acute inflammatory responses as well as chronic fibrotic alterations of the skin. Cutaneous radiation fibrosis evokes a complex of therapeutic problems. However, therapeutic options, apart from surgical approaches, are limited. PATIENTS AND METHODS: Five female patients suffering from severe cutaneous fibrosis were treated with interferon-gamma on a low-dose regimen, 3 x 100 microg/week subcutaneously for 6 months, then once per week for another 6 months. In 4 patients, skin thickness was measured with high-frequency (20 MHz) ultrasound in a clinically well-defined target skin lesion. In 1 patient, nuclear magnetic resonance imaging was performed to quantify the extent of cutaneous radiation fibrosis and to monitor the therapeutic outcome. RESULTS: All patients suffered from radiation-induced cutaneous fibrosis. Additionally, in 1 patient, a fistula, as assessed by lymph vessel scintigraphy, and in another patient a radiation ulcer was diagnosed. In all patients, reduction of radiation-induced fibrosis could be documented. Both fistula and radiation ulcer regressed completely under interferon-gamma therapy. CONCLUSION: Low-dose interferon-gamma therapy is a new and effective treatment modality for cutaneous radiation fibrosis caused by radiation therapy. The positive impact of interferon-gamma on our patients warrants randomized double-blind trials on therapy of radiation fibrosis.

Adolescent↗
PubMed2001

[Circumscribed myxedema of the upper and lower extremities--a rate cutaneous manifestation of Basedow disease. Case report and review of the literature].

A 63 year old man presented with circumscribed myxedema surprisingly involving both the arms and legs. He had a history of thyroiditis with hyperthyroidism and an infiltrative ophthalmopathy leading to the diagnosis of Graves disease. At the time of presentation the patient had already been treated with radioactive iodine and undergone endonasal orbital decompression. We review the pathogenesis and treatment of Graves disease and discuss the first therapeutic attempt with PUVA-bath therapy.

Biopsy↗
PubMed2001

Competitive polymerase chain reaction used to diagnose cutaneous leishmaniasis in German soldiers infected during military exercises in French Guiana.

A competitive polymerase chain reaction (PCR) followed by enzyme-linked-immunoassay-based verification of PCR products has been developed, which facilitated the diagnosis of leishmaniasis in two German soldiers who underwent survival training in the jungle of French Guiana and returned with therapy-resistant pyoderma-like lesions. After treatment with liposomal amphotericin B, the skin manifestations disappeared, and leishmania DNA could no longer be detected by PCR. In the context of growing military involvement in areas where leishmaniasis is prevalent, this assay may help detect or, due to its internal controls, exclude cases of infection with this parasite.

Adult↗
PubMed2001

Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve.

Rapid nerve impulse conduction depends on specialized membrane domains in myelinated nerve, the node of Ranvier, the paranode, and the myelinated internodal region. We report that GPI-linked contactin enables the formation of the paranodal septate-like axo-glial junctions in myelinated peripheral nerve. Contactin clusters at the paranodal axolemma during Schwann cell myelination. Ablation of contactin in mutant mice disrupts junctional attachment at the paranode and reduces nerve conduction velocity 3-fold. The mutation impedes intracellular transport and surface expression of Caspr and leaves NF155 on apposing paranodal myelin disengaged. The contactin mutation does not affect sodium channel clustering at the nodes of Ranvier but alters the location of the Shaker-type Kv1.1 and Kv1.2 potassium channels. Thus, contactin is a crucial part in the machinery that controls junctional attachment at the paranode and ultimately the physiology of myelinated nerve.

Aging↗
PubMed2000

Ultrasound-guided fine-needle aspiration cytology in the early detection of melanoma metastases.

BACKGROUND: The early detection and treatment of tumor recurrences in melanoma patients is dependent on reliable, sensitive, and specific techniques to verify suspected tumor metastases. As of now, fine-needle aspiration cytology (FNAC) has yet to establish itself in the routine follow-up of melanoma patients. METHODS: FNAC procedures were performed in melanoma patients with palpable tumors or nonpalpable, ultrasonically suspicious lesions. Cytodiagnostic evaluation of fine-needle samples obtained from suspicious lesions was performed morphologically. Findings were validated either by histopathologic diagnosis or prolonged clinical follow-up. RESULTS: The cytologic examination of 739 FNACs from 330 melanoma patients was conducted within 1 day of sampling. Complications were not observed. This study showed a sensitivity of 97.9% and a specificity of 100.0%. Moreover, in 158 FNACs derived from lesions with a diameter less than 1 cm a sensitivity of 94.6% was achieved. Diagnosis of metastatic melanoma with unknown primary tumor was established in 20 cases. CONCLUSIONS: FNAC is very reliable for the early detection of melanoma metastases. FNAC is a swift method free of complications and is able to replace diagnostic surgery completely for nonmalignant lesions in a large number of patients. Moreover, FNAC is especially useful in combination with ultrasound in melanoma follow-up and can enable diagnosis of lesions smaller than 1 cm without impairment of sensitivity or specificity.

Adolescent↗
PubMed2000

Vegf, Vegf-B, Vegf-C and their receptors KDR, FLT-1 and FLT-4 during the neoplastic progression of human colonic mucosa.

Because the crucial role of angiogenesis has been demonstrated in tumor growth and metastasis, the present study was undertaken to characterize the relative expression of vascular endothelial growth factors VEGF (vascular endothelial growth factor), VEGF-B, VEGF-C, and their receptors KDR (kinase insert domain-containing receptor), FLT-1 (fms-like tyrosine kinase), and FLT-4 in human colonic cancers, in relation to the Astler-Coller pathological classification, and to prognosis. VEGF and VEGF-B gene expression was quantified by Northern blot in 72 tumor samples matched with control tissues. VEGF gene expression was 1.4 times higher in adenocarcinomas than in control tissues (p = 0.02), but did not increase further between Astler-Coller tumor stages A and D, and did not correlate with disease recurrence for patients at stages B2 or C. In adenomas, VEGF mRNA levels were not significantly different from those in the paired control colonic mucosa. The expression pattern of VEGF isoforms, mainly identified by RT-PCR (reverse-transcriptase-coupled polymerase chain reaction) as VEGF121 and VEGF165 and to a lesser extent VEGF189, was comparable in tumor and control tissues. VEGF-B mRNA levels were unchanged during the neoplastic progression of colonic mucosa. In contrast to KDR and FLT-4, the expression of VEGF-C and FLT-1 genes increased in some pathological tissues. These results provide evidence that the early and sustained increase in VEGF transcripts and the expression of multiple angiogenic factors and receptors contribute to the development of colon cancer, and thus constitute a putative target for anti-angiogenic drug therapy.

Adult↗
PubMed2000

[Sporotrichosis--fixed cutaneous and lymphocutaneous form].

Two patients were infected with sporotrichosis; one had the fixed cutaneous form, the other the lymphocutaneous form. Sporotrichosis schenckii was identified in both with a culture from a tissue biopsy. Both patients were successfully treated with itraconazole, one received 100 mg and the other 200 mg itraconazole daily over a 3 months period.

Adult↗
PubMed2000

The radiation accident in Georgia: clinical appearance and diagnosis of cutaneous radiation syndrome.

BACKGROUND: Eleven male Georgian soldiers were accidentally exposed to radiation by cesium 137 during their training in a military exercise camp in Lilo, Georgia between November 1996 and May 1997. OBJECTIVE: The characteristic sequelae of accidental cutaneous irradiation and available diagnostic methods are described. METHODS: Magnetic resonance imaging (MRI) of radiation ulcers was performed in all patients; thermography was performed in 2. In 7 patients ulcers and white macules were examined with high-frequency 20 MHz sonography; histologic results were obtained from all patients. RESULTS: Predominant lesions were radiation ulcers in 11 patients and white hairless macules in 7. MRI showed ulcers down to the muscles and an increase of signal intensity in the musculature in 9 cases. The corresponding muscle histology demonstrated vasculitis in 7 patients and necrosis in 2. In 2 patients, MRI signal intensity of the musculature was normal. In 3 patients, 20 MHz sonography showed dermal defects; 1 patient had cutaneous fibrosis. Thermography demonstrated hypothermic zones with extended inflammatory zones adjacent to the radiation ulcers in both patients examined. CONCLUSION: High-frequency 20 MHz sonography, MRI, and thermography are useful noninvasive methods for diagnosis of the extent of cutaneous radiation syndrome and for therapy planning.

Adult↗
PubMed2000

Simulated molecular evolution in a full combinatorial library.

BACKGROUND: The Darwinian concept of 'survival of the fittest' has inspired the development of evolutionary optimization methods to find molecules with desired properties in iterative feedback cycles of synthesis and testing. These methods have recently been applied to the computer-guided heuristic selection of molecules that bind with high affinity to a given biological target. We describe the optimization behavior and performance of genetic algorithms (GAs) that select molecules from a combinatorial library of potential thrombin inhibitors in 'artificial molecular evolution' experiments, on the basis of biological screening results. RESULTS: A full combinatorial library of 15,360 members structurally biased towards the serine protease thrombin was synthesized, and all were tested for their ability to inhibit the protease activity of thrombin. Using the resulting large structure-activity landscape, we simulated the evolutionary selection of potent thrombin inhibitors from this library using GAs. Optimal parameter sets were found (encoding strategy, population size, mutation and cross-over rate) for this artificial molecular evolution. CONCLUSIONS: A GA-based evolutionary selection is a valuable combinatorial optimization strategy to discover compounds with desired properties without needing to synthesize and test all possible combinations (i.e. all molecules). GAs are especially powerful when dealing with very large combinatorial libraries for which synthesis and screening of all members is not possible and/or when only a small number of compounds compared with the library size can be synthesized or tested. The optimization gradient or 'learning' per individual increases when using smaller population sizes and decreases for higher mutation rates.

Algorithms↗
PubMed2000

High-diversity combinatorial libraries.

The synthesis of complex chemical structures by combinatorial chemistry has gained considerable interest. New chemical methods have been developed that enable the synthesis of compound libraries exhibiting structural diversities similar to those of natural products. The concept of 'chemical genomics' has been introduced, reflecting a new quality of understanding and creating the relationship between diverse artificial chemical structures with the space of biological responses and possible protein ligands.

Combinatorial Chemistry Techniques↗
PubMed2000

Intermittent administration of parathyroid hormone (1-37) improves growth and bone mineral density in uremic rats.

BACKGROUND: Parathyroid hormone (PTH) is secreted in a pulsatile fashion. Continuous infusion of PTH(1-84) resulted in a net decrease in trabecular bone volume. Differential effects have been reported following an intermittent application of PTH. We investigated the effects of a continuous infusion and of an intermittent (2 times daily subcutaneously) administration of PTH(1-37) on growth and bone mineral density (BMD) in healthy and uremic rats. METHODS: Two-stage subtotal nephrectomy was performed on 130 g female Sprague-Dawley rats. PTH(1-37) or solvent was administered through minipumps in sham-operated and uremic rats (60 microg/kg x day for 2 weeks). The effect of intermittent administration was tested with a subcutaneous injection of solvent: 30 microg/kg PTH(1-37) two times per day, 100 pmol calcitriol (C)/kg two times per day, or both. The length (snout-tailtip) and BMD were measured at the start of uremia and at sacrifice. BMD was measured by peripheral quantitative computer tomography at the proximal tibia, 6 and 12 mm distal of the kneejoint space. Femur bone morphology was assessed by x-rays, and calcium content was measured by atomic absorption spectrophotometry. RESULTS: Length gain was not altered by the continuous infusion of PTH. In contrast, it was significantly increased by intermittent PTH (control solvent 5.35 +/- 0.37 cm vs. control PTH 6.19 +/- 0.47 cm; uremia solvent 4.78 +/- 0.20 cm vs. uremia PTH 6.17 +/- 0.36 cm; P < 0.05). Intermittent PTH but not C increased BMD in uremic rats (Delta total BMD 134 + 13.3 vs. 76.3 +/- 11.5 mg/mL; P < 0.05). X-rays revealed increased bone mass following treatment with PTH but not with C. Uremia decreased bone calcium content (64 +/- 0.3 vs. 73. 3 +/- 2.5 mg/mL), which was normalized by PTH (80 +/- 3.6 mg/mL, P < 0.05) but not by C (69 +/- 1.9 mg/mL). CONCLUSION: Pulsatile administration of PTH does not adversely affect, but improves longitudinal growth independent of concomitant treatment with C. At the same time PTH increases BMD and the calcium content of bone.

Animals↗
PubMed2000

Correlation of positive RT-PCR for tyrosinase in peripheral blood of malignant melanoma patients with clinical stage, survival and other risk factors.

The clinical value of the reverse transcription polymerase chain reaction (RT-PCR) assay for tyrosinase in peripheral blood of melanoma patients is still under debate. A total of 212 blood samples from 212 melanoma patients in all clinical stages (AJCC) were examined. Erythrocytes were lysed prior to RNA extraction by phenol precipitation from 2.7 ml of blood. cDNA for tyrosinase PCR was synthesized using random hexamers. Positive tyrosinase RT-PCR results were obtained in 11% of 106 stage I patients, 18% of 56 stage II patients, 31% of 26 stage III patients and 67% of 24 stage IV patients. After a median follow-up of 36 months (range 26-41), stage III patients with positive RT-PCR for tyrosinase had a shortened disease-free interval as compared to negative patients (P < 0.01). In stage IV patients, median overall survival was 8 months in case of a positive RT-PCR in contrast to 12 months in case of a negative test. While univariate analysis showed sex and primary tumour location associated with positive RT-PCR, multiple regression analysis revealed clinical stage and detection of tyrosinase transcripts in peripheral blood as best prognostic factors. Hazard ratios for disease-free survival were 19.7 (confidence interval (CI) 8.53-45.5, P = 0.0001) for metastatic vs primary disease and 2.96 (CI 1.49-5.89, P = 0.002) for positive vs negative tyrosinase RT-PCR. The corresponding hazard ratios for overall survival were 97.0 (CI 12.7-741, P = 0.0001) and 4.33 (CI 1.69-11.1, P= 0.002). Our results emphasize the importance of tyrosinase RT-PCR testing in peripheral blood.

Adult↗