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Treatment of the facial angiofibromas of tuberous sclerosis.

Tuberous sclerosis is an inherited syndrome with mental retardation, epilepsy, and acne rosacea being the classic triad of manifestations. The facial skin problems can present a cosmetic deformity or, as in the three patients presented here, can produce difficulties with hygiene and nasal breathing. Various approaches to treatment have been described over the last century, but no long-term results have been presented. Because of the full-thickness skin involvement, complete removal is not practical, and treatment should be directed toward acceptable long-term results with minimal surgical morbidity. Shaving and dermabrasion of the involved area produce very satisfactory results, but long-term follow-up of approximately 10 years reveals that there is a variable amount of recurrence and that subsequent treatment will be required.

Adult↗

Necrotizing vasculitis of the skin and uterine cervix associated with minocycline therapy for acne vulgaris.

In recent years, minocycline has become a commonly used agent for the treatment of acne vulgaris and rosacea. With this increased use have come reports of severe and in some cases life-threatening toxicity, often occurring in otherwise healthy young women after prolonged courses of minocycline. These adverse reactions include hepatotoxicity, drug-induced lupus erythematosus, eosinophilic pneumonitis, and hypersensitivity syndrome. We describe a 35-year-old woman who had necrotizing vasculitis of the skin and uterine cervix after 2 years of minocycline therapy for acne vulgaris. Skin and cervical biopsies revealed acute inflammation involving through-and-through necrosis of vessel walls with thrombosis, focal fibrinoid change, and a perivascular lymphohistiocytic infiltrate. The disease fully resolved within 3 months of discontinuance of the minocycline therapy. Patients should be informed of these rare but potentially serious adverse effects before the initiation of minocycline therapy. Early recognition of these complications can result in complete resolution.

Acne Vulgaris↗

The different mechanisms of gametophytic self-incompatibility.

Self-incompatibility (SI) involves the recognition and rejection of self or genetically identical pollen. Gametophytic SI is probably the most widespread of the SI systems and, so far, two completely different SI mechanisms, which appear to have evolved separately, have been identified. One mechanism is the RNase system, which is found in the Solanaceae, Rosaceae and Scrophulariaceae. The other is a complex system, so far found only in the Papaveraceae, which involves the triggering of signal transduction cascade(s) that result in rapid pollen tube inhibition and cell death. Here, we present an overview of what is currently known about the mechanisms involved in controlling pollen tube inhibition in these two systems.

Calcium Signaling↗

Saponin biosynthesis in Saponaria vaccaria. cDNAs encoding beta-amyrin synthase and a triterpene carboxylic acid glucosyltransferase.

Saponaria vaccaria (Caryophyllaceae), a soapwort, known in western Canada as cowcockle, contains bioactive oleanane-type saponins similar to those found in soapbark tree (Quillaja saponaria; Rosaceae). To improve our understanding of the biosynthesis of these saponins, a combined polymerase chain reaction and expressed sequence tag approach was taken to identify the genes involved. A cDNA encoding a beta-amyrin synthase (SvBS) was isolated by reverse transcription-polymerase chain reaction and characterized by expression in yeast (Saccharomyces cerevisiae). The SvBS gene is predominantly expressed in leaves. A S. vaccaria developing seed expressed sequence tag collection was developed and used for the isolation of a full-length cDNA bearing sequence similarity to ester-forming glycosyltransferases. The gene product of the cDNA, classified as UGT74M1, was expressed in Escherichia coli, purified, and identified as a triterpene carboxylic acid glucosyltransferase. UGT74M1 is expressed in roots and leaves and appears to be involved in monodesmoside biosynthesis in S. vaccaria.

Amino Acid Sequence↗

Purification and Characterization of a Novel (R)-Mandelonitrile Lyase from the Fern Phlebodium aureum.

Using high-performance liquid chromatography and nuclear magnetic resonance we identified vicianin as the cyanogenic compound of Phlebodium aureum. The (R)-hydroxynitrile lyase involved during cyanogenesis in the catabolism of the aglycon ([R]-mandelonitrile) was purified to apparent homogeneity. The purified holoenzyme is a homomultimer with subunits of Mr = 20,000. At least three isoforms of the enzyme exist. In contrast to other hydroxynitrile lyases, mandelonitrile lyase (MDL) from P. aureum was not inhibited by sulfhydryl- or hydroxyl-modifying reagents, suggesting a different catalytic mechanism. The enzyme is active over a broad temperature range, with maximum activity between 35 and 50[deg]C, and a pH optimum at 6.5. In contrast to (R)-MDLs isolated from several species of the Rosaceae family, (R)-MDL from P. aureum is not a flavoprotein. The substrate specificity was investigated using immobilized enzyme and diisopropyl ether as solvent. The addition of cyanide to aromatic and heterocyclic carbonyls is catalyzed by this (R)-MDL, whereas aliphatic carbonyls are poorly converted.

Journal Article↗

Molecular cloning of mannose-6-phosphate reductase and its developmental expression in celery.

Compared with other primary photosynthetic products (e.g. sucrose and starch), little is known about sugar alcohol metabolism, its regulation, and the manner in which it is integrated with other pathways. Mannose-6-phosphate reductase (M6PR) is a key enzyme that is involved in mannitol biosynthesis in celery (Apium graveolens L.). The M6PR gene was cloned from a leaf cDNA library, and clonal authenticity was established by assays of M6PR activity, western blots, and comparisons of the deduced amino acid sequence with a celery M6PR tryptic digestion product. Recombinant M6PR, purified from Escherichia coli, had specific activity, molecular mass, and kinetic characteristics indistinguishable from those of authentic celery M6PR. Sequence analyses showed M6PR to be a member of the aldo-keto reductase superfamily, which includes both animal and plant enzymes. The greatest sequence similarity was with aldose-6-phosphate reductase (EC 1.1.1.200), a key enzyme in sorbitol synthesis in Rosaceae. Developmental studies showed M6PR to be limited to green tissues and to be under tight transcriptional regulation during leaf initiation, expansion, and maturation. These data confirmed a close relationship between the development of photosynthetic capacity, mannitol synthesis, and M6PR activity.

Amino Acid Sequence↗

Evidence for the involvement of an oxidative stress in the initiation of infection of pear by Erwinia amylovora.

Involvement of an oxidative burst, usually related to incompatible plant/pathogen interactions leading to hypersensitive reactions, was investigated with Erwinia amylovora, the causal agent of fire blight of Maloideae subfamily of Rosaceae, in interaction with pear (Pyrus communis; compatible situation) and tobacco (Nicotiana tabacum; incompatible situation). As expected, this necrogenic bacterium induced in tobacco a sustained production of superoxide anion, lipid peroxidation, electrolyte leakage, and concomitant increases of several antioxidative enzymes (ascorbate peroxidases, glutathion reductases, glutathion-S-transferases, and peroxidases), in contrast to the compatible pathogen Pseudomonas syringae pv tabaci, which did not cause such reactions. In pear leaves, however, inoculations with both the disease- and the hypersensitive reaction-inducing bacteria (E. amylovora and P. syringae pv tabaci, respectively) resulted in superoxide accumulation, lipid peroxidation, electrolyte leakage, and enzyme induction at similar rates and according to equivalent time courses. The unexpected ability of E. amylovora to generate an oxidative stress even in compatible situation was linked to its functional hrp (for hypersensitive reaction and pathogenicity) cluster because an Hrp secretion mutant of the bacteria did not induce any plant response. It is suggested that E. amylovora uses the production of reactive oxygen species as a tool to provoke host cell death during pathogenesis to invade plant tissues. The bacterial exopolysaccharide could protect this pathogen against the toxic effects of oxygen species since a non-capsular mutant of E. amylovora induced locally the same responses than the wild type but was unable to further colonize the plant.

Ascorbate Peroxidases↗

Structural and transcriptional analysis of the self-incompatibility locus of almond: identification of a pollen-expressed F-box gene with haplotype-specific polymorphism.

Gametophytic self-incompatibility in Rosaceae, Solanaceae, and Scrophulariaceae is controlled by the S locus, which consists of an S-RNase gene and an unidentified "pollen S" gene. An approximately 70-kb segment of the S locus of the rosaceous species almond, the S haplotype-specific region containing the S-RNase gene, was sequenced completely. This region was found to contain two pollen-expressed F-box genes that are likely candidates for pollen S genes. One of them, named SFB (S haplotype-specific F-box protein), was expressed specifically in pollen and showed a high level of S haplotype-specific sequence polymorphism, comparable to that of the S-RNases. The other is unlikely to determine the S specificity of pollen because it showed little allelic sequence polymorphism and was expressed also in pistil. Three other S haplotypes were cloned, and the pollen-expressed genes were physically mapped. In all four cases, SFBs were linked physically to the S-RNase genes and were located at the S haplotype-specific region, where recombination is believed to be suppressed, suggesting that the two genes are inherited as a unit. These features are consistent with the hypothesis that SFB is the pollen S gene. This hypothesis predicts the involvement of the ubiquitin/26S proteasome proteolytic pathway in the RNase-based gametophytic self-incompatibility system.

Amino Acid Sequence↗

Loss of pollen-S function in two self-compatible selections of Prunus avium is associated with deletion/mutation of an S haplotype-specific F-box gene.

Recently, an S haplotype-specific F-box (SFB) gene has been proposed as a candidate for the pollen-S specificity gene of RNase-mediated gametophytic self-incompatibility in Prunus (Rosaceae). We have examined two pollen-part mutant haplotypes of sweet cherry (Prunus avium). Both were found to retain the S-RNase, which determines stylar specificity, but one (S3' in JI 2434) has a deletion including the haplotype-specific SFB gene, and the other (S4' in JI 2420) has a frame-shift mutation of the haplotype-specific SFB gene, causing amino acid substitutions and premature termination of the protein. The loss or significant alteration of this highly polymorphic gene and the concomitant loss of pollen self-incompatibility function provides compelling evidence that the SFB gene encodes the pollen specificity component of self-incompatibility in Prunus. These loss-of-function mutations are inconsistent with SFB being the inactivator of non-self S-RNases and indicate the presence of a general inactivation mechanism, with SFB conferring specificity by protecting self S-RNases from inactivation.

Amino Acid Substitution↗

Anti-inflammatory effects of antimicrobial agents: an in vivo study.

Antimicrobials are used emperically in a variety of inflammatory dermatoses such as rosacea and dermatitis herpetiformis, although these diseases are not believed to be of bacterial etiology. We have used potassium iodide ointment to induce follicular pustules and have found in this in vivo model properties of antimicrobials not related to their antibacterial actions. Topical demethylchlortetracycline and erythromycin (5%) lead to suppression of KI-induced inflammation (erythema, pustules) and systemic use of these drugs as well as diaminodiphenylsulfone produces the same effect.

Administration, Oral↗

The histologic spectrum of cutaneous sarcoidosis: a study of twenty-eight cases.

BACKGROUND: Naked sarcoidal granulomas (NSGs) are the characteristic histologic finding in sarcoidosis. This descriptive study was designed to identify the frequency of other histologic changes in cutaneous sarcoidosis. METHODS: The slides from 28 sequential biopsies previously diagnosed as sarcoidosis in patients with known systemic sarcoidosis were reviewed. RESULTS: Classic NSGs were identified in 25 biopsies (89%). Four biopsies contained tuberculoid granulomas, two with neutrophils suggesting infection (cultures negative). Five biopsies contained interstitial granulomas that resembled granuloma annulare and necrobiosis lipoidica in one case each. Additional histologic findings included birefringent foreign material in 14 biopsies (50%), focal necrosis (43%), elastophagocytosis (39%), linear peri-neural granulomas resembling leprosy (25%), increased dermal mucin (18%) and lichenoid inflammation (14%) [two with plasma cells resembling syphilis (7%)]. In all but three cases, the clinical morphology of the lesions suggested sarcoidosis. Special stains for mycobacteria and fungi were negative. CONCLUSIONS: The histologic changes in cutaneous sarcoidosis are more diverse than previously recognized. In sarcoidosis, foreign material may be a frequent nidus for cutaneous granuloma formation. Histologic examination without the clinical history could lead to a misdiagnosis of leprosy, syphilis, other infectious granulomas, rosacea, granuloma annulare, necrobiosis lipoidica, and foreign body reaction in selected cases from this series.

Adult↗

Influence of oral metronidazole on the endocrine milieu and sebum excretion rate.

As part of a study of the mechanism of metronidazole's efficacy in the treatment of acne and rosacea, its effects on the endocrine milieu and sebum excretion rate were assessed. Thirteen healthy males received oral metronidazole treatment (500 mg/day) for 4 weeks. Serum sex hormone levels were determined in all 13 subjects and the sebum excretion rate was determined in seven of them, before and after treatment. We measured serum levels of estrone (E1), estradiol (E2), total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG). There were no significant changes in E1, T, FT, DHT, or SHBG levels, but E2 and DHEA-S levels decreased significantly after treatment. In all seven subjects in whom the sebum excretion rates were determined, the amount of facial skin surface lipids decreased significantly after treatment. These results suggest that metronidazole exerts its clinical effects through suppressing the sebum excretion by a mechanism other than anti-androgenic action.

Administration, Oral↗

Two cases of angiosarcoma of the face.

Angiosarcoma is a rare vascular malignant tumor most commonly seen on the scalp of elderly people. We report here two cases of angiosarcoma of the face in 74- and 75-year-old males. It is very unusual to find the development of an angiosarcoma with a rosacea on the face. To the best of our knowledge, only three such cases have been reported.

Aged↗

Respiratory allergy to peach leaves and lipid-transfer proteins.

BACKGROUND: Several lipid-transfer proteins (LTPs) have been identified as important food allergens, especially in fruits of the Rosaceae family. The major peach (Prunus persica) allergen has been identified, sequenced and designated Pru p 3. OBJECTIVE: To present Pru p 3 as an aeroallergen able to induce occupational asthma. METHODS: A thorough investigation was performed in a fruit grower with occupational asthma. Skin prick-prick tests with peach leaves and prick tests with perennial respiratory allergens and pollens, fruits and peach leaf extracts were done. Serum-specific IgE was tested for peach leaf, peach fruit, peach skin and respiratory allergens that were positive in skin prick tests. Specific bronchial provocation tests (BPTs) with extracts of peach leaf were also done. Before and 24 h after the BPT, BPTs with methacholine and sputum induction were done. The IgE reactivity pattern to peach leaf and fruit extracts and to Pru p 3 was identified by using SDS-PAGE and immunoblotting. Blotting inhibition of peach leaf extract by Pru p 3 was also performed. The putative allergen was quantified in leaf and fruit skin extracts with ELISA based on an anti-Pru p 3 antibody. RESULTS: Skin tests were positive for peach leaf and fruit. The BPT was positive, with immediate and delayed response. This test induced a decrease in PD20 (dose of agonist that induces a 20% fall in FEV1) methacholine and an increase in eosinophils and eosinophil cationic protein in sputum. Peach leaf extract contained concentrations of Pru p 3 similar to those found in peach skin. Specific IgE immunodetection showed that patient's sera reacted with Pru p 3, and with a single major band from the peach leaf extract fully inhibited by Pru p 3. CONCLUSION: Pru p 3 from peach leaves can act as a respiratory allergen and cause occupational rhinoconjunctivitis and asthma.

Adult↗

Natural and recombinant molecules of the cherry allergen Pru av 2 show diverse structural and B cell characteristics but similar T cell reactivity.

BACKGROUND: Cherry allergy is often reported in the context of allergy to other fruits of the Rosaceae family and pollinosis to trees because of cross-reactive allergens. Allergic reactions to cherry are reported by 19-29% of birch pollen-allergic patients. Pru av 2, identified as a thaumatin-like protein (TLP) from sweet cherry, was recognized by the majority of cherry-allergic patients in immunoblotting. OBJECTIVES: In order to investigate the structural characteristics and the immunoglobulin (Ig)E- and T cell reactivity of cherry-derived TLP, recombinant Pru av 2 was expressed in Escherichia coli and natural Pru av 2 was purified. METHODS: Parallel-His and FLAG expression vectors were used for recombinant production of Pru av 2 in the cytoplasm and the periplasm of E. coli. Natural Pru av 2 was purified from fresh cherries and verified by N-terminal sequencing. Structural characterization was performed using circular dichroism (CD) measurements, and the biologic activity was measured in a glucanase assay. Using cherry-specific sera, the IgE-binding ability of recombinant and natural Pru av 2 was investigated in IgE-ELISA and the T cell reactivity was studied in proliferation assays. Results Natural Pru av 2 revealed thaumatin-like structural features and bound IgE of 50% of cherry-allergic patients. It was demonstrated to be enzymatically active. Recombinant Pru av 2 expressed in the cytoplasm of E. coli exhibited a slightly different folding compared with the natural protein. It was not recognized by IgE from cherry-allergic subjects, but retained the ability to stimulate T lymphocytes. Periplasmic recombinant Pru av 2 was able to bind an anti-grape TLP antibody and cherry-specific IgE. CONCLUSIONS: We prepared two recombinant model TLPs from cherry, and compared their molecular characteristics as well as their IgE-binding activity and T cell interactions in relation to the natural counterpart. The cytoplasmic recombinant Pru av 2 can be used as a hypoallergenic variant in allergen-specific immunotherapy, whereas the periplasmic protein can be included in a component-resolved diagnosis.

Adult↗

The role of profilin and lipid transfer protein in strawberry allergy in the Mediterranean area.

BACKGROUND: In contrast to other Rosaceae fruit, only few cases of patients with adverse reactions to strawberry are listed in literature. OBJECTIVE To identify allergenic proteins in strawberry and to express and characterize recombinant strawberry lipid transfer protein (LTP; rFra a 3). METHODS: Established apple-allergic patients were recruited on the basis of a reported allergic reaction to strawberry (n=28, confirmed by double-blind placebo-controlled food challenge in four patients) or on the basis of IgE reactivity to LTP (n=34). Sensitization to purified natural and recombinant allergens was assessed by RAST, immunoblot (inhibition) and basophil histamine release (BHR). A strawberry cDNA library was screened for genes homologous to known fruit allergens. Fra a 3 was cloned and expressed in the yeast Pichia pastoris and compared with peach and apple LTP by RAST, immunoblot-inhibition and BHR tests. RESULTS: Genes homologous to Bet v 1, Bet v 6, profilin and LTP were identified in a strawberry cDNA library. In BHR the rFra a 3 induced histamine release at a 100-fold higher concentration than peach LTP. RAST inhibition showed high cross-reactivity to peach and apple LTP, although IgE reactivity was lower by a factor 5. On strawberry immunoblot, patients' IgE showed reactivity to a Bet v 1 homologue, profilin, LTP and high-molecular weight bands. CONCLUSION: In addition to a Bet v 1 homologue, strawberry also contains IgE-binding profilin and LTP. The rFra a 3 has less allergenic potency than peach and apple LTP, and therefore is an interesting tool for future immunotherapy. Fra a 3 does not seem to be clinically relevant.

Allergens↗

Occult basal-cell carcinoma within rhinophyma.

Rhinophyma, the end stage in the development of rosacea, is characterized by sebaceous hyperplasia, fibrosis, follicular plugging and telangiectasia. Although it is commonly considered a cosmetic problem, it can result in gross distortion of soft tissue and in airway obstruction. Previously, basal-cell carcinoma (BCC) has been reported in association with rhinophyma. We are reporting an additional case in which the patient had been delaying treatment because of the 'cosmetic nature' of this condition.

Basal Cell Carcinoma↗

Acinetobacter baumanii folliculitis in a patient with AIDS.

Gram-negative folliculitis usually involves the face and develops in patients with acne or rosacea during long-term antibiotic therapy. Numerous pathogens have been found, but not, until now, Acinetobacter baumanii which has previously been recognized as an important cause of nosocomial infections and hospital outbreaks. We report here a case of A. baumanii folliculitis of the face, neck, arms and upper part of trunk in a patient with AIDS responding to intravenous treatment with ticarcillin-clavulanic acid. The bacterium was not found on healthy skin and the source of the infection remained unknown.

AIDS-Related Opportunistic Infections↗