Introducing Elinor for monitoring the governance and management of area-based conservation.

Monitoring the governance and management effectiveness of area-based conservation has long been recognized as an important foundation for achieving national and global biodiversity goals and enabling adaptive management. However, there are still many barriers that prevent conservation actors, including those affected by governance and management systems from implementing conservation activities and programs and from gathering and using data on governance and management to inform decision-making across spatial scales and through time. We explored current and past efforts to assess governance and management effectiveness and barriers actors face in using the resulting data and insights to inform conservation decision-making. To help overcome these barriers, we developed Elinor, a free and open-source monitoring tool that builds on the work of Nobel Prize winner Elinor Ostrom to facilitate the gathering, storing, sharing, analyzing, and use of data on environmental governance and management across spatial scales and for areas under different governance and management types. We consider the process of codesigning and piloting Elinor with conservation scientists and practitioners and the main components of the assessment and online data system. We also consider how Elinor complements existing approaches by addressing governance and management in a single assessment at a high level for different types of area-based conservation, providing flexible options for data collection, and integrating a data system with an assessment that can support data use and sharing across different spatial scales, including global monitoring of the Global Biodiversity Framework. Although challenges will continue, the process of developing Elinor and the tool itself offer tangible solutions to barriers that prevent the systematic collection and use of governance and management data. With broader uptake, Elinor can play a valuable role in enabling more effective, inclusive, and durable area-based conservation.

Introducción de Elinor para el monitoreo de la gobernanza y la gestión de la conservación con base en zonas geográficas Resumen El monitoreo de la efectividad de la gobernanza y de la gestión de la conservación basada en zonas geográficas ha sido reconocido durante mucho tiempo como una base importante para alcanzar las metas nacionales y mundiales de la biodiversidad y permitir un manejo adaptativo. Sin embargo, todavía existen barreras que evitan que los actores de la conservación, incluidos aquellos afectados por los sistemas de gobernanza y gestión, implementen actividades y programas de conservación y recopilen y usen datos de la gobernanza y la gestión para informar las decisiones a lo largo de las escalas espaciales y a través del tiempo. Exploramos los esfuerzos hechos en la actualidad y en el pasado para evaluar la efectividad de la gobernanza y la gestión así como las barreras que los actores enfrentan al usar los datos y el conocimiento resultantes para informar la toma de decisiones de conservación. Para ayudar a derribar estas barreras desarrollamos Elinor, una herramienta de monitoreo gratuita y de software libre que parte del trabajo de la ganadora del Premio Nobel Elinor Ostrom, para facilitar la recopilación, almacenamiento, divulgación, análisis y uso de los datos sobre la gobernanza y la gestión ambiental en las escalas espaciales y para las zonas con diferentes tipos de gobernanza y gestión. Planteamos co­diseñar y pilotear Elinor con los científicos y practicantes de la conservación y usando los componentes principales del sistema de evaluación y de datos en línea. También planteamos cómo Elinor complementa las estrategias existentes al abordar la gobernanza y la gestión en una sola evaluación a un nivel elevado para diferentes tipos de conservación basada en zonas geográficas, lo que proporciona opciones flexibles para la colecta de datos, e integramos un sistema de datos con una evaluación que soporta el uso y divulgación de datos en diferentes escalas espaciales, incluido el Marco Mundial para la Biodiversidad. Aunque los retos seguirán existiendo, el proceso de desarrollo de Elinor y la propia herramienta ofrecen soluciones tangibles a las barreras que previenen la colecta sistemática y el uso de datos de la gobernanza y la gestión. Con una mayor aceptación, Elinor puede tener un papel importante en el momento de hacer posible una conservación basada en zonas geográficas más eficaz, integradora y duradera.

Phylogeny and morphology of new species of Globisporangium.

An isolate originally obtained from pond water in Osaka in 1992 and identified as Pythium marsipium, was subsequently classified as Globisporangium marsipium. According to molecular phylogenetic analyses based on the internal transcribed spacer regions of the nuclear ribosomal RNA and mitochondrial cytochrome c oxidase subunit 1 genes, this isolate was shown to represent a new species, described here as G. lacustre sp. nov. In addition, two further new combinations are introduced in Globisporangium as G. camurandrum and G. takayamanum based on their DNA phylogeny.

Prognostic usefulness of arm circumference and nutritional screening tools in older patients with cardiovascular disease.

BACKGROUND AND AIM: Arm circumference (AC) and nutritional screening tools have been shown to have prognostic capability in patients with cardiovascular disease (CVD). This study aimed to compare the prognostic predictive capabilities of AC and nutritional screening tools in older patients with CVD. METHODS AND RESULTS: The study population consisted of 949 admitted patients ≥60 years old with CVD. Patients underwent AC measurement and nutritional screening before hospital discharge. We used the controlling nutritional status index (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI) as nutritional screening tools. The end point of the study was all-cause mortality. The mean age of the study population was 72.3 ± 7.2 years, and 68.2% of the patients were male. A total of 130 deaths occurred over a median follow-up period of 2.2 years (interquartile range, 1.1-3.8 years). After adjusting for other prognostic factors, AC (hazard ratio [HR]: 0.59; p < 0.001), CONUT (HR: 0.82; p = 0.016), GNRI (HR: 0.77; p = 0.040), and PNI (HR: 0.80; p = 0.014) were significant predictors of mortality. However, adding AC to the multivariate-adjusted model (0.739 vs. 0.714, respectively; p = 0.037), but not CONUT, GNRI, or PNI (0.724, 0.717, and 0.723 vs. 0.714; p = 0.072, p = 0.306, and p = 0.127, respectively), significantly increased the area under the curve on receiver operating characteristic curve. CONCLUSIONS: AC, but not nutritional screening tools, plays a complementary role to preexisting prognostic factors for predicting prognosis in older patients with CVD.

The use of tissue microarrays for semiquantitative evaluation of ATPaseC1 expression is ineffective.

We described earlier the possible role of ATPaseC1 expression as a diagnostic and prognostic marker for oral cancer; others have reported its use for tumors of the lung and breast. We assessed ATPaseC1 expression in a sample of oral squamous cell carcinoma (OSCC) using tissue microarrays (TMAs) to analyze the relation between ATPaseC1 expression and clinical, histopathological and prognostic parameters. We performed a retrospective study of 48 cases of OSCC. We constructed TMAs using two different regions of each tumor. V-ATPaseC1 immunohistochemistry was performed and assessed semiquantitatively. ATPaseC1 staining was observed in most of the neoplastic cells in all tumors. Staining was diffusely cytoplasmic and, to a lesser extent, nuclear. The degree of concordance between the measurements performed in tissue microarray 1 (TMA1) and tissue microarray 2 (TMA2), as evaluated using the intra-class correlation coefficient (ICC), was low. We found great variability in the immunohistochemical staining of the different regions of each tumor. We found 16 cases with mild expression (33.3%), 20 with moderate expression (41.7%) and 12 with intense expression (25%). Differences in the clinical-pathological variables studied were not statistically significant. The difficulty of immunohistochemical evaluation, the heterogeneity of the carcinomas and the fact that evaluation of expression requires semiquantitative analysis render the reliability of the results obtained from TMA-based techniques questionable.

Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.

BACKGROUND: Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is a rare form of congenital myopathy, which is pathologically diagnosed by the presence of more than 99% of type 1 fiber, with no specific structural changes. Its pathogenic mechanism is still unknown. We recently reported that almost all patients with central core disease (CCD) with ryanodine receptor 1 gene (RYR1) mutations in the C-terminal domain had type 1 fibers, nearly exclusively, in addition to typical central cores. OBJECTIVE: To investigate whether CNMDU1 is associated with RYR1 mutation. METHODS: We studied 10 unrelated Japanese patients who were diagnosed to have CNMDU1 based on clinical features and muscle pathology showing more than 99% type 1 muscle fibers. We extracted genomic DNA from frozen muscles and directly sequenced all 106 exons and their flanking intron-exon boundaries of RYR1. RESULTS: Four of 10 patients had a heterozygous mutation, three missense and one deletion, all in the C-terminal domain of RYR1. Two missense mutations were previously reported in CCD patients. Clinically, patients with mutations in RYR1 showed milder phenotype compared with those without mutations. CONCLUSION: Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) in 40% of patients is associated with mutations in the C-terminal domain of RYR1, suggesting that CNMDU1 is allelic to central core disease at least in some patients.

Modifications of PARP Medium Using Fluazinam, Miconazole, and Nystatin for Detection of Pythium spp. in Soil.

The standard Pythium selective medium PARP (pimaricin + ampicillin + rifampicin + pentachloronitrobenzene [PCNB] agar), was modified by replacing PCNB and pimaricin with other antifungal agents. Several antifungal agents such as fluazinam, miconazole, 2,4,5,6-tetrachloroisophthalonitrile (TPN), iminoctadine triacetate, tolclofos-methyl, captan, and nystatin, initially were screened for effects on Pythium growth. Based on these results, the following three media were developed: PARF (pimaricin + ampicillin + rifampicin + fluazinam agar), NARF (nystatin + ampicillin + rifampicin + fluazinam agar), and NARM (nystatin + ampicillin + rifampicin + miconazole agar). New media were comparable with PARP on yield of naturally occurring Pythium spp. from two different types of soil using the soil-dilution plating technique. PARF and NARF were significantly better than PARP on inhibition of non-pythiaceous microbes on the soil-dilution plates, but were significantly lower than PARP on the rate of mycelial growth of six of eight isolates belonging to seven species of Pythium. NARM was equivalent to PARP on inhibition of non-pythiaceous microbes except for Fusarium oxysporum, and was significantly better than PARP on rate of mycelial growth of five of eight isolates of Pythium.

First Report of Pythium aphanidermatum on Basella rubra in Japan.

Basella rubra L. (Indian spinach, Japanese name Tsurumurasaki) is cultivated worldwide as an ornamental and its aerial parts are consumed as a vegetable and health food. A severe rot of leaves, stems, and roots was found on B. rubra cv. Midori grown in a commercial field at Naruto-City (34°11'N, 134°36(E) in Tokushima Prefecture, Japan from May to September 2004. More than 50% of approximately 2,100 plants in the field were destroyed by the disease. Soft, black lesions appeared initially at the base of the stems in 2- to 5-month-old plants and enlarged gradually upward and downward within 2 days after plant injury caused by heavy rainfall. A fluffy, white mass of mycelium appeared on the surface of lesions under moist conditions. A Pythium species was routinely isolated from rotted stems and roots and identified as Pythium aphanidermatum (Edson) Fitzpatrick on the basis of its morphology on a grass leaf water culture (2). Characteristics of isolate OPU743 (NBRC No. 101556, MAFF No. 239847) included hyphae as much as 10 µm wide, terminal oogonia 17.8 to 28.8 µm in diameter, and monoclinous or diclinous antheridia 8.8 to 10.9 µm wide, either terminal or intercalary, with one or rarely two per oogonium. Oospores were aplerotic, 13.5 to 22.6 µm in diameter. Sporangia were terminal or occasionally intercalary, and either inflated filamentous hyphae or complexes of swollen hyphal branches were present in cultures. Cardinal temperatures for growth on potato carrot agar were 10°C minimum, 37°C optimum, and 40°C maximum with a daily radial growth rate of 32.9 mm at 25°C. Pathogenicity tests were conducted on potted 3-month-old B. rubra (cv. Midori). A wound (1 mm deep and 5 mm long made by a razor) on the surface of the stem of the plant was inoculated with an 8-mm-diameter agar disk of isolate OPU743 (grown at 25°C for 48 h on potato dextrose agar) attached to a stem of the plant using a paraffin film. The inoculated plants were placed in transparent plastic bags and kept in a growth chamber at 24 to 26°C with continuous light (82 to 126 µmol·m-2·s-1). The experiment was done four times with three plants in each experiment. The same number of plants was used for the noninoculated control. Dark brown rot of stems and leaves developed on 66.7% of inoculated plants within 2 days after inoculation. P. aphanidermatum reisolated from diseased tissues was morphologically identical to the original isolate OPU743. Noninoculated control plants showed no symptoms. P. aphanidermatum has been described on B. rubra in Brazil (1), but has not been reported from other regions of the world. To our knowledge, this is the first report of P. aphanidermatum on B. rubra in Japan. References: (1) C. F. Robbs. A Lavoura 74:43, 1972. (2) A. J. Van Der Plaats-Niterink. Stud. Mycol. 21:1, 1981.

Distribution of Pythium porphyrae, the Causal Agent of Red Rot Disease of Porphyrae spp., in the Ariake Sea, Japan.

Distribution of Pythium porphyrae, the causal agent of red rot disease of Porphyra spp., in seafloor sediment was investigated in the Ariake Sea, Japan. A total of 170 samples of each 200 ml of sediment was collected from the seafloor at a total of 13 sites across the sea from 1998 to 2002. Each sample was filtered through two layers of nylon mesh with pore sizes of 100 and 15 µm. The residue on 15 µm mesh was assayed by a soil plating technique using a semiselective medium for P. porphyrae and by polymerase chain reaction (PCR) using species-specific primers. P. porphyrae were detected in 6 out of 13 sites and 2 out of 10 sites surveyed by soil plating and PCR, respectively. The representative isolate of P. porphyrae from the sediment was identical to the Porphyra thallus isolate from the same sea based on pathogenicity to the thallus, morphology, and rDNA internal transcribed spacer sequences. Recovery of P. porphyrae propagules in the sediment was up to 60 CFU per 100 ml of the fresh sample and was consistently higher in May than in the other months. The results suggest that P. porphyrae is distributed in the seafloor sediment in a wide area of the Ariake Sea.

First Report of Root Rot of Cocoyam Caused by Pythium myriotylum in Sri Lanka.

Root rot of cocoyam (Xanthosoma sagittifolium L. Schott) caused by Pythium myriotylum Drechsler is a major disease of this crop in Africa (1,2) but is unreported from other regions of the world. During September 1999, commercially grown cocoyam (cv. Ratu-kiri-ala) in Gampaha (7°05'N, 80°00'E), Sri Lanka suffered from severe root rot. Initial symptoms were water-soaked lesions at the root tips that gradually enlarged to rot the entire root system and tuber. Wilting and yellowing of leaves were observed in advanced stages of disease. A Pythium sp. was regularly isolated from the affected roots and an isolate, SC5, was identified as P. myriotylum on the basis of morphology and the internal transcribed spacer (ITS) rDNA sequence. Characteristics of isolate SC5, grown on a grass-leaf water culture (3) were main hyphae up to 8.5 µm wide, oogonia terminal or intercalary (22.5 to 33.8 µm in diameter), antheridia diclinous occasionally monoclinous, one to eight per oogonium, stalks branched, often more or less loosely enveloping the oogonium, antheridium clavate or crook-necked, making apical contact with the oogonium, breadth of antheridium 2.5 to 7.0 µm, oospores aplerotic (17.0 to 22.5 µm in diameter), oospore wall 0.8 to 2.0 µm in thickness, sporangia terminal or intercalary, filamentous, inflated lobulate, and digitate, of variable length, breadth of sporangia 7.0 to 17.5 µm, formed in water; zoospores formed at 25°C, and diameter of encysted zoospores 10.0 to 12.5 µm. Cardinal temperatures on potato carrot agar 8°C minimum, 34°C optimum, and 37°C maximum with daily radial growth rate for 34°C at 32.8 mm. The ITS rDNA sequence of the isolate matched the sequences of P. myriotylum in GenBank (Accession Nos. AB095051 and AF452156) and isolate CBS254.70 used for the species description by van der Plaats-Niterink (3). The sequence of SC5 has been deposited in GenBank, Accession No. DQ102701. Pathogenicity tests used potted cocoyam plants (20 cm high), planted in an autoclaved potting mix. Four agar disks (8 mm in diameter) of isolate SC5 grown at 25°C for 48 h on potato dextrose agar was mashed and injected at a depth of 2 to 3 cm in the soil around the roots. Inoculated plants were placed in transparent plastic bags and kept for 7 days in a growth chamber maintained at 24 to 26°C with continuous light (52 to 98 µmol m-2·s-1). The experiment was carried out twice with three replications for each test. Dark brown rotting on roots and wilting of leaves were observed in 7 days after the inoculation. P. myriotylum was reisolated from diseased tissues and found to be morphologically identical to the original isolate SC5. Noninoculated control plants remained healthy. On the basis of the symptoms, morphological and molecular characteristics and confirmation of pathogenicity, P. myriotylum is the causal agent of root rot of cocoyam. To our knowledge, this is the first report of P. myriotylum causing root rot of cocoyam in Sri Lanka. References: (1) S. Nzietchueng. L'agronomie Tropicale 38:321, 1983. (2) R. P. Pacumbaba et al. J. Phytopathol. 135:265, 1992. (3) A. J. Van Der Plaats-Niterink. Stud. Mycol. 21:1, 1981.

First Report of Stem Rot of Guiana Chestnut (Pachira aquatica) Caused by Pythium splendens.

Guiana chestnut is a perennial tropical plant that has recently become popular as a potted ornamental in Japan. In October 2001, severe stem rot occurred on Guiana chestnut plants grown in a greenhouse in Mie Prefecture, Japan. Water-soaked lesions appeared initially at the base of the stems and enlarged gradually toward the tops of plants. The affected tissues were softened and turned dark brown. Rotting was observed in the vascular bundles with advanced disease development. Globose hyphal swellings were numerous on diseased stems. Sections from diseased stems were cleaned by washing with running tap-water, placed on water agar, and incubated at 25°C. A species of Pythium was identified on the basis of morphological and cultural characteristics (1) and isolated consistently from the rotted stems of diseased plants. All isolates produced abundant hyphal swellings that were globose, smooth, 12 to 39 µm in diameter, mostly terminal, dark colored, and with dense granulated contents. Zoospores were absent. All isolates were of the compatibility '+ type' with production of sexual organs when paired with cultures of the '- type' tester isolate of Pythium splendens Braun (CBS462.48). Oogonia produced by crossings between Guiana chestnut isolates and isolate CBS462.48 were terminal or intercalary, globose, smooth-walled, and 32 to 38 µm in diameter. Antheridia were terminal, one to three per oogonium, sac-like, and diclinous. Oospores were single, aplerotic, globose, and 28 to 32 µm in diameter. The thickness of the oospore wall ranged from 1 to 2 µm. The internal transcribed spacer rDNA sequences of representative isolate OPU591 from Guiana chestnut matched those of CBS462.48 (similarity 99.2%) and have been deposited in GenBank under the Accession No. AY375242. Pathogenicity tests were conducted on potted Guiana chestnut plants (30 cm high and 7 to 10 cm in diameter at base of the stem) using isolate OPU591. A mycelial suspension from one culture, grown at 25°C for 7 days on water agar, was inoculated onto a single plant. Prior to inoculation, a wound (10 mm deep and 30 mm long) was made on the surface at the stem base on five plants. The mycelial suspension was poured onto the base of the stems of five wounded and five nonwounded plants. In addition, five wounded and five nonwounded, noninoculated plants were used as controls. Plants were maintained in a greenhouse for 8 weeks after inoculation. The temperature and relative humidity in the greenhouse ranged from 25 to 30°C and 65 to 75%, respectively. Dark-brown rotting developed on the stems of all wounded, inoculated plants by 20 days after inoculation. P. splendens was isolated from diseased tissues and found to be morphologically identical to the original isolate. This confirmed P. splendens as the causal agent of the disease. Disease did not develop on nonwounded inoculated plants or noninoculated plants. To our knowledge, this is the first report of P. splendens on Guiana chestnut. Potted plants of Guiana chestnut are often injured by frequent transplanting and transferring. Such injuries may have predisposed the plant to infection by P. splendens. Reference: (1) A. J. van der Plaats-Niterink. Page 1 in: Monograph of the Genus Pythium. Studies in Mycology Vol. 21, Centraalbureau Voor Schimmelcultures, Baarn, the Netherlands, 1981.

[Polymorphism of six Alu-insertions in residents of Morocco: comparative study in Arab and Berber populations and residents of Casablanca]. / Polimorfism shesti Alu-insertsii u zhitelei Marokko: sravnitel'noe izuchenie v populiatsiiakh Arabov, Berberov i zhitelei Kasablanki.

Alu elements are the largest family of short tandem interspersed elements (SINEs) in human who have arisen to a copy number with an excess of 500,000 copies per haploid human genome and mobilize through an RNAse polymerase III derived transcript in a process termed "retroposition." Several features make Alu insertions a powerful tool used in population genetic studies: the polymorphic nature of many Alu insertions, the stability of an Alu insertion event and, furthermore, the ancestral state of an Alu insertion is known to be the absence (complete and exact) of the Alu element at a particular locus and the presence of an Alu insertion at the site that forward mutational change. Here we report on the distribution of six polymorphic Alu insertions in a general Moroccan population and in the Arab and Berber populations from Morocco and their relationships with other populations previously studied. Our results show that there is a small difference between Arabs and Berbers and that the Arab population was closer to African populations than Berber population which is closest to Europeans.

Expression of the GLI2 oncogene and its isoforms in human basal cell carcinoma.

BACKGROUND: Mutations of the patched (Ptc) gene, a developmental regulator implicated in the signalling pathway via sonic hedgehog (Shh) and smoothened (Smo), play an essential pathogenic role in the development of basal cell carcinomas (BCCs). We previously reported the upregulation of Shh signal transducers, including Ptc, Smo and hedgehog-interacting protein, in BCCs. In vertebrates, specific downstream effectors in the Shh signalling pathway include three zinc-finger transcription factors, Gli1, Gli2 and Gli3. Gli1 possesses only an activation domain, while Gli2 and Gli3 contain both activation and repression domains. It remains unclear which of these transcription factors are responsible for the development of BCCs. OBJECTIVES: To examine the expression pattern of Gli2 mRNA by human BCCs in comparison with those by normal human skin and various skin tumours. METHODS: We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin. RESULTS: We found that Gli2 mRNA expression was enhanced in the BCCs we examined, whereas there was no significant increase in other skin tumours or normal skin. Of four spliced Gli2 isoforms designated Gli2alpha, beta, gamma and delta, the expression of Gli2beta mRNA was increased the most in BCCs. CONCLUSIONS: As Gli2beta is an isoform spliced at the first splicing site containing a repression domain and consists of an intact activation domain, its overexpression may lead to the upregulation of the Shh signalling pathway, thereby inducing BCCs.

Chilling resistances of isolates of Pythium ultimum var. ultimum from the Arctic and Temperate Zones.

Chilling resistances in moss pathogenic fungi, Pythium ultimum var. ultimum, from Longyearbyen, Svalbard (78 degree N, 15 degree E), located in the Arctic Zone and in the same isolates from Temperate Zone, were determined. Both strains had similar optimum growth temperatures. However, the strains from Svalbard could grow and survive at 0 - 5 degrees C. In addition, chilling treatment induced irregular mycelial morphology in the Arctic isolates. On the other hand, the isolates from Japan did not grow at temperatures below 5C and were destroyed after chilling stress (0 degree C for 3 days or at 4 degrees C for 1 week). The results suggested that isolates from Svalbard highly adapted to the severe spring condition in Polar environments.

Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein, by human basal cell carcinoma.

BACKGROUND: Aberrant activation of the hedgehog pathway has been identified in various human tumours, including familial and sporadic basal cell carcinomas (BCCs). It has been postulated that binding of sonic hedgehog protein (SHH) to its receptor, patched protein (PTC), releases the inhibitory effect of PTC against smoothened protein (SMO), another protein of the SHH signalling pathway. The positive SMO signalling is not downregulated in BCCs because of the mutational inactivation of PTC. Recently, hedgehog-interacting protein (HIP) was found to bind to SHH directly and attenuate SHH signalling like PTC, while its expression was induced by SHH signals. OBJECTIVES: To examine the expression patterns of HIP, SHH and PTC gene mRNA by human BCCs, in comparison with those by normal human skin and various skin tumours. METHODS: We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin. RESULTS: We found that the mRNA expression of both HIP and PTC genes was enhanced in all samples of BCCs, whereas none of the other skin tumours tested exhibited an increased level of such mRNAs as compared with normal skin. The transcription of the SHH gene, however, was at a baseline level in most BCCs. CONCLUSIONS: These results indicate that both HIP and PTC gene expression are specifically involved in the development of BCCs, and that the production of HIP is linked with the expression of the PTC gene but not the SHH gene.

No evidence of deregulated patched-hedgehog signaling pathway in trichoblastomas and other tumors arising within nevus sebaceous.

Nevus sebaceous is a congenital malformation of the skin within which a number of neoplasms showing adnexal differentiation may arise. Recently, deletions in the patched gene region were reported in nevus sebaceous and constitutive activation of the patched-hedgehog signaling pathway was implicated in the development of tumors arising within nevus sebaceous. To substantiate further a role of the patched-hedgehog signaling pathway in secondary tumors arising within nevus sebaceous, we examined 11 nevus sebaceous associated with secondary tumors for loss of heterozygosity of the patched gene region by microsatellite polymerase chain reaction and patched mRNA expression by in situ hybridization. Unexpectedly, however, none of the tumors (including eight trichoblastomas) and nevus sebaceous lesions showed loss of heterozygosity at any polymorphic loci close to the patched gene. Further more, none of the nevus sebaceous lesions and secondary tumors gave detectable signals for patched mRNA. In contrast, four of 11 sporadic basal cell carcinomas, that were examined for comparison, showed loss of heterozygosity at the patched gene locus (p <0.05), and moderate to strong signals for patched mRNA was observed in all seven basal cell carcinoma tumors examined (p <0.0001). Additional investigation by reverse transcription-polymerase chain reaction in four basal cell carcinomas and two nevus sebaceous tumors also showed the expression of Gli-1, another target gene in the patched-hedgehog signaling pathway, in all the basal cell carcinomas samples but not in any of the nevus sebaceous tumors examined. The findings in this study do not support the view that the deregulation of the patched-hedgehog signaling pathway is involved in the pathogenesis of nevus sebaceous and associated tumors, and show that, although morphologically similar, trichoblastomas and basal cell carcinomas have a different molecular pathogenesis.

Central core disease and congenital neuromuscular disease with uniform type 1 fibers in one family.

We report a family in which the father had central core disease and his son had congenital neuromuscular disease with uniform type 1 fibers. This is the first report of such a combination. Although they had no recognized mutation in the ryanodine receptor gene, it is highly likely that the son also had central core disease but without core structures. The absence of cores may be due to the muscle sample or the young age of the patient since core structures have been reported to increase with age. Although the prevalence of core structures in individual muscles is unknown, there is a possibility of sampling error. In some patients, congenital neuromuscular disease with uniform type 1 fibers is closely related to or identical with central core disease.

[A case of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II)].

We reported a male infant with multiple acyl CoA dehydrogenase deficiency, probably due to electron transfer flavoprotein dehydrogenase deficiency. He was noted to have severe muscle weakness, a high serum creatine kinase (CK) level up to 6920 IU/L, lipid storage myopathy and fatty liver at 6 months of age. A GC/MS analysis of urinary organic acids showed excess excretion of dicarboxylic acids, including glutaric, 2-hydroxyglutaric, adipic, suberic, sebacic, malonic, ethylmalonic and methylsuccinic acids. On a urinary acylglycine analysis, hexanoylglycine and suberylglycine were increased, but not isovalerylglycine, in amount. No ketosis was noted. The muscle pathology showed increased oil-red O positive lipid droplets of various sizes indicative of lipid storage myopathy. There was diffuse decrease in the activity of cytochrome c oxidase. No ragged-red fibers were noted. His clinical symptoms improved remarkably after the administration of riboflavin (100 mg/day) and L-carnitine (1000 mg/day). He was then diagnosed as having probable riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. The glutaryl CoA dehydrogenase activity in lymphocytes was normal, as were the alpha- and beta-subunits of electron transfer flavoprotein. These findings led us to suspect electron transfer flavoprotein dehydrogenation deficiency. Although he had several episodes of short-term deterioration in clinical and laboratory findings, he developed normally with normal intelligent till 10 years of age.