Publications by authors named "Hiroshi Uezato"

79 Publications

Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador: the vector Lutzomyia sand flies and reservoir mammals.

Acta Trop 2018 Feb 7;178:264-275. Epub 2017 Dec 7.

Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi, Japan.

The vector Lutzomyia sand flies and reservoir host mammals of the Leishmania parasites, causing the Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador were thoroughly reviewed, performing a survey of literatures including our unpublished data. The Peruvian L. (V.) peruviana, a principal Leishmania species causing Andean-CL in Peru, possessed three Lutzomyia species, Lu. peruensis, Lu. verrucarum and Lu. ayacuchensis as vectors, while the Ecuadorian L. (L.) mexicana parasite possessed only one species Lu. ayacuchensis as the vector. Among these, the Ecuadorian showed a markedly higher rate of natural Leishmania infections. However, the monthly and diurnal biting activities were mostly similar among these vector species was in both countries, and the higher rates of infection (transmission) reported, corresponded to sand fly's higher monthly-activity season (rainy season). The Lu. tejadai sand fly participated as a vector of a hybrid parasite of L. (V.) braziliensis/L. (V.) peruviana in the Peruvian Andes. Dogs were considered to be principal reservoir hosts of the L. (V.) peruviana and L. (L.) mexicana parasites in both countries, followed by other sylvatic mammals such as Phyllotis andium, Didelphis albiventris and Akodon sp. in Peru, and Rattus rattus in Ecuador, but information on the reservoir hosts/mammals was extremely poor in both countries. Thus, the Peruvian disease form demonstrated more complicated transmission dynamics than the Ecuadorian. A brief review was also given to the control of vector and reservoirs in the Andes areas. Such information is crucial for future development of the control strategies of the disease.
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http://dx.doi.org/10.1016/j.actatropica.2017.12.008DOI Listing
February 2018

Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador: the causative Leishmania parasites and clinico-epidemiological features.

Acta Trop 2018 Jan 7;177:135-145. Epub 2017 Oct 7.

Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi, Japan.

This study provides comprehensive information on the past and current status of the Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador, mainly focusing on the causative Leishmania parasites and clinico-epidemiological features. Available information and data including our unpublished works were analyzed thoroughly. Endemic regions of the Andean-CL (uta) in Peru run from the north Piura/Cajamarca to the south Ayacucho at a wide range of the Pacific watersheds of the Andes through several departments, while in Ecuador those exist at limited and spotted areas in the country's mid-southwestern two provinces, Azuay and Chimborazo. The principal species of the genus Leishmania are completely different at subgenus level, L. (Viannia) peruviana in Peru, and L. (Leishmania) mexicana and L. (L.) major-like (infrequent occurrence) in Ecuador. The Peruvian uta is now prevalent in different age and sex groups, being not clearly defined as found in the past. The precise reasons are not known and should be elucidated further, though probable factors, such as emergence of other Leishmania parasites, non-immune peoples' migration into the areas, etc., were discussed briefly in the text. The Andean-CL cases in Ecuador are more rural than before, probably because of a rapid development of the Leishmania-positive communities and towns, and the change of life-styles of the inhabitants, including newly constructed houses and roads in the endemic areas. Such information is helpful for future management of the disease, not only for Leishmania-endemic areas in the Andes but also for other endemic areas.
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http://dx.doi.org/10.1016/j.actatropica.2017.09.028DOI Listing
January 2018

High Prevalence of Distinct Human Herpesvirus 8 Contributes to the High Incidence of Non-acquired Immune Deficiency Syndrome-Associated Kaposi's Sarcoma in Isolated Japanese Islands.

J Infect Dis 2017 10;216(7):850-858

Department of Dermatology, University of the Ryukyus, Graduate School of Medicine, Okinawa, Japan.

Background: Non-acquired immune deficiency syndrome (AIDS) Kaposi's sarcoma (KS) is extremely rare in Japan but highly endemic in Okinawa, especially in Miyako Islands. We aimed to elucidate the exact incidence and cause of this high prevalence.

Methods: Non-AIDS KS cases in Okinawa Prefecture over the past 31 years were reviewed, and human herpesvirus 8 (HHV8) seroprevalence in Miyako Islands was determined. We examined whole-genome sequences of 3 HHV8 strains and performed whole-exome sequencing of 4 male patients from Miyako Islands.

Results: Approximately half of the non-AIDS KS cases in Okinawa Prefecture were from Miyako Islands. The age-adjusted incidence rate was 0.87/105 per year for Miyako Islands and 0.056/105 per year for the rest of Okinawa. Human herpesvirus 8 seroprevalence was 15.4% in Miyako Islands. The 3 HHV8 genomes isolated from Miyako islanders formed a phylogenetically branch distinct from those of previously sequenced HHV8 strains and shared specific mutations in 9 proteins. These mutations were verified in Okinawan patients other than those from Miyako Islands. Whole-exome sequencing of the 4 male Miyako Islanders did not reveal shared pathogenic mutations.

Conclusions: Miyako Islands are an endemic area of non-AIDS KS. The high rate of a distinct HHV8 may contribute to the high incidence of KS in the region.
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http://dx.doi.org/10.1093/infdis/jix424DOI Listing
October 2017

Depletion of Epidermal Langerhans Cells in the Skin Lesions of Pellagra Patients.

Am J Dermatopathol 2017 Jun;39(6):428-432

*Department of Dermatology, University of the Ryukyus, Okinawa, Japan; †Department of Dermatology, Tone-chuo Hospital, Numata, Japan; ‡Department of Dermatology, Gunma University, Maebashi, Japan; §Department of Dermatology, Wakayama Medical University, Wakayama, Japan; ¶Department of Dermatology, Nagasaki University, Nagasaki, Japan; and ‖Department of Dermatology, Saitama Medical University Saitama Medical Center, Kawagoe, Japan.

Pellagra is a nutrient deficiency disease caused by insufficient niacin levels. Recent studies have shown that numbers of epidermal Langerhans cells decreased in other diseases caused by nutritional deficiencies, including necrolytic migratory erythema and acrodermatitis enteropathica. Epidermal Langerhans cells are capable of modulating or even halting the inflammatory reaction. The aim of this study was to examine changes in the number of Langerhans cells and other dendritic cells, and maturation of epidermal Langerhans cells in the lesional and adjacent non-lesional skin in pellagra patients. Seven pellagra patients and 10 healthy individuals who served as controls were included. The number and distribution of dendritic cells and other cutaneous cells were examined by immunohistochemistry. Epidermal Langerhans cells decreased considerably in the skin lesions of pellagra patients, whereas other dendritic cells did not change. The decrease in the number of Langerhans cells was positively correlated with the histological severity of skin lesions. As the number of Langerhans cells was not reduced in the undisturbed neighboring skin, the depletion of epidermal Langerhans cells did not precede skin damage but was a cause of prolonged severe inflammation.
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http://dx.doi.org/10.1097/DAD.0000000000000654DOI Listing
June 2017

Pediatric case of oral mucous pemphigus complicated by protein-losing gastroenteropathy.

J Dermatol 2016 Nov 30;43(11):1392-1394. Epub 2016 Apr 30.

Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.

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http://dx.doi.org/10.1111/1346-8138.13417DOI Listing
November 2016

Geographic Distribution of Leishmania Species in Ecuador Based on the Cytochrome B Gene Sequence Analysis.

PLoS Negl Trop Dis 2016 07 13;10(7):e0004844. Epub 2016 Jul 13.

Departamento de Parasitologia y Medicina Tropical, Facultad de Ciencias Medicas, Universidad Catolica de Santiago de Guayaquil, Guayaquil, Ecuador.

A countrywide epidemiological study was performed to elucidate the current geographic distribution of causative species of cutaneous leishmaniasis (CL) in Ecuador by using FTA card-spotted samples and smear slides as DNA sources. Putative Leishmania in 165 samples collected from patients with CL in 16 provinces of Ecuador were examined at the species level based on the cytochrome b gene sequence analysis. Of these, 125 samples were successfully identified as Leishmania (Viannia) guyanensis, L. (V.) braziliensis, L. (V.) naiffi, L. (V.) lainsoni, and L. (Leishmania) mexicana. Two dominant species, L. (V.) guyanensis and L. (V.) braziliensis, were widely distributed in Pacific coast subtropical and Amazonian tropical areas, respectively. Recently reported L. (V.) naiffi and L. (V.) lainsoni were identified in Amazonian areas, and L. (L.) mexicana was identified in an Andean highland area. Importantly, the present study demonstrated that cases of L. (V.) braziliensis infection are increasing in Pacific coast areas.
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http://dx.doi.org/10.1371/journal.pntd.0004844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943627PMC
July 2016

Diffuse and disseminated cutaneous leishmaniasis: clinical cases experienced in Ecuador and a brief review.

Trop Med Health 2016 14;44. Epub 2016 Mar 14.

Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.

Background: In Ecuador, cutaneous leishmaniasis (CL) is prevalent countrywide, but only one case of diffuse-CL and two cases of disseminated-CL were experienced during our research activities more than 30 years from 1982 to date. These three patients suffered from multiple lesions distributed at a wide range of the body surface, revealing difficulty to clinically differentiate each other.

Methods: There is a considerable confusion of the use and/or differentiation of the terminologies (terms) between the two disease forms, diffuse-CL and disseminated-CL. One of the aims of the present study is to clarify the difference between the two disease forms, mainly based on the cases experienced in Ecuador.

Results: The disseminated-CL case newly reported here was clinically very similar to the diffuse-CL case, but the former showed the following marked differences from the latter: (1) the organisms isolated were identified as the parasites of Leishmania (Viannia) guyanensis/panamensis, which are also known as the causative agents of disseminated-CL in different endemic countries of the New World; (2) the patient was sensitive against antimonials; and (3) mucosal involvement was observed, which is never observed in diffuse-CL.

Conclusions: In the text, three clinical cases, one diffuse-CL and two disseminated-CL, were presented. Furthermore, a bibliographic comparison of the features between the two disease forms was made, and a brief comment was also given.
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http://dx.doi.org/10.1186/s41182-016-0002-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934146PMC
July 2016

A rapid molecular diagnosis of cutaneous leishmaniasis by colorimetric malachite green-loop-mediated isothermal amplification (LAMP) combined with an FTA card as a direct sampling tool.

Acta Trop 2016 Jan 26;153:116-9. Epub 2015 Oct 26.

Laboratory of Parasitology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. Electronic address:

Leishmaniasis remains one of the world's most neglected diseases, and early detection of the infectious agent, especially in developing countries, will require a simple and rapid test. In this study, we established a quick, one-step, single-tube, highly sensitive loop-mediated isothermal amplification (LAMP) assay for rapid detection of Leishmania DNA from tissue materials spotted on an FTA card. An FTA-LAMP with pre-added malachite green was performed at 64°C for 60min using a heating block and/or water bath and DNA amplification was detected immediately after incubation. The LAMP assay had high detection sensitivity down to a level of 0.01 parasites per μl. The field- and clinic-applicability of the colorimetric FTA-LAMP assay was demonstrated with 122 clinical samples collected from patients suspected of having cutaneous leishmaniasis in Peru, from which 71 positives were detected. The LAMP assay in combination with an FTA card described here is rapid and sensitive, as well as simple to perform, and has great potential usefulness for diagnosis and surveillance of leishmaniasis in endemic areas.
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http://dx.doi.org/10.1016/j.actatropica.2015.10.013DOI Listing
January 2016

Dermoscopic observation of acquired digital fibrokeratoma developed on the dorsum of the fourth left toe.

J Dermatol 2016 Jan 5;43(1):107-8. Epub 2015 Oct 5.

Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

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http://dx.doi.org/10.1111/1346-8138.13152DOI Listing
January 2016

A Novel Chromosomal Translocation Associated With COL1A2-PDGFB Gene Fusion in Dermatofibrosarcoma Protuberans: PDGF Expression as a New Diagnostic Tool.

JAMA Dermatol 2015 Dec;151(12):1330-1337

Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Importance: Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer that develops in the deep dermis to subcutaneous adipose tissues. A COL1A1-PDGFB gene fusion, leading to the constitutive expression of PDGFB, is the tumorigenic mechanism in most DFSP cases.

Objectives: To evaluate the specificity of PDGFB expression as a diagnostic marker of DFSP and to determine whether other pathomechanisms (ie, gene fusions) exist in patients with DFSP without the COL1A1-PDGFB fusion gene.

Design, Setting, And Participants: All patients with DFSP registered in the pathologic database of the University of the Ryukyus from January 1, 1997, through December 31, 2013, and Gunma University from January 1, 1996, through December 31, 2011, were included in this analysis. Samples were obtained from 30 patients presenting with DFSP tumors. We examined the clinicopathologic characteristics and the expression of PDGFB, PDGFRβ, PDGFRα, CD34, nestin, factor XIIIa, fibronectin, α-smooth muscle actin, S-100 protein, and Ki-67 in 30 DFSP cases and 48 non-DFSP mesenchymal tumor cases by immunohistochemical analysis. We then analyzed tumor tissues for the presence of the COL1A1-PDGFB fusion gene. We also tested whether other genes enriched in fibroblasts formed fusion products with PDGFB by reverse transcription-polymerase chain reaction analysis, using gene-specific primers.

Main Outcomes And Measures: We aimed to analyze tumor tissues for the presence of the COL1A1-PDGFB fusion gene to investigate expression of PDGFB in DFSP tumors.

Results: PDGFB expression was detected in 28 (93%) of 30 patients with DFSP. PDGFB was not homogenously expressed in DFSP tumor cells, whereas CD34 and nestin were often expressed throughout the tumor mass. In 1 DFSP tumor, the COL1A1-PDGFB fusion gene was not detected even though PDGFB was expressed. We identified a novel COL1A2-PDGFB fusion gene in this tumor.

Conclusions And Relevance: Our findings indicate that PDGFB protein is expressed in most DFSP tumors and may be a useful diagnostic tool when used in conjunction with CD34 and nestin expression analysis. These PDGFB expression data, in addition to our discovery of a novel PDGF fusion gene, strongly support the concept that DFSP is a PDGFB-dependent tumor type.
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http://dx.doi.org/10.1001/jamadermatol.2015.2389DOI Listing
December 2015

Ayadualin, a novel RGD peptide with dual antihemostatic activities from the sand fly Lutzomyia ayacuchensis, a vector of Andean-type cutaneous leishmaniasis.

Biochimie 2015 May 24;112:49-56. Epub 2015 Feb 24.

Department of Parasitology, Kochi Medical School, Kochi University, Kochi, Japan; Centro de Biomedicina, Universidad Central del Ecuador, Quito, Ecuador; Prometeo, Secretaría Nacional de Educacion Superior, Ciencia, Tecnologia e Innovacion (SENESCYT), Ecuador.

Sequence analysis of the Lutzomyia (Lu.) ayacuchensis salivary gland cDNA library identified a short peptide containing an RGD (Arg-Gly-Asp) sequence flanked by two cysteine residues in the C-terminal end as the most abundant transcript. In the present study, a recombinant protein of the RGD-containing peptide, designated ayadualin, was expressed in Escherichia coli and its activity was characterized. Ayadualin inhibited both collagen and ADP-induced platelet aggregations by interfering with the binding of integrin αIIbβ3 to fibrinogen. The RGD sequence and cysteine residues located on both sides of the RGD sequence were essential for the inhibitory action. Moreover, ayadualin efficiently inhibited the intrinsic blood coagulation pathway irrespective of the RGD sequence. Measuring the enzymatic activity of coagulation factors using chromogenic substrates revealed that ayadualin efficiently inhibited factor XIIa (FXIIa) activity in a dose-dependent manner. In addition, pre-incubation of ayadualin with FXII inhibited FXIIa activity, while activated FXIIa was not affected by ayadualin, indicating that ayadualin inhibits the activation of FXII, but not enzymatic activity of FXIIa. These results indicated that ayadualin plays an important role in the blood feeding of Lu. ayacuchensis by inhibiting host hemostasis via dual mechanisms.
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http://dx.doi.org/10.1016/j.biochi.2015.02.011DOI Listing
May 2015

Primary cutaneous mucormycosis caused by Mucor irregularis in an elderly person.

J Dermatol 2015 Feb 16;42(2):210-4. Epub 2014 Dec 16.

Department of Dermatology, University of the Ryukyus Graduate School of Medicine, Okinawa, Japan.

Primary cutaneous mucormycosis is a rare but often lethal severe fungal infection, which usually occurs in immunocompromised patients. We report a case of primary cutaneous mucormycosis caused by Mucor irregularis in an elderly patient. Seven months after the surgical dissection of the involved skin, cutaneous mucormycosis recurred at the peripheral edge of the skin graft. Shortly subsequent to the administration of liposomal amphotericin B, the remaining skin lesion was excised again. M. irregularis is rarely but increasingly reported as a cause of mucormycosis in immunocompetent individuals, especially in Asian farmers. M. irregularis may be largely disseminated in the soils of Asia and thus the trivial trauma at the time of farm work may be a trigger for the onset. These cases tend to leave severe cosmetic damage even in healthy individuals, although the vital prognosis is not affected.
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http://dx.doi.org/10.1111/1346-8138.12736DOI Listing
February 2015

Genetic divergence in populations of Lutzomyia ayacuchensis, a vector of Andean-type cutaneous leishmaniasis, in Ecuador and Peru.

Acta Trop 2015 Jan 12;141(Pt A):79-87. Epub 2014 Oct 12.

Department of Parasitology, Kochi Medical School, Kochi University, Kochi, Japan; Prometeo, Secretaria Nacional de Educacion Superior, Ciencia, Tecnologia e Innovacion (SENESCYT), Quito, Ecuador; Centro de Biomedicina, Universidad Central del Ecuador, Quito, Ecuador.

Haplotype and gene network analyses were performed on mitochondrial cytochrome oxidase I and cytochrome b gene sequences of Lutzomyia (Lu.) ayacuchensis populations from Andean areas of Ecuador and southern Peru where the sand fly species transmit Leishmania (Leishmania) mexicana and Leishmania (Viannia) peruviana, respectively, and populations from the northern Peruvian Andes, for which transmission of Leishmania by Lu. ayacuchensis has not been reported. The haplotype analyses showed higher intrapopulation genetic divergence in northern Peruvian Andes populations and less divergence in the southern Peru and Ecuador populations, suggesting that a population bottleneck occurred in the latter populations, but not in former ones. Importantly, both haplotype and phylogenetic analyses showed that populations from Ecuador consisted of clearly distinct clusters from southern Peru, and the two populations were separated from those of northern Peru.
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http://dx.doi.org/10.1016/j.actatropica.2014.10.004DOI Listing
January 2015

An imported case of cutaneous leishmaniasis caused by Leishmania (Leishmania) donovani in Japan.

J Dermatol 2014 Oct 16;41(10):926-8. Epub 2014 Sep 16.

Department of Dermatology, Fukuoka University Hospital, Fukuoka, Japan.

Leishmaniasis is a major world health problem, and 12 million people are estimated to be infected in 88 countries. There have been few reports of leishmaniasis in Japan and all were of foreign origin; therefore diagnosis is difficult for Japanese physicians. There are 21 different pathogenic Leishmania species, and identification is obtained by polymerase chain reaction (PCR). Here we report an imported case of leishmaniasis by Leishmania (Leishmania) donovani infection from Sri Lanka. L. (L.) donovani usually causes visceral leishmaniasis, but in this case, the patient manifested cutaneous leishmaniasis. The identification of Leishmania species by PCR and investigation of the patient's background such as nationality and disease endemicity are important for diagnosis and treatment. This is the first report of cutaneous leishmaniasis by L. (L.) donovani in Japan.
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http://dx.doi.org/10.1111/1346-8138.12609DOI Listing
October 2014

A case of mucocutaneous leishmaniasis diagnosed by serology.

J Dermatol 2014 Aug 16;41(8):739-42. Epub 2014 Jul 16.

Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan.

A 43-year-old Japanese Bolivian male had been suffering from a right leg ulcer after an insect bite during his residence in Bolivia. The ulcer healed after herbal medicine treatment. Ten years later, the patient had symptoms of nasal obstruction, nasal bleeding, and pharyngodynia, which were accompanied by a destructive ulcer with surrounding erythema involving the right nostril apex and columella. Papillary, irregular mucosal lesions were seen on the soft palate. Giemsa staining and polymerase chain reaction (PCR) using biopsy specimens of the papillary mucosal lesions on the soft palate failed to identify Leishmania parasites. However, the IgG antibody test was positive for Leishmania (Leishmania) donovani, and the dot enzyme-linked immunosorbent assay (dot-ELISA) using five Leishmania antigens L. (L.) mexicana, L. (L.) amazonensis, Leishmania (Viannia) guyanensis, L. (V.) braziliensis, and L. (V.) panamensis was positive. Combined, the findings suggested mucocutaneous leishmaniasis. Treatment with liposomal amphotericin B was started but was soon terminated because of palpitation, epigastralgia and facial flushing. It is sometimes difficult to identify the parasites in lesions of mucocutaneous leishmaniasis and serological tests are useful for such occasions.
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http://dx.doi.org/10.1111/1346-8138.12564DOI Listing
August 2014

Population genetics of Leishmania (Leishmania) major DNA isolated from cutaneous leishmaniasis patients in Pakistan based on multilocus microsatellite typing.

Parasit Vectors 2014 Jul 16;7:332. Epub 2014 Jul 16.

Department of Disease Control, Laboratory of Parasitology, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo 060-0818, Japan.

Background: Cutaneous leishmaniasis (CL) is a major and fast increasing public health problem, both among the local Pakistani populations and the Afghan refugees in camps. Leishmania (Leishmania) major is one of the etiological agents responsible for CL in Pakistan. Genetic variability and population structure have been investigated for 66 DNA samples of L. (L.) major isolated from skin biopsy of CL patients.

Methods: Multilocus microsatellite typing (MLMT), employing 10 independent genetic markers specific to L. (L.) major, was used to investigate the genetic polymorphisms and population structures of Pakistani L. (L.) major DNA isolated from CL human cases. Their microsatellite profiles were compared to those of 130 previously typed strains of L. (L.) major from various geographical localities.

Results: All the markers were polymorphic and fifty-one MLMT profiles were recognized among the 66 L. (L.) major DNA samples. The data displayed significant microsatellite polymorphisms with rare allelic heterozygosities. A Bayesian model-based approach and phylogenetic analysis inferred two L. (L.) major populations in Pakistan. Thirty-four samples belonged to one population and the remaining 32 L. (L.) major samples grouped together into another population. The two Pakistani L. (L.) major populations formed separate clusters, which differ genetically from the populations of L. (L.) major from Central Asia, Iran, Middle East and Africa.

Conclusions: The considerable genetic variability of L. (L.) major might be related to the existence of different species of sand fly and/or rodent reservoir host in Sindh province, Pakistan. A comprehensive study of the epidemiology of CL including the situation or spreading of reservoirs and sand fly vectors in these foci is, therefore, warranted.
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http://dx.doi.org/10.1186/1756-3305-7-332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223516PMC
July 2014

Isolation of dermatophytes and related species from domestic fowl (Gallus gallus domesticus).

Mycopathologia 2014 Aug 22;178(1-2):135-43. Epub 2014 Jun 22.

Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.

We investigated 793 bird combs [645 chickens and 148 fighting cocks (Shamo)] to determine the prevalence of dermatophytes and their related fungal species. The targeted fungal species were recovered from 195 of the 793 examined birds (24.6 %). Prevalence ratios were compared in temperate (the mainland) and subtropical (Nansei Islands) areas, genders, strains, breeding scale (individual and farm), and housing system (in cage and free ranging). The frequency of the fungal species in the mainland, males, fighting cocks, breeding scale by individual nursing, and free-range housing system exhibited significantly higher positive ratios than that in the other groups. A total of 224 dermatophytes and related species were isolated, including 101 Arthroderma (Ar.) multifidum, 83 Aphanoascus (Ap.) terreus, five Uncinocarpus queenslandicus, two U. reesii, two Ap. pinarensis, one Amauroascus kuehnii, one Ar. simii, one Gymnoascus petalosporus, one Microsporum gallinae, and 28 Chrysosporium-like (Chrysosporium spp.) isolates, which were identified using internal transcribed spacer regions of ribosomal RNA gene sequences. The predominant fungal species in the mainland was Ap. terreus and that in the Nansei Islands was Ar. multifidum. Pathogenic fungal species to humans and animals were limited to M. gallinae and Ar. simii, which corresponded to 0.025 % of the isolates in this study.
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http://dx.doi.org/10.1007/s11046-014-9758-0DOI Listing
August 2014

Glossal pigmentation caused by the simultaneous uptake of iron and tea.

Eur J Dermatol 2014 Jul-Aug;24(4):493-4

Department of Dermatology, Graduate School and Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0125, Japan.

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http://dx.doi.org/10.1684/ejd.2014.2371DOI Listing
November 2015

Varicella zoster virus encephalopathy in a patient with psoriatic arthritis treated with anti-TNFα agents.

Eur J Dermatol 2014 May-Jun;24(3):398-9

Department of Dermatology, Graduate School and Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0125, Japan.

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http://dx.doi.org/10.1684/ejd.2014.2331DOI Listing
May 2015

Development of a loop-mediated isothermal amplification method for rapid mass-screening of sand flies for Leishmania infection.

Acta Trop 2014 Apr 2;132:1-6. Epub 2014 Jan 2.

Laboratory of Parasitology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan. Electronic address:

Entomological monitoring of Leishmania infection in leishmaniasis endemic areas offers epidemiologic advantages for predicting the risk and expansion of the disease, as well as evaluation of the effectiveness of control programs. In this study, we developed a highly sensitive loop-mediated isothermal amplification (LAMP) method for the mass screening of sand flies for Leishmania infection based on the 18S rRNA gene. The LAMP technique could detect 0.01 parasites, which was more sensitive than classical PCR. The method was robust and could amplify the target DNA within 1h from a crude sand fly template without DNA purification. Amplicon detection could be accomplished by the newly developed colorimetric malachite green (MG)--mediated naked eye visualization. Pre-addition of MG to the LAMP reaction solution did not inhibit amplification efficiency. The field applicability of the colorimetric MG-based LAMP assay was demonstrated with 397 field-caught samples from the endemic areas of Ecuador and eight positive sand flies were detected. The robustness, superior sensitivity, and ability to produce better visual discriminatory reaction products than existing LAMP fluorescence and turbidity assays indicated the field potential usefulness of this new method for surveillance and epidemiological studies of leishmaniasis in developing countries.
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http://dx.doi.org/10.1016/j.actatropica.2013.12.016DOI Listing
April 2014

CD8⁺ tumor-infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma.

Int J Cancer 2014 May 18;134(10):2393-402. Epub 2013 Nov 18.

Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Tumor-infiltrating lymphocytes (TILs) have been reported as a prognostic factor in various cancers and are a promising target for immunotherapy. To investigate whether TILs have any impact on the prognosis of angiosarcoma patients, 55 non-treated patients (40 patients at stage 1 with cutaneous localized tumors, 4 patients at stage 2 with lymph node metastases and 11 patients at stage 3 with distant metastases) with angiosarcoma were evaluated retrospectively by immunohistochemistry stained CD4, CD8, FOXP3 and Ki67. The Kaplan-Meier method was used to estimate overall survival with patients at stage 1. Survival differences were analyzed by the log-rank test. Patients with higher numbers of CD8(+) TILs in their primary tumors survived significantly longer compared with patients with lower values. Moreover, the number of CD8 in TILs was positively correlated with a distant metastasis-free period. The total number of primary TILs (CD4 plus CD8) and CD8(+) primary TILs of stage 3 patients with distant metastases was positively correlated with their overall survival. To evaluate whether CD8(+) effector T cells are activated or differentiated, flow cytometric analysis of peripheral blood mononuclear cells (PBMC) was performed. The percentages of CD8(+) T cells producing IFN-γ in PBMC were significantly higher in patients with angiosarcoma (n = 10) compared not only with that of healthy controls (n = 20) but also patients with advanced melanoma (n = 11). These results suggest that anti-tumor immunity is clinically relevant in angiosarcoma.
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http://dx.doi.org/10.1002/ijc.28581DOI Listing
May 2014

Detection of human papilloma virus type 60 in a case of ridged wart.

Eur J Dermatol 2013 Jul-Aug;23(4):558-9

Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, and 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.

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http://dx.doi.org/10.1684/ejd.2013.2092DOI Listing
June 2014

Fixed eruption due to quinine in tonic water: a case report with high-performance liquid chromatography and ultraviolet A analyses.

J Dermatol 2013 Aug 3;40(8):629-31. Epub 2013 Jun 3.

Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Fixed drug eruption is a common cutaneous adverse reaction in young patients with a characteristic clinical appearance. However, the diagnosis and identification of the substance may be difficult if food or food additives provoke the fixed eruption. A 26-year-old man had a history of two episodes of cutaneous erythema with residual pigmentation. Close examination of the history including his diet in addition to an oral challenge test and patch testing led to the diagnosis of fixed eruption secondary to quinine in tonic water. We examined for the presence of quinine in commercially available brands of tonic water using ultraviolet A and irradiation and high-performance liquid chromatography. Both Schweppes and CANADA DRY brands of tonic water emitted fluorescent light upon ultraviolet A irradiation, and contained quinine at concentrations of 67.9 and 61.3 mg/L, respectively. Quinine contained in some tonic waters may trigger fixed eruption.
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http://dx.doi.org/10.1111/1346-8138.12195DOI Listing
August 2013

Dissemination of panton-valentine leukocidin-positive methicillin-resistant Staphylococcus aureus in Okinawa, Japan.

J Dermatol 2013 Jan 1;40(1):34-8. Epub 2012 Nov 1.

Department of Dermatology, University of the Ryukyus, Okinawa, Japan.

Panton-Valentine leukocidin (PVL) is a pore-forming cytotoxin that is produced by Staphylococcus aureus closely associated with skin and soft-tissue infections (SSTI). PVL-positive S. aureus strains have been identified worldwide, including in the USA; however, few studies have reported the presence of these strains in Japan. In this study, we prospectively investigated the prevalence of PVL in S. aureus strains from outpatients presenting with SSTI in Okinawa and characterized the PVL-positive S. aureus strains by polymerase chain reaction (PCR) and multilocus sequence typing (MLST). From 2008-2010, 499 clinical samples were obtained from 497 people. S. aureus was identified in 274 samples, and 36% (99 of 274) were methicillin-resistant S. aureus (MRSA). Seventeen (6.2%) PVL-positive S. aureus strains were detected by PCR, and 12 of the 17 PVL-positive strains were MRSA. Most PVL-positive S. aureus caused furuncles or carbuncles. Nine of the 17 PVL-positive isolates had an ST8 MRSA genotype and most harbored SCCmec type IVa and the arcA gene of the arginine catabolic mobile element, which is identical to the USA300 clone prevalent in the USA. PVL-positive S. aureus strains were more likely to be resistant to erythromycin (65%) and levofloxacin (53%). PVL-positive S. aureus strains have emerged and are spreading as a causative pathogen for SSTI in Okinawa.
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http://dx.doi.org/10.1111/j.1346-8138.2012.01569.xDOI Listing
January 2013

Analysis of salivary gland transcripts of the sand fly Lutzomyia ayacuchensis, a vector of Andean-type cutaneous leishmaniasis.

Infect Genet Evol 2013 Jan 18;13:56-66. Epub 2012 Sep 18.

Laboratory of Parasitology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Japan.

The saliva of blood sucking insects contains potent pharmacologically active components that assist them in counteracting the host hemostatic and inflammatory systems during blood feeding. In addition, sand fly salivary proteins affect host immunity and have the potential to be a vaccine against Leishmania infection. In the present study, the salivary gland transcripts of Lutzomyia ayacuchensis, a vector of cutaneous leishmaniasis in Ecuadorian and Peruvian Andes, were analyzed by sequencing randomly selected clones of the salivary gland cDNA library of this sand fly. This resulted in the identification of the most abundant transcripts coding for secreted proteins. These proteins were homologous to the salivary molecules present in other sand flies including the RGD-containing peptide, PpSP15/SL1 family protein, yellow-related protein, putative apyrase, antigen 5-related protein, D7 family protein, and 27 kDa salivary protein. Of note, homologues of maxadilan, an active vasodilator abundantly present in saliva of Lutzomyia longipalpis, were not identified. This analysis is the first description of salivary proteins from a sand fly of the subgenus Helcocyrtomyia and from vector of cutaneous leishmaniasis in the New World. The present analysis will provide further insights into the evolution of salivary components in blood sucking arthropods.
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http://dx.doi.org/10.1016/j.meegid.2012.08.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873855PMC
January 2013

Isolation of Microsporum gallinae from a fighting cock (Gallus gallus domesticus) in Japan.

Med Mycol 2013 Feb 19;51(2):144-9. Epub 2012 Jul 19.

Department of Molecular Biology, Faculty of Veterynary Medicine, Azabu University, Kanagawa, Japan.

A case of tinea corporis caused by Microsporum gallinae was found in 2011 in Okinawa, located in the southern part of Japan. The patient was a 96-year-old, otherwise healthy, Japanese man, who had been working as a breeder of fighting cocks for more than 70 years. He was bitten on his right forearm by one of the cocks and a few weeks later, two erythematous macules appeared on the right forearm, accompanied by a slight itchy sensation. While the first isolate of this dermatophyte was recovered from the region by Miyasato et al. in 2011, it was not obtained from the same fighting cock owned by the patient. However, frequent exchanges of fighting cocks and special domestic breeds of chickens related to fighting, mating, and/or bird fairs are common among the fans and breeders. We investigated 238 chickens and 71 fighting cocks in Okinawa and in the suburbs of Tokyo (Chiba, Tokyo, Ibaraki, and Sizuoka). One isolate of M. gallinae from a fighting cock in Chiba Prefecture in the Tokyo metropolitan area exhibited a different genotype, with a single base difference from the patient isolate based on the internal transcribed spacer 1-5.8s-ITS2 regions (ITS1-5.8S-ITS2) of the ribosomal RNA gene sequence. The isolation of M. gallinae from a fighting cock on the mainland of Japan is the first such finding in animals in our country.
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http://dx.doi.org/10.3109/13693786.2012.701766DOI Listing
February 2013

Deep venous thrombosis and pulmonary embolism secondary to co-administration of thalidomide and oral corticosteroid in a patient with leprosy.

J Dermatol 2012 Aug 28;39(8):711-4. Epub 2012 Feb 28.

Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Nishihara Chuo Dermatological Office, Naha, Okinawa, Japan.

A 58-year-old Japanese man with a 2-year history of multidrug therapy for borderline lepromatous leprosy presented with skin lesions suggestive of erythema nodosum leprosum (ENL) and was treated with an oral corticosteroid. As attempts to taper the oral corticosteroid resulted in the appearance of new lesions, thalidomide was added along with cyclosporin. Two months after the introduction of thalidomide, deep venous thrombosis (DVT) occurred in both legs and anticoagulant therapy was started without cessation of thalidomide. Pulmonary embolism developed 1 month after the appearance of DVT, and these thromboembolic events were believed to be due to thalidomide. This case highlights the need for vigilance against venous thromboembolism when corticosteroid and thalidomide are co-administrated for the treatment of ENL.
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http://dx.doi.org/10.1111/j.1346-8138.2011.01484.xDOI Listing
August 2012

Systemic lupus erythematosus complicated with protein-losing enteropathy: a case report and review of the published works.

J Dermatol 2012 May 31;39(5):454-61. Epub 2011 Oct 31.

Department of Dermatology, Graduate School of Medicine, University of Ryukyus, Okinawa, Japan.

A 45-year-old man was referred to our hospital with a history of multiple erythematous skin lesions of several months' duration. Blood examination revealed extreme hypoproteinemia and hypoalbuminemia, as well as the presence of antinuclear antibodies. A skin biopsy specimen showed liquefaction degeneration at the dermoepidermal junction and dense lymphocyte and neutrophil infiltration around the vessels and appendages in the upper and middle dermis. Chest X-ray and computed tomography showed a pleural effusion and thoracic paracentesis revealed a mononuclear cell-dominant cell infiltration, suggestive of serositis. Technetium-99m ((99m)Tc)-labeled human serum albumin scintigraphy and α(1)-antitrypsin clearance revealed protein leakage along the digestive tracts from the stomach to the jejunum. From the above findings, the patient was diagnosed with systemic lupus erythematosus (SLE) complicated by protein-losing enteropathy (PLE). Treatment with oral prednisolone significantly improved his clinical symptoms and hypoalbuminemia. This case highlighted the utility of (99m)Tc-labeled human serum albumin scintigraphy and α(1)-antitrypsin clearance in the diagnosis of PLE. We also present a published work review on PLE associated with connective tissue disease revealing a relatively higher prevalence in patients of Asian ethnicity, including Japanese.
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http://dx.doi.org/10.1111/j.1346-8138.2011.01404.xDOI Listing
May 2012
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