bluuebunny/crossref_metadata_2025 huggingface dataset:
Analgesic tolerance to morphine is regulated by PPARγ
Authors: de Guglielmo Giordano , Kallupi Marsida , Scuppa Giulia , Stopponi Serena , Demopulos Gregory , Gaitanaris George , Ciccocioppo Roberto
Published: July 2014

Background and Purpose

Opioid drugs are potent analgesics. However, their chronic use leads to the rapid development of tolerance to their analgesic effects and subsequent increase of significant side effects, including drug dependence and addiction. Here, we investigated the role of PPARγ in the development of analgesic tolerance to morphine in mice.

Experimental Approach

We monitored analgesia on alternate days using the tail immersion test.

Key Results

Daily administration of morphine (30 mg·kg−1, bid) resulted in the rapid development of tolerance to thermal analgesia. Co‐administration of pioglitazone (10 and 30 mg·kg−1, bid) significantly attenuated the development and expression of tolerance. However, pretreatment with GW‐9662 (5 mg·kg−1, bid), a selective PPARγ antagonist, completely abolished this effect. Injection of GW‐9662 and a lower dose of morphine (15 mg·kg−1, bid) accelerated the development of tolerance to its antinociceptive effect. Subsequently, we found that conditional neuronal PPARγ knockout (KO) mice develop a more rapid and pronounced tolerance to morphine antinociception compared with wild‐type (WT) controls. Moreover, in PPARγ KO mice, pioglitazone was no longer able to prevent the development of morphine tolerance.

Conclusions and Implications

Overall, our results demonstrate that PPARγ plays a tonic role in the modulation of morphine tolerance, and its pharmacological activation may help to reduce its development. These findings provide new information about the role of neuronal PPARγ and suggest that combining PPARγ agonists with opioid analgesics may reduce the development of tolerance and possibly attenuate the potential for opioid abuse.
In vivo properties of KNT‐127, a novel δ opioid receptor agonist: receptor internalization, antihyperalgesia and antidepressant effects in mice
Authors: Nozaki C , Nagase H , Nemoto T , Matifas A , Kieffer B L , Gaveriaux‐Ruff C
Published: July 2014

Background and Purpose

Activation of δ opioid (DOP) receptors regulates pain and emotional responses, and also displays ligand‐biased agonism. KNT‐127 (1,2,3,4,4a,5,12,12a‐octahydro‐2‐methyl‐4aβ,1β‐([1,2]benzenomethano)‐2,6‐diazanaphthacene‐12aβ,17‐diol) is a novel DOP receptor agonist inducing analgesia and antidepressant effects in mice. Here, we have assessed KNT‐127 for (i) analgesia against chronic inflammatory pain; (ii) effects on depression, locomotion and DOP receptor internalization; and (iii) for cross‐tolerance to analgesic and antidepressant effects of acute treatment by other DOP receptor agonists.

Experimental Approach

Inflammatory pain was induced by complete Freund's adjuvant injection into tail or hindpaw, and thermal and mechanical sensitivities were determined in mice. Locomotor and antidepressant‐like effects were measured using actimetry and forced swim test respectively. In vivo KNT‐127 selectivity and internalization were assessed using DOP receptor knockout mice and knock‐in mice expressing fluorescent‐tagged DOP receptors. KNT‐127 was injected acutely at 0.1–10.0 mg·kg−1 or administered chronically at 5 mg·kg−1 daily over 5 days.

Key Results

Acute treatment with KNT‐127 reversed inflammatory hyperalgesia, produced an antidepressant‐like effect but induced neither hyperlocomotion nor receptor sequestration. Chronic treatment with KNT‐127 induced tolerance and cross‐tolerance to SNC80‐induced analgesia, but no tolerance to SNC80‐evoked hyperlocomotor or antidepressant‐like effects.

Conclusions and Implications

The DOP receptor agonist KNT‐127 induced agonist‐specific acute and chronic responses, at both behavioural and cellular levels. It displays activities similar to the other recently reported DOP agonists, AR‐M1000390, ADL5747 and ADL5859, and differs from SNC80. SNC80 differs from the other DOP receptor agonists including KNT‐127, by exhibiting ligand‐biased tolerance at this receptor.
Therapeutic perspectives of epigenetically active nutrients
Authors: Remely M , Lovrecic L , de la Garza A L , Migliore L , Peterlin B , Milagro F I , Martinez A J , Haslberger A G
Published: July 2014

Many nutrients are known for a wide range of activities in prevention and alleviation of various diseases. Recently, their potential role in regulating human health through effects on epigenetics has become evident, although specific mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged as a new and promising field in current epigenetics research in the past few years. In particular, polyphenols, as part of the central dynamic interaction between the genome and the environment with specificity at physiological concentrations, are well known to affect mechanisms underlying human health. This review summarizes the effects of dietary compounds on epigenetic mechanisms in the regulation of gene expression including expression of enzymes and other molecules responsible for drug absorption, distribution, metabolism and excretion in cancer, metabolic syndrome, neurodegenerative disorders and hormonal dysfunction.

Linked Articles

This article is part of a themed section on Epigenetics and Therapy. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐11
Application of Agriculture‐Developed Demographic Analysis for the Conservation of the Hawaiian Alpine Wekiu Bug
Authors: EIBEN JESSE , RUBINOFF DANIEL
Published: July 2014

Insects that should be considered for conservation attention are often overlooked because of a lack of data. The detailed information necessary to assess population growth, decline, and maximum range is particularly difficult to acquire for rare and cryptic species. Many of these difficulties can be overcome with the use of life table analyses and heat energy accumulation models common in agriculture. The wekiu bug (Nysius wekiuicola), endemic to the summit of one volcanic mountain in Hawaii, is a rare insect living in an environmentally sensitive alpine stone desert, where field‐based population assessments would be inefficient or potentially detrimental to natural and cultural resources. We conducted laboratory experiments with the insects by manipulating rearing temperatures of laboratory colonies and made detailed observations of habitat conditions to develop life tables representing population growth parameters and environmental models for wekiu bug phenology and demographic change. Wekiu bugs developed at temperatures only found in its environment on sunny days and required the thermal buffer found on cinder cones for growth and population increase. Wekiu bugs required approximately 3.5 months to complete one generation. The bug developed optimally from 26 to 30 °C, temperatures that are much higher than the air temperature attains in its elevational range. The developmental temperature range of the species confirmed a physiological reason why the wekiu bug is only found on cinder cones. This physiology information can help guide population monitoring and inform habitat restoration and conservation. The wekiu bug was a candidate for listing under the U.S. Endangered Species Act, and the developmental parameters we quantified were used to determine the species would not be listed as endangered or threatened. The use of developmental threshold experiments, life table analyses, and degree day modeling can directly inform otherwise unobservable habitat needs and demographic characteristics of extremely rare insects.

Aplicación de Análisis Demográfico de Desarrollo Agrícola para la Conservación del Insecto Weiku Alpino Hawaiano
Donor acute kidney injury and short‐term graft outcome in renal transplantation
Authors: Jacobi Johannes , Rebhan Dirk , Heller Katharina , Velden Joachim , Hilgers Karl F. , Wullich Bernd , Eckardt Kai‐Uwe , Amann Kerstin U.
Published: July 2014

Background

With increased waiting times for kidney transplantation, marginal organs from expanded criteria donors (ECD) are increasingly offered for allocation. In addition to ECD status, donors may have suffered from acute kidney injury (AKI) prior to organ procurement.

Methods

In this retrospective cohort study, we studied short‐term allograft function in 517 kidney transplants performed between the years 2008–2014. Recipients of allografts from deceased organ donors were categorized as standard criteria donors (SCD) or ECD with or without AKI defined by RIFLE criteria.

Results

Of 382 deceased donations, 174 (45.5%) were classified as ECD and 63 (16.5%) fulfilled AKI criteria. Donor creatinine on hospital admission was similar, whereas creatinine before organ procurement differed (p < 0.001). Despite these differences, serum creatinine and eGFR at discharge and after one yr showed only minor differences between kidneys with or without AKI. In multivariate linear regression analyses, donor AKI was not a predictor of one‐yr allograft function.

Conclusions

Given the poor prognosis of dialysis patients and the increase in waiting time, kidneys from SCD and ECD donors with AKI should be allocated for transplantation. In case of ECD donors with AKI, recipients should be informed about the possibility of permanent non‐function or early graft loss.
Recurrent Right Ventricular Takotsubo Cardiomyopathy in a Patient with Recurrent Aspiration
Authors: Chandorkar Aditya , Codolosa J. Nicolás , Lippmann Michael L. , Pressman Gregg S. , Sta Cruz Joanna P.
Published: July 2014

Takotsubo cardiomyopathy is described as transient hypokinesis of the apical and mid‐segments of the left ventricle with hypercontractile basal segments triggered by emotional or physical stress. Variants with basal hypokinesis and apical hyperkinesis have been described, as well as simultaneous involvement of the right ventricle (RV). Proposed mechanisms include myocardial “stunning” due to excessive catecholamine release. The echocardiographic presentation of Takotsubo cardiomyopathy may be related to differences in regional sympathetic innervation and catecholamine receptor density in the myocardium in the setting of high levels of circulating catecholamines. We describe the first case of isolated, recurrent RV Takotsubo cardiomyopathy reported in the literature.
Initial characterization of an unidentified Armillaria isolate from Serbia using LSU‐IGS1 and TEF‐1‐α genes
Authors: Keča N. , Klopfenstein N. B. , Kim M.‐S. , Solheim H. , Woodward S.
Published: July 2014

Armillaria species have a global distribution and play variable ecological roles, including causing root disease of diverse forest, ornamental and horticultural trees. Accurate identification of Armillaria species is critical to understand their distribution and ecological roles. This work focused on characterizing an unidentified Armillaria isolate from a Serbian forest using pairing, sequencing of the partial large subunit and intergenic spacer‐1 regions of rDNA (LSU‐IGS1) and the translation elongation factor‐1 alpha gene (tef‐1α) genes, and phylogenetic analyses. Despite previously obtained LSU‐IGS1 RFLP patterns that matched the newly described North American Armillaria altimontana, pairing tests and phylogenetic analyses of LSU‐IGS1 and tef‐1α sequences clearly demonstrate that the unidentified isolate is not A. altimontana. Based on LSU‐IGS1, Armillaria gallica isolates were polyphyletic, and the Serbian isolate clustered with a subset of European A. gallica isolates within a well‐supported clade (99%). Based on tef‐1α, the Serbian isolate appeared as a separate, well‐supported clade (97%) that was basal to other poorly resolved, polyphyletic clades containing European A. gallica isolates. It is speculated that the unidentified Armillaria isolate from Serbia could represent an evolutionary ancestral state because of its separate, basal position compared with other clades comprising polyphyletic European A. gallica isolates. Alternatively, this unidentified Serbian isolate could represent an unusual hybrid because of its high‐level sequence heterogeneity, represented by multiple two‐nucleotide codes, within tef‐1α. Further characterization is needed to confirm the taxonomic status and ecological/evolutionary significance of this unique, unknown Armillaria isolate from Serbia.
A micro RNA‐146a polymorphism is associated with coronary restenosis
Authors: Hamann L. , Glaeser C. , Schulz S. , Gross M. , Franke A. , Nöthlings U. , Schumann R. R.
Published: July 2014

The association of the miRNA‐146a polymorphism rs2910164 with atherosclerosis and restenosis was investigated. We found no association with atherosclerosis; however, we found a negative association for the G/C (P = 0.007) and a positive association for the C/C genotype with the risk of restenosis, which is the main drawback for cardiac surgery.
First report on the antibody verification of MICA epitopes recorded in the HLA epitope registry
Authors: Duquesnoy R. J. , Mostecki J. , Marrari M. , da Silva A. S. , da Mata Sousa L. C. D. , do Monte S. J. H.
Published: July 2014

The International Registry of HLA Epitopes (http://epregistry.com.br) has been recently established as a tool to understand antibody responses to HLA mismatches. These epitopes are defined structurally by three‐dimensional molecular modelling and amino acid sequence differences between HLA antigens. A major goal was to identify HLA epitopes that have been verified experimentally with informative antibodies. This report addresses the identification of MICA epitopes. Our analysis included published information about MICA antibody reactivity in sera from sensitized patients as well as data from our own laboratories. This report describes twenty‐one MICA epitopes verified with antibodies which have primarily been tested in Luminex assays with single alleles. The epitopes correspond to distinct eplets that are often defined by single residues. The Registry is still a work‐in‐progress and will become a useful resource for HLA professionals interested in histocompatibility testing at the epitope level and investigating antibody responses to HLA mismatches in transplant patients.
Individually tailored ultrasound‐assisted prompted voiding for institutionalized older adults with urinary incontinence
Authors: Iwatsubo Eiji , Suzuki Motofumi , Igawa Yasuhiko , Homma Yukio
Published: July 2014

Objectives

To assess individually tailored ultrasound‐assisted prompted voiding as a means of managing urinary incontinence in hospitalized elderly patients.

Methods

A total of 88 incontinent elderly individuals who were inpatients in general hospitals were included. Each individual's mean bladder volume before starting to void (voided urine volume plus residual urine volume) was regarded as the optimal bladder volume. Bladder volume was regularly monitored with an ultrasound device, and when the urine volume had reached the individual's optimal bladder volume, the subject was prompted to void. The outcomes were evaluated on the basis of scores on a four‐grade scale for items in six domains: urine volume, voiding function, urinary control, physical and cognitive function for toileting, and caregivers' burden in regard to continence care. The score for use of a pad/diaper, an item of urinary control domain, was used as the primary outcome measure.

Results

A total of 80 participants were included for analysis. After ultrasound‐assisted prompted voiding care for a 4‐week period, the score for use of a pad/diaper in 50 out of 80 participants (62.5%) had decreased, and 21 out of 80 participants (26.3%) no longer required the use of a pad/diaper at all. The scores of the other 30 out of 80 participants (37.5%) were unchanged. The improvement was not significantly affected by patients' backgrounds at baseline. The mean scores in the domains of urinary control, physical function, cognitive function and caregivers' burden improved significantly.

Conclusion

The present preliminary study suggests that individually tailored ultrasound‐assisted prompted voiding can improved urinary incontinence of institutionalized elderly patients. Further studies are worth carrying out.
Comprehensive Analysis of 28 Patients with Latex Allergy and Prevalence of Latex Sensitization among Hospital Personnel
Authors: Mitsuya Kaoru , Iseki Hiromi , Masaki Tomoko , Hamakawa Motoko , Okamoto Hiroyuki , Horio Takeshi
Published: July 2014

Recently anaphylactic shock caused by latex gloves and medical instruments has been discussed as an important problem in surgical operations. Patients with contact urticaria or anaphylaxis due to natural rubber latex were first reported in Japan in 1993, and the number of cases is gradually increasing. In the present study, we analyzed 28 patients examined in our clinic from 1993 to 1998. The diagnosis of latex allergy was made on the basis of clinical history, latex specific IgE antibody, skin test, and use test. The 3 male and 25 female patients included 20 nurses, 4 doctors, 2 housewives, one animal hospital employee, and one worker in a senile rehabilitation center. The majority were health care workers. Contact urticaria from rubber gloves was the most common clinical symptom. Some of the patients developed severe attacks of anaphylaxis. During the period from 1995 to 1997, we also performed a questionnaire study and a serum examination of latex specific IgE antibody among the personnel of our university hospital. The screening test for the antibody was more reliable than our questionnaire study in detecting latex‐sensitive persons. The prevalence of latex allergy was found to be 4.6%. This indicates that not only dermatologists but also all hospital workers should be aware of this type of allergy.
Epstein‐Barr Virus‐associated Recurrent Necrotic Papulovesicles with Repeated Bacterial Infections Ending in Sepsis and Death: Consideration of the Relationship between Epstein‐Barr Virus Infection and Immune Defect
Authors: Yoon Tae Young , Yang Tae Ho , Hahn Youn Soo , Huh Joo Ryung , Kim Youn Soo
Published: July 2014

The disease of Epstein‐Barr virus (EBV) ‐associated recurrent necrotic papulovesicles is a distinct clinicopathologic entity different from classic hydroa vacciniforme (HV). A few patients have been reported as atypical HV with systemic involvement, development of lymphoma, and poor prognosis. We describe a patient with recurrent necrotic papulovesicles and multiple varioliform scars in both sun‐exposed and covered areas. In contrast to cases of previously reported atypical HV, our patient suffered from repeated bacterial infections on various sites ending in sepsis and death, but without malignant transformation. EBV was detected in the lymphoid cells from the skin lesions by anti‐latent membrane protein (LMP) antibody and in situ hybridization. We suggest that the repeated bacterial infections in this case raise the possibility of an association of EBV infection with increased susceptibility to bacterial infections.
Extensive Partial Unilateral Lentiginosis
Authors: Romiti Ricardo , Harnache Juan David , Neto Cyro Festa , Kreuter Alexander , Altmeyer Peter , Jansen Thomas
Published: July 2014

Partial unilateral lentiginosis is a rare pigmentary disorder characterized by multiple lentigines on otherwise normal skin affecting one side of the body. The histology is that of a lentigo. We report two young men with an extensive form of partial unilateral lentiginosis affecting the skin. No systemic abnormalities could be identified.
An Indian Case of Keratoderma Hereditarium Mutilans (Vohwinkel's Syndrome) Associated with Ichthyosiform Dermatosis
Authors: Vijaikumar Marykolandainathen , Thappa Devinder Mohan , Jeevankumar Balasubramanian
Published: July 2014

Keratoderma hereditarium mutilans (KHM) or Vohwinkel's syndrome (VS) is usually inherited as an autosomal dominant disease, but a recessive type has occasionally been described. We report a 19‐year‐old male born to consanguineous parents, who presented with KHM associated with generalized ichthyosiform dermatosis. On examination, his generalized ichthyosiform dermatosis was accompanied by severe ‘honey comb’ like palmoplantar keratoderma and marked hyperhidrosis. Bilateral fifth toes showed complete constricting bands just distal to the metatarsophalangeal joints leading to pseudoainhum. The histopathologic examination of a biopsy from the sole showed hyperkeratosis, marked parakeratosis, hypergranulosis, acanthosis, and a few mononuclear cells in the papillary dermis, consistent with the diagnosis of KHM. Several hereditary disorders may show varying degrees of hyperkeratosis and constriction of digits; their differentiating features are discussed. This case is reported for its rarity and interesting associated findings.
A Case of Pedunculated Malignant Melanoma of the Vaginal Mucosa
Authors: Kimura Chu , Furuya Kazuhiko
Published: July 2014

We report an 84‐year‐old Japanese woman who presented with a pedunculated malignant melanoma of the vaginal mucosa. Mucosal melanoma is believed to be more common in Japan than other countries, but such tumors of the vulvovaginal region are quite unusual. In our patient, three tumors were connected by a narrow pedicle. Three black tumors measuring 5–10 mm in diameter with a common pedicle were seen on the vaginal mucosa at five o'clock from the cervix. The tumors were hanging from the narrow pedicle. On histologic examination, they were diagnosed as malignant melanoma. Resection was done with a distal margin of 3 cm from the tumors and a margin of 1 cm from the cervix. The patient has had no evidence of local recurrence or distant metastasis. In our patient, the three main tumors had a common pedicle, which seems to be a unique finding. Since pedunculated malignant melanomas are rare, making a clinical diagnosis is difficult. Although pedunculated melanomas are recognized as having a high malignant potential because these lesions are generally thick, a relatively good outcome is sometimes reported. In our patient, there was no tumor infiltration into the dermis of the pedicle, and this may be one reason for the good outcome at present. There has been no previous report of a mucosal melanoma consisting of three tumors like those in the present patient.
Unusual Urticarias
Authors: Black Anne Kobza
Published: July 2014

Typical urticarial lesions are transient cutaneous swellings of sudden onset, often itchy, persisting for less than 24 hours and resolving to leave normal appearing skin. Angioedema lesions are similar subcutaneous lesions. Atypical urticarias persist for longer than 24 hours, may be painful and bruised in appearance and accompanied with severe systemic symptoms. Conditions where prolonged weals are present include delayed pressure urticaria and urticarial vasculitis. These conditions do not respond well to antihistamine therapy. In delayed pressure urticaria, weals appear after a delay of hours at sites of sustained pressure on the skin and occur in association with ordinary chronic ‘idiopathic’ urticaria. Weals of urticarial vasculitis show histological features of venulitis, and can be accompanied by arthralgia and abdominal pain. Rarely, the condition is due to infective or autoimmune disease. Urticarial diseases, sometimes with features of urticarial vasculitis, and with associated systemic features include Schnitzler's Syndrome, Still's disease and Muckle‐Wells syndrome. The latter syndrome is linked with chromosome 1q44, as is autosomal dominant cold urticaria, an unusual physical urticaria. Persistent cholinergic erythema, a variant of cholinergic urticaria, has been mistaken for a drug eruption or cutaneous mastocytosis. Rarely, food and exercise induced urticaria and anaphylaxis occur when exercise follows a specific food or any meal within a few hours. The early stages of inflammatory disease may be mistaken for urticaria and angioedema, but lesions usually persist for longer than 48 hours and are accompanied by epidermal changes.
100 Years of Japanese Dermatology: A Perspective from Abroad
Authors: Holubar Karl , Fatović‐Ferenčic Stella
Published: July 2014

The development of Japanese dermatology is reviewed from the times of the founding fathers and Keizo Dohi to today. Tribute is paid to the heroes of the first hour. Thereafter, an evaluation of Japanese‐authored papers in the leading journal of the field (JID) over four decades is presented, taking a triennial slot in each. The contribution of Japanese‐authored papers has increased substantially over this period.
Rod‐shaped Bodies Resembling Birbeck Granule‐like Structures in Endothelial Cells of Dermal Capillaries in Generalized Granuloma Annulare
Authors: Kohn Sarah , Friedman‐Birnbaum Rachel
Published: July 2014

A previous study demonstrated that, in generalized granuloma annulare in the epidermis, the Langerhans' cell section area and the number of Langerhans' cell granules or Birbeck granules per cell section were increased, suggesting an active state of these Langerhans' cells. Reexamination by transmission electron microscopy of the same tissue, but in samples also containing dermal tissue, from the same subjects revealed endothelial cells with rod‐shaped bodies resembling Birbeck granules or Birbeck granule‐like structures. This finding has not been previously described in blood vessels of human skin and is described here.
A Clinico‐Mycological Study of Dermatophytoses in Nepal
Authors: Agarwalla Arun , Jacob Mary , Sethi Manoj , Parija Subash C. , Singh Narendra P.
Published: July 2014

A clinico‐mycological study of 100 cases of dermatophytosis was done in the B.P. Koirala Institute of Health Sciences in the eastern region of Nepal. The incidence of dermatophytoses in this study was 4.54% with a M: F ratio of 2.5: 1. The commonest age group was 11‐20 years old. A single clinical type was found in 68%; 32% had two or more clinical types. The study revealed tinea corporis (43%) as the most common clinical type followed by tinea cruris (33%) and tinea pedis (20%). Positive culture was obtained in 94% of cases. A total of eight different species of dermatophytes were isolated with T. rubrum (45.74%) as the most common species followed by T. mentagrophytes (26.6%), T. tonsurans (11.7%), M. audouinii (8.36%), E. floccosum (4.26%), T. schoenlenii (2.13%), T. violaceum (2.13%) and T. verrucosum (1.06%).
Churg‐Strauss Syndrome with Renal Involvement: A Case Report
Authors: Kitoh Akihiko , Nobuhara Satomi , Takahashi Kenzo , Nishigori Chikako , Miyachi Yoshiki
Published: July 2014

We report a case of Churg‐Strauss syndrome with renal involvement. A 51‐year‐old woman was admitted to our hospital in April of 1999 complaining of abdominal pain and severe diarrhea followed by multiple purpura on both legs. A diagnosis of Churg‐Strauss syndrome was made on the basis of the presence of preceding asthma, eosinophilia, increased IgE, and the histological findings of a biopsy taken from the purpura. Creatinine clearance level at admission was low (43.3 ml/min) and urinalysis revealed proteinuria and microscopic hematuria. These abnormalities were improved with systemic steroid therapy. Renal involvement seems to be more common than previously reported in Churg‐Strauss syndrome.
Malignant Melanoma Cells in the Eccrine Apparatus
Authors: Kiryu Hiromaro , Imayama Shuhei
Published: July 2014

A case of malignant melanoma arising on the sole of a 75‐year‐old Japanese man is presented. Histopathologically, in addition to the intraepidermal and intradermal malignant melanoma cells reaching the upper part of the dermis, cells were also found in the deep part of the ductal epithelium of the eccrine apparatus. Melanoma cells, and melanocytic nevus cells as well, are rarely found within the epithelial structure of sweat glands, yet they are frequently found in that of hair follicles. In order to avoid a residue of melanoma cells in the deep part of the eccrine apparatus, a fairly deep excision should be performed even for thin melanoma.
A Case of Cutaneous Disseminated Sporotrichosis
Authors: Liu Xiaoming , Lin Xiran
Published: July 2014

We described a case of cutaneous disseminated sporotrichosis. The condition was diagnosed based on isolation and identification of Sporothrix schenckii from the lesions. The patient was otherwise normal, including a negative HIV test. The blood culture did not grow S. schenckii. However, spores were detected in the biopsy histological sections and stained positively with PAS staining and ConA and LCA lectin histochemistry.
Mucocutaneous Manifestations of Secondary Syphilis in North Indian Patients: A Changing Scenario?
Authors: Kumar Bhushan , Gupta Somesh , Muralidhar Sivaram
Published: July 2014

During the 1990s, no studies of various clinical presentations of syphilis have been published in the indexed literature. However, a change in the clinical profile of secondary syphilis was expected during the last decade with the rapid spread of the HIV epidemic. The objective was to study the mucocutaneous manifestations of secondary syphilis in patients attending the STD clinic at the Postgraduate Institute of Medical Education & Research Chandigarh, India, during the last decade and to compare them with other similar studies published during the 1980s. All patients who were diagnosed with secondary syphilis in our STD clinic from 1990 to 1999 were examined and investigated. Serological response was measured at 3, 6, 9, 12, and 24 months post‐treatment or until serological negativity was reached. Fifty‐three patients (males=34, female=19) during this period were found to have secondary syphilis. The most common symptoms were as follows‐skin rash 38 (71.7%), lymphadenopathy 26 (49%), persistent chancre 4 (7.5%), nodular syphilides 2 (3.8%), lues maligna 2 (3.8%), patches in the oral mucosa 6 (11.3%), condylomata lata 14 (26.4%), split papules 2 (3.8%). Five patients had a thin and conspicuous genital scar of the healed primary chancre. Three patients were HIV seropositive (1 patient each with lues maligna, lichenoid, and nodular syphilides). With the spread of the HIV epidemic, atypical muco‐cutaneous manifestations of secondary syphilis may be seen more frequently than before and may pose problems in diagnosis. In the present study, six patients had atypical manifestations, and three of them were HIV seropositive.
Gene Therapy
Authors: Badiavas Evangelos V. , Falanga Vincent
Published: July 2014

With recent advances in molecular biology, the ability to transfer genes to patients is becoming a reality. Ongoing clinical trials using gene transfer techniques have illustrated the potential and pitfalls of this new therapeutic modality for the treatment of a wide variety of disorders. While these techniques are not currently a part of routine clinical practice, it is only a matter of time until some form of gene therapy is approved for general use in the clinic. This review highlights some of the basic methods used in current gene therapy protocols. The objective of this review is to familiarize practitioners with these concepts so they can more effectively follow the progress of this emerging technology and better inform their patients.
Degenerated Neurilemoma (Ancient Schwannoma)
Authors: Ishihara Tsuyoshi , Ono Tomomichi
Published: July 2014

We report a case of degenerated neurilemoma in a 65‐year‐old Japanese woman. A tumor in the right thigh histopathologically showed a mixture of Antoni type A and B patterns, and contained prominent blood vessels with hyalinized walls, but no calcification. The tumor cell nuclei of middle areas were large, hyperchromatic and often multilobed but lacked mitotic figures. The mucinous areas had few tumor cells. Antoni type A and B areas were S‐100 protein positive, while mucinous areas and hyalinized vessels were negative.
Palpable Purpura at the Site of Previous Herpes Zoster in Association with Mixed Cryoglobulinemia and Hepatitis C Virus Infection
Authors: Cecchi Roberto , Giomi Andrea , Paoli Simone
Published: July 2014

A 70‐year‐old woman affected with chronic active hepatitis C and mixed cryoglobulinemia presented a palpable purpura on her abdominal skin in a metameric configuration, fourteen months after a herpes zoster in the same site. Histopathology showed a small vessel leukocytoclastic vasculitis in the superficial dermis. Post‐zoster eruptions are variable, and their spectrum is still expanding, although the pathogenesis remains to be elucidated. Perhaps our case represents an isomorphic reaction, because this palpable purpura, probably related to HCV infection, occurred several months after herpes zoster.
Calciphylaxis in a Patient with End‐Stage Renal Disease
Authors: Kim Young‐Jo , Chung Byoung‐Soo , Choi Kyu‐Chul
Published: July 2014

Calciphylaxis is a rare and life‐threatening condition of progressive cutaneous necrosis secondary to small and medium‐sized vessel calcification. It is seen almost exclusively in patients with end‐stage renal disease and secondary hyperparathyroidism. We experienced a case of 67‐year‐old man with calciphylaxis that manifested with characteristic skin lesions, pathologic findings, and laboratory changes. His skin lesions began as painful erythematous patches and subsequently progressed to necrotic ulcers with eschars on the distal aspect of the extremities. Pathologically, calcification was found in small and medium‐sized blood vessels in the deep dermis and subcutaneous tissue. His serum calcium was 9.5 mg/dL, phosphorus was 7.8 mg/dL, and nPTH was 99.9 pg/mL. The patient had been treated with surgical debridement and other supportive treatment. However, he eventually underwent an amputation below the right knee and died from sepsis.
Desmosomes: Structure and Function in Normal and Diseased Epidermis
Authors: McMillan James R. , Shimizu Hiroshi
Published: July 2014

Desmosomes are important epidermal adhesion complexes that are characterized by a cell‐specific expression of transmembrane cadherins and plaque‐associated molecules. Desmosomes have so far, been implicated in three main disease types: autoimmune diseases that involve desmosome components (such as pemphigus vulgaris and pemphigus foliaceus), congenital diseases that affect intracellular calcium channels (such as Hailey‐Hailey disease and Darier disease) and congenital diseases that directly affect desmosomal structural components. The identification of the first congenital defect affecting a desmosome component was in the gene for plakophilin 1 which caused an autosomal recessive skin fragility‐ectodermal dysplasia syndrome with skin, hair and nail defects. Subsequently, either a haploinsufficiency of desmoplakin or a defect in desmoglein 1 was found to underlie the autosomal dominant condition Striate Palmoplantar Keratoderma. In addition, plakoglobin has been shown to be defective in Naxos disease, which results in a cardiomyopathy and growth of abnormal hair. These findings pave the way for the discovery of further cell cohesion‐related diseases and will help to greatly increase our understanding of the specific function of desmosome and other epithelial junction components.
Sentinel Lymph Nodes Study in 30 Cases of Melanoma
Authors: Ishihara Tsuyoshi , Nakamura Atsushi , Kageshita Toshiro , Ono Tomomichi
Published: July 2014

In 30 cases of melanoma, we attempted to detect sentinel lymph nodes using 1–2% patent blue dye and were able to detect them in 27 cases (90%): 19 cases out of 21 cases in the groin area (90%), 5 out of 5 cases in the axilla area (100%), and 3 out of 4 cases in the neck area (75%). The numbers of sentinel lymph nodes were one in 16 cases, two in 7 cases, three in 2 cases, and four in 2 cases. The cases with three and four nodes were all in the groin area. In 22 cases, tumor metastasis was negative in sentinel lymph nodes. Sentinel lymph nodes were detected in 36 out of 174 samples, and tumor metastasis was negative except in these sentinel lymph nodes (false negative 0%). In the groin area, sentinel lymph nodes were located around the femoral and great saphenous vein junction. In the axilla area, sentinel lymph nodes were located in the central, lateral and subscapular lymph nodes. In the head and neck area, sentinel lymph nodes were found in the submandibular and occipital lymph nodes. The positions of sentinel lymph nodes differed a little with tumor location. By accumulating cases, it should become possible to predict the positions of sentinel lymph nodes before operations. Sentinel lymph node biopsy is easy and requires only a small incision.
Analysis of the Vascularity of an Atelocollagen Sponge Substitute Dermis in the Human
Authors: Ishihara Tsuyoshi , Ono Tomomichi
Published: July 2014

Atelocollagen sponge had been developed as a new beneficial dermal substitute. However, histologic studies of the vascularity of an atelocollagen sponge substitute dermis in humans are very rare. The purpose of this study was to determine the distribution of blood vessels in an artificial dermis made of atelocollagen affixed to human tissue. The artificial dermis was used in 21 cases and at 23 sites, and biopsies were performed. The samples were stained with anti‐human blood type A, B, and H monoclonal antibodies. Angiogenesis in the upper layer of the artificial dermis was recognizable within 14 days after affixing the artificial dermis. We concluded that a skin graft taken 14 days after affixing the artificial dermis would be successful, even though the granulation tissue formation might not be completed and the color would most likely remain white. The lower layer of the angiogenesis spread in a horizontal direction like an expanded network of blood vessels, while the middle and upper layers of angiogenesis spread perpendicularly to form upward growth when two cases were examined in various spots. The data suggested that the sponge construction of artificial dermis not only became a scaffold for the invasion of collagen, but it also facilitated construction of near normal dermis with regard to the construction of blood vessels.
Clinical Course of 44 Cases of Localized Type Vitiligo
Authors: Zaima Hiroyuki , Koga Michiyuki
Published: July 2014

Vitiligo is often classified into three types, generalized, segmental, and localized, on the basis of their distribution pattern. It is also classified into type A (non‐dermatomal or non‐segmental) and type B (dermatomal or segmental) vitiligo on the basis of both the distribution pattern and physiological function (1). The natural courses of type A and type B vitiligo are characteristic and quite different from each other. Whereas type A vitiligo appears at any age and progresses throughout the patient's life span, type B vitiligo affects the young and stabilizes within a few years (2). Segmental type vitiligo corresponds to type B, and generalized type vitiligo is the late stage of type A. However, no one has observed the course and character of localized type vitiligo, and its nosological position in A/B classification is unclear. We followed 44 cases of localized type vitiligo for periods of 6 months to 8 years. In 3 of the 44 patients, new white patches developed within the same dermatome as their affected areas in the first 12 months and stabilized in a short period. Therefore, these patients were diagnosed as type B vitiligo. In 15 patients, vitiligo developed in other dermatomal areas; the earliest case at 9 months, and others later on. The new white patches continue to develop for a long period, so these patients were diagnosed with type A vitiligo. In 26 of the 44 patients, the vitiligo remained localized within the period of observation. It is concluded that most localized type vitiligo is the early stage of type A, but a small number of cases belong to the early stage of type B.
A Case of Cellular Schwannoma of the Skin Presenting as a Large Ulcerated Tumor on the Ankle
Authors: Kang Sook‐Kyoung , Chang Sung‐Eun , Choi Jee‐Ho , Sung Kyung‐Jeh , Moon Kee‐Chan , Koh Jai‐Kyoung
Published: July 2014

Cellular schwannoma (CS) is a rare, benign, nerve sheath tumor. It is slowly growing and painless, and it shows a predilection for the paravertebral region of the mediastinum and the retroperitoneum. CS rarely occurs in the skin. It has more cellular and more atypical cytological features than ordinary schwannoma but follows a benign clinical course. The key histological feature is a distinct predominance of cellular Antoni A tissue. Herein we report a case of CS presenting as a 5 × 5 × 3 cm, ulcerated and protruding tumor on the left ankle and describe its indolent clinical course.
Docetaxel Induced Durable Response in Advanced Extramammary Paget's Disease: A Case Report
Authors: Oguchi Shinji , Kaneko Miwako , Uhara Hisashi , Saida Toshiaki
Published: July 2014

The patient was a 54‐year‐old Japanese man with a seven‐month history of an eroded lesion on the scrotum. Skin biopsy confirmed the diagnosis of extramammary Paget's disease, and a CT scan revealed multiple metastases to the lymph nodes along the iliac artery and aorta. The patient underwent combination chemotherapy with mitomycin C, epirubicin, vincristine, cisplatin, and 5‐fluorouracil. After two courses of the regimen, the primary lesions on the scrotum regressed, however, the lymph node metastases did not respond. A regimen of continuous administration of low‐dose cisplatin and 5‐fluorouracil was not effective for the metastases either. Hence, administration of docetaxel at a dose of 60 mg/m2/every four weeks was started. After two courses, the lymph node metastases decreased by 75% compared to the pre‐treatment size, and the effect was judged a partial response. The major toxicities were neutropenia, alopecia, pitting edema, and facial erythema, but these were tolerable. Five courses of this regimen were followed by four courses of weekly administration of 25 mg/m2 docetaxel. The partial response persisted for more than 12 months and the patient was able to enjoy daily life. Docetaxel may be an effective drug for patients with advanced extramammary Paget's disease.
Pseudoxanthoma Elasticum: Report of a Case without any Mutations in 5 Exons of the MRP6 Gene
Authors: Ohtani Toshio , Furukawa Fukumi
Published: July 2014

Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder of connective tissue. We describe a patient with PXE who does not have mutations in exons 16, 24, 27, 28, and 30 of the MRP6 gene.
Sweet's Syndrome Evolved from Recurrent Erythema Nodosum in a Patient with Myelodysplastic Syndrome
Authors: Nishie Wataru , Kimura Tetsunori , Kanagawa Michiyo
Published: July 2014

A 63‐year‐old man had painful nodules on his lower legs. Microscopic examination showed septal and lobular panniculitis composed of lympho‐histiocytic infiltrates. Based on the clinical and histopathological findings, the diagnosis of erythema nodosum (EN) was made. Nonsteroidal anti‐inflammatory drugs were temporarily effective, but the eruptions had repeated to the present, and 16 months later, myelodysplastic syndrome (MDS) was diagnosed. Then, 6 months later, he developed a high fever and edematous fresh red‐colored nodules on his neck, arm and upper trunk. Histopathologically, a diffuse, dense, dermal infiltrate of neutrophils was seen, and Sweet's syndrome (SS) was diagnosed. SS is known to develop in patients with MDS, and EN is one of the dermatoses that occur in conjunction with hematoproliferative disorders. Furthermore, SS evolving from recurrent EN and the simultaneous occurrence of SS and EN have been reported in some patients. In our case, we suggest that some mediators such as cytokines associated with MDS might have first induced EN, and then, as the MDS developed, they were replaced by others that caused SS.
Increased Microorganisms DNA Levels in Peripheral Blood Monocytes from Psoriatic Patients Using PCR with Universal Ribosomal RNA Primers
Authors: Okubo Yukari , Oki Noriko , Takeda Hidemi , Amaya Misato , Ito Sonoko , Osada Masako , Utsumi Masako , Koga Michiyuki , Kawashima Hisashi
Published: July 2014

It has long been suspected that systemic and focal infections cause or exacerbate psoriatic lesions. We previously showed that peripheral blood monocytes in psoriatic patients are activated and overproduce inflammatory cytokines. In addition, it has been reported that macrophages activated by ingesting microorganisms release tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β. Therefore we hypothesized that the monocytes in psoriatic patients may be activated by ingesting microorganisms and overproduce inflammatory cytokines. We examined the detection of microorganism DNA in monocytes from 15 patients with psoriasis vulgaris and from 12 healthy controls. DNA was extracted from monocytes, and a polymerase chain reaction (PCR) assay was performed for the detection using universal primers from conserved regions of the bacterial 16S ribosomal RNA gene or the fungal 18S rRNA gene. At the same time, we calculated the psoriasis area and severity index (PASI) scores and analyzed their correlations with the microorganisms DNA levels. The results showed that bacterial 16S DNA levels in monocytes were significantly higher in psoriatic patients than in controls. The fungal 18S DNA levels were also higher in psoriatic patients than in controls, but the differences were not significant. Although the microorganisms DNA levels in monocytes of psoriatic patients were high, there was no correlation between the bacterial DNA levels in monocytes of the psoriatics and PASI scores. Our study suggests that monocytes in psoriatic patients engulf more bacteria than there in controls, causing an activation of monocytes and triggering the formation of new lesions in the initial stages of psoriasis.
Kikuchi's Disease (Histiocytic Necrotizing Lymphadenitis) with Cutaneous Involvement
Authors: Imai Ken , Yokozeki Hiroo , Nishioka Kiyoshi
Published: July 2014

We report a case of Kikuchi's disease (histiocytic necrotizing lymphadenitis) in a 22‐year‐old Japanese man who presented with cervical and axillary lymphadenopathy and who developed edema of lips with desquamation and erosions and transient indurated erythematous papules on the face, neck and upper extremities. A lymph node biopsy specimen showed the typical necrotizing lymphadenitis of Kikuchi's disease. A skin biopsy specimen showed a dense, lymphohistiocytic, superficial, deep perivascular, and interstitial infiltrate, papillary dermal edema, and abundant nuclear debris with a conspicuous absence of neutrophils, paralleling the nodal histology of Kikuchi's disease. CD68 immunohistochemistry showed many plasmacytoid monocytes. Oral corticosteroid (prednisolone 40 mg) therapy improved the skin lesions and other clinical symptoms. Lip involvement by Kikuchi's disease has not been reported, and should be included as one of the possible cutaneous manifestations of Kikuchi's disease.
A Synovial Sarcoma beneath the Pectoralis Major Muscle
Authors: Yano Toshie , Inoue Chizuko , Yano Kenji
Published: July 2014

Synovial sarcoma is a rare malignant neoplasm that develops most frequently in the extremities. A 68‐year‐old man presented with a painful mass on the right side of his chest with a 10‐year history. Gross findings revealed a mass beneath the pectoralis major muscle. The pathologic findings showed the tumor was predominantly composed of spindle cells the arranged in compact interdigitating fascicles and scattered epithelial nests were seen. A diagnosis of synovial sarcoma was made.
Pseudoxanthoma Elasticum
Authors: Ohtani Toshio , Furukawa Fukumi
Published: July 2014

Pseudoxanthoma elasticum (PXE) is a heritable disease characterized by dermal, ocular, and vascular lesions that result from degeneration of the elastic fibers. Recently, the ATP‐binding cassette subfamily C member 6 (ABCC6) gene has been demonstrated to be responsible for PXE, and 43 mutations have been identified to date. However, it is still unknown how mutations in the ABCC6 gene can lead to manifestations of PXE.