Two sisters reveal autosomal recessive inheritance of epidermodysplasia verruciformis: a case report.

BACKGROUND: Epidermodysplasia verruciformis is a rare genodermatosis characterized by a unique susceptibility to cutaneous human papillomaviruses infection. Most patients show autosomal recessive patterns of inheritance. CASE PRESENTATION: We report a case of two sisters with clinically epidermodysplasia verruciformis specific lesions on the face, neck, trunk, and extremities. PCR analysis indicated the presence of human papillomavirus type 5 in the lesions. Electron microscopic examination showed viral-like particles in keratinocyte nuclei and the stratum corneum of the epidermodysplasia verruciformis lesions. In addition, we examined the EVER1 and EVER2 genes using eight different primer pairs without finding any nonsense or frameshift mutations in the gDNA from lymphocytes of the elder sister. CONCLUSIONS: In this report, the patient's parents did not have epidermodysplasia verruciformis lesions or a consanguineous marriage. EV did not develop in the elder sister until five years of age, so the parents did not perceive EV as an inherited disease. The probability that EV developed in both sisters was only 6.25%. Thus, it is rare for both sisters to develop epidermodysplasia verruciformis lesions considering that the parents were presumed to be carriers and the disease reveal an autosomal recessive pattern of inheritance.

[Current situation of available back-up beds for terminal home care patients].

The Palliative Care Unit at Heiwa Hospital has 16 beds, and offers inpatient support in general wards, as well as back-up beds in emergencies in collaboration with local home care support clinics. For two years from January 2012 to December 2013, there were 1,213 cases where patients were seen for initial outpatient visits at the Department of Palliative Care. At the time of the initial visit, visiting medical care had been introduced for 25% of the cases. Although 59% of the patients who visited our department are hospitalized, 20% of inpatients have been hospitalized at the request of their home care physician. The availability of back-upbeds offers patients and their families, as well as related medical institutions, a sense of security, and enables home care to continue. The significance of back-upbeds will become even more important in the future.

Efficacy of Touch Imprint Cytology in Intraoperative Diagnosis of Invasive Mucinous Adenocarcinoma of the Lung: A Case Report and Literature Review.

A preoperative diagnosis of the peripheral small lung nodule is often difficult, and an intraoperative frozen section diagnosis (FSD) is performed to guide treatment strategy. However, invasive mucinous adenocarcinoma (IMA) is prone to be overlooked because of the low sample quality and weak atypia. We herein report a case of IMA, in which touch imprint cytology (TIC) revealed diagnostic efficacy. A 74-year-old male with a small, subsolid nodule in the right upper lobe underwent a thoracoscopic wedge resection. A grayish brown, 10 × 7 mm-sized nodule was observed on the cut surface. Intraoperative FSD revealed lung tissue with mild alveolar septal thickening and stromal fibrosis but without overt atypia. Meanwhile, TIC revealed mucus and a few epithelial cells with intranuclear inclusions, which pathologists evaluated as reactive. Finally, focal organizing pneumonia was tentatively diagnosed, and surgery was finished without any additional resection. However, permanent section diagnosis revealed a microinvasive mucinous adenocarcinoma. Nuclear inclusions were confirmed in tumor cells. In the intraoperative setting, TIC may be more advantageous than FSD in observing nuclear inclusions and mucus. Mucinous background and nuclear inclusion on TIC may suggest IMA even if FSD does not suggest malignancy in an intraoperative diagnosis of the peripheral small lung nodule.

An unusual cytological presentation of solid pseudopapillary neoplasm of the pancreas mimicking adenoid cystic carcinoma: a case report and literature review.

Endoscopic ultrasound-guided fine-needle aspiration has become the common procedure for the diagnosis of pancreatic mass, and cytological examination is usually the first approach. Solid pseudopapillary neoplasm (SPN) cytologically represents papillary structures of branching capillaries surrounded by discohesive neoplastic cells. However, it may present various degrees of tissue degeneration, causing diagnostic challenges. Here, we report a 21-year-old female who had a 2-cm-sized mass in the pancreas head. Cytological examination revealed clumps of small round/oval cells that represented microcystic configurations with mucus, mimicking adenoid cystic carcinoma or mucinous adenocarcinoma. Cercariform cells, nuclear grooves/folding, and cytoplasmic vacuoles were not observed. Histopathological examination revealed confluent small glandular structures containing acidic mucus. The tumor cells were positively stained for ß-catenin, CD10, and CD56, and negative for chromogranin A and E-cadherin, suggesting SPN, micropseudocystic variant. This variant has been scarcely described, but we should recognize it for accurate cytological triage of pancreatic tumors.

[Creating a good relationship between hospital and clinic for the support of end-of-life home care patients-usefulness of questionnaires to indicate the capacity of home care-supporting clinics for palliative care].

We have been practicing palliative care for terminal cancer patients at outpatient sections, patient wards, by home care, and by visiting nursing stations for the last 4 years. After the establishment of our palliative care unit in June 2011, it became difficult for us to provide sufficient home care support by ourselves, because of the increasing number of the patients and their widespread locations. It is therefore necessary to cooperate with regional medical clinics in order to support the patients who need home care even after their condition deteriorates. To determine the extent to which the home care-supporting clinics perform palliative care, we used an original questionnaire. Twenty-five clinics agreed to the publication of their names as our cooperating clinics. The number of patients who received palliative care at home from home care clinics after visiting our hospital increased from 8% to 14%, and the rate of patients who died at home also increased from 10% to 13%. Information about cooperating with home care clinics is very important and the improvement of palliative care skills necessary for home care doctors to continue their support for End-Of-Life cancer patients. Furthermore, the hospital should offer a strict and timely backup when the condition of patients treated at home suddenly deteriorates.

Combination of carbon dioxide laser therapy and artificial dermis application in plantar warts: human papillomavirus DNA analysis after treatment.

BACKGROUND: Various laser therapies have been used to treat viral warts, and numerous successful results have been reported, but plantar warts are notoriously difficult to treat and eradicate. MATERIALS & METHODS: This study included 35 lesions in 31 patients (17 female, 14 male) with plantar warts. We used a carbon dioxide (CO2) laser for incisions, and the defect was covered with artificial dermis. Follow-up periods ranged from 3 to 12 months. Overall, we examined the presence or absence of human papillomaviruses (HPVs) DNA in the lesional skin of all cases and at the excisional site after treatment in 20 cases. RESULTS: Thirty-one of 35 lesions (88.6%) achieved complete clearance after one treatment session. We observed local recurrence in four lesions (11.4%). The application of salicylic acid was effective in treating minor recurrent cases. After complete remission, HPV DNA was not detected in the upper epidermis of the postoperative site. No significant scars or severe pain were seen in any patients. CONCLUSION: A combination of CO2 laser therapy and artificial dermis application effectively treated the majority of plantar warts after one treatment, with complete and rapid clearance and no persistent pain. The authors have indicated no significant interest with commercial supporters.

Unique peptide:N-glycanase of Caenorhabditis elegans has activity of protein disulphide reductase as well as of deglycosylation.

Peptide:N-glycanase (PNGase) is the enzyme responsible for de-N-glycosylation of misfolded glycoproteins in the cytosol. Here, we report the molecular identification and characterization of PNGase (png-1, F56G4.5) from Caenorhabditis elegans. This enzyme released both high mannose- and complex-type N-glycans from glycopeptides and denatured glycoproteins. Deglycosylation activity was inhibited by Zn(2+) and z-VAD-fmk, but not by EDTA. PNG-1 has a thioredoxin-like domain in addition to a transglutaminase domain, the core domain of PNGases, and exhibited protein disulphide reductase activity in vitro. Our biochemical studies revealed that PNG-1 is a unique bifunctional protein possessing two enzyme activities.

Feeling of ear fullness in acute sensorineural hearing loss.

CONCLUSIONS: This study revealed two characteristic findings of the feeling of ear fullness (FEF) in acute sensorineural hearing loss (ASNHL). First, that the appearance of FEF was not associated with the auditory function on audiograms; and second, that the disappearance of FEF is clearly associated with the hearing prognosis. OBJECTIVE: FEF appears frequently in patients with ASNHL. However, there are few reports on this symptom and its mechanism has yet to be clarified. So we tried to investigate the character of FEF in ASNHL. PATIENTS AND METHODS: In this study, observations were made during the period from the first medical examination to 2 months after obtaining a steady audiogram on 227 ears from unilateral ASNHL cases, and the relationship between FEF and the audiograms was analyzed. RESULTS: The FEF prevalence at the first medical examination was about 80% for any audiogram shape or hearing threshold. Moreover, the better the hearing prognosis, the higher the improvement rate of FEF.

New plication technique for the treatment of congenital penile curvature.

Introduction: Conditions that cause curvature of the erect penis also lead to difficulties with intercourse. The present study presents an effective surgical treatment for congenital penile curvature. Methods: Between March 1996 and August 2004, 49 patients were diagnosed with congenital penile curvature at the Toho University Omori Hospital Reproduction Center, Tokyo. Of these, 27 eligible patients underwent surgical treatment. The operative technique used involved the tunica albuginea being exposed and a number of vertical incisions were made through its superficial layers. The superficial layer of the tunica albuginea was then resected using scissors. Inverted plication sutures were then placed in the raw surface of the corpus cavernosum using 2-0 nylon. In addition, 2-0 polyglactic acid (Vicryl) sutures were placed on either side of each nylon suture knot. Results: Of a total of 49 patients, 27 eligible patients underwent surgical treatment with no serious postoperative complications. All 27 patients were able to sustain intercourse. There were no new cases of erectile dysfunction, penile pain or penile shortening. There were no recurrences of penile curvature. Conclusions: This new partial thickness shaving, inverted sutures reinforced with dissolving sutures plication method is an extremely effective surgical treatment for congenital penile curvature, with a superior safety profile. (Reprod Med Biol 2005; 4: 255-258).

Prognosis for sudden sensorineural hearing loss: a retrospective study using logistical regression analysis.

Sudden sensorineural hearing loss (SSNHL) remains a controversial problem with respect to etiology and the factors that might predict prognosis. We used logistical regression analysis to determine which factors are most strongly related to outcome for patients with SSNHL. In so doing, we employed a retrospective chart-review study. The study group consisted of 296 patients (296 ears). The outcome of SSNHL was cured (full recovery) in 64, recovered (partial recovery) in 175, and no change in 57. We performed separate analyses on those in the no-change and partial-recovery groups and on those in the no-change and full-recovery groups. The following factors were studied as explanatory variables: age; number of days until presentation; vestibular symptom; initial mean hearing level at 0.25 kHz, 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz; and treatments (steroids, satellite ganglion block). In the first analysis, for patients in the no-change and recovered groups, the factors most strongly related to outcome were the number of days until presentation and age. The second analysis, for the nochange and cured groups, revealed that the number of days until presentation, vestibular symptom, age, and initial mean hearing level were most strongly related to outcome. Our results will increase the ability to predict the outcome for SSNHL.

Human papillomavirus infection in actinic keratosis and bowen's disease: comparative study with expression of cell-cycle regulatory proteins p21(Waf1/Cip1), p53, PCNA, Ki-67, and Bcl-2 in positive and negative lesions.

We examined the presence of human papillomavirus (HPV) DNA in tissues of premalignant skin lesions, i.e., actinic keratosis (n = 13) and Bowen's disease (n = 62), taken from 69 Japanese immunocompetent and renal transplant recipient patients. Detection and typing of HPV DNA were performed using polymerase chain reaction (PCR) and sequence analysis or restriction fragment length polymorphism (RFLP) analysis, respectively. The positivity rates of HPV DNA in tissues of actinic keratosis and Bowen's disease were 77% and 65%, respectively. Twenty-seven HPV types were detected in 50 (67%) premalignant skin lesions, in which Z95963 (accession no. in the EMBL Databank), Z95968, AJ010823, and AJ000151 have been described as partial sequences of unknown HPV types. Furthermore, 2 unknown types, HPVX1 and HPVX2, were found in specimens of actinic keratosis. Sequence analysis showed that HPVX1 is related to HPV-37 (86.1% sequence homology) and that HPVX2 is related to HPV-38 (79.7%). These results indicate that various mucosal and epidermodysplasia verruciformis-related HPV types are associated with the pathogenesis of actinic keratosis and Bowen's disease. In addition, 24 specimens of HPV-positive or HPV-negative premalignant skin lesions were examined immunohistochemically for proliferating cells to determine biological differences between HPV-positive and HPV-negative lesions. Immunohistochemistry for p21(Waf1/Cip1), p53, proliferating cell nuclear antigen (PCNA), Ki-67, and Bcl-2 revealed that there was no significant difference in the cell proliferation activity between HPV-positive and HPV-negative lesions, suggesting that HPV infection alone does not induce cell proliferation in those lesions.

Interlaboratory comparison in HercepTest assessment of HER2 protein status in invasive breast carcinoma fixed with various formalin-based fixatives.

Although formalin-based fixatives are used in pathologic laboratories, there is no strictly standardized fixation protocol in Japan. To examine interlaboratory variation caused by different conditions of fixation in the assessment of human epidermal growth factor receptor (HER) 2 status on pathologic tissues, 274 archival invasive breast carcinomas from 5 different laboratories were evaluated using the HercepTest. In 1 laboratory in which 10% neutral buffered formalin was used, as recommended by the manufacturer, the overexpression rate was 22.4% and fell within the statistical expected range (20%-30%) for HER2 overexpression in breast carcinomas. The overexpression rates in the other 4 laboratories, in which either 20% nonbuffered formalin or 15% neutral buffered formalin was used, were near the expected range for HER2 overexpression. To clarify the influence of prolonged formalin fixation on the HercepTest, we compared 1-day with 7-day fixations using 36 cases fixed with 20% nonbuffered formalin. Of the 36 cases, 7 showed 3+ staining with 1-day fixation and sustained the same scoring results with 7-day fixation, although the staining intensities in these cases were reduced with the prolonged fixation. These results indicated that the immunohistochemical assessment of HER2 status with the HercepTest was comparatively resistant to prolonged fixation conditions and provided stable staining results in positive cases, particularly 3+ patients.

Olfactory event-related potentials in normal subjects and patients with smell disorders.

We developed a device to record olfactory event-related potentials (OERP) from the human scalp. Methyl-cyclopentenolone was used as the odorant element. A total of 50 stimuli were delivered. Each stimulus lasted 0.5 sec and was delivered once every three inspirations. Normal OERPs were obtained with this device. The positive peak latencies were approximately 350 msec (P1) and 700 msec (P2), respectively. OERPs were also recorded in 40 patients with smell disorders. A positive response at about 300-400 msec was recorded in 7 patients (all females, 15-59 years old). The other 33 patients showed no response. The high potential area of this positive peak was located in the centro-occipital region of the scalp. The latency and the high potential area of this peak were similar to P1 recorded in normal subjects. The source of this peak was considered identical to that of P1. This may be a response to the trigeminal nerve during odor administration. P2 was not recorded in the patients with smell disorders. P2 may therefore be a response to the olfactory nerve.

Electroencephalographic changes during intravenous olfactory stimulation in humans.

The intravenous olfaction test with thiamin propyl disulfide (TPD) is a simple procedure widely used in Japan. An olfactory stimulus is provided by intravenous injection of TPD (2 ml) over the course of 20 sec. The subject smells n-propyl mercaptan (a decomposition product of TPD discharged from the blood into alveoli) in expired air after treatment. In this preliminary study we recorded electroencephalograms (EEGs) in normal subjects during three stages: 1) eyes-closed rest (prestimulus), 2) olfactory sensation after TPD injection, and 3) disappearance of sensation. In each of these stages, we calculated and compared EEG powers according to the band components of each electrode position. This study was designed a) to evaluate by frequency analysis EEG changes during olfactory sensation after TPD injection, and b) to identify the most significant changes in EEG power according to frequency band and electrode location. During the intravenous olfactory stimulation, alpha 2 and beta 2 waves were activated over the frontal and temporal regions. After disappearance of olfactory sensation, these waves decreased in the same regions. EEG powers returned to prestimulus levels.

[Magnetoencephalographic responses to odor and non-odor by fast Fourier transformation analysis in humans].

Magnetoencephalographic (MEG) responses to odor (amyl-acetate) and non-odor stimuli for 1 second were recorded in 9 healthy volunteers (right handed) with a dual 37-channel SQUID (Magnes, Bti Co.) and evaluated by fast Fourier transformation analysis, with the following results: 1. On MEG analysis, the spectral density increase in the left mid-central region at a frequency of 7 Hz was significantly greater in response to odor than in response to non-odor stimuli. This greater increase is apparently related to the presence of the odor perception mechanism in the orbital frontal area, a major center of the olfactory system. 2. Both increased and decreased spectral density areas at a frequency of 8 Hz were observed over the right hemisphere when no stimuli was compared with non-odor and no stimulus compared with odor. These changes may reflect a high level of vigilance caused by stimulation. 3. When no stimulus was compared with non-odor stimulation, a significant spectral density increase at a frequency of 11 Hz was noted. Similar trends were observed at frequencies of 11 and 12 Hz when no stimulus was compared with odor. These findings indicated increased attention in response to random presentation of odor and non-odor. 4. Significant differences at frequencies from 14 to 24 Hz were noted in the contralateral hemisphere when no stimulus was compared with odor stimuli. MEG spectral densities at 21 and 22 Hz were also noted in the contralateral hemisphere when no stimulus was compared with non-odor stimulus. These differences apparently arise from the response of the somato-sensory cortex to non-odor stimuli and amyl-acetate. Alternation of MEG spectral densities at frequencies from 14 to 17 Hz and 23 to 24 Hz in the left hemisphere was noted when no stimulus was compared with non-odor and no stimulus was compared with odor. These results appear to be related to "emotions" of pleasantness and unpleasantness evoked by non-odor and odor.

Molecular cloning and characterisation of a novel type of human papillomavirus 160 isolated from a flat wart of an immunocompetent patient.

More than 150 types of Human papillomaviruses (HPVs) have been isolated from numerous cutaneous and/or mucosal lesions. Flat wart samples on the face from 36 immunocompetent patients were collected and screened for HPV. From one sample, we cloned a putative novel genotype. The novel type consisted of 7779 bp in length with a GC content of 47.1%, containing open reading frames for putative early proteins (E1, E2, E4, E6, and E7) and two late proteins (L1 and L2). Homology searches and phylogenetic analyses indicated that it belonged to Alphapapillomavirus (Alpha-PV) species 2 and most closely resembled HPV 3. The virus fulfilled the definition of a novel type, and was named HPV 160 by the Reference Center for Papillomaviruses. The putative E7 protein of HPV 160 as well as HPV 29, 77, and 78 contained the Leu-X-Cys-X-Glu pRB-binding motif but other Alpha-PV species 2 (HPV 3, 10, 28, 94, 117, and 125) did not have this conserved motif.

Specific substance of Maruyama (SSM) suppresses immune responses in atopic dermatitis-like skin lesions in DS-Nh mice by modulating dendritic cell functions.

BACKGROUND: Specific substance of Maruyama (SSM) is a carcinostatic immunotherapeutic agent extracted from Mycobacterium tuberculosis. The efficacy of SSM induced interleukin(IL)-12 and IFN-γ production, and inhibition of IL-4, resulting in a shift from Th2 to Th1 in vivo. OBJECTIVE: The DS-Nh mice are a model of human atopic dermatitis (AD), which spontaneously develop dermatitis under conventional conditions. In this study, to determine whether SSM can prevent the development of skin lesions in a murine model of AD. METHODS: DS-Nh mice were injected with SSM 5 days per week for 11 weeks. Pharmacological, histological and serological studies were performed to investigate the therapeutic effect of SSM for DS-Nh mice. Analysis of cytokines responses to SSM using quantitative RT-PCR and flow cytometry were also performed to evaluate their therapeutic mechanisms in these AD model mice. RESULTS: Clinically, erythema, erosions, excoriation, and edema were observed in DS-Nh mice at 16 weeks of age, which advanced with age. Histologically, the relative number of mast cells increased in DS-Nh mice. SSM treatment alleviated the clinical and histological findings in accord with reduced serum IgE level, and increased IgG2a level. TSLP expression was not induced, but IL-1ß, IL-12, IL-17A, and IFN-γ were induced in SSM-treated DS-Nh mice. Overall, SSM treatments increased the number of activated DCs in lesions. SSM induced CD80, CD86, and MHC class II expression on bone marrow-derived DCs. CONCLUSIONS: SSM enhanced IL-12 production, but suppressed TSLP expression, resulting in a shift from Th2 to Th1 responses. This shift suppressed AD-like skin lesions in a similar fashion as the BCG vaccine. Therefore, SSM may be a useful adjuvant for suppressing skin lesions in AD models.