Prognostic value of increased intraepithelial lymphocytes and lymphocytic clonality in dogs with chronic enteropathy or small-cell lymphoma.

The clinical significance of severe infiltration of small intraepithelial lymphocytes (IEL) and the results of polymerase chain reaction for antigen receptor rearrangement (PARR) in dogs with chronic enteropathy (CE) and small-cell lymphoma (SCL) are controversial. This cohort study aimed to evaluate the prognostic significance of the IEL and PARR results in dogs with CE or SCL. Although definitive diagnostic histopathological criteria for SCL in dogs have yet to be established, dogs with the histopathological findings of severe IEL infiltration were diagnosed with SCL in this study. One hundred and nineteen dogs were recruited, with 23 dogs classified as having SCL and 96 dogs as having CE. The positive rate of PARR was 59.6 % (71/119) in the duodenum and 57.7 % (64/111) in the ileum. Subsequently, three dogs with SCL and four dogs with CE developed large-cell lymphoma (LCL). The median overall survival (OS) of dogs with SCL was 700 days (range, 6-1410 days), and that of dogs with CE was not reached. In the log-rank test, shorter OS was observed in cases with histopathological SCL (P = 0.035), clonal TCRγ rearrangement in the duodenum (P = 0.012), and clonal IgH rearrangement in the ileum (P < 0.0001). The Cox proportional hazards model adjusted for sex and age showed that histopathological SCL (hazard ratio [HR] 1.74; 95 % confidence interval [CI], 0.83-3.65), duodenal clonal TCRγ rearrangement (HR, 1.80; 95 % CI, 0.86-3.75), and ileal clonal IgH rearrangement (HR, 2.28; 95 % CI, 0.92-5.70) could shorten overall survival, although their 95 % CIs included 1.0. These results indicate that severe IEL infiltration could be a useful histopathological feature for diagnosing SCL, and clonality-positive results could be a negative prognostic factor in dogs with CE. Furthermore, the development of LCL should be carefully monitored in dogs with CE and SCL..

Inferior oblique muscle of the eye: its foetal development with special reference to understanding of the frequent variants in adults.

BACKGROUND AND MATERIALS AND METHODS: To provide better understanding of frequent variations of the inferior oblique (IO) of adult extraocular muscles, we observed sagittal and horizontal histological sections of the eye and orbits from 32 foetuses (7-34 weeks of gestational age; 24-295 mm of crown-rump length). RESULTS: In early foetuses (7-8 weeks), the IO was restricted at an antero-infero-medial angle of the future orbit. In contrast to extraocular recti, the IO appeared to extend along the mediolateral axis and had no definite tendon. At midterm, the IO tendon became evident. Sometimes, the IO muscle belly attached to the inferior rectus or, the IO tendon divided into two laminae to enclose the lateral rectus. At late-term, a multilayered sheath was evident around the sclera and, via one or some of the fascial layers, the IO was communicated with a fascia enclosing the inferior rectus. At midterm and late-term, the IO originated not only from the maxilla near the orbicularis oculi origin but also from a vein-rich fibrous tissue around the lacrimal sac. Both origins were muscular without intermittent tendon or ligament. Therefore, the fascial connection as well as a direct contact between the IO and the inferior or lateral rectus seemed to provide variant muscular bridges as reported in adults. Moreover, the two attachment sites at the origin seemed to provide double muscle bellies of the adult IO. CONCLUSIONS: Consequently, the present specimens contained seeds of any types of adult variations. The muscle fibres from the lacrimal sac might play a role for the lacrimal drainage.

Surgical treatment for non-tuberculous mycobacterial pulmonary disease: analysis of prognostic factors.

BACKGROUND: The surgical treatment for non-tuberculous mycobacterial pulmonary disease (NTM-PD) has an important adjunctive role and reported outcomes have been generally good; however, the prognostic factors remain unclear.METHODS: Sixty-one patients with NTM-PD who underwent surgical resection for a therapeutic purpose from January 2000 to March 2017 at five affiliated institutions were enrolled. We explored the factors that influence complications and prognosis by retrospectively referring to the medical records.RESULTS: The mean age of the present cohort was 61.8 ± 11.4 years. The pathogen was Mycobacterium avium complex in 49 patients, M. abscessus in 5. The most common indications were refractory to medication in 39. The surgical techniques employed were lobectomy or further resection in 49, sublobar resection in 8, with video-assisted thoracoscopic surgery in 21. Sputum culture conversion rate was 95.1%. Univariate analysis of factors associated with deterioration revealed significant differences related to age (P = 0.025), pre-operative albumin level (P = 0.001) and development of postoperative complications (P = 0.037), while pre-operative albumin level alone was a significant factor in multivariate analysis (P = 0.009).CONCLUSION: Outcomes after resection were generally good in the present cases. Nutritional status, as indicated by albumin level, may affect prognosis after surgical treatment.

Construction and validation of a scoring system to predict resistance to chemotherapeutic drugs using gene expression profiles in canine lymphoma.

The present study aimed to verify the changes in the expression levels of 13 candidate genes associated with chemotherapy resistance and to construct a scoring system to predict resistance to these drugs. The expression levels of the 13 candidate genes were compared between 20 dogs with lymphoma that were sensitive to drugs used in CHOP-based protocol and 16 dogs with lymphoma that were resistant to these drugs. The expression levels of six genes; ASNS, CCR3, CALCA, FCER1A, LOC448801, and EDNRB were significantly different between the two groups. A scoring system to predict resistance to cyclophosphamide, doxorubicin and vincristine, which are used in CHOP-based protocol, was constructed based on expression levels of the six genes in these 36 dogs using logistic regression models. After internal validation, sensitivity and specificity of the scoring system were 0.759 and 0.853, respectively. External validation was conducted in another cohort of 33 dogs with lymphoma, and sensitivity and specificity of the scoring system were 0.800 and 0.696, respectively. In conclusion, this study identified six genes associated with resistance to drugs used in CHOP-based protocol in canine lymphoma and proposed a novel scoring system to predict resistance to these drugs. This system might be beneficial in selecting the most appropriate chemotherapy protocol for individual dogs with lymphoma.

Generation of a neutralizing antibody against RD114-pseudotyped viral vectors.

The feline endogenous RD114 glycoprotein has proved to be an attractive envelope to pseudotype both retroviral and lentiviral vectors. As a surface protein, its detection on packaging cells as well as viral particles would be useful in different fields of its use. To address this, we generated a monoclonal antibody against RD114 by immunization of rats, termed 22F10. Once seroconversion was confirmed, purified 22F10 was cloned into murine Fc and characterized with a binding affinity of 10nM. The antibody was used to detect RD114 and its variant envelopes on different stable viral packaging cell lines (FLYRD18 and WinPac-RD). 22F10 was also shown to prevent the infections of different strains of RD-pseudotyped vectors but not related envelope glycoproteins by blocking cell surface receptor binding. We are the first to report the neutralization of viral particles by a monoclonal αRD114 antibody.

Peculiar clinical features of cellulitis in peripheral lymphedema.

Although the occurrence of cellulitis in lymphedema (LE) is believed to be an infection-related event, many findings in its clinical course seem to suggest that it is unlikely to be an infection. Therefore, we tried to clarify the specific features of cellulitis in LE. In-hospital courses of cellulitis obtained from medical charts were reviewed in the patients with leg LE (LE; 24 patients, 72admissions), chronic venous insufficiency (CVI; 28 patients, 29 admissions), and leg cellulitis secondary to wound infection without underlying disease (N; 42 patients, 42 admissions). The patients with LE complained of less local pain (peak numerical scale; LE: 1.4 ± 1.7, CVI: 4.1 ± 2.5, N: 3.2 ±2.0, p < 0.0001), showed an abnormally higher peak procalcitonin level (LE: 33.8 ± 34.8 (N = 7), CVI: 2.9 ± 5.8 (N = 8), N: 0.4 ± 0.6(N = 10), p < 0.05), and required fewer antibiotics (LE: 1.1 ± 0.3, CVI: 1.8 ± 0.9, N: 1.5 ± 0.9, p < 0.0001). These findings suggested that the occurrence of cellulitis in LE seems unlikely to be an infection-related type of cellulitis similar to that found in CVI.

Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Upper critical field reaches 90 tesla near the Mott transition in fulleride superconductors.

Controlled access to the border of the Mott insulating state by variation of control parameters offers exotic electronic states such as anomalous and possibly high-transition-temperature (Tc) superconductivity. The alkali-doped fullerides show a transition from a Mott insulator to a superconductor for the first time in three-dimensional materials, but the impact of dimensionality and electron correlation on superconducting properties has remained unclear. Here we show that, near the Mott insulating phase, the upper critical field Hc2 of the fulleride superconductors reaches values as high as ∼90 T-the highest among cubic crystals. This is accompanied by a crossover from weak- to strong-coupling superconductivity and appears upon entering the metallic state with the dynamical Jahn-Teller effect as the Mott transition is approached. These results suggest that the cooperative interplay between molecular electronic structure and strong electron correlations plays a key role in realizing robust superconductivity with high-Tc and high-Hc2.

Bone metabolic microarray analysis of ligature-induced periodontitis in streptozotocin-induced diabetic mice.

BACKGROUND AND OBJECTIVE: Periodontal disease is a chronic infectious disease that results in bone loss. Many epidemiological studies have reported the progression of periodontal tissue destruction in patients with diabetes; however, the associated mechanism remains unclear. In this study, we comprehensively investigated how diabetes affects the periodontal tissue and alveolar bone loss using a ligature-induced periodontitis model in streptozotocin-induced diabetic (STZ) mice. MATERIAL AND METHODS: Diabetes was induced by intraperitoneal injection with streptozotocin in 6-wk-old C57/BL6J male mice. A silk ligature was tied around the maxillary left second molar in 9-wk-old wild-type (WT) and STZ mice. Bone loss was evaluated at 3 and 7 d after ligation. mRNA expression levels in the gingiva between the two groups were examined by DNA microarray and quantitative polymerase chain reaction at 1, 3 and 7 d post-ligation. Tartrate-resistant acid phosphatase and alkaline phosphatase staining of the periodontal tissue was performed for evaluation of osteoclasts and osteoblasts in histological analysis. RESULTS: In the gingiva, hyperglycemia upregulated the osteoprotegerin (Opg) mRNA expression and downregulated Osteocalcin mRNA expression. In the ligated gingiva, tumor necrosis factor-α (Tnf-α) mRNA expression was upregulated at 1 d post-ligation in STZ mice but not in WT mice. At 3 d post-ligation, alveolar bone loss was observed in STZ mice, but not in WT mice. Significantly severe alveolar bone loss was observed in STZ mice compared to WT mice at 7 d post-ligation. Bone metabolic analysis using DNA microarray showed significant downregulation in the mRNA expression of glioma-associated oncogene homologue 1 (Gli1) and collagen type VI alpha 1 (Col6a1) at the gingiva of the ligated site in STZ mice compared to that in WT mice. Quantitative polymerase chain reaction showed that Gli1 and Col6a1 mRNA expression levels were significantly downregulated in the gingiva of the ligated site in STZ mice compared to WT mice. Histological analysis showed lower alkaline phosphatase activity in STZ mice. In addition, an increased number of tartrate-resistant acid phosphatase-positive multinucleated cells were observed at the ligated sites in STZ mice. CONCLUSIONS: These results suggest that an imbalance of bone metabolism causes osteoclastosis in insulin-deficient diabetes, and that alveolar bone loss could occur at an early phase under this condition.

Solitary pulmonary nodules due to non-tuberculous mycobacteriosis among 28 resected cases.

BACKGROUND: In some patients, non-tuberculous mycobacteria (NTM) infections manifest in solitary nodules (solitary nodular [SN] type) generally caused by Mycobacterium avium complex (MAC). In patients treated using surgical resection, the American Thoracic Society guidelines state that postoperative chemotherapy is not necessary in the absence of lesions, although there have been a few reports of such cases. METHODS: Twenty-eight patients diagnosed with NTM who underwent solitary pulmonary nodule resection at Toneyama Hospital, Osaka, Japan, between January 2000 and October 2012 were enrolled. We evaluated the influence of the surgical procedure and chemotherapy on outcomes in this retrospective study. RESULTS: Of the 28 patients, 12 were males and 16 were females; the mean age was 58.6 ± 13.2 years. Twenty-five patients were asymptomatic and bronchoscopy was performed in 18; only 2 had a definitive diagnosis of NTM. The pathogen responsible was MAC in 27 patients and M. kansasii in 1. The surgical procedure used was wedge resection in 22 patients, segmentectomy in 1 and lobectomy in 5. Postoperative chemotherapy was administered to 9 patients. Twenty-six patients had no recurrence. CONCLUSION: We believe that wedge resection is a valid surgical intervention for SN type NTM; additional postoperative chemotherapy is unnecessary in cases with no residual lesions in the operated lung lobe.

Two-stage laparoscopic treatment for strangulated inguinal, femoral and obturator hernias: totally extraperitoneal repair followed by intestinal resection assisted by intraperitoneal laparoscopic exploration.

PURPOSE: Total extraperitoneal preperitoneal (TEP) repair is widely used for inguinal, femoral, or obturator hernia treatment. However, mesh repair is not often used for strangulated hernia treatment if intestinal resection is required because of the risk of postoperative mesh infection. Complete mesh repair is required for hernia treatment to prevent postoperative recurrence, particularly in patients with femoral or obturator hernia. CASES: We treated four patients with inguinocrural and obturator hernias (a 72-year-old male with a right indirect inguinal hernia; an 83-year-old female with a right obturator hernia; and 86- and 82-year-old females with femoral hernias) via a two-stage laparoscopic surgery. All patients were diagnosed with intestinal obstruction due to strangulated hernia. First, the incarcerated small intestine was released and then laparoscopically resected. Further, 8-24 days after the first surgery, bilateral TEP repairs were performed in all patients; the postoperative course was uneventful in all patients, and they were discharged 5-10 days after TEP repair. At present, no hernia recurrence has been reported in any patient. CONCLUSION: The two-stage laparoscopic treatment is safe for treatment of strangulated inguinal, femoral, and obturator hernias, and complete mesh repair via the TEP method can be performed in elderly patients to minimize the occurrence of mesh infection.

Molecular-based allergy diagnosis of allergic bronchopulmonary aspergillosis in Aspergillus fumigatus-sensitized Japanese patients.

BACKGROUND: Distinguishing between patients with allergic bronchopulmonary aspergillosis (ABPA) and Aspergillus fumigatus (Af)-sensitized asthmatic patients without ABPA is sometimes difficult owing to the IgE-cross-reactivity between Af and other fungal allergens. OBJECTIVE: To establish the usefulness of molecular-based allergy diagnostics using allergen components from Af in distinguishing ABPA from Af-sensitized asthma without ABPA. METHODS: Sera from Japanese patients with ABPA (n = 53) and Af-sensitized asthma without ABPA (n = 253) were studied. The levels of IgE and IgG antibodies to allergen components from Af and IgE antibodies to different fugal allergen extracts were measured by ImmunoCAP. Comorbid atopic dermatitis (AD) was taken into consideration in the sensitization profile analysis. RESULTS: Patients with ABPA possessed significantly higher levels of IgE antibodies to Asp f 1, and Asp f 2 than asthmatic patients without ABPA. The areas under the receiver operating characteristic curves for the levels of IgE to Asp f 1 and Asp f 2 as diagnostic markers of ABPA were 0.75 and 0.78, respectively. The presence of IgE positivity to Asp f 1 and/or Asp f 2 resulted in increased sensitivity while losing little specificity. Comorbid AD was associated with higher levels of IgE to Asp f 6 (manganese superoxide dismutase from Af, a ubiquitous pan-allergen in fungi) and low but positive levels of IgE to other Af-components, which hampered the serological discrimination of ABPA. CONCLUSIONS AND CLINICAL RELEVANCE: The levels of IgE to Asp f 1 and/or Asp f 2 can effectively differentiate ABPA from Af-sensitized asthma, suggesting that the amounts of IgE specific for these molecules are markers for genuine Af-sensitization in ABPA. However, comorbid AD must be taken into consideration in the interpretation of high IgE to Asp f 6. Establishing of IgE-sensitization profiles using panel of Af-allergen components provides valuable information for distinguishing genuine vs. cross-reactive sensitization in Af-sensitized patients.

The 3-second auditory conditioned stimulus is a more effective stressor than the 20-second auditory conditioned stimulus in male rats.

Using fear-conditioning model, we have used a 3-s auditory conditioned stimulus (CS) as a stressor and observed fear and stress responses during a specific experimental period regardless of the presence or absence of the CS. Because the CS was extremely short compared with the experimental period, we observed responses primarily in the absence of the CS. In contrast, most studies in the literature have analyzed responses in the presence of the CS. Therefore, the characteristics of fear and stress responses in the absence of the CS remain to be clarified. To clarify this, we compared the characteristics of fear and stress responses elicited by a 3-s auditory CS with those observed during a 20-s auditory CS. The basolateral complex of the amygdala (BLA), but not the bed nucleus of the stria terminalis (BNST), participated in the fear response elicited by the 3-s CS, whereas both the BLA and BNST were involved in the response observed during the 20-s CS. Additional analyses revealed that the BNST participated in the fear response during the 20-s CS when the CS was paired with a 0.75-mA, but not with a 0.9-mA, foot shock, and to the contextual CS. In addition, the fear response elicited by the 3-s CS was more resistant to extinction than that during the 20-s CS. Finally, the 3-s CS produced more intense freezing and corticosterone secretion than the 20-s CS. On the basis of these characteristics, we conclude that the 3-s auditory CS is a more effective stressor than the 20-s auditory CS. Our findings also suggest that foot shock intensity is an additional determinant in the type of fear response induced by the CS.

Fine mapping of a major quantitative trait locus, qLG-9, that controls seed longevity in rice (Oryza sativa L.).

KEY MESSAGE: We fine-mapped a quantitative trait locus, qLG - 9, for seed longevity detected between Japonica-type and Indica-type cultivars. qLG - 9 was mapped in a 30-kb interval of the Nipponbare genome sequence. A quantitative trait locus, qLG-9, for seed longevity in rice has previously been detected on chromosome 9 by using backcross inbred lines derived from a cross between Japonica-type (Nipponbare) and Indica-type (Kasalath) cultivars. In the present study, the chromosomal location of qLG-9 was precisely determined by fine-scale mapping. Firstly, allelic difference in qLG-9 was verified by QTL analysis of an F2 population derived from a cross between Nipponbare and NKSL-1, in which a segment of Kasalath chromosome 9 was substituted in Nipponbare genetic background. Then, we selected F2 plants in which recombination had occurred near qLG-9 and performed F3 progeny testing on these plants to determine the genotype classes of qLG-9. Eventually, qLG-9 was mapped in a 30-kb interval (defined by two markers, CAPSb and CHPa12) of the Nipponbare genome sequence. This allowed us to nominate positional candidate genes of qLG-9. Additionally, we developed near-isogenic lines (NIL) for qLG-9 by marker-assisted selection. qLG-9 NIL showed significantly higher seed longevity than isogenic control of Nipponbare. These results will facilitate cloning of the gene(s) underlying qLG-9 as well as marker-assisted transfer of desirable genes for seed longevity improvement in rice.

Primordial germ cell migration in the yellowtail kingfish (Seriola lalandi) and identification of stromal cell-derived factor 1.

Primordial germ cells (PGCs) are progenitors of the germ cell lineage, giving rise to either spermatogonia or oogonia after the completion of gonadal differentiation. Currently, there is little information on the mechanism of PGCs migration leading to the formation of the primordial gonad in perciform fish. Yellowtail kingfish (Seriola lalandi) (YTK) (order Perciforms) inhabit tropical and temperate waters in the southern hemisphere. Fundamental details into the molecular basis of larval development in this species can be easily studied in Australia, as they are commercially cultured and readily available. In this study, histological analysis of YTK larvae revealed critical time points for the migration of PGCs to the genital ridge, resulting in the subsequent development of the primordial gonad. In YTK larvae at 3, 5, 7 and 10 days post hatch (DPH), PGCs were not yet enclosed by somatic cells, indicating the primordial gonad had not yet started to form. While at 15, 18 and 20 DPH PGCs had already settled at the genital ridge and started to become enclosed by somatic cells indicating the primordial gonad had started to develop. A higher number of PGCs were observed in the larvae at 15 and 18 DPH indicating PGCs proliferation, which corresponds with them becoming enclosed by the somatic cells. Directional migration of PGCs toward the genital ridge is a critical event in the subsequent development of a gonad. In zebrafish, mouse and chicken, stromal-cell derived factor (SDF1) signalling is one of the key molecules for PGC migration. We subsequently isolated from YTK the SDF1 (Slal-SDF1) gene, which encodes for a 98-residue precursor protein with a signal peptide at the N-terminus. There is spatial conservation between fish species of four cysteine residues at positions C9, C11, C34 and C49, expected to form disulphide bonds and stabilize the SDF structure. In YTK, Slal-SDF1 gene expression analyses shows that this gene is expressed in larvae from 1 to 22 DPH and demonstrates distinct spatial localisation in the larvae at 7 DPH. These results provide a platform for further studies into the molecular machinery of PGC migration in yellowtail kingfish, as well as other perciform fish species.

Bortezomib, C1-inhibitor and plasma exchange do not prolong the survival of multi-transgenic GalT-KO pig kidney xenografts in baboons.

Galactosyl-transferase KO (GalT-KO) pigs represent a potential solution to xenograft rejection, particularly in the context of additional genetic modifications. We have performed life supporting kidney xenotransplantation into baboons utilizing GalT-KO pigs transgenic for human CD55/CD59/CD39/HT. Baboons received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human C1 inhibitor combined with cyclophosphamide or bortezomib with or without 2-3 plasma exchanges. One baboon received a control GalT-KO xenograft with the latter immunosuppression. All immunosuppressed baboons rejected the xenografts between days 9 and 15 with signs of acute humoral rejection, in contrast to untreated controls (n = 2) that lost their grafts on days 3 and 4. Immunofluorescence analyses showed deposition of IgM, C3, C5b-9 in rejected grafts, without C4d staining, indicating classical complement pathway blockade but alternate pathway activation. Moreover, rejected organs exhibited predominantly monocyte/macrophage infiltration with minimal lymphocyte representation. None of the recipients showed any signs of porcine endogenous retrovirus transmission but some showed evidence of porcine cytomegalovirus (PCMV) replication within the xenografts. Our work indicates that the addition of bortezomib and plasma exchange to the immunosuppressive regimen did not significantly prolong the survival of multi-transgenic GalT-KO renal xenografts. Non-Gal antibodies, the alternative complement pathway, innate mechanisms with monocyte activation and PCMV replication may have contributed to rejection.

Search for bosonic superweakly interacting massive dark matter particles with the XMASS-I detector.

Bosonic superweakly interacting massive particles (super-WIMPs) are a candidate for warm dark matter. With the absorption of such a boson by a xenon atom, these dark matter candidates would deposit an energy equivalent to their rest mass in the detector. This is the first direct detection experiment exploring the vector super-WIMPs in the mass range between 40 and 120 keV. With the use of 165.9 day of data, no significant excess above background was observed in the fiducial mass of 41 kg. The present limit for the vector super-WIMPs excludes the possibility that such particles constitute all of dark matter. The absence of a signal also provides the most stringent direct constraint on the coupling constant of pseudoscalar super-WIMPs to electrons. The unprecedented sensitivity was achieved exploiting the low background at a level 10(-4) kg-1 keVee-1 day-1 in the detector.

Detection of human papillomavirus (HPV) in patients with squamous cell carcinoma and the clinical characteristics of HPV-positive cases.

BACKGROUND: The association between human papillomavirus (HPV) and squamous cell carcinoma (SCC) has been reported; however, the prevalence of HPV infection varies, and the clinical characteristics of HPV-positive cases remain unknown. OBJECTIVES: To elucidate the frequency of HPV infection in a series of Japanese patients with SCC and to identify the characteristics of HPV-positive cases. METHODS: We evaluated 38 patients with SCC treated at our department. HPV typing was performed using SCC samples from different body sites. Immunohistochemical staining for HPV proteins and p16(INK) (4a) was performed, in addition to polymerase chain reaction and in situ hybridization. The clinical characteristics of the HPV-positive cases were clarified. RESULTS: Two genital lesions were positive for HPV type 16. Both cases showed basaloid features histopathologically, and were considered to have SCC that had arisen from bowenoid papulosis. p16(INK) (4a) expression was observed in 11 cases, including the two HPV-positive cases. CONCLUSIONS: The present study indicates that the prevalence of HPV is not high and that bowenoid papulosis is an HPV-associated precancerous lesion. Further investigation is necessary to assess the relationship between HPV infection and SCC.