[Jejunal stromal tumor concomitant ectopic pancreas in a young man with sarcoidosis:a case report].

During a medical health check, a 29-year-old man was presented to our hospital with iron deficiency anemia. He had no significant medical history in his family. Despite being diagnosed with ocular sarcoidosis 5 years ago, he had no vision problems. Physical examination revealed normal vital signs and a nontender abdomen;however, his eyelid conjuvitis was pale, and he became aware of fatigue when moving vigorously. He had upper gastrointestinal endoscopy and colonoscopy, but there was no evidence of bleeding detected. A contrasted mass 30mm in size was discovered on abdominal contrast-enhanced computed tomography at the dorsal wall of the proximal jejunum. Positron emission tomography showed an accumulation image in the bilateral hilar lymph and upper jejunum. A 30-mm submucosal tumor with a central depression in the upper jejunum was discovered using a double-balloon enteroscopy. We performed biopsies from the depression margin and tattoo marking on the oral side of the tumor. Even though the biopsies specimen revealed granulation tissue, the patient was referred to surgery and underwent a partial jejunum resection because the tumor was diagnosed as the cause of anemia. The operation went smoothly, and the patient was discharged on the seventh postoperative day. Histological examination showed a proliferation of densely packed spindle cells with prominent nuclear palisading. The immunohistochemical examination revealed that c-kit and CD34 were highly expressed, whereas desmin and S-100 proteins were not. Ki-67 expression demonstrated a very low proliferative index (2%). We discovered gastrointestinal stromal tumors (GIST), as well as an ectopic pancreas. GIST is extremely rare in young people, and the coexistence of ectopic pancreas and sarcoidosis has never been reported.

[A Case of Lobular Carcinoma In Situ Occurring in a Fibroadenoma of the Breast].

The patient was a 43-year-old premenopausal woman with a 14×11 mm tumor in upper outer quadrant of the left breast, diagnosed as a fibroepithelial lesion using core needle biopsy. Resection was performed. Histopathologically, the resected specimen was diagnosed as a fibroadenoma with lobular carcinoma in situ(LCIS). Tamoxifen was administered as endocrine therapy to reduce recurrence risk. We report a case of LCIS accidentally discovered by surgical resection of a benign tumor.

[Laparoscopic Hepatic Resection for a Hepatic Perivascular Epithelioid Cell Tumor-A Case Report].

A 50-year-old female who had a liver tumor was referred to our hospital for further examination. Abdominal CT and MRI revealed a 2 cm tumor in liver segment 2 that was suspected to be HCC. On the basis of the CT and MRI findings, the patient underwent needle biopsy. The pathological findings suggested the possibility of perivascular epithelioid cell tumor (PEComa). Accordingly, we performed laparoscopic liver segmentectomy. As a hepatic PEComa is relatively rare, the current case serves as an important reminder to consider PEComa in the differential diagnosis of liver tumors.

[The case of a giant malignant phyllodes tumor of the breast].

A 75-year-old female patient complained of a mass in her left breast 2 years ago. The patient experienced a rapid enlargement of the mass 2 months later and visited our hospital. A computed tomography (CT) scan indicated a 25-cm tumor with infiltration of the left breast skin. Pectoral muscle invasion was considered. Swelling of the axillary lymph node and remote metastases were not found. A needle biopsy indicated a phyllodes tumor. A pectoral muscle-preserving mastectomy was undertaken. The tumor weighed 7.1 kg. Pathological examination indicated hyperplasia of the stroma and part of the epithelium, which had invaded the skin layer and fatty tissue. The pathological diagnosis was a malignant phyllodes tumor. This paper reports the case of a giant malignant phyllodes tumor.

Ultraviolet B-induced expression of amphiregulin and growth differentiation factor 15 in human lens epithelial cells.

PURPOSE: Epidemiological and experimental studies have revealed that exposure to ultraviolet B (UVB) light can induce cataractogenesis. The objective of this study was to determine gene expression changes in human lens epithelial cells in response to UVB exposure and identify factors that can be involved in UVB-induced cataractogenesis. METHODS: SV40 T-antigen-transformed human lens epithelial cells (SRA01/04) were irradiated at various UVB-energy levels (10-80 mJ/cm²) and checked for viability. An irradiation condition of 30 mJ/cm² was adopted for transcriptome analysis. Total RNAs isolated from UVB-exposed and unexposed cells at 12 h and 24 h after UVB exposure were examined for global gene expression changes using Affymetrix Human Gene 1.0 ST array. mRNA levels of specific genes were examined by RT-PCR and real-time PCR, and protein levels in the conditioned media were assayed by ELISA. To examine mRNA expression in human lens, primary cultured human lens epithelial (HLE) cells were prepared from surgically removed lens epithelium, and used for UVB-irradiation and expression analysis. Effects of certain gene products on SRA01/04 cell metabolism were examined using commercially available recombinant proteins. RESULTS: Expression of most the genes analyzed was essentially unchanged (between 0.5 and 2.0 fold) in UVB-irradiated cells compared to non-irradiated cells at both 12 and 24 h after UVB exposure. Sixty one and 44 genes were upregulated more than twofold by UVB exposure at 12 h and 24 h, respectively. Emphasis was placed on genes encoding extracellular proteins, especially growth factors and cytokines. A total of 18 secreted protein genes were upregulated more than twofold at either or both time points. Amphiregulin (AREG) and growth differentiation factor 15 (GDF15) were chosen because of their higher upregulation and novelty, and their upregulation was confirmed in SRA01/04 cells using RT-PCR and real-time PCR analysis. AREG and GDF15 protein levels in conditioned media significantly increased at all UVB-energy points at 24 h, while they were scarcely detectable at 12 h. AREG and GDF15 mRNA levels were also significantly upregulated in UVB-irradiated primary cultured HLE cells compared with the corresponding control culture. AREG significantly stimulated ³H-thymidine and ³H-leucine uptake in SRA01/04 cells as did a positive control epidermal growth factor (EGF). Recombinant GDF15 did not stimulate ³H-thymidine incorporation at any concentration tested, but significantly stimulated ³H-leucine uptake. RT-PCR analysis demonstrated that primary cultured HLE and SRA01/04 cells expressed not only epidermal growth factor receptor (EGFR) mRNA but also transforming growth factor ß receptors (TGFBR1 and TGFBR2) mRNAs. CONCLUSIONS: These results indicate that AREG and GDF15 produced in response to UVB exposure can affect the growth and protein synthesis of lens epithelial cells, suggesting that they have autocrine and paracrine roles related to pathological changes of lens tissue during long-term UVB exposure.

Vitreous and aqueous penetration of orally and topically administered moxifloxacin.

AIM: It was the aim of this study to compare the pharmacokinetics of moxifloxacin (MFLX) hydrochloride in rabbits after topical and oral administration. METHODS: Three 50-µl applications of MFLX (0.5%) topical ophthalmic solution were instilled into the cul-de-sac of New Zealand white rabbits at 15-min intervals. Aqueous and vitreous samples were collected and analyzed 30-240 min after the final instillation. Assays were performed using high-performance liquid chromatography. MFLX (16 mg/kg of body weight) was administered orally. Drug concentrations in aqueous, vitreous and serum samples, collected at 30-360 min after administration, were determined using high-performance liquid chromatography. RESULTS: After topical administration, the maximum concentrations of MFLX in the aqueous and vitreous samples were 10.2 ± 1.6 µg/ml (30 min; n = 6) and 0.10 ± 0.03 µg/ml (30 min; n = 6), respectively. After oral administration, the maximum concentrations in the aqueous, vitreous and serum samples were 0.9 ± 0.3 µg/ml (120 min; n = 6), 0.7 ± 0.2 µg/ml (240 min; n = 6) and 1.6 ± 0.9 µg/ml (120 min; n = 6), respectively. The percentages of serum MFLX concentration in the aqueous and vitreous samples after oral administration were 55.2 and 41.7%, respectively. CONCLUSIONS: The aqueous concentration of MFLX was about 10-fold higher after topical than after oral administration. However, intravitreal MFLX concentrations after oral administration were about 7-fold higher than those after topical administration. The MFLX concentrations in the aqueous humor following oral administration exceeded the minimum inhibitory concentration for 90% of the bacteria involved in ocular infection.

Cyclin-dependent kinase inhibitor p16 and p21 expression, and cell cycle change in human lens epithelial cell line SRA 01/04 following contact inhibition in normal culture.

PURPOSE: To describe the pattern of expression of the cyclin-dependent kinase inhibitors (CDKIs) p16, p21 and p27, and the cell cycle in SRA 01/04 cells relative to contact inhibition. METHODS: SRA 01/04 cells were grown to overconfluence under normal conditions. At various phases of the cell growth, cells were assayed by flow cytometry and Western blotting for the expression of CDKIs. RESULTS: Expression of p16 was detected from early logarithmic growth to stationary phases, during which the number of cells in G(0)/G(1) increased from 46 to 69%. Expression of p21 was detected only during the overgrowth phase, when 60% of the cells were in G(0)/G(1). Expression of p27 was not observed in SRA 01/04 cells. CONCLUSIONS: p16 expression was likely mediated by G(0)/G(1) arrest to induce contact inhibition in SRA 01/04. p21 expression may be related to withdrawal, and p27 deficiency may be related to the immortality of this cell line. It is possible for p16 to stop proliferation of lens epithelial cells like progressing posterior capsular opacification, by overexpression to mimic contact inhibition.

Distribution of corneal spherical aberration in a Tanzanian population.

PURPOSE: To investigate the distribution of corneal spherical aberration (SA) in Tanzanian people of African descent, and to examine the correlation between corneal SA and ocular parameters. DESIGN: Cross-sectional population-based study. METHODS: Residents aged 40 years and older in three villages in the Mkuranga district in Tanzania were enlisted as study participants. Corneal higher-order aberrations (HOAs) for the right eye were measured with a wavefront analyzer (KR-1W, Topcon) and calculated for the central 6.0-mm zone. Corneal curvature radius (CR), corneal astigmatism, and axial length (AL) were also measured and their correlation with corneal SA was assessed. RESULTS: The right eyes of 657 participants (336 male, 321 female) were analyzed. The mean age of the subjects was 57.2 ± 10.3 years (mean ± SD). The mean corneal SA (Zernike spherical aberration coefficient C40) was 0.188 ± 0.095 µm (-0.242 to 0.613). The SAs in about three-quarters of all subjects were between 0.10 and 0.30 µm. The root mean squares of total corneal HOAs and the third- and fourth-order aberrations were 0.629 ± 0.250 µm, 0.539 ± 0.236 µm, and 0.269 ± 0.110 µm, respectively. Corneal SA showed weak significant correlations with CR (Spearman's rank correlation coefficient, r = -0.177, p < 0.001), corneal astigmatism (r = -0.142, p < 0.001), AL (r = -0.168, p < 0.001), and age (r = -0.085, p < 0.05). CONCLUSIONS: This finding may be beneficial for selecting aspheric intraocular lens in this population.

Ultraviolet B-induced Otx2 expression in lens epithelial cells promotes epithelial-mesenchymal transition.

Ultraviolet (UV) radiation of eyes is a major risk factor for cataractogenesis, although the molecular mechanisms underlying this process remain poorly understood and genes that are affected by UV radiation have not been fully identified. In this study, we examined the UV-related gene regulation in lens epithelial cells (LECs) of mouse eyes and investigated the molecular mechanisms of UV-triggered cataractogenesis. Forty-one genes were significantly upregulated in LECs following UVB exposure in vivo in two independent experiments. Among these, Otx2 was strongly upregulated in LECs, suggesting that it may act as an upstream regulator of UVB-induced changes in gene expression. Accordingly, Otx2 overexpression in LECs in vitro induced morphological changes in cell shapes. Epithelial-mesenchymal transition (EMT)-related molecules, such as TGFß2, αSMA and fibronectin were upregulated in Otx2-overexpressing LECs, concomitant with suppression of lens fiber cell marker genes, such as CRYAA and DNASEIIB. In vitro experiments suggested that UVB upregulated Otx2 through hydrogen peroxide generation. Aberrant upregulation of Otx2 in LECs following UV irradiation induces the EMT and alteration of the lens cell characteristics, likely contributing to cataractogenesis.

Safety comparison of additives in antiglaucoma prostaglandin (PG) analog ophthalmic formulations.

PURPOSE: To investigate the safety of five types of antiglaucoma prostaglandin analog ophthalmic formulations, and to clarify their differences in accordance with contained additives (preservatives and surface-active agents). METHODS: THE FOLLOWING FIVE TYPES OF OPHTHALMIC SOLUTIONS AND THREE TYPES OF ADDITIVES WERE INVESTIGATED: latanoprost (Xalatan(®); latanoprost), tafluprost (Tapros(®); tafluprost), bimatoprost (Lumigan(®); bimatoprost), travoprost (Travatan(®); travoprost), travoprost (Travatan Z(®); travoprost-Z), benzalkonium chloride (BAK), polyoxyethylene hardening castor oil 40 (HCO-40), and polysorbate 80 (P-80). These experimental solutions were exposed to the cultured cells of a rabbit-derived corneal cell line for a certain time, and the exposure time causing 50% cell damage (CD50), indicated by the ratio of viable cells to total cells was calculated (in vitro). In addition, corneal resistance (CR) was measured and CR ratio (post-treatment CR/pretreatment CR × 100) was calculated (in vivo). RESULTS: CD50 of each ophthalmic solution was the longest with tafluprost, followed by travoprost-Z, bimatoprost, travoprost, and latanoprost. CD50 of 0.005%, 0.01%, and 0.02% BAK was 14.5 minutes, 8.1 minutes, and 4.0 minutes, respectively. The number of viable cells decreased to 60%, 8 minutes after exposure with HCO-40, and 30 minutes after being exposed to P-80. The CR ratio was 81.0% with travoprost and 82.0% with latanoprost, indicating a significant posttreatment reduction of CR (P < 0.05). The CR ratio did not decrease after treatment with tafluprost, travoprost-Z, or bimatoprost. The CR ratio of 0.005%, 0.01%, and 0.02% BAK was 105.0%, 90.5%, and 68.7%, respectively, and that of HCO-40 and P-80 was 108.7% and 114.2%, respectively. CONCLUSION: BAK, HCO-40, and P-80 were thought to be involved in corneal injuries caused by each ophthalmic solution. Corneal injuries due to surface action were observed when using HCO-40 and P-80. When HCO-40 was combined with BAK, it induced micellar BAK and reduced corneal injuries by BAK.

Change in retinal image contrast with age in eyes with transparent lenses.

PURPOSE: To compare and evaluate changes in the retinal image with age in Japanese adults with transparent crystalline lenses. SETTING: Shibuya-ku, Tokyo, Japan. DESIGN: Cross-sectional study. METHODS: The study comprised right eyes with corrected distance visual acuity better than 0.0 logMAR. A point-spread function analyzer (PSF-1000) was used to measure retinal image contrast with 3.0 mm pupils under maximum mydriasis. A wavefront analyzer (KR9000PW) was used to measure higher-order aberrations (HOAs) with 4.0 mm pupils. The lens transparency property was estimated by the backward light-scattering intensity of each layer of the lens and the optical distance (mm) photographed by an anterior segment analysis system (EAS-1000). The Pearson product-moment correlation (R(2)) was used for statistical analysis; the significance level was 5%. RESULTS: The study comprised 269 patients (mean age 39.7 years ± 7.7 [SD]). The retinal image contrast degenerated significantly with age; the largest difference was seen with the 0.423 logMAR optotype, for which the decrease was 5.4% every decade. Backward light-scattering intensity (R(2) = 0.030, P<.01) and HOAs (R(2) = 0.032, P<.01) correlated negatively with retinal image contrast. CONCLUSION: Retinal image contrast in eyes with transparent lenses degenerated with age. The decrease was most prominent at the middle frequency domain and was due to the increase in HOAs and light-scattering intensity.

Identification of the COL2A1 mutation in patients with type I Stickler syndrome using RNA from freshly isolated peripheral white blood cells.

Stickler syndrome type I is caused by mutations in the type II collagen gene (COL2A1), which is specifically expressed in cartilage and vitreous humor. We developed a simple and noninvasive strategy for identifying the COL2A1 mutation using RNA from freshly isolated peripheral white blood cells and identified a new 3' splice site mutation in a Japanese family with Stickler syndrome. RNA was isolated from a patient's peripheral white blood cells that had been incubated with cycloheximide, an inhibitor of nonsense-mediated mRNA decay. COL2A1 cDNA fragments covering the entire coding region were obtained by RT-polymerase chain reaction cloning using a high-fidelity DNA polymerase and sequenced. Whole sequencing of the patient's cDNA resulted in identification of a 49-bp deletion in the region corresponding to exon 18. The deletion introduced a premature termination codon. Targeted genome sequencing identified a base substitution at the A (-2) position of the 3' splice acceptor site of intron 17. This mutation led to utilization of the cryptic splice site, which is located 49 bases downstream of the normal splice site and causes aberrant mRNA splicing, resulting in a 49-base deletion in the patient's mRNA. Our method is much easier than conventional genomic screening and provides a simple and noninvasive diagnostic test for patients with Stickler syndrome.