Tissue factor expression in human pterygium

Purpose: A pterygium shows tumor-like characteristics, such as proliferation, invasion, and epithelial–mesenchymal transition (EMT). Previous reports suggest that tissue factor (TF) expression is closely related to the EMT of tumor cells, and subsequent tumor development. In this study, we analyzed the expression and immunolocalization of TF in pterygial and normal conjunctival tissues of humans. Methods: Eight pterygia and three normal bulbar conjunctivas, surgically removed, were used in this study. Formalinfixed, paraffin-embedded tissues were submitted for immunohistochemical analysis with anti-TF antibody. Double staining immunohistochemistry was performed to assess TF and alpha-smooth muscle actin (α-SMA) or epidermal growth factor receptor (EGFR) expression in the pterygia. Results: Immunoreactivity for TF was detected in all pterygial tissues examined. TF immunoreactivity was localized in the cytoplasm of basal, suprabasal, and superficial epithelial cells. The number of TF-immunopositive cells in pterygial epithelial cells was significantly higher than in normal conjunctival epithelial cells (p<0.001). TF immunoreactivity was detected in α-SMA-positive or -negative pterygial epithelial cells. EGFR immunoreactivity was detected in pterygial epithelium, which was colocalized with TF. Conclusions: These results suggest that TF plays a potential role in the pathogenesis and development of a pterygium, and that TF expression might be involved through EMT-dependent and -independent pathways

Association between Histological Types and Enhancement of Dynamic CT for Primary Lung Cancer

The aim of this study was to explore enhancement patterns of different types of primary lung cancers on 2-phase dynamic computed tomography (CT). This study included 217 primary lung cancer patients (141 adenocarcinomas [ADs], 48 squamous cell carcinomas [SCCs], 20 small cell lung carcinomas [SCLCs], and 8 others) who were examined using a 2-phase dynamic scan. Regions of interest were identified and mean enhancement values were calculated. After excluding the 20 SCLCs because these lesions had different clinical stages from the other cancer types, the mean attenuation values and subtractions between phases were compared between types of non-small cell lung carcinomas (NSCLCs) using the Kruskal–Wallis test. Late phase attenuation and attenuation of the late minus unenhanced phase (LMU) of SCCs were significantly higher than those of ADs (p<0.05). To differentiate SCC and AD in the late phase, a threshold of 80.21 Hounsfield units (HU) gave 52.9% accuracy. In LMU, a threshold of 52.16 HU gave 59.3% accuracy. Dynamic lung CT has the potential to aid in differentiating among NSCLC types

Extranodal marginal zone B-cell lymphoma involving superior rectus muscle : A clinicopathological case report

A 66-year-old female had suffered from proptosis in the left eye (OS) and double vision for 1 month due to abnormality of the superior rectus muscle. Visual acuity was noted as 20/20 in both eyes (OU). Eye movement showed limited OS supraduction. Magnetic resonance imaging revealed an indistinct mass in the orbit involving the superior rectus muscle. A biopsy specimen of the orbital tumor led to the histological diagnosis of extranodal marginal zone B-cell lymphoma. Radiotherapy with a total dosage of 30 Gy was administered, which subsequently resolved the tumor. However, the supraduction limitation of ocular movement remained unchanged. Supraduction limitation is due to muscular contraction disorder of the superior rectus muscle, caused by direct lymphoma cell invasion

Conjunctival lymphoma arising from reactive lymphoid hyperplasia

Extra nodal marginal zone B-cell lymphoma (EMZL) of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH) of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU). Specimens from conjunctival tumors in the right eye, oculus dexter (OD), revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig) light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS), and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH) region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy

Comparative Studies on Doses and Total Amounts of Chinoform Administered on SMON and Non-SMON Patients

In order to elucidate the relationship between SMON (subacute myelo-optico-neuropathy) and chinoform, we carried out comparative studies on the doses and total amounts of chinoform preparations on the both patients of SMON and non-SMON admitted in Hospital I where SMON is most endemic in Okayama Prefecture, during the period of 1968, 1969 and 1970, to the total of 7,374 cases, and those treated in 1969 at Hospitals P and Q located in other districts, amounting to 11,953 and 7,290 cases respectively, all inclusive of SMON and non-SMON patients. The results are briefly summarized as follows. 1. Of the SMON patients in Hospital I, the ratio of those not receiving chinoform administration prior to the onset of SMON to the total SMON cases proved to be 8 to 55 cases in 1968, 32 to 52 cases in 1969, and 2 to 7 cases in 1970, indicating that the incidence in 1969 is very high. What is more, there is a considerable difference according to the fiscal year, thus giving no uniform results. Even at Hospital P the administration of chinoform cannot be confirmed in 2 cases out of 15 SMON patients and at Hospital Q in 2 out of 5 cases prior to the beginning of neurological symptomes of SMON. 2. In the region around Hospital I there was observed the highest incidence of SMON in the first half of the fiscal year 1969, and thereafter the incidence decreased rapidly from the latter half of 1969. However, We can find no evidence as to substantiate changes in the chinoform administration from the results of chinoform administered to general non-SMON patients. 3. The ratio of SMON patients to the total cases treated with chinoform at Hospital I proved to be 13.9% in 1968, 29.6% in 1969, and 5.7% in 1970, and at Hospital P it was 2.7% in 1969 and at Hospital Q 1.8%. 4. As to the age range of general patients receiving chinoform, the incidence of those non-SMON cases proves to be highest in twenties and thirties irrespective of sex and this finding doesnot coincide at all with the known propensity of SMON being more apt to occur in females of middle age. 5. As is obvious from these findings, our comparative studies conducted on the effects of chinoform to patients in the three hospitals do not yield any evidence to prove direct relationship between the chinoform administration and the onset of SMON

Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization.

Purpose: To investigate the applicability of serine/arginine-rich protein kinase (SRPK)-specific inhibitor, SRPIN340, for attenuation of choroidal neovascularization (CNV) formation using a mouse model. Methods: Laser photocoagulation was performed to induce CNV in C57BL/6J mice, followed by intravitreal injection of SRPIN340 or vehicle. Seven days after the treatment, the CNV size was evaluated using a flatmount technique. Protein levels of vascular endothelial growth factor (VEGF) and inflammation-associated molecules, such as monocyte chemoattractant protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1, in the retinal pigment epithelium-choroid complex were measured with enzyme-linked immunosorbent assay. Expression levels of total Vegf, exon 8a-containing Vegf isoforms, and F4/80 (a specific marker for macrophage) were assessed using real-time PCR. Results: SRPIN340 inhibited CNV formation in a dose-dependent manner. Compared with the vehicle, SRPIN340 significantly decreased the protein levels of VEGF, MCP-1, ICAM-1, and consequently inhibited macrophage infiltration. Furthermore, SRPIN340 suppressed the gene expression levels of total Vegf and exon 8a-containing Vegf isoforms. Conclusions: SRPIN340, a specific inhibitor of SRPK, suppressed Vegf expression and attenuated CNV formation. Our data suggest the possibility that SRPIN340 is applicable for neovascular age-related macular degeneration as a novel chemical therapeutics

Expression of vascular endothelial growth factor C in human pterygium

Purpose: Vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3 mediate lymphangiogenesis. In this study, we analyzed the expression of VEGF-C and VEGFR-3 as well as lymphatic vessels in the pterygium and normal conjunctiva of humans. Methods: Fifteen primary nasal pterygia and three normal bulbar conjunctivas, surgically removed, were examined in this study. The lymphatic vessel density (LVD) and blood vessel density (BVD) were determined by the immunolabeling of D2-40 and CD31, markers for lymphatic and blood vessels, respectively. VEGF-C and VEGFR-3 expression in pterygial and conjunctival tissue proteins was detected by Western blotting. Expressions of VEGF-C and VEGFR-3 were evaluated using immunohistochemistry. Results: The LVD was significantly higher in the pterygium than normal conjunctiva (p<0.05). Western blot demonstrated high-level expression of VEGF-C and VEGFR-3 in the pterygium compared with normal conjunctiva. VEGF-C immunoreactivity was detected in the cytoplasm of pterygial and normal conjunctival epithelial cells. The number of VEGF-C-immunopositive cells in pterygial epithelial cells was significantly higher than in normal conjunctival cells (p<0.05). VEGFR-3 immunoreactivity was localized in the D2-40-positive lymphatic endothelial cells. Conclusions: The present findings suggest the potential role of VEGF-C in the pathogenesis and development of a pterygium through lymphangiogenesis and the VEGF-C/VEGFR-3 pathway as a novel therapeutic target for the human pterygium

Conjunctival lymphoma arising from reactive lymphoid hyperplasia

Abstract Extra nodal marginal zone B-cell lymphoma (EMZL) of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH) of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU). Specimens from conjunctival tumors in the right eye, oculus dexter (OD), revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig) light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS), and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH) region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.</p