ELUCIDATING THE ROLE OF CD44 EXPRESSION ON MESENCHYMAL STEM CELLS WITHIN THE TUMOR MICROENVIRONMENT

The tumor microenvironment is comprised of a vast array of heterogeneous cells including both normal and neoplastic cells. The tumor stroma recruitment process has been exploited for an effective gene delivery technique using bone marrow derived MSC. Targeted migration of the MSC toward the tumor microenvironment, while successful, is not yet fully understood. This study was designed to assess the role of CD44 in the migration of MSC toward the tumor microenvironment and to determine the implications of CD44-deficient MSC within the tumor stroma. Inhibition of MSC migration was evaluated through a variety of methods in vitro and in vivo including CD44 receptor knockdown, CD44 antagonists, CD44 neutralizing antibodies and small molecule inhibitor of matrix metalloproteinases. Blocking CD44 signaling through MMP inhibition was characterized by lack of intracellular domain cleavage and lead to the decrease in Twist gene expression. A functional relationship between CD44 and Twist expression was confirmed by chromatin immunoprecipitation. Next, a series of murine tumor models were used to examine the role of CD44 deficient stroma within the tumor microenvironment. Labeled transgenic CD44 knockout (KO) MSC or wild type (WT) C57/B6 MSC were used to analyze the stromal incorporation within murine breast carcinomas (EO771 and 4T1). Subsequent tumors were analyzed for vessel formation (CD31), and the presence of tumor associated fibroblast (TAF) markers, α-smooth muscle actin (α-SMA), fibroblast activation protein (FAP), and fibroblast specific protein (FSP). The tumors with CD44KO MSC cells had less vessel formation than the tumors with WT MSC. The lack of fibroblastic TAF population as defined by FAP/FSP expression by the CD44KO MSC admixed tumors suggest that the bone marrow derived population of MSC were unable to contribute to the fibroblastic stromal population. Subsequently, a bone marrow transplantation experiment confirmed the endogenous migratory deficiencies of the CD44KO bone marrow derived stromal cells toward the tumor microenvironment in vivo. WT mice with CD44KO bone marrow had less CD44KOderived tumor stroma compared to mice with WT bone marrow. These results indicate that CD44 is crucial to stromal cell migration and incorporation to the tumor microenvironment as TAF

Here Comes My Daddy, Now! : Oh Pop! Oh Pop! Oh Pop!

https://digitalcommons.library.umaine.edu/mmb-vp/1451/thumbnail.jp

The assessment of disability related to vision performance-based measure in diabetic retinopathy.

PURPOSE: To validate a third-generation performance-based measure of visual function titled Assessment of Disability Related to Vision (ADREV) in a study population of patients with diabetic retinopathy. DESIGN: Prospective, cross-sectional study. METHODS: Patients with nonproliferative or proliferative diabetic retinopathy, free from ocular comorbidity, were recruited from a single institute and completed the ADREV, the 25-Item National Eye Institute Visual Functioning Questionnaire (VFQ-25), and a clinical ophthalmic examination. Correlation, regression, and bootstrap analysis were conducted to determine the relationship between ADREV scoring and each of the study\u27s clinical and self-report measures of visual ability, while controlling for potential confounders. RESULTS: Ninety-one patients with diabetic retinopathy completed the study and analysis showed that the ADREV total and subscale scores shared a stronger relationship with the clinical measures of visual function than did the VFQ total and subscale scores. Regression analysis revealed that binocular visual acuity, contrast sensitivity, and better eye visual field were the best predictors of ADREV performance. CONCLUSIONS: The ADREV performance measure is a valid instrument for the assessment of disability related to vision in patients with diabetic retinopathy. Furthermore, the assessments provided by ADREV were more related to traditional clinical indicators of visual impairment than were the results of the self-report measure, specifically the VFQ-25

Electrical Detection and Magnetic-Field Control of Spin States in Phosphorus-Doped Silicon

Electron paramagnetic resonance of ensembles of phosphorus donors in silicon has been detected electrically with externally applied magnetic fields lower than 200 G. Because the spin Hamiltonian was dominated by the contact hyperfine term rather than by the Zeeman terms at such low magnetic fields, superposition states $\alpha{}| \uparrow \downarrow >+\beta{}| \downarrow \uparrow >$ and $-\beta{}| \uparrow \downarrow > + \alpha{}| \downarrow \uparrow >$ were formed between phosphorus electron and nuclear spins, and electron paramagnetic resonance transitions between these superposition states and $| \uparrow \uparrow >$ or $| \downarrow \downarrow >$ states are observed clearly. A continuous change of $\alpha{}$ and $\beta{}$ with the magnetic field was observed with a behavior fully consistent with theory of phosphorus donors in silicon.Comment: 6 pages, 5 figure

Consecutive bilateral decompression retinopathy after mitomycin C trabeculectomy: a case report.

BACKGROUND: After a successful trabeculectomy, a sudden intraocular pressure decrease may alter the intracranial to intraocular pressure ratio and cause decompression retinopathy. Frequent Valsalva maneuvers may also play a role in its pathogenesis. This condition may manifest as multiple retinal hemorrhages, edema of the optic disc, macular edema, or a sudden decrease in visual acuity postoperatively. Outcomes for patients are usually good, with spontaneous resolution occurring within a matter of weeks. It has been rarely reported in the literature as a bilateral condition. CASE PRESENTATION: We present a case of consecutive bilateral decompression retinopathy in a 54-year-old severely obese Caucasian woman (body mass index 37 kg/m(2)) with open angle glaucoma and a poor history of medical therapeutic compliance, who chose surgical treatment based on her inability to consistently use ocular drops. Our patient underwent a trabeculectomy with mitomycin C in both eyes, with surgeries taking place 3 months apart. After the first surgery, 2 weeks postoperatively, she complained of decreased visual acuity. Examination of her right eye fundus revealed multiple retinal hemorrhages and disc edema. There was a similar pattern in her left eye, this time including maculopathy. Her visual acuity and fundoscopic changes resolved spontaneously over a period of a month in both cases. Currently, our patient has well-controlled bilateral intraocular pressure, ranging between 14 and 16 mmHg, without hypotensive medication. CONCLUSIONS: Decompression retinopathy is a potential complication after glaucoma surgery, but has rarely been described as a bilateral consecutive condition. A comprehensive approach could help to anticipate its occurrence and manage it

Unaltered myocilin expression in the blood of primary open angle glaucoma patients

PURPOSE: To investigate the expression of the myocilin gene (MYOC) in the blood of primary open angle glaucoma (POAG) patients to determine if altered systemic expression is playing a role. METHODS: Patients (n=47) were eligible for inclusion if they met standard clinical criteria for POAG. Control subjects (n=27) were recruited who were free from glaucoma by examination. RNA was extracted from leukocytes of patients and controls and converted to cDNA by reverse transcriptase enzyme, and quantitative PCR was used to assess expression levels of MYOC and the house keeping gene β-globulin (HBB). The ratio of MYOC expression to HBB expression for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: Mean gene expression values were statistically similar in POAG patients and controls for both MYOC (p≤0.55) and HBB (p≤0.48). MYOC/HBB ratios were also statistically indistinguishable between POAG patients and controls (p≤0.90). MYOC/HBB ratios were not significantly associated with age, sex, or ethnicity of patients within the POAG group. Similarly, MYOC/HBB ratios were not significantly associated with clinical parameters related to POAG severity, including maximum intraocular pressure, vertical cup-to-disk ratio, static perimetry mean deviation, or static perimetry pattern standard deviation. CONCLUSIONS: MYOC expression is not altered in the blood of POAG patients, unlike MYOC expression in trabecular meshwork (TM) cultures. These results suggests that MYOC expression is not altered systemically but rather that MYOC expression may contribute to POAG pathogenesis in specific tissues such as TM

Patient education in glaucoma: what do patients know about glaucoma?

PURPOSE: To evaluate the knowledge glaucoma patients have about their disease and its treatment. METHODS: One hundred and eighty-three patients were interviewed at the Glaucoma Service of Wills Eye Hospital (Philadelphia, USA, Group 1) and 100 at the Glaucoma Service of University of Campinas (Campinas, Brazil, Group 2). An informal, relaxed atmosphere was created by the interviewer before asking a list of 18 open-ended questions. RESULTS: In Group 1, 44% of the 183 patients did not have an acceptable idea about what glaucoma is, 30% did not know the purpose of the medications they were taking, 47% were not aware of what was an average intraocular pressure, and 45% did not understand why visual fields were examined. In Group 2, 54% gave unsatisfactory answers to the question What is glaucoma? , 54% did not know the purpose of the medications they were taking, 80% were not aware of what was an average intraocular pressure, and 94% did not understand why visual fields were examined (p\u3c0.001). Linear regression analysis demonstrated that level of education was positively correlated to knowledge about glaucoma in both groups (r=0.65, p=0.001). CONCLUSION: This study showed that patients\u27 knowledge about glaucoma varies greatly, and that in an urban, American setting, around one third of the patients have minimal understanding, whereas in an urban setting in Brazil around two thirds of patients were lacking basic information about glaucoma. Innovative and effective methods are needed to correct this situation

Pigment Dispersing Factors and Their Cognate Receptors in a Crustacean Model, With New Insights Into Distinct Neurons and Their Functions

Pigment dispersing factors (PDFs, or PDHs in crustaceans) form a structurally related group of neuropeptides found throughout the Ecdysozoa and were first discovered as pigmentary effector hormones in crustaceans. In insects PDFs fulfill crucial neuromodulatory roles, most notably as output regulators of the circadian system, underscoring their central position in physiological and behavioral organization of arthropods. Intriguingly, decapod crustaceans express multiple isoforms of PDH originating from separate genes, yet their differential functions are still to be determined. Here, we functionally define two PDH receptors in the crab Carcinus maenas and show them to be selectively activated by four PDH isoforms: PDHR 43673 was activated by PDH-1 and PDH-2 at low nanomolar doses whilst PDHR 41189 was activated by PDH-3 and an extended 20 residue e-PDH. Detailed examination of the anatomical distribution of all four peptides and their cognate receptors indicate that they likely perform different functions as secreted hormones and/or neuromodulators, with PDH-1 and its receptor 43,673 implicated in an authentic hormonal axis. PDH-2, PDH-3, and e-PDH were limited to non-neurohemal interneuronal sites in the CNS; PDHR 41189 was largely restricted to the nervous system suggesting a neuromodulatory function. Notably PDH-3 and e-PDH were without chromatophore dispersing activity. This is the first report which functionally defines a PDHR in an endocrine system in a crustacean and to indicate this and other putative roles of this physiologically pivotal peptide group in these organisms. Thus, our findings present opportunities to further examine the endocrine and circadian machinery in this important arthropod phylum

Patient Education In Glaucoma: What Do Patients Know About Glaucoma?

To evaluate the knowledge glaucoma patients have about their disease and its treatment. One hundred and eighty-three patients were interviewed at the Glaucoma Service of Wills Eye Hospital (Philadelphia, USA, Group 1) and 100 at the Glaucoma Service of University of Campinas (Campinas, Brazil, Group 2). An informal, relaxed atmosphere was created by the interviewer before asking a list of 18 open-ended questions. In Group 1, 44% of the 183 patients did not have an acceptable idea about what glaucoma is, 30% did not know the purpose of the medications they were taking, 47% were not aware of what was an average intraocular pressure, and 45% did not understand why visual fields were examined. In Group 2, 54% gave unsatisfactory answers to the question What is glaucoma?, 54% did not know the purpose of the medications they were taking, 80% were not aware of what was an average intraocular pressure, and 94% did not understand why visual fields were examined (p<0.001). Linear regression analysis demonstrated that level of education was positively correlated to knowledge about glaucoma in both groups (r=0.65, p=0.001). This study showed that patients' knowledge about glaucoma varies greatly, and that in an urban, American setting, around one third of the patients have minimal understanding, whereas in an urban setting in Brazil around two thirds of patients were lacking basic information about glaucoma. Innovative and effective methods are needed to correct this situation.69923-

Absence of altered expression of optineurin in primary open angle glaucoma patients

PURPOSE: To investigate the expression level of the optineurin gene (OPTN) in the blood of primary open angle glaucoma (POAG) patients to determine if altered expression is playing a role in primary open angle glaucoma systemically. METHODS: Patients (n=47) were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. Control subjects (n=27) were recruited who were free from glaucoma by examination. DNA from patient was sequenced to look for possible mutations in the coding region of OPTN or its promoter. RNA was extracted from leukocytes of patients and controls and converted to cDNA by reverse transcriptase enzyme, and quantitative PCR was used to assess expression levels of OPTN and the β-globulin gene. The ratio of OPTN expression to β-globulin gene expression for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: No mutation(s) were detected in any of the patients after sequencing the full OPTN gene and its promoter region. Mean OPTN (p≤0.35), and β-globulin (p≤0.48) gene expression values were statistically similar in POAG patients and controls. OPTN/β-globulin (p≤0.83) ratios were also indistinguishable between POAG patients and controls. OPTN/β-globulin ratios were not significantly associated with age, sex, or ethnicity of patients within the POAG group. Similarly, OPTN/β-globulin ratios were not significantly affected by ethnicity or clinical parameters related to POAG severity including maximum intraocular pressure, vertical cup-to-disk ratio, static perimetry mean deviation, or static perimetry pattern standard deviation. CONCLUSIONS: OPTN expression is not altered in the blood of POAG patients, suggesting that OPTN expression is not changed systemically and implying that other mechanisms are involved in POAG pathogenesis