Rosalyn A. Jurjus

Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1.

We have reported previously that syndecan-1 (Sdc1)-null mice show delayed re-epithelialization after skin and corneal wounding. Here, we show that primary keratinocytes obtained from Sdc1-null mice and grown for 3-5 days in culture are more proliferative, more adherent and migrate more slowly than wt keratinocytes. However, the migration rates of Sdc1-null keratinocytes can be restored to wild-type levels by replating Sdc1-null keratinocytes onto tissue culture plates coated with fibronectin and collagen I, laminin (LN)-332 or onto the matrices produced by wild-type cells. Migration rates can also be restored by treating Sdc1-null keratinocytes with antibodies that block α6 or αv integrin function, or with TGFβ1. Antagonizing either β1 integrin function using a function-blocking antibody or TGFβ1 using a neutralizing antibody reduced wild-type keratinocyte migration more than Sdc1-null keratinocyte migration. Cultures of Sdc1-null keratinocytes accumulated less collagen than wild-type cultures but their matrices contained the same amount of LN-332. The Sdc1-null keratinocytes expressed similar total amounts of eight different integrin subunits but showed increased surface expression of αvβ6, αvβ8, and α6β4 integrins compared with wild-type keratinocytes. Whereas wild-type keratinocytes increased their surface expression of α2β1, αvβ6, αvβ8, and α6β4 after treatment with TGFβ1, Sdc1-null keratinocytes did not. Additional data from a dual-reporter assay and quantification of phosphorylated Smad2 show that TGFβ1 signaling is constitutively elevated in Sdc1-null keratinocytes. Thus, our results identify TGFβ1 signaling and Sdc1 expression as important factors regulating integrin surface expression, activity and migration in keratinocyte and provide new insight into the functions regulated by Sdc1.

Primary dermal fibroblasts derived from sdc-1 deficient mice migrate faster and have altered alphav integrin function.

The goal of this study is to determine whether dermal fibroblasts lacking syndecan‐1 (sdc1) show differences in integrin expression and function that could contribute to the delayed skin and corneal wound healing phenotypes seen in sdc‐1 null mice. Using primary dermal fibroblasts, we show that after 3 days in culture no differences in α‐smooth muscle actin were detected but sdc‐1 null cells expressed significantly more αv and β1 integrin than wildtype (wt) cells. Transforming growth factor β1 (TGFβ1) treatment at day 3 increased αv‐ and β1‐integrin expression in sdc‐1 null cells at day 5 whereas wt cells showed increased expression only of αv‐integrin. Using time‐lapse studies, we showed that the sdc‐1 null fibroblasts migrate faster than wt fibroblasts, treatment with TGFβ1 increased these migration differences, and treatment with a TGFβ1 antagonist caused sdc‐1 null fibroblasts to slow down and migrate at the same rate as untreated wt cells. Cell spreading studies on replated fibroblasts showed altered cell spreading and focal adhesion formation on vitronectin and fibronectin‐coated surfaces. Additional time lapse studies with β1‐ and αv‐integrin antibody antagonists, showed that wt fibroblasts expressing sdc‐1 had activated integrins on their surface that impeded their migration whereas the null cells expressed αv‐containing integrins which were less adhesive and enhanced cell migration. Surface expression studies showed increased surface expression of α2β1 and α3β1 on the sdc‐1 null fibroblasts compared with wt fibroblasts but no significant differences in surface expression of α5β1, αvβ3, or αvβ5. Taken together, our data indicates that sdc‐1 functions in the activation of αv‐containing integrins and support the hypothesis that impaired wound healing phenotypes seen in sdc‐1 null mice could be due to integrin‐mediated defects in fibroblast migration after injury.

ORIGINAL RESEARCH – BASIC SCIENCE: Primary dermal fibroblasts derived from sdc-1 deficient mice migrate faster and have altered αv integrin function

The goal of this study is to determine whether dermal fibroblasts lacking syndecan‐1 (sdc1) show differences in integrin expression and function that could contribute to the delayed skin and corneal wound healing phenotypes seen in sdc‐1 null mice. Using primary dermal fibroblasts, we show that after 3 days in culture no differences in α‐smooth muscle actin were detected but sdc‐1 null cells expressed significantly more αv and β1 integrin than wildtype (wt) cells. Transforming growth factor β1 (TGFβ1) treatment at day 3 increased αv‐ and β1‐integrin expression in sdc‐1 null cells at day 5 whereas wt cells showed increased expression only of αv‐integrin. Using time‐lapse studies, we showed that the sdc‐1 null fibroblasts migrate faster than wt fibroblasts, treatment with TGFβ1 increased these migration differences, and treatment with a TGFβ1 antagonist caused sdc‐1 null fibroblasts to slow down and migrate at the same rate as untreated wt cells. Cell spreading studies on replated fibroblasts showed altered cell spreading and focal adhesion formation on vitronectin and fibronectin‐coated surfaces. Additional time lapse studies with β1‐ and αv‐integrin antibody antagonists, showed that wt fibroblasts expressing sdc‐1 had activated integrins on their surface that impeded their migration whereas the null cells expressed αv‐containing integrins which were less adhesive and enhanced cell migration. Surface expression studies showed increased surface expression of α2β1 and α3β1 on the sdc‐1 null fibroblasts compared with wt fibroblasts but no significant differences in surface expression of α5β1, αvβ3, or αvβ5. Taken together, our data indicates that sdc‐1 functions in the activation of αv‐containing integrins and support the hypothesis that impaired wound healing phenotypes seen in sdc‐1 null mice could be due to integrin‐mediated defects in fibroblast migration after injury.

Anatomical knowledge retention in third-year medical students prior to obstetrics and gynecology and surgery rotations

Surgical anatomy is taught early in medical school training. The literature shows that many physicians, especially surgical specialists, think that anatomical knowledge of medical students is inadequate and nesting of anatomical sciences later in the clinical curriculum may be necessary. Quantitative data concerning this perception of an anatomical knowledge deficit are lacking, as are specifics as to what content should be reinforced. This study identifies baseline areas of strength and weakness in the surgical anatomy knowledge of medical students entering surgical rotations. Third‐year medical students completed a 20–25‐question test at the beginning of the General Surgery and Obstetrics and Gynecology rotations. Knowledge of inguinal anatomy (45.3%), orientation in abdominal cavity (38.8%), colon (27.7%), and esophageal varices (12.8%) was poor. The numbers in parentheses are the percentage of questions answered correctly per topic. In comparing those scores to matched test items from this cohort as first‐year students in the anatomy course, the drop in retention overall was very significant (P = 0.009) from 86.9 to 51.5%. Students also scored lower in questions relating to pelvic organs (46.7%), urogenital development (54.0%), pulmonary development (17.8%), and pregnancy (17.8%). These data showed that indeed, knowledge of surgical anatomy is poor for medical students entering surgical clerkships. These data collected will be utilized to create interactive learning modules, aimed at improving clinically relevant anatomical knowledge retention. These modules, which will be available to students during their inpatient surgical rotations, connect basic anatomy principles to clinical cases, with the ultimate goal of closing the anatomical knowledge gap. Anat Sci Educ 7: 461–468.

Curricular response to increase recall and transfer of anatomical knowledge into the obstetrics/gynecology clerkship.

Deficits in retention of anatomy knowledge from the preclinical years to clinical application on the wards have been well documented in the medical education literature. We developed and evaluated a web and laboratory‐based curriculum to address deficits in anatomy knowledge retention and to increase anatomy knowledge recall through repetition and application of clinical concepts during the obstetrics and gynecology (Ob/Gyn) core clinical clerkship. Using principles of adult learning and instructional design, a curriculum was designed consisting of (1) interactive, case‐based e‐modules reviewing clinically relevant anatomical topics and (2) a hands‐on laboratory session reinforcing the content of the e‐modules, with the practice of clinical techniques using anatomical cadaveric dissections. The curriculums effectiveness was evaluated by using multiple choice testing and comparing baseline and final test scores. For questions testing content directly covered in this curriculum, mean final scores increased by 14.3% (P < 0.001). In contrast, for questions not directly addressed in this curriculum, mean final scores did not increase significantly, only by 6.0% (P = 0.31). Questions related to the uterus showed the greatest gains in final scores (30.3% improvement, P = 0.002). A curriculum with web‐based preparatory material and a hands‐on gross anatomy laboratory session effectively addresses deficits in anatomy retention and improves anatomical knowledge recall for medical students on a clinical clerkship. In the future, the authors plan to conduct a multicenter study to further evaluate the ability of this curriculum to improve clinically relevant anatomical knowledge. Anat Sci Educ 9: 337–343.

Once Upon a Microscopic Slide: The Story of Histology

For centuries, histology has maintained its remarkable place in the medical curriculum. However, its teaching has been influenced by the new technological advancement that has reshaped medicine teaching into a more modern student-friendly form. Since its inception in the 18th century, the discipline of histology has progressed hand in hand with the advancements in microscopy and microscopic technologies, including immunohistochemistry. In the traditional curriculum of USA medical schools, especially after the first Flexner’s report of 1910, histology was considered as very essential topic for a physician studying the “Art and Science” of medicine. In this era, the teaching relied more on the light microscope and to some extent on the electron microscope. However, the field nowadays, after the second Flexner’s report, which stressed the importance of integrating clinical topics in the curriculum, is shifting towards the use of more electronic resources for teaching. Such new resources rely on information technology and electronic imaging modalities which are considered to be more student-friendly, time efficient, consistent in conveying the images, promote self-learning and are less costly. In fact, in the last 25 years, most universities started relying on virtual microscopy with limited use of the light microscopy by the students. Such an approach facilitated curricular integration of histology into histopathology and provided the opportunity to promote self-learning and clinical relevance. In the era of competency-based curriculum, histology remains an essential and indispensable basic science in the integrated modules

ASSOCIATION BETWEEN HELYCOBACTER PYOLRI INFECTION AND PATHOLOGICAL ORAL MANIFESTATIONS

Data from the literature are controversial regarding the presence of Helicobacter pylori (H. pylori) in dental plaque and its association with gastric infection. One of the possible mechanisms suggested for re-infection is the recolonization with H. pylori from dental plaque. The purpose of this review was to determine whether dental plaque, poor oral hygiene, and periodontal disease were risk factors for H. pylori infection.

ORIGINAL RESEARCH - BASIC SCIENCE: Primary dermal fibroblasts derived from sdc-1 deficient mice migrate faster and have altered αv integrin function: Migration differences in sdc-1 null fibroblasts

The goal of this study is to determine whether dermal fibroblasts lacking syndecan‐1 (sdc1) show differences in integrin expression and function that could contribute to the delayed skin and corneal wound healing phenotypes seen in sdc‐1 null mice. Using primary dermal fibroblasts, we show that after 3 days in culture no differences in α‐smooth muscle actin were detected but sdc‐1 null cells expressed significantly more αv and β1 integrin than wildtype (wt) cells. Transforming growth factor β1 (TGFβ1) treatment at day 3 increased αv‐ and β1‐integrin expression in sdc‐1 null cells at day 5 whereas wt cells showed increased expression only of αv‐integrin. Using time‐lapse studies, we showed that the sdc‐1 null fibroblasts migrate faster than wt fibroblasts, treatment with TGFβ1 increased these migration differences, and treatment with a TGFβ1 antagonist caused sdc‐1 null fibroblasts to slow down and migrate at the same rate as untreated wt cells. Cell spreading studies on replated fibroblasts showed altered cell spreading and focal adhesion formation on vitronectin and fibronectin‐coated surfaces. Additional time lapse studies with β1‐ and αv‐integrin antibody antagonists, showed that wt fibroblasts expressing sdc‐1 had activated integrins on their surface that impeded their migration whereas the null cells expressed αv‐containing integrins which were less adhesive and enhanced cell migration. Surface expression studies showed increased surface expression of α2β1 and α3β1 on the sdc‐1 null fibroblasts compared with wt fibroblasts but no significant differences in surface expression of α5β1, αvβ3, or αvβ5. Taken together, our data indicates that sdc‐1 functions in the activation of αv‐containing integrins and support the hypothesis that impaired wound healing phenotypes seen in sdc‐1 null mice could be due to integrin‐mediated defects in fibroblast migration after injury.