Molecular cloning of agonistic and antagonistic monoclonal antibodies against human 4-1BB.

Previously, we prepared two different monoclonal antibodies (mAbs) against human 4-1BB (CD137): an agonistic mAb BBK-1 and an antagonistic mAb BBK-2. In this paper, we describe the molecular cloning of these two mAbs and present comparisons of their amino acid sequences. cDNAs encoding the heavy (H) and light (L) chains of the two mAbs were cloned by screening of cDNA libraries constructed from hybridomas secreting these mAbs. Comparisons of amino acid sequences of the two mAbs showed that, while the constant regions of the H and L chains were identical between the two mAbs, the variable region showed 45% identity in H chains and 48% identity in L chains. This suggests that these two mAbs recognize different epitopes of 4-1BB and may have different effects on the activity of 4-1BB.     

An ultrastructural study of Elschnig's pearls in the pseudophakic eye

In two pseudophakic human eyes, obtained post mortem, Elschnig's pearls were visible biomicroscopically. One eye contained a medallion lens and the other an iridocapsular lens (implanted for 53 months and 39 months, respectively). The medallion lens was fixed to the iris but was not attached to the Soemmerring's ring. Elschnig's pearls and star-shaped cells were found on the posterior capsule in the pupillary space. One loop of the iridocapsular lens was encased in the Soemmerring's ring whereas the other was located between the iris and the lens remnants. The Elschnig's pearls were on the anterior side of the ring; only a few were in the pupillary space. Two other pseudophakic eyes with clear posterior capsules also contained small numbers of Elschnig's pearls on or just near the peripheral lens remnants.     

Revisit on congenital bronchopulmonary vascular malformations: a haphazard branching theory of malinosculations and its clinical classification and implication.

We propose a haphazard branching theory to support the concept of bronchopulmonary malinosculations, and we apply this theory to classify congenital bronchopulmonary vascular malformation (BPVM) based on the anatomical results we have found. Between January 1990 and December 1997, a total of 22 pediatric patients (10 male and 12 female), aged 2 days to 14 years (median, 19.6 months), with congenital BPVM were enrolled in this retrospective study. Study modalities include the clinical features and plain chest films (n = 22) plus at least two of the following: echocardiography (n = 13), barium esophagraphy (n = 2), bronchoscopy (n = 4), contrast bronchography (n = 8), high-resolution direct coronal CT (n = 1) and electron beam or ultrafast CT (n = 1) of the chest, MRI (n = 10), MRA (n = 1), contrast cineangiocardiography (n = 9), surgery (n = 11), or autopsy (n = 2). The salient clinical features were recurrent lung infections in 14 patients, acute respiratory distress in 13, associated cardiovascular malformations in 8, dextroversion in 7, congestive heart failure in 7, dextrocardia in 4, and complex congenital heart diseases in 4. There were abnormal openings (malinosculations) of the pulmonary airway in 20 patients: to an artery in 12, to a vein in 8, and to the lung parenchyma in 9. These 22 patients with congenital BPVM can be classified into bronchial malinosculation (10 cases), arterial malinosculation (2 cases), and bronchoarterial malinosculation (10 cases). Congenital BPVM can be classified in terms of bronchopulmonary malinosculation based upon a haphazard branching theory, in which abnormal communications between two independent systems (primitive foregut system and aortic-pulmonary arch system) occurred coincidentally rather than causally.     

Changes in outcome with sphincter preserving surgery for rectal cancer in Korea, 1991-2000.

AIM: To report the clinical and oncological data of patients operated on for rectal cancers 3-5 cm from the AV over a 10 year period, including the Sphincter preservation (SP) rate. METHODS: We reviewed medical records of 304 patients with rectal cancers 3-5 cm from the AV who underwent surgical resection from January 1991 through December 2000. The 10 years were divided into three periods based on the introduction of new surgical techniques, specifically, ultralow anterior resection (ULAR) with double stapling in March 1994 and ULAR with coloanal anastomosis in April 1997. The rates of SP, complications and patient survival during these periods were compared. RESULTS: The SP rate increased significantly over the 10 years, from 16.4% in period I (January 1991-February 1994), to 53.0% in period II (March 1994-March 1997), to 86.5% in period III (April 1997-December 2000) (p<0.001). Over time, the age of the patients increased (p=0.004), the length of the distal resection margin became shorter (p=0.005), and the rate of lymph node metastasis increased (p=0.016). The factors significantly influencing SP were the period (p<0.001) and the distance from the AV (p<0.001). Over time, morbidity did not increase, and overall and disease free survival rates did not decrease. In contrast, the overall survival of N2 cases significantly increased over time (p=0.0492). CONCLUSION: Over 10 years, the SP rate in rectal cancers 3-5 cm from the AV was significantly increased by the introduction of the double stapling and coloanal anastomosis techniques. These surgical methods, however, had no effect on morbidity, disease free survival and overall survival rates.     

Regulation of NGF gene expression in CNS glia by cell-cell contact.

Nerve growth factor (NGF) gene expression in central nervous system (CNS) glia appears to be associated with active glial growth. To study the underlying molecular mechanisms, we examined the effects of a number of growth-related factors on NGF mRNA expression in glial cultures. Our results suggest that glial membrane interaction, as a consequence of growth, actively inhibits NGF gene expression in CNS glia.     

Critical size defect in the canine mandible.

OBJECTIVE: The purpose of this study was to determine the minimum size defect in a canine mandible that would not spontaneously heal during the dog's natural life (the critical size defect). STUDY DESIGN: Sixteen adult female mongrel dogs underwent continuity resection on both sides of the mandible to create bilateral defects. In 8 dogs, mandibular defects ranging from 5 to 20 mm were created with periosteal resection. In the other 8 dogs, mandibular defects ranging from 30 to 60 mm were created preserving the periosteum. The dogs were then killed at 6 months and the defects examined using radiographs and histologic analysis. RESULTS: When the periosteum was removed, mandibular defects greater than 15 mm failed to heal across the entire defect. However, when the periosteum was preserved, mandibular defects needed to be greater than 50 mm in order to fail to heal. CONCLUSION: The critical size defect in a canine mandible model is 15 mm when the periosteum is removed and 50 mm when the periosteum is preserved.     

Teaching scholars programs: faculty development for educators in the health professions.

OBJECTIVE: This article 1) provides an overview of formal Health Sciences Teaching Scholars Programs as presented in medical education literature and 2) presents information about an innovative multidiscipline Teaching Scholars Program. METHOD: Health Sciences Teaching Scholars Programs and similar programs were reviewed in the medical education literature to identify similar and dissimilar characteristics. The WVU Teaching Scholars Program highlighted in this article is presented with a discussion of goals, objectives, target audiences, course length, session frequency, program topics, learning methods, and assessments of the programs. A summary of the WVU Teaching Scholars Program and two Teaching Scholars Programs at McGill University and the University of Toronto were presented at the Association for American Medical Colleges (AAMC) annual meeting in 2006 for input from the general medical education audience. RESULTS: Comparisons of Health Sciences Teaching Scholars Programs reveal that successful programs are uniquely shaped by their educational environments. Scholars report that they value learning new teaching methods and improving their educational careers. CONCLUSION: Teaching Scholars Programs are valuable for the development of enhancing both teaching and scholarship in Health Sciences Programs and must adapt to the uniqueness of their respective educational environments and must continue to nurture scholars beyond graduation.