Historical development of monoclonal antibody therapeutics

Since the first publication by Kohler and Milstein on the production of mouse monoclonal antibodies (mAbs) by hybridoma technology, mAbs have had a profound impact on medicine by providing an almost limitless source of therapeutic and diagnostic reagents. Therapeutic use of mAbs has become a major part of treatments in various diseases including transplantation, oncology, autoimmune, cardiovascular, and infectious diseases. The limitation of murine mAbs due to immunogenicity was overcome by replacement of the murine sequences with their human counterpart leading to the development of chimeric, humanized, and human therapeutic antibodies. Remarkable progress has also been made following the development of the display technologies, enabling of engineering antibodies with modified properties such as molecular size, affinity, specificity, and valency. Moreover, antibody engineering technologies are constantly advancing to enable further tuning of the effector function and serum half life. Optimal delivery to the target tissue still remains to be addressed to avoid unwanted side effects as a result of systemic treatment while achieving meaningful therapeutic effect.     

Persistence and Complex Evolution of Fluoroquinolone-Resistant Streptococcus pneumoniae Clone

Prolonged outbreaks of multidrug-resistant Streptococcus pneumoniae in health care facilities are uncommon. We found persistent transmission of a fluroquinolone-resistant S. pneumoniae clone during 2006–2011 in a post–acute care facility in Israel, despite mandatory vaccination and fluoroquinolone restriction. Capsular switch and multiple antimicrobial nonsusceptibility mutations occurred within this single clone. The persistent transmission of fluoroquinolone-resistant S. pneumoniae during a 5-year period underscores the importance of long-term care facilities as potential reservoirs of multidrug-resistant streptococci.     

Third trimester abnormal oral glucose tolerance test and adverse perinatal outcome

Objective: To compare perinatal outcome of women after third trimester oral glucose tolerance test (GTT) following normal glucose challenge test (GCT) stratified by test results.

Study design: Retrospective cohort study of women delivered in a tertiary, university affiliated medical center (2007–2012). Inclusion criteria were women with a normal 50?g GCT (<140?mg/dl) followed by GTT, who delivered a live-born fetus >28 gestational weeks. Gestational diabetes mellitus (GDM) was defined as ≥2 pathological values on GTT (Carpenter and Coustan’s criteria). Perinatal outcome was stratified by GTT results: normal (if all 4 values were normal), single pathological value or GDM. Logistic regression analysis was utilized to adjust outcomes to potential confounders.

Results: Overall, 323 women met inclusion criteria. Of them, 277 (85.8%) had 4 normal values, 32 (9.9%) had a single pathological value and 14 (4.3%) had late-onset GDM. Infants of mothers diagnosed and treated as GDM had lower birth weights, compared to non-diabetics and those with a single pathological value GTT. Mothers with GTT ≥1 pathological values had statistically insignificant higher rates of cesarean delivery. However, this difference was not significant after adjustment to potential confounders.

Conclusion: Treatment of late-onset GDM may lead to lower birthweights, presumably due to glucose control. No association was found with cesarean delivery or neonatal outcome.     

Adnexal Torsion during Pregnancy: Outcomes after Surgical Intervention—A Retrospective Case-Control Study

Study Objective

To investigate the pregnancy and neonatal outcomes of surgical treatment for adnexal torsion (AT) during pregnancy.

Immunomodulation of vascular endothelium: effects of ultraviolet B irradiation on vein allograft rejection

Prosthetic grafts of vein allografts are inadequate as small-diameter vessel substitutes. We have applied ultraviolet B (UVB) irradiation to modulate the immunogenicity of vein allografts to avoid immunologic injury. The veins of male ACI rats were irradiated with UVB (60 mJ/cm2) in situ and transplanted to male ACI rats (autografts) and female Lewis rats (allografts). Nonirradiated veins served as controls. At 4, 7, 14, and 28 days, all grafts were patent and were studied for morphologic changes by scanning electron microscopy and for immunogold labeling of major histocompatibility complex class II antigen expression. In autografts, scanning electron microscopy demonstrated minimal endothelial loss after grafting, regardless of UVB irradiation. Untreated allografts showed severe endothelial injury 4, 7, and 14 days after transplantation. UVB irradiation of veins protected allografts from injury to the endothelium and basement membrane. Major histocompatibility complex class II-positive endothelial cells were not seen in autografts but were seen in 40% of cells 4 days after transplantation in untreated allografts. UVB-treated allografts showed MHC class II antigen expression labeling of 20% of the endothelial cells. Barr body analysis demonstrated the donor origin of these endothelial cells. UVB irradiation of rat vein allografts prolongs endothelial survival while decreasing endothelial surface expression of class II antigens. These data suggest that modification of vein immunogenicity with UVB irradiation may permit functional survival of small-vessel allografts without chronic immunosuppression.     

Hereditary amyloidosis

A review of hereditary amyloidoses is provided by papers from a 1969 international symposium on primary amyloidosis. These discussions allow comparison of the amyloid neuropathy with onset in the lower extremities (Portuguese-Japanese families), the neuropathy with onset in the upper extremities (Indiana-Maryland families), the neuropathy and nephropathy of the Iowa family, and the amyloidosis of familial Mediterranean fever. The importance of studies of genetic entities in understanding the pathogenesis of amyloidosis is emphasized.