A computational approach to matching multiple sclerosis-related, IGH CDR3s with a MBP epitope.

In multiple sclerosis (MS), T-cell receptors (TCRs) and antibodies specifically target the main structural proteins of myelin, including myelin basic protein (MBP), especially a specific, canonical, immunoglobulin (IG)-targeted MBP epitope. Efficient computational analyses to diagnose or monitor autoimmune conditions, which could have broad applicability in clinical trials or in diagnoses, remains a challenge. As such, we considered the possibility that focusing on the immunoglobin heavy chain (IGH) complementarity determining region-3 (CDR3) amino acid sequences could support the development of an efficient, convenient, and user-friendly approach to detecting or assessing IGH targets in MS.

Large-cell transformation of a composite lymphoma.

Composite lymphoma is a rarely reported entity, defined as two or more morphologically distinct types of lymphoma at the same anatomic site, occurring either synchronously or metachronously. Since 1978, about 100 case reports of composite lymphoma have been cited, many involving combinations of low-grade B-cell lymphomas. To our knowledge, no cases of large-cell transformation of composite lymphoma have yet been described.

Development and evaluation of a real-time PCR assay for detection of Klebsiella pneumoniae carbapenemase genes.

We developed a novel real-time PCR assay to detect Klebsiella pneumoniae carbapenemases (KPCs) and used this assay to screen clinical isolates of K. pneumoniae and Klebsiella oxytoca for the presence of bla(KPC) genes. The TaqMan real-time PCR assay amplified a 399-bp product from the bla(KPC) gene.

The use of knockout mouse technology to achieve tissue selective expression of angiotensin converting enzyme.

The resin angiotensin system (RAS) plays an essential role in blood pressure regulation and electrolyte homeostasis. The effecter peptide of the RAS, angiotensin II, is produced by angiotensin converting enzyme (ACE) in multiple tissues. Genetic deletion of ACE in mice resulted a phenotype of low blood pressure, anemia and kidney defects.

Role of the N-terminal catalytic domain of angiotensin-converting enzyme investigated by targeted inactivation in mice.

Angiotensin-converting enzyme (ACE) produces the vasoconstrictor angiotensin II. The ACE protein is composed of two homologous domains, each binding zinc and each independently catalytic. To assess the physiologic significance of the two ACE catalytic domains, we used gene targeting in mice to introduce two point mutations (H395K and H399K) that selectively inactivated the ACE N-terminal catalytic site.

Role of bradykinin in angiotensin-converting enzyme knockout mice.

Angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin system. Whereas ACE is responsible for the production of angiotensin II, it is also important in the elimination of bradykinin. Constitutively, the biological function of bradykinin is mediated through the bradykinin B(2) receptor.

New approaches to genetic manipulation of mice: tissue-specific expression of ACE.

The renin-angiotensin system (RAS) plays a central role in body physiology, controlling blood pressure and blood electrolyte composition. ACE.1 (null) mice are null for all expression of angiotensin-converting enzyme (ACE).

Mice lacking endothelial ACE: normal blood pressure with elevated angiotensin II.

Recently, the concept of local renin-angiotensin systems (RAS) capable of generating angiotensin II apart from the circulation has received considerable attention. To investigate this, we generated ACE 1/3 mice in which one allele of ACE is null and the second allele was engineered to express ACE on the surface of hepatocytes. ACE 1/3 mice express no endothelial ACE and lack ACE within the lungs.

Impaired urine concentration and absence of tissue ACE: involvement of medullary transport proteins.

ACE.2 mice lack all tissue angiotensin-converting enzyme (ACE) but have 33% of normal plasma ACE activity. They exhibit the urine-concentrating defect and hyperkalemia present in mice that lack all ACE, but in contrast to the complete knockout, ACE.