Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity.

Background: The use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity.

Methods: We stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand.

The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain.

Replication of human cytomegalovirus (HCMV) is characterized by a tight virus-host cell interaction. Cyclin-dependent protein kinases (CDKs) are functionally integrated into viral gene expression and protein modification. The HCMV-encoded protein kinase pUL97 acts as a CDK ortholog showing structural and functional similarities.

Proteomic analysis of the multimeric nuclear egress complex of human cytomegalovirus.

Herpesviral capsids are assembled in the host cell nucleus before being translocated into the cytoplasm for further maturation. The crossing of the nuclear envelope represents a major event that requires the formation of the nuclear egress complex (NEC). Previous studies demonstrated that human cytomegalovirus (HCMV) proteins pUL50 and pUL53, as well as their homologs in all members of Herpesviridae, interact with each other at the nuclear envelope and form the heterodimeric core of the NEC.

Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus.

The NKG2D receptor is one of the most potent activating natural killer cell receptors involved in antiviral responses. The mouse NKG2D ligands MULT-1, RAE-1, and H60 are regulated by murine cytomegalovirus (MCMV) proteins m145, m152, and m155, respectively. In addition, the m138 protein interferes with the expression of both MULT-1 and H60.

Combined X-ray diffraction and QM/MM study of the Burkholderia cepacia lipase-catalyzed secondary alcohol esterification.

To understand the origin of high enantioselectivity of Burkholderia cepacia lipase (BCL) toward secondary alcohol, (R,S)-1-phenoxy-2-hydroxybutane (1), and its ester (E1), we determined the crystal structure of BCL complexed with phosphonate analogue of S-E1 and accomplished a series of MM, MC, and QM/MM studies. We have found that the inhibitor in the S configuration binds into the BCL active site in the same manner as the R isomer, with an important difference: while in case of the R-inhibitor the H-bond between its alcohol oxygen and catalytic His286 can be formed, in the case of the S-inhibitor this is not possible. Molecular modeling for both E1 enantiomers revealed orientations in which all hydrogen bonds characteristic of productive binding are formed.

Murine cytomegalovirus regulation of NKG2D ligands.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes morbidity risk in immunologically suppressed and immunodeficient patients including congenital infections. Approaches to curb the consequences of HCMV infections are restricted by a lack of complete understanding of viral pathogenesis. The infection of mice with murine cytomegalovirus (MCMV) as a model of HCMV infection has been particularly useful in elucidating the role of innate and adaptive immune response mechanisms.

The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60.

Members of the alpha- and beta-subfamily of herpesviridae encode glycoproteins that specifically bind to the Fc part of immunoglobulin (Ig)G. Plasma membrane resident herpesviral Fc receptors seem to prevent virus-specific IgG from activating antibody-dependent effector functions. We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation of NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 and H60 from the cell surface.

Selective down-regulation of the NKG2D ligand H60 by mouse cytomegalovirus m155 glycoprotein.

Both human and mouse cytomegaloviruses (CMVs) encode proteins that inhibit the activation of NK cells by down-regulating cellular ligands for the activating NK cell receptor NKG2D. Up to now, three ligands for the NKG2D receptor, named RAE-1, H60, and MULT-1, have been identified in mice. The resistance of mouse strains to murine CMV (MCMV) infection is determined by their ability to generate an effective NK cell response.

NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145.

The NK cell-activating receptor NKG2D interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (MCMV). We set out to define the viral gene product regulating murine UL16-binding protein-like transcript (MULT)-1, a newly described NKG2D ligand. We show that MCMV infection strongly induces MULT-1 gene expression, but surface expression of this glycoprotein is nevertheless completely abolished by the virus.

Diagnosis and treatment of liver hydatid disease.

Background/aims: Human echinococcosis is endemic in some areas of the world, including Mediterranean countries. The liver is the most frequent seat of echinococcosis, involved in about 70% of cases. Because there is still no effective medical therapy, surgery remains the treatment of choice.

[Nodular lymphoid hyperplasia of the colon and terminal ileum. Case report].

A patient admitted to our hospital because of diarrhea and hematochesia is presented. These complaints appeared eight months before, and were not accompanied by other disturbances. All hematological, biochemical and microbiological findings were normal, but endoscopic, x-ray and histologic examination of the gastrointestinal tract showed nodular lymphoid hyperplasia of the colon and terminal ileum.

A scoring system for early differentiation of the etiology of acute pancreatitis.

Background: The purpose of this study was to find a new scoring system for early differentiation between the two commonest etiologies of acute pancreatitis (biliary and alcoholic), because biliary pancreatitis can be treated early by endoscopic sphincterotomy, whereas such treatment is unnecessary in alcoholics.

Methods: One hundred and forty-five patients satisfied the requirements for participation in the study and were divided into groups A (alcoholic pancreatitis) and B (biliary pancreatitis). Seven variables (serum and urine amylase, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), lipase/amylase (L/A) ratio, and erythrocyte mean corpuscular volume (MCV)) that differed in a statistically significant manner between patients of the two groups were included in the scoring system.

Biochemical parameters in the early differentiation of the etiology of acute pancreatitis.

Objectives: We undertook a retrospective study to define the usefulness of various biochemical parameters in differentiation between alcoholic and nonalcoholic acute pancreatitis.

Methods: One hundred sixty-seven patients were divided into groups A (alcoholic pancreatitis) and NA (nonalcoholic pancreatitis). Group NA was further subdivided into groups B (biliary pancreatitis) and NANB (nonalcoholic, nonbiliary pancreatitis).