Arg-gingipain a DNA vaccine induces protective immunity against infection by Porphyromonas gingivalis in a murine model

Arginine-specific cysteine proteinases (RgpA and RgpB) produced by the periodontal pathogen Porphyromonas gingivalis are suspected virulence factors and are involved in interrupting host defense mechanisms as well as in penetrating and destroying periodontal connective tissues. To induce a protective immune response against P. gingivalis, we constructed an rgpA DNA vaccine. BALB/c mice were immunized intradermally by Gene Gun with plasmid DNA carrying rgpA. Antibody responses against P. gingivalis were determined by an enzyme-linked immunosorbent assay. The rgpA DNA vaccine induced high levels of serum antibodies against P. gingivalis. Sera from the rgpA DNA vaccine-immunized mice diminished the proteolytic activity of RgpA and RgpB and inhibited the binding of P. gingivalis to a type I collagen sponge. Moreover, the sera effectively reduced the hemagglutination of P. gingivalis, indicating that the hemagglutinin activity of the organism is associated with RgpA. We found with a murine abscess model that mice immunized with the rgpA DNA vaccine were resistant to an invasive P. gingivalis W50 challenge. These results suggest that the rgpA DNA vaccine induced specific antibodies against the enzyme and that this vaccine could confer protective immunity against P. gingivalis infection.     

Improvement of blood compatibility on cellulose dialysis membrane. 2. Blood compatibility of phospholipid polymer grafted cellulose membrane.

The blood compatibility of a cellulose haemodialysis membrane whose surface was grafted with a methacrylate having a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine, was evaluated with attention to platelet adhesion to the membrane surface and complement activation induced by the membrane. When the original cellulose membrane came in contact with platelet-rich plasma for 30 min, numerous platelets adhered to the surface and aggregated. On the other hand, the membrane grafted with 2-methacryloyloxyethyl phosphorylcholine effectively suppressed platelet adhesion and activation. This effect became more pronounced with increasing surface distribution. Especially, the 2-methacryloyloxyethyl phosphorylcholine grafted membranes, whose distribution exceeded 0.27, completely inhibited platelet adhesion, even when the contact time was 180 min. Moreover, the complement activation was also reduced with increased 2-methacryloyloxyethyl phosphorylcholine distribution on the surface of the membrane.     

Potential predictors of the onset of focal intestinal perforation in extremely low birth weight infants based on an analysis of coagulation and fibrinolysis markers at birth: A case-control study based on ten years of experience at a single institution

Purpose: We aimed to investigate potential predictors of focal intestinal perforation (FIP) in extremely low birth weight infants (ELBWIs) among coagulation and fibrinolysis markers at birth.Methods: We reviewed the medical records of FIP patients and their coagulation and fibrinolysis markers at birth between 2010 and 2019, and matched patients according to gestational age. FIP was diagnosed based on macroscopic intestinal perforation with a punched-out lesion without necrosis. Patient characteristics and blood test results, including coagulation and fibrinolysis marker levels, were compared between the groups.Results: Two hundred forty ELBWIs were enrolled in this study (FIP, n = 18; controls, n = 222). In the FIP group, the gestational age at birth was significantly younger (p = 0.023) and the birth weight was significantly lower (p = 0.007) in comparison to the control group. Furthermore, the FIP group showed significantly lower levels of fibrinogen (p = 0.027) and factor XIII (F-XIII) (p = 0.007). The receiver operating characteristics curves for fibrinogen and F-XIII revealed that the 95% confidence intervals of fibrinogen and F-XIII were 0.530–0.783 (p = 0.027), and 0.574–0.822 (p = 0.007), respectively.Conclusions: This is the first report focusing on coagulation and fibrinolysis markers in FIP patients at birth. The fibrinogen and F-XIII values at birth are potential predictors of FIP in ELBWIs.Type of Study: Study of Diagnostic Test (Case Control Study)Level of Evidence: Level IV     

Outcome of advanced renal cell carcinoma arising in end-stage renal disease: comparison with sporadic renal cell carcinoma

Clinical and Experimental Nephrology - The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited. Patients diagnosed with...     

Preparation of Asialofetuin-Labeled Liposomes with Encapsulated Human Interferon-γ and Their Uptake by Isolated Rat Hepatocytes

The selective delivery of human recombinant interferon (IFN)- to isolated rat hepatocytes was studied with asialofetuin (AF)-labeled liposomes. AF-liposomes containing buffer solution were initially prepared by the detergent removal method, and IFN- was subsequently encapsulated by the freeze-thawing method without loss of activity. Virtually no free [³²P]IFN- was internalized into isolated rat hepatocytes, whereas AF-liposomes containing [³²P]IFN- were taken up to a significant degree. Liposomal binding to the hepatocytes (estimated at 4°C) was one-fifth of the uptake (estimated at 37°C). Since the uptake was inhibited by the addition of free AF, AF-liposomes may be taken up by the action of galactose-binding protein on the hepatocytic cell surface. The liposome preparation method reported in this paper provides a useful means for the encapsulation of unstable macromolecules into AF-liposomes. AF-liposomes were found effectively to carry IFN- into hepatocytes in vitro.     

A new model rat with acute bronchiolitis and its application to research on the toxicology of inhaled particulate matter

The aim of the present study was to establish a useful animal model that simulates humans sensitive to inhaled particulate matter (PM). We have developed a new rat model of acute bronchiolitis (Br) by exposing animals to NiCl2 (Ni) aerosols for five days. Three days following the Ni exposure, the animals developed signs of tachypnea, mucous hypersecretion, and bronchiolar inflammation which seemed to progress quickly during the fourth to fifth day. They recovered from lesions after four weeks in clean air. To assess the sensitivity of the Br rats to inhaled particles, two kinds of PM of respirable size were tested with doses similar to or a little higher to the recommended threshold limit values (TLVs) for the working environment in Japan. Titanium dioxide (TiO2 = Ti) was chosen as an inert and insoluble particles and vanadium pentoxide (V2O5 = V), as a representative soluble and toxic airborne material. The Br rats exposed to either Ti or V were compared the pathological changes in the lungs and the clearance of particles to those in normal control or Br rats kept in clean air. The following significant differences were observed in Br rats: 1. delayed recovery from pre-existing lesions or exacerbated inflammation, 2. reductions in deposition and clearance rate of inhaled particles with the progress of lesions. The present results suggest that Br rats are more susceptible to inhaled particles than control rats. Therefore, concentrations of particulate matter lower than the TLVs for Japan, which have no harmful effects on normal lungs, may not always be safe in the case of pre-existing lung inflammation.     

Pituitary adenomas treated by microsurgery with or without Gamma Knife surgery: experience in 122 cases

The clinical outcome of 122 patients with pituitary adenomas treated by microsurgery and/or Gamma Knife radiosurgery (GKRS) was analyzed to evaluate patient selection criteria and the role of GKRS. Sixty-six resections were performed in 59 patients. All tumors were macroadenomas, except for 5 ACTH-producing adenomas. Twenty-four of the 31 hypersecreting adenomas showed normal serum hormone values after treatment. Postoperative complications were rhinorrhea, cranial nerve palsies, and a small thalamic infarct. GKRS was performed on 18 of the operated patients because of residual tumors, mostly in the cavernous sinus. Thirty-five of the 63 patients treated by GKRS were followed for more than 2 years. All adenomas except 2 were stable or had decreased in size. Eleven of 17 functioning adenomas showed normal serum hormone values after treatment. It is concluded that tumors that compress the optic pathway should be removed and that residual tumors in the cavernous sinus are good indications for radiosurgery.