h-BN nanosheets as simple and effective additives to largely enhance the activity of Au/TiO2 plasmonic photocatalysts.

The activity of Au nanoparticle-loaded P25 TiO2 (Au/P25) plasmonic photocatalysts, evaluated by the oxidative decomposition of formic acid in water under visible light irradiation, was enhanced up to 3 times by simply mixing Au/P25 with photocatalytically inactive h-BN nanosheets as a result of electron transfer from photoexcited Au/TiO2 to the h-BN nanosheets and retardation of the charge recombination.

Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma.

Antibody-drug conjugates (ADCs) are potent cytotoxic drugs linked to antibodies through chemical linkers, and allow specific targeting of drugs to neoplastic cells. The expression of CD22 is limited to B-cells, and we show that CD22 is expressed on the vast majority of non-Hodgkin's lymphomas (NHLs). An ideal target for an ADC for the treatment of NHL would have limited expression outside the B-cell compartment and be highly effective against NHL. We generated an ADC consisting of a humanized anti-CD22 antibody conjugated to the anti-mitotic agent maytansine with a stable linker (anti-CD22-MCC-DM1). Anti-CD22-MCC-DM1 was broadly effective in in vitro killing assays on NHL B-cell lines. We did not find a strong correlation between in vitro potency and CD22 surface expression, internalization of ADC or sensitivity to free drug. We show that anti-CD22-MCC-DM1 was capable of inducing complete tumor regression in NHL xenograft mouse models. Further, anti-CD22-MCC-DM1 was well tolerated in cynomolgus monkeys and substantially decreased circulating B-cells as well as follicle size and germinal center formation in lymphoid organs. These results suggest that anti-CD22-MCC-DM1 has an efficacy, safety and pharmacodynamic profile that support its use as a treatment for NHL.

Expression and activity of transglutaminase II in spontaneous tumours of dogs and cats.

Tissue transglutaminase II (TGase II) is a dual function protein with both transamidating and guanidine triphosphate (GTP)-binding capabilities. Previous studies have implicated TGase as a pro-apoptotic molecule; however, our recent findings indicate that TGase II may act as a survival factor in various cell types. The purpose of this study was to survey TGase II expression in normal tissue and spontaneous tumours of dogs and cats, by Western blotting and immunohistochemistry. Bladder, liver and adrenal gland exhibited prominent expression of TGase II while other tissues, including mammary gland, displayed limited expression and activity. TGase II GTP-binding in normal tissues was proportional to the level of expression in all tissues examined. Normal mammary tissue and that showing benign hyperplasia did not express TGase II. However, 11/25 (44%) of canine mammary carcinomas and 10/12 (83%) of feline mammary carcinomas strongly expressed TGase II in either a stromal, cellular or combined pattern. The pattern of expression was not related to the classification of mammary carcinoma (solid, tubulopapillary, complex or anaplastic), except that two anaplastic canine mammary carcinomas showed prominent TGase II expression. Two canine mammary carcinoma cell lines showed prominent TGase expression, and when the TGase activity was inhibited, the cells became more sensitive to doxorubicin-induced cell death. Thus, TGase II was significantly expressed in mammary cancers from dogs and cats and immunoreactivity of TGase II was similar to that reported in humans beings. The pro-survival effect of TGase II in canine mammary carcinoma cell lines was similar to that previously reported in humans patients.

Feline systemic reactive angioendotheliomatosis: eight cases and literature review.

A rare, multisystemic intravascular proliferative disorder was identified postmortem in eight cats. The majority of these cats died or were euthanized following episodes of dyspnea, lethargy, and anorexia. Microscopic examination revealed occlusive, intraluminal proliferations of spindle cells within small vessels. The heart was consistently involved, and myocardial dysfunction was the probable cause of illness in all cats. Immunohistochemically, the majority of intravascular cells expressed von Willebrand factor, and a smaller number expressed smooth muscle actin, compatible with a dual population of endothelial cells and pericytes, suggesting a reactive rather than a neoplastic process. Four cases of a similar feline vascular disorder from the veterinary literature are reviewed. The histopathology resembles reactive angioendotheliomatosis in humans, a benign cutaneous intravascular endothelial and pericytic proliferative condition. However, in contrast, this feline disease is multisystemic and fatal. We propose the name "feline systemic reactive angioendotheliomatosis" for this unique, idiopathic disorder of domestic cats.

FGF signal transduction in PC12 cells: comparison of the responses induced by endogenous and chimeric receptors.

Rat phaeochromocytoma (PC12) cells respond to many growth factors and produce different phenotypes, including neurite outgrowth. Receptor tyrosine kinases (RTK), which activate multiple signalling pathways in response to ligand binding, initiate many of these. One such family of receptors, the fibroblast growth factor receptor (FGFR), has four different members and expresses at least three of these in PC12 cells. A chimeric tyrosine kinase receptor, consisting of the extracellular domain of human plasma-derived growth factor receptor-beta (hPDGFR-beta) and the transmembrane and intracellular region of FGFR1 (designated PFR1), was constructed and was stably transfected into cloned PC12 cell lines. This chimera, which can be activated without stimulating endogenous RTK including other FGFR, induces neurite outgrowth in a PDGF-dependent manner. By altering the protocol for preparing the retroviral vectors, cells with a wide range of expression levels can be obtained. The amount of these chimeric receptors seems to correlate with the time and the intensity of response as observed in neurite outgrowth assays. Analysis of proteins implicated in FGFR1 signalling indicates that upon stimulation, a tyrosine phosphorylated protein designated FRS2 associates with SOS, Grb2 and the receptor. The chimeric receptor appears entirely similar to that observed for the stimulation of native PC12 cells with FGF2. These results support the view that FRS2 is the dominant FGFR1 signalling entity in PC12 cells.

Evolutionary conservation of histone macroH2A subtypes and domains.

Histone macroH2A is an unusual core histone that contains a large non-histone region, and a region that resembles a full length H2A. We examined theconservation of this novel structural arrangement by cloning chicken macroH2A cDNAs and comparing them to their rat counterparts. The amino acid sequences of the two known macroH2A subtypes are >95% identical between these species despite evolutionary separation of approximately 300 million years. The H2A region of macroH2A is completely conserved, and thus is even more conserved than conventional H2A in these species. The origin of the non-histone domain was examined by comparing its sequence to proteins found in bacteria and RNA viruses. These comparisons indicate that this domain is derived from a gene that originated prior to the appearance of eukaryotes, and suggest that the non-histone region has retained the basic function of its ancestral gene.

Calcification in carcinoma of the stomach: report of a case.

By upper gastrointestinal series, a 57 years-old woman was pointed out to have scattered calcifications along the greater curvature of the stomach. On computerized tomography, the calcifications distributed in the irregularly thickened gastric wall. With a diagnosis of calcified mucinous adenocarcinoma showing Borrmann type III, total gastrectomy with splenectomy was carried out. The characteristics of this lesion were briefly presented with a review of the literature.

[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the first report). Study on effectiveness and safety in mono-therapy with aztreonam. A study of aztreonam in the Perinatal Co-research Group].

Pharmacokinetics and clinical study of aztreonam (AZT) in neonates and premature infants were conducted with the following results: 1. Pharmacokinetics (1) Serum concentrations of AZT at 30 minutes after one-shot intravenous injection of 10 mg/kg and 20 mg/kg to neonates including premature infants were 20.6-26.6 micrograms/ml and 38.5-46.4 micrograms/ml, respectively, and decreased thereafter. A dose response was observed in the serum concentrations with administration of AZT 10 mg/kg and 20 mg/kg. (2) Serum half-lives (T1/2) tended to be shorter in both mature and premature infants as their day-ages increased and T1/2 tended to be prolonged in premature infants compared with mature infants. (3) Changes in serum concentration upon one-hour intravenous drip infusion of AZT 20 mg/kg were very similar to those upon one-shot intravenous injection. (4) Urinary excretions in the first 6 hours after one-shot intravenous injection of AZT 10 mg/kg or 20 mg/kg tended to increase in mature infants as they grew and showed excretion rate of 26.2-54.3% but those in premature infants did not show any specific tendency with rate of 17.5-45.1%. Urinary excretions upon intravenous drip-infusion showed a tendency very similar to those upon intravenous injection. 2. Clinical studies (1) Clinically evaluable cases of AZT treatment were 88 cases (91 diseases), in which pathogenic organisms were identified in 56 cases (Group A), i.e., sepsis 9, purulent meningitis 2, pneumonia 8, urinary tract infection (UTI) 33 and others. Total efficacy rate was 98.2% including "excellent" (39), "good" (16) and "fair" (1). Number of cases in which pathogenic organisms were unknown (Group B) was 11, i.e., suspected sepsis (4), pneumonia (3) and intrauterine infection (4) and the efficacy rate was 100% with "excellent" (4) and "good" (7). Thus, both group A and B showed excellent results. AZT was also given to 24 cases for prophylaxis and all the cases showed prophylactic effect of AZT.4+ Bacteriologically AZT was deemed effective in 53 cases out of 56 (Group A) with identified pathogens "eradicated" and "unchanged" (2), thus the bacterial eradication rate was 96.2%. (3) A minor degree of loose feces was observed in 1 (1.3%) of 80 cases as a side effect. Abnormal laboratory test values found were eosinophilia (3 cases), elevation of GOT and GPT (2), platelet-increase (1), elevation of GOT (1), and thrombocytopenia.elevation of GOT.GPT.LDH (1). Every one of these was of a minor degree and transient. From the above pharmacokinetics and clinical results, standard dosage of AZT to neonates and premature infants should be in a unit dose of 20 mg/kg, twice daily to those with ages between 0 and 3 days, and 2 to 3 times daily to those with ages 4 days and above, by intravenous injection or intravenous drip infusion.

[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the second report). Study on effectiveness and safety in combination therapy using aztreonam and ampicillin. A study of aztreonam in the Perinatal Co-research Group].

Pharmacokinetics and clinical effects were studied in a combination therapy with aztreonam (AZT) and ampicillin (ABPC) in neonates and premature infants. The results obtained are summarized as follows. 1. Pharmacokinetics (1) Average serum concentrations at 30 minutes after one-shot intravenous injection of AZT 20 mg/kg and ABPC 25 mg/kg to a 4-7 days age-group of neonates were 41.3 (AZT) and 30.5 (ABPC) micrograms/ml, respectively. They gradually decreased to 14.7 and 2.7 micrograms/ml at 6 hours after the administration, but the concentration of AZT was always higher than that of ABPC. (2) Serum half-lives (T1/2) in the 4-7 days age-group were 3.61 hours for AZT and 1.42 hours for ABPC, thus T1/2 of AZT was longer. However, T1/2 of AZT was scarcely affected in the concomitant administration of ABPC. (3) Urinary excretion of AZT in the concomitant administration to the 4-7 days age-group was 52.7%, which was the same or a little higher comparing to that in AZT alone administration. 2. Clinical studies (1) AZT and ABPC were concomitantly administered to 160 cases and 133 cases were evaluated for efficacy. Pathogenic organisms were identified in 29 cases (Group A) and the efficacy rate was 86.2% (25/29). The number of cases in which pathogenic organisms were not identified (Group B) was 50 and in this group, the efficacy rate was excellent, 94.0% (47/50). AZT and ABPC were concomitantly administered to 54 cases for prophylaxis and in all the cases the administrations showed prophylactic effect. (2) Bacterial changes were confirmed in 21 of the 29 cases in which pathogenic organisms were identified initially and all of these 21 cases showed bacterial eradication, i.e., the bacterial eradication rate in the treatment was 100%. (3) There were 2 cases in which side-effects were observed among the analyzed 152 cases (1.3%). The side effects found were 1 case each of diarrhea and eruption. Abnormal laboratory values were found in 23 cases (15.9%), i.e., eosinophilia (9 cases), platelet-increase (4), elevation of GOT (4), elevation of GOT and GPT (3) and others (3). From the above pharmacokinetics and clinical results, the combination therapy of AZT and ABPC is considered to be one of the useful empiric antibiotic-therapies when pathogenic organisms are unknown in the infections of neonates and premature infants.

[Clinical and pharmacokinetic evaluations of cefuzonam in children].

A new parenteral cephalosporin antibiotic, cefuzonam (L-105, CZON), was evaluated for its safety, efficacy and pharmacokinetics in children. Twenty-two cases of bacterial infections including pneumonia, lung abscess, sepsis, urinary tract infection and soft tissue infections were treated with CZON. Clinical effective rate was 95%. Serum half-lives of CZON were 1.04-1.33 hours in children with normal renal and hepatic functions. Significant depressions of the normal fecal flora were observed and diarrhea or loose stool was encountered in 7 of the 22 treated cases (32%).