Acute necrotic stomatitis (noma) associated with methicillin-resistant Staphylococcus aureus infection in a newly acquired rhesus macaque (Macaca mulatta)

Backgroud A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis. Methods To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied. Results Staphylococcus aureus and Enterococcus faecalis were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin‐resistant Staphylococcus aureus infection. Vancomycin and ampicillin‐sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion. Conclusions Simian noma associated with methicillin‐resistant Staphylococcus aureus (MRSA) had not previously been reported in non‐human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.     

An oro-facial disease 'noma (cancrum oris)' in a Japanese monkey (Macaca fuscata): clinical signs, clinicopathological features, and response to treatment

BACKGROUND: A Japanese monkey developed severe oro-facial lesions that were called noma in humans. Although extensive destruction of both the buccal regions occurred with rapid progress, author successfully treated the lesions with povidone-iodine, enrofloxacin, chymotrypsin, a glycyrrhizin preparation, and a basic fibroblast growth factor. METHODS: Author clinicopathologically investigated this disease during the treatment. RESULTS: In the subcutaneous and muscular tissues, the lesions developed characteristic changes such as dissolving collagen fibers and muscular tissues phagocytosed by giant and epitheloid cells. The monkey showed a notable increase in creatine kinase activities. The present examinations revealed severe invasive findings in muscular tissues, which were accompanied by infections of beta-hemolytic streptococcus Group C. This monkey was negative for simian immunodeficiency virus antibody; however, infection with simian D retrovirus was not ruled out. CONCLUSIONS: Simian noma was a rapidly devastating disease, which destroyed the muscle tissues of oro-facial structure. Nonhuman primates are the only species that develop oro-facial lesions, corresponding to noma in humans.     

Selective reversal of drug resistance in drug-resistant lung adenocarcinoma cells by tumor-specific expression of MDR1 ribozyme gene mediated by retrovirus

According to the fact that CEA gene expressed only in lung adenocarcinoma and not in normal lung cells, a retroviral vector (pCEAMR) was constructed which carried the CEA promoter coupled to MDR1 ribozyme gene. pCEAMR was introduced into drug-resistant lung adenocarcinoma cells GAOK with CEA expression and HeLaK without CEA expression; the expression of pCEAMR and drug resistance in the infected cells were analyzed in vitro and in vivo ; pCEAMR expressed only in CEA-producing GAOK cells and not in non-CEA-producing HeLa cells. The drug resistance to doxorubicin (DOX) decreased 91.5% in the infected GAOK cells and did not change in the infected HeLa cells. In nude mice, DOX could obviously inhibit the growth of the infected GAOK tumors, and had no effect on the growth of the infected HeLa cells. These results indicated that MDR1 ribozyme gene regulated by CEA promoter expressed only in human adenocarcinoma cells and reversed their drug resistance selectively. This gene-drug therapy might serve as an effe     

Mitochondrial respirasome works as a single unit and the cross-talk between complexes I,III2 and IV stimulates NADH dehydrogenase activity

Ustilago maydis is an aerobic basidiomycete that depends on oxidative phosphorylation for its ATP supply, pointing to the mitochondrion as a key player in its energy metabolism. Mitochondrial respiratory complexes I, III₂, and IV occur in supramolecular structures named respirasome. In this work, we characterized the subunit composition and the kinetics of NADH:Q oxidoreductase activity of the digitonine-solubilized respirasome (1600 kDa) and the free-complex I (990 kDa). In the presence of 2,6-dimethoxy-1,4-benzoquinone (DBQ) and cytochrome c, both the respirasome NADH:O₂ and the NADH:DBQ oxidoreductase activities were inhibited by rotenone, antimycin A or cyanide. A value of 2.4 for the NADH oxidized/oxygen reduced ratio was determined for the respirasome activity, while ROS production was less than 0.001% of the oxygen consumption rate. Analysis of the NADH:DBQ oxidoreductase activity showed that respirasome was 3-times more active and showed higher affinity than free-complex I. The results suggest that the contacts between complexes I, III₂ and IV in the respirasome increase the catalytic efficiency of complex I and regulate its activity to prevent ROS production.     

Focal palatine erosion associated with dental malocclusion in captive cheetahs

A severe palatine disorder caused by maloccluded molars was discovered in captive adult cheetahs at the San Diego Wild Animal Park. This defect has been labeled focal palatine erosion (FPE). Subsequently, a total of 59 cheetahs from several institutions have been examined to evaluate the occurrence and etiology of this disorder. Maloccluded lower molars contacting the palatal mucosa appear to be the primary source of irritation. Infection develops when decaying food and grass particles become lodged in the resulting defect. Eventually, complete palatine perforation results which can extend into the nasal passages and eventually lead to systemic disorders. Of 59 cheetahs studied, 15 displayed various stages of FPE. Examination of 26 museum skull specimens revealed four cases of palatine perforation. These four were from a group of eight animals that were zoo raised. Focal palatine erosion appears to be a result of dietary factors. All cheetahs with FPE received a commercially prepared soft diet while in captivity. The lack of normal biting, tearing, and pulling action associated with natural prey capture and consumption could result in malocclusion caused by atrophy from disuse of the masticatory apparatus. Improper occlusion could also stem from insufficient wear or unsynchronized development of the opposing dental arches. All but two cases of FPE were found in cheetahs imported from a limited area in southwest Africa in 1970, or their offspring. Since molar size and jaw structure can be inherited, there may be genetic factors involved but more data are needed to support this idea. Treatment includes changing diet, reducing the height of the offending molar, controlling infection, eliminating irritants, and in some cases, surgical reconstruction.     

Septate junctions between digestive vacuoles in human malacoplakia

Typical septate junctions between digestive vacuoles in phagocytic cells of human malacoplakia are described in this paper. Evidence for a honeycomb pattern of hexagonal subunits is presented for their cleft material. Junctions were not observed between other organelles or in cells other than phagocytes. It is assumed that the septate junctions described here may reflect a pathological change in the organization of the membrane components of digestive organelles.     

GDF11 exhibits tumor suppressive properties in hepatocellular carcinoma cells by restricting clonal expansion and invasion

Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain stemness features, despite some controversies in age-related studies. GDF11 has been poorly investigated in cancer, particularly in those with stemness capacity, such as hepatocellular carcinoma (HCC), one of the most aggressive cancers worldwide. Here, we focused on investigating the effects of GDF11 in liver cancer cells. GDF11 treatment significantly reduced proliferation, colony and spheroid formation in HCC cell lines. Consistently, down-regulation of CDK6, cyclin D1, cyclin A, and concomitant upregulation of p27 was observed after 24 h of treatment. Interestingly, cell viability was unchanged, but cell functionality was compromised. These effects were potentially induced by the expression of E-cadherin and occludin, as well as Snail and N-cadherin repression, in a time-dependent manner. Furthermore, GDF11 treatment for 72 h induced that cells were incapable of sustaining colony and sphere capacity in the absent of GDF11, up to 5 days, indicating that the effect of GDF11 on self-renewal capacity is not transient. Finally, in vivo invasion studies revealed a significant decrease in cell migration of hepatocellular carcinoma cells treated with GDF11 associated to a decreased proliferation judged by Ki67 staining. Data show that exogenous GDF11 displays tumor suppressor properties in HCC cells.     

Phenylethanolamine-N-methyltransferase:alcohol and the mechanism of action

Mixed-solvent systems of methanol and other alcohols and water were used to study the properties of bovine phenylethanolamine-N-methyltransferase. The presence of methanol decreased the binding affinity of the enzyme for its amine substrate but did not alter the maximum velocity. The change in binding was accompanied by an alkaline shift in the pK of an ionizable group in the active site. The well-known property of enzyme inhibition by substrate was also alleviated. Increasing the pH of the medium, in the presence or absence of methanol, increased the maximum velocity but did not alter substrate inhibition. It is proposed that substrate inhibition is due in part to the ionic state of a single unidentified ionizable group in the active site of the enzyme and to a slow release of product. Evidence that an essential, pH-dependent sulfhydryl modulates product release is presented. The properties of phenylethanolamine-N-methyl-transferase are quite responsive to changes in pH, ionic strength, and water content so that the enzyme may well be regulated at the microenvironmental level.