Isolation of enteroaggregative escherichia coli (EAggEC) from patients with diarrheal disease in an outbreak case of overseas tour

Twenty four patients out of 78 Cambodia tourists (31%) suffered from diarrhea and/or abdominal pain. Though the stools of 20 patients were examined in some local health centers and institutes, well-known pathogens were detected in only a low level and the cause of the outbreak remained unclear. We suspected the enteroaggregative Escherichia coli (EAggEC) as a cause of this outbreak. We examined E. coli strains isolated from stools of 8 patients (Okayama:7, Aichi:1) at first by the PCR method targeted both the aggR and the astA genes related to the virulence factors of EAggEC. As a result, the E. coli strains with positive aggR and/or astA genes were isolated from 8 patients. And the E. coli strains with positive both aggR gene and clump formation isolated from 3 patients adhered aggregatively to HEp-2 cells and accordingly identified as EAggEC. The plasmid profiles, PFGE patterns and drug resistance patterns of these EAggECs agreed completely. From these results, we concluded that at least 3 patients were infected with EAggEC of the same origin. Though we could not examine all samples from 20 patients, it is possible that the still uncommon EAggEC might be a cause of the outbreak. The E. coli strains with positive aggR gene did not always aggregatively adhered to HEp-2 cells. So we recommend to perform stepwise EAggEC screening tests by the PCR and the clump formation, and final confirmation test by the aggregative adhesion to HEp-2 cells.     

Upper gastrointestinal bleeding arising from metastatic testicular tumor

We report a young man with a testicular tumor in whom the first symptom was upper gastrointestinal bleeding. This was caused by invasion of the duodenum by a metastatic lesion in a retroperitoneal lymph node. Metastatic testicular tumor is a rare cause of upper gastrointesinal bleeding. Diagnosis was difficult because the primary lesion could not be found initially. In young men with upper gastrointestinal bleeding, the possibility of metastatic testicular tumor should be investigated.     

I. Excretory products of the sterol biosynthetic pathway in the MER-29-treated rat II. Excretion of MER-29

MER-29 was previously shown to inhibit cholesterol biosynthesis at a stage in the biosynthetic pathway following the formation of the sterol nucleus. Theoretically, this action could cause the accumulation of sterol precursors of cholesterol, while reducing the level of cholesterol itself in animal tissues.

Under conditions of-almost complete inhibition of cholesterol biosynthesis in the rat, both cholesterol and total unsaponifiable matter are reduced in plasma; in liver, lung and spleen, cholesterol is reduced, and unsaponifiable matter is either unchanged or reduced slightly. Overall, therefore, cholesterol precursors do not appear to accumulate in sufficient quantity to make up the cholesterol deficit entirely.

The fate of the precursors was determined by following the fecal excretion of radioactivity derived from labelled mevalonic acid in MER-29-treated rats. These rats, like controls, excreted the label in the fecal bile acids and unsaponifiable matter, indicating the fate of the cholesterol precursors. There was an increased turnover of the sterol pathway in the MER-29-treated animals, reflecting reduced pool of labelled intermediates. A slightly greater fraction of the excreted radioactivity appeared in the bile acid fraction in the MER-29 rats, indicating that the sterols occurring immediately before the site of inhibition may be more readily converted to bile acids than is cholesterol.

The excretion of MER-29 was followed after oral administration of the drug labelled in a central position with carbon-14. The principal route of excretion is in the feces, which accounted for 30 per cent of the administered dose in 48 hours; 7 per cent occurred in urine. The material excreted in urine was not unchanged drug. In bile fistula rats, 23 per cent of an oral dose of MER-29 was excreted in the bile in 24 hours.     

Histopathological incidence of facial canal dehiscence in otosclerosis

The objective of this study was to evaluate the histopathological incidence of facial canal dehiscence in otosclerosis cases compared with non-otosclerotic controls. 133 temporal bones from 84 otosclerosis (35 unilateral otosclerosis, 49 bilateral otosclerosis) cases were compared to 102 age-matched normal temporal bones from 70 subjects (38 unilateral normal cases, 32 bilateral normal cases). Temporal bones were serially sectioned in the horizontal plane at a thickness of 20 μm, and were stained with hematoxylin and eosin. We evaluated the location and the invasion of otosclerosis to the facial canal and incidence of facial canal dehiscence under light microscopy. Facial canal was subdivided into four portions: (1) the geniculate ganglion, (2) the tensor tympani muscle, (3) the oval window, and (4) mastoid. The incidence of facial canal dehiscence in otosclerosis [66 temporal bones (49.6%)] was significantly lower than normal controls [67 control temporal bones (65.7%)] in the oval window area (P = 0.019). Temporal bones with otosclerotic invasion to the thin bone of the canal were significantly less likely to have dehiscence [10 temporal bones (31.3%)] compared to the otosclerotic bones without invasion [56 temporal bones (55.5%)] (P = 0.025). There was no significant difference in the incidence of facial canal dehiscence between temporal bones with and without otosclerosis in the entire segment of facial nerve. Our findings in this study suggest that otosclerotic lesions have the potential to close dehiscence of the facial canal in the oval window area.     

Adenocarcinoma of the uterine cervix with choriocarcinomatous and hepatoid differentiation: report of a case.

A case of adenocarcinoma of the uterine cervix that showed choriocarcinomatous and hepatoid differentiation was encountered in a 65-year-old woman. She presented with genital bleeding and had multiple metastatic nodules in the lungs. At operation, a large, hemorrhagic, and necrotic tumor was found in the uterine cervix. The major portion of the tumor consisted of typical choriocarcinoma admixed with minor areas of hepatoid carcinoma and endocervical adenocarcinoma. Human chorionic gonadotropin and alpha-fetoprotein were detected in tumor cells in the choriocarcinomatous and hepatoid areas, respectively. The patient died of pulmonary metastasis 4 months after the operation. The coexistence of choriocarcinomatous and hepatoid carcinoma in an endocervical adenocarcinoma has not been reported previously. Both heterotopic components were probably derived from aberrant differentiation (or neometaplasia) of the somatic epithelial cells of the endocervical adenocarcinoma.     

The neuroprotective factor Wld fails to mitigate distal axonal and neuromuscular junction (NMJ) defects in mouse models of spinal muscular atrophy

Spinal muscular atrophy (SMA) is a common autosomal recessive neurodegenerative disorder in humans. Amongst the earliest signs of neurodegeneration are severe and progressive defects of the neuromuscular synapse. These defects, characterized by poor terminal arborization and immature motor endplates, presumably result in a loss of functional synapses. The slow Wallerian degeneration (Wld^s) mutation in rodents has been shown to have a protective effect on mouse models of motor neuron disease by retarding axonal die-back and preventing neuromuscular synapse loss. In this study we tested the effects of the Wld^s mutation on the disease phenotype of SMA model mice. Consistent with previous reports, the mutation slows axon and neuromuscular synapse loss following nerve injury in wild-type as well as in SMA mice. However, the synaptic defects found in severely affected SMA patients and model mice persist in the double (Wld^s;SMA) mutants. No delay in disease onset was observed and survival was not significantly altered. Finally, Wld^s had no effect on the striking phrenic nerve projection defects that we discovered in SMA model mice. Our results indicate that the reported protective effects of Wld^s are insufficient to mitigate the neuromuscular phenotype due to reduced SMN protein, and that the mechanisms responsible for distal defects of the motor unit in SMA are unlikely to be similar to those causing neurodegeneration in genetic mutants such as the pmn mouse which is partially rescued by the Wld^s protein.     

The combination of silencing BAG3 and inhibition of the JNK pathway enhances hyperthermia sensitivity in human oral squamous cell carcinoma cells

Hyperthermia (HT) is a widely used physical treatment for various cancers, but its effect is often insufficient because of cytoprotective effects of heat shock proteins. BAG3, a co-chaperone of the heat shock protein 70, is a stress-inducible protein and demonstrates a cytoprotective property against various stresses, including heat stress. Here, we examined the effects of silencing the BAG3 on the sensitivity to HT in human oral squamous cell carcinoma (OSCC) HSC-3 cells. HT (44 °C, 90 min) was significantly increased in apoptotic cells concomitant with the activations of caspase-3 and c-Jun N-terminal kinase (JNK) pathway. Furthermore, the sensitivity to HT was remarkably enhanced in BAG3-downregulated HSC-3 cells. Interestingly, the effects of this combination treatment were significantly enhanced in the cells pretreated with a JNK inhibitor, SP600125. These findings indicated that the disruption of functions of both BAG3 and the JNK pathway may become an option in HT therapy in OSCC cells.