MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways.

BACKGROUND: MicroRNAs (miRNAs) have been shown to play major roles in carcinogenesis in a variety of cancers. The aim of this study was to determine the miRNA expression signature of oral squamous cell carcinoma (OSCC) and to investigate the functional roles of miR-26a and miR-26b in OSCC cells. METHODS: An OSCC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were performed to investigate cell proliferation, migration, and invasion in OSCC cells. In silico database and genome-wide gene expression analyses were performed to identify molecular targets and pathways mediated by miR-26a/b. RESULTS: miR-26a and miR-26b were significantly downregulated in OSCC. Restoration of both miR-26a and miR-26b in cancer cell lines revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our data demonstrated that the novel transmembrane TMEM184B gene was a direct target of miR-26a/b regulation. Silencing of TMEM184B inhibited cancer cell migration and invasion, and regulated the actin cytoskeleton-pathway related genes. CONCLUSIONS: Loss of tumour-suppressive miR-26a/b enhanced cancer cell migration and invasion in OSCC through direct regulation of TMEM184B. Our data describing pathways regulated by tumour-suppressive miR-26a/b provide new insights into the potential mechanisms of OSCC oncogenesis and metastasis.

Identification of tumour suppressive microRNA-451a in hypopharyngeal squamous cell carcinoma based on microRNA expression signature.

BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) has a very poor prognosis because of its high rates of regional and distant metastasis. Identification of differentially expressed miRNAs and their regulated molecular targets in tumour cells might enhance our understanding of the molecular mechanisms of metastasis in human cancers. METHODS: A HSCC miRNA signature was constructed by array-based methods. Functional studies of microRNA-451a (miR-451a) and target genes were performed to investigate cell proliferation, migration and invasion by cancer cell lines. To identify miR-451a-regulated molecular targets, we adopted gene expression analysis and in silico database analysis. RESULTS: Our miRNA signature revealed that miR-451a was significantly downregulated in HSCC. Restoration of miR-451a in cancer cell lines revealed that this miRNA significantly inhibited cancer cell migration and invasion. Our data demonstrated that the gene coding for endothelial and smooth muscle cell-derived neuropilin-like molecule (ESDN/DCBLD2) was a direct target of miR-451a regulation. Silencing of ESDN inhibited cell migration and invasion by cancer cells. CONCLUSIONS: Loss of tumour suppressive miR-451a enhanced cancer cell migration and invasion in HSCC through direct regulation of ESDN. Our miRNA signature and functional analysis of targets regulated by tumour suppressive miR-451a provide new insights into the potential mechanisms of HSCC oncogenesis and metastasis.

[Clinical evaluation of SM-4300 and antibiotics combinations against severe bacterial infections in surgery].

SM-4300, a newly developed human immunoglobulin preparation for intravenous use, has been evaluated clinically in 11 patients with severe bacterial infections in the combination therapy with antibiotics in the surgery. SM-4300 was administered to the patients, for whom antibiotics alone had not been effective, at a dosage of 2.5 or 5 g/day with continuous use of the same antibiotics. The results obtained were as follows: Clinical effects of SM-4300 were excellent in 1 case, good in 2, fair in 4, poor in 3 and unknown in 2. The efficacy rate was summarized as 30.0%, and the rate including fair response was 70.0%. No subjective and objective clinical side effect was observed. No abnormal laboratory finding was observed. Clinical usefulness of SM-4300 were usefulness in 3 cases, fairly usefulness in 2, useless in 3 and unevaluable in 4. The usefulness rate was 37.5%, and the rate including fairly usefulness was 62.5%. In conclusion, combination therapy with SM-4300 and antibiotics was considered to be safe and effective against severe bacterial infections in the surgery.

[Nutritional status of patients with decubitus ulcers, and changes in the skin blood flow when the sacral region was compressed].

We studied the relationship between decubitus ulcers and changes in skin blood flow with respect to the presence or absence of a decompression medium. We also studied the relationship between decubitus ulcers and the results of biochemical tests that reflect nutritional status. Two groups of inpatients with decubitus ulcers in areas other than the sacral region were studied: One used cloth diapers and the other used paper diapers. Skin blood flow was measured with a laser Doppler blood flowmeter and a sheet of polyurethane (decompression medium) in the sacral region. Data were also obtained from patients with and without decubitus ulcers, and whose levels of albumin, total cholesterol, and triglyceride for three months were known. When the decompression medium was used, skin blood flow changed significantly after body position was changed in the patients who used paper diapers. Nutritional analyses showed significant differences in the levels of albumin and total cholesterol between patients with and without decubitus ulcers. The levels of albumin and total cholesterol were lower in the patients with decubitus ulcers than in those without decubitus ulcers. Because the cloth diapers acted as a compression factor, even an externally applied decompression medium did not suppress the reductions in skin blood flow.

[Hemodynamics of the lower extremities in patients with decubitus ulcers using the ultrasonic Doppler method].

Our clinical experience indicates that decubitus ulcers with tissue loss/necrosis extending beyond the subcutaneous fat in aged patients are liable to become refractory and that most of these patients experience a cold feeling/cyanosis in the lower extremities. In order to determine the relationship between the severity of the decubitus ulcers and the hemodynamics in the lower extremities, we conducted a blood flow test using the ultrasonic Doppler method on the lower extremities in patients. Sixty-eight inpatients (38 men, 30 women, with an average age of 80.5 +/- 7.6 years old) were selected. B-mode tomographs were obtained with an ultrasonic diagnostic apparatus. The power Doppler method was used to measure blood flow rate, vascular lumen diameter, and intravascular blood flow at the dorsalis pedis artery, posterior tibial artery, peroneal artery furcation, and femoral artery. The subjects were divided into three groups: patients without decubitus ulcers; patients with mild to moderate decubitus ulcers of IAET Classification grade I-III; and patients with severe decubitus ulcers (IAET Classification grade IV), and the measurements were compared among the groups. The results revealed a tendency for the vascular lumen to become narrowed and intravascular blood flow to be reduced at all sites as decubitus ulcers increased in severity and showed the hemodynamics in the lower extremities to be particularly poor in the severe group. We measured the hemodynamics in the lower extremity with the ultrasonic Doppler method from the viewpoint of decubitus ulcer prevention and found differences in blood flow in the lower extremities according to the severity of decubitus ulcers. A reduction in blood flow in the lower extremities is considered to indirectly indicate a susceptibility to decubitus ulcers and to serve as a sign of its exacerbation. We consequently considered the test to be useful and concluded that deterioration of hemodynamics due to the progress of arteriosclerosis is one of the causes of decubitus ulcer exacerbation.

Computer simulation of parkinsonian tremor.

A computer simulation of tremor using a mathematical model is presented, which integrates the traditional two theories; 'peripheral feedback theory' for physiological tremor and central oscillator theory' for Parkinsonian tremor. The model includes a basic stretch-reflex loop, which is modulated by the central nervous system through the gamma fibres. Fatigue of intrafusal fibres, which results from chronic stimulation by the gamma system, is assumed to be the main cause of Parkinsonian tremor. A computer simulation using the model shows that both physiological tremor and Parkinsonian tremor can be caused by the varying contractivity of the intrafusal fibres.

Effects of mechanical stimulation in measurement of thermal pain threshold.

The improved thermal dolorimeter developed by Fukumoto has made it easy to measure thermal pain thresholds, but mechanical stimulations may be included as the probe is pressed into the skin. In order to evaluate these effects of mechanical stimulation on the improved thermal dolorimeter, the pain threshold temperatures were measured by a probe pressed to the human skin surface with weighting loads from 0.5 to 2.5 kgf. The loads of 2.0-2.5 kgf felt invasive to 8 of the 12 subjects, i.e., they experienced pain and numbness. The threshold temperature of one of these subjects, who developed water blisters around load-added area on the skin after the experiments, exceeded 50 degrees C. The result that no significant difference could be found among the thresholds at the loads of over 2.0 kgf suggests the load of less than 2.0 kgf should be kept to execute proper experiments. In order to investigate other effects on thermal property by compressing, the blood flow was measured when the skin was compressed and three dimensional heat transfer simulations were conducted. The results of the simulations demonstrated that the temperatures of the heat source which were measurable in practice differed approximately 1 to 2 degrees C from the true thresholds. The velocity of heating is also increased and subjects will be given stronger feelings of heating.

Continuous chitosan hydrolyzate production by immobilized chitosanolytic enzyme from Enterobacter sp. G-1.

Chitosanolytic enzymes from Enterobacter sp. G-1 were immobilized on various carriers to continuously hydrolyze chitosan. Four different carriers were tested: FE-3901 (strong basic anion exchange resin, ionic binding), glutaraldehyde-treated FE-4612 (weak basic anion exchange resin, cross-linking), Chitopearl (chitosan beads), and alginate calcium. Glutaraldehyde-treated FE-4612 and Chitopearl immobilized more protein than the others. The enzyme immobilized on FE-3901 had the greatest activity. The activity of enzyme immobilized on FE-3901 decreased rapidly when exposed to a continuous flow of 1% chitosan. The enzyme immobilized with Chitopearl retained more than 50% of its original activity after 17 days, and the activity was fully restored by re-immobilization.

Analysis of pathological tremors using the autoregression model.

The usefulness of analysis of acceleration data using an autoregression model (AR) for differential diagnosis of Parkinson's disease and other diseases with tremors was investigated. The order of the AR model used in this study was 7, in accordance with Akaike's final prediction error criterion. The subjects included 19 patients with Parkinson's disease; 21 patients with essential tremor, which mainly appears in old people, as well as Parkinson's disease; and 13 healthy old people as a control group. The results of analysis of acceleration data showed that the first prediction coefficient, just as the main tremor frequency, was a useful parameter for differentiating patients in the Parkinson's disease patient group and essential tremor patient group. The seventh prediction coefficient was found to be a useful parameter for distinguishing pathological tremors observed in Parkinson's disease and essential tremor disease from physiological tremors observed in healthy people. Although the usefulness of other prediction coefficients for differential diagnosis of Parkinson's disease and other diseases with tremors has not yet been clarified, the results of this study showed that information obtained from AR model parameters in addition to information on main tremor frequency is useful for the diagnosis of Parkinson's disease.

Prepulse effects on the interaction of intense femtosecond laser pulses with high-Z solids

Kalpha emission of high-Z solid targets irradiated by an intense, short (<100 fs) laser pulse in the 10 keV region is shown to be sensitive to the electron energy cutoff, which is strongly dependent on the density gradient of the plasma corona formed by a long prepulse. The absorption rate of short laser pulses, the hot electron distribution, and x-ray emission from a Cu slab target are studied via a hybrid model, which combines the hydrodynamics, collisional particle-in-cell, and Monte Carlo simulation techniques, and via a direct spectroscopic measurement. An absorption mechanism originating from the interaction of the laser pulse with plasma waves is found to increase the absorption rate by over 30% even for a very short, s-polarized laser pulse. Calculated and measured x-ray spectra are in good agreement, confirming the electron energy cutoff.