The binding of substrates and inhibitors to the metal center of myoinositol monophosphatase

The synthetic substrate anthraniloyl-beta-glycerol-P binds to myoinositol monophosphatase with a Kd = 5 microM at pH 7.5. The anthraniloyl chromophore, excited at 330 nm, sensitizes the long lived luminescence of bound Tb(III) at 490, 545, 585 and 620 nm. Assuming a mechanism of radiationless energy transfer, the actual distance of separation between the donor-acceptor pair was calculated to be R = 10 A. Tb(III) binds to the monophosphatase with a Kd = 2 microM, whereas Ca-(II) displaces the lanthanide at concentrations above 0.1 mM. The binding studies support the notion that Tb(III), Ca(II) and Mg(II) interact with a common binding site on the protein. Phosphate ion, a strong competitive inhibitor, perturbs the luminescence of bound Tb(III), whereas the substrate beta-glycero-P has no effect on the luminescence yield and long-lived emission of bound Tb(III). It is suggested that the phosphate group of the substrate is not in direct contact with the metal ion coordinated to several amino acid residues of the enzyme.     

Treatment of radiation-induced nervous system injury with heparin and warfarin

When radiation is used to treat nervous system cancer, exposure of adjacent normal nervous system tissue is unavoidable, and radiation-induced injury may occur. Acute injury is usually mild and transient, but late forms of radiation-induced nervous system injury are usually progressive and debilitating. Treatment with corticosteroids, surgery, and antioxidants is often ineffective. We treated 11 patients with late radiation-induced nervous system injuries (eight with cerebral radionecrosis, one with a myelopathy, and two with plexopathies, all unresponsive to dexamethasone and prednisone) with full anticoagulation. Some recovery of function occurred in five of the eight patients with cerebral radionecrosis, and all the patients with myelopathy or plexopathy. Anticoagulation was continued for 3 to 6 months. In one patient with cerebral radionecrosis, symptoms recurred after discontinuation of anticoagulation and disappeared again after reinstitution of treatment. We hypothesize that anticoagulation may arrest and reverse small-vessel endothelial injury--the fundamental lesion of radiation necrosis--and produce clinical improvement in some patients.     

Development of the bi-directional ultrasound system for base of tongue imaging

The use of conventional ultrasound systems to image the upper airway has been limited because ultrasound energy is attenuated by the air column. In an attempt to study upper airway geometry, we developed a computer controlled bi-directional ultrasound system which combines two conventional ultrasound devices with computer image processing to yield images of upper airway structures. Human studies and cadaver studies were performed to evaluate the system. Images acquired by the bi-directional ultrasound system were comparable to images from 3D volume rendered CT scans. This system may provide valuable data in the study of upper airway physiology and pathology.     

Concentration-response relationships for adenosine agonists during preconditioning of rabbit cardiomyocytes

Although adenosine receptors have been implicated in the induction of preconditioning in a variety of experimental models, there is controversy concerning the specific adenosine receptor subtypes mediating this effect. Concentration-protection relationships for adenosine and adenosine agonists in rabbit cardiomyocytes were used to characterize the role of adenosine receptor subtypes in preconditioning. Isolated cells were ischemically preconditioned or pre-incubated for 10 min with increasing concentrations of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), APNEA (N6-2-(4-aminophenyl)ethyladenosine), or BNECA (N6-benzyl-5'-N-ethyl-carboxamidoadenosine) in the presence or absence of 1 or 10 microM of the selective A1-adenosine antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine). Following a 30-min post-incubation period, cells were pelleted, layered with oil and ischemically incubated for 180 min. Injury was assessed by osmotic swelling and trypan blue exclusion of sequential samples, and determination of the areas beneath the mortality curves. Adenosine produced a broad concentration-protection curve which was displaced to the right by DPCPX. The curve for A1-selective agonist CCPA was biphasic, with an initial response below 1 nM and a second above 1 microM. DPCPX abolished the early response leaving a steep monophasic curve between 0.1 and 10 microM CCPA. The APNEA curve appeared moriophasic, the major slope occurring between 1-100 nM; DPCPX (1 microM) shifted the concentration-response curve approximately 30-fold and decreased the slope. Adenosine receptor agonist BNECA produced preconditioning characterized by a shallow monophasic concentration-protection curve with a maximal effect of 49% and an EC50 of approximately 5 nM; DPCPX shifted the BNECA concentration-protection relationship approximately 40-fold with only a modest increase in slope. Analysis of the data suggests that induction of preconditioning results from interaction of agonists with the A1 receptor and a second adenosine receptor having properties consistent with the A3 receptor. Adenosine, CCPA, APNEA, BNECA and DPCPX each appear to be selective for the A1 adenosine receptor subtype in isolated rabbit cardiomyocytes.     

Priapism: etiology and management

Priapism is a urologic emergency. All patients should receive prompt urologic consultation. Management is based on prompt recognition, differentiation between low- and high-flow priapism, reversal of any potential precipitating factors, and the use of corporal aspiration/irrigation combined with intracavernosal alpha-agonist injection therapy. It cannot be over-emphasized that severely prolonged erections are associated with the development of irreversible problems with erectile function and, therefore, immediate and aggressive management is mandatory.     

Image compression in digital mammography: effects on computerized detection of subtle microcalcifications

Our previous receiver operating characteristic (ROC) study indicated that the detection accuracy of microcalcifications by radiologists is significantly reduced if mammograms are digitized at 0.1 mm x 0.1 mm. Our recent study also showed that detection accuracy by computer decreases as the pixel size increases from 0.035 mm x 0.035 mm. It is evident that very large matrix sizes have to be used for digitizing mammograms in order to preserve the information in the image. Efficient compression techniques will be needed to facilitate communication and archiving of digital mammograms. In this study, we evaluated two compression techniques: full frame discrete cosine transform (DCT) with entropy coding and Laplacian pyramid hierarchical coding (LPHC). The dependence of their efficiency on the compression parameters was investigated. The techniques were compared in terms of the trade-off between the bit rate and the detection accuracy of subtle microcalcifications by an automated detection algorithm. The mean-square errors in the reconstructed images were determined and the visual quality of the error images was examined. It was found that with the LPHC method, the highest compression ratio achieved without a significant degradation in the detectability was 3.6:1. The full frame DCT method with entropy coding provided a higher compression efficiency of 9.6:1 at comparable detection accuracy. The mean-square errors did not correlate with the detection accuracy of the microcalcifications. This study demonstrated the importance of determining the quality of the decompressed images by the specific requirements of the task for which the decompressed images are to be used. Further investigation is needed for selection of optimal compression technique for digital mammograms.     

The cholesterol-lowering properties of a psyllium-based breakfast cereal in hamsters

Hamsters were fed high fiber diets containing cellulose, wheat bran or psyllium. The psyllium was incorporated into high fiber, ready-to-eat (RTE) flakes that were used to formulate the test diet. All the diets contained 0.125% cholesterol. The study was terminated after three weeks. Food intake, weight gain and feed efficiency were not significantly different in the three groups. Serum total and HDL cholesterol levels were reduced significantly by the psyllium diet. Serum triglycerides were 26% lower in the hamsters fed psyllium but because of the large variation the difference did not reach statistical significance. Liver total cholesterol and cholesteryl ester levels were significantly lower in the hamsters fed psyllium. Liver triglycerides were highest in the psyllium-fed hamsters and liver phospholipid levels were similar in the three groups. Liver cholesterol and triglyceride levels were higher in hamsters fed cellulose than in those fed wheat bran. Psyllium formulated into an RTE cereal was effective in reducing serum and liver cholesterol levels in hamsters.     

Clinical and historical predictors of dental caries on radiographs

Jet injection can be used to introduce genes into the cells of differentiated tissues of living animals and organ cultures. When a solution of plasmid DNA is jet injected into a selected tissue or organ, cells lying in or near the path of the jet injection are transfected with the DNA and the introduced gene(s) are expressed. Since there is minimal morbidity from each jet injection, multiple injections can be performed at the same or nearby sites. Both mRNA and protein expression from transfected genes can be quantitated using standard methods. In addition, the technique is an efficient means of DNA immunization. Methodology for using jet injection to transfer plasmid DNA into the cells of skin, fat, mammary gland, and muscle are described.