Inflammatory myofibroblastic tumor of the nasal cavity.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with a variable natural history and biologic behavior, ranging from completely benign to malignant with fatal outcome. We report a case of benign IMT in the left nasal cavity with radiologic features mimicking angiofibroma. We also demonstrate the hypervascular nature of this disease on angiography and the contribution of preoperative embolization in assisting surgical excision and minimizing the potential uncontrolled intraoperative bleeding.

Kinetics of base misinsertion by DNA polymerase I of Escherichia coli.

A simple kinetic analysis of the values of kcat and KM for base insertion and misinsertion during DNA replication is presented and applied to the problem of base misinsertion by DNA polymerase I of Escherichia coli. The role of minor tautomeric forms of deoxynucleoside triphosphates (dNTPs) in purine x pyrimidine mismatching has been examined and it has been shown that the misinsertion frequency via this route should be close to the tautomerization constant in solution and is independent of any effect of the polymerase on the tautomerization of a dNTP when bound. Kinetic data on purine x pyrimidine mismatching indicate that the dNTP in a polymerase-DNA-mismatched-dNTP complex is predominantly in the major tautomeric form. The mutagenic effect of Mn2+ in DNA replication is shown to be mediated by decreasing the values of kcat/KM for the insertion of correct dNTPs, whilst the values of this rate constant for misinsertion are relatively unaffected or increased.

Primary non-Hodgkin's lymphoma of the prostate.

We report the results of treating a patient with stage IIBE primary large B-cell non-Hodgkin's lymphoma of the prostate. Complete remission was achieved following aggressive chemotherapy and consolidation radiotherapy. The patient remains in clinical remission 2 years after presentation.

Evaluation of therapeutic effectiveness of transarterial chemoembolization for hepatocellular carcinoma: correlation of dynamic susceptibility contrast-enhanced echoplanar imaging and hepatic angiography.

The objective of this study was to evaluate the therapeutic effectiveness of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI). Seventeen patients with histopathologically proven HCC were included in this study. All patients underwent MR examinations with conventional T1- and T2-weighted images, gadolinium-enhanced images, and DSC-MRI before TACE treatment. Hepatic blood volume (HBV) maps were reconstructed from the time-intensity curves. The same MRI sequences and techniques were repeated 24 h and 6 weeks after TACE. Serial changes in tumor perfusion on HBV maps were correlated with vascularity in hepatic angiography. All tumors were hypointense on T1-weighted images and hyperintense on T2-weighted images. Heterogeneous enhancement was observed in all tumors before and immediately after TACE. Hyperperfusion was noted in most of the tumors on HBV map before TACE and moderate to marked hypoperfusion following TACE. The degree of tumor perfusion on HBV map correlated well with the vascularity in angiography. In conclusion, the noninvasive nature of DSC-MRI is useful to evaluate the effectiveness of TACE. Invasive procedures, such as angiography, are seldom necessary.

Reaction of the anionic acetylation agent methyl acetyl phosphate with D-3-hydroxybutyrate dehydrogenase.

Methyl acetyl phosphate is a competitive inhibitor of the reduction of acetoacetate by D-3-hydroxybutyrate dehydrogenase. The material also irreversibly inactivates the enzyme. The kinetics of the inactivation are consistent with methyl acetyl phosphate acetylating the conjugate base of a hydrogen bond donor. Protection offered by a substrate analogue (methyl acetonylphosphonate) in the presence of coenzyme implicates reaction at the cationic active site. Reversible protection by the amino group reagent 2,3-dimethylmaleic anhydride suggests that methyl acetyl phosphate reacts with an amino group. Sulfhydryl reagents and acetyl phosphate, a poorer acetylating agent, do not inactivate the enzyme. The pH dependence of the inactivation suggests that the acetylation occurs at a site that has a pKa of 8.2. The utility of methyl acetyl phosphate and other acyl phosphate monoesters in reacting with lysines adjacent to cationic sites of enzymes, hemoglobin, and histones is noted.

Inhibition of bacterial D-3-hydroxybutyrate dehydrogenase by substrates and substrate analogues.

D-3-Hydroxybutyrate dehydrogenase (Pseudomonas lemoignei, EC 1.1.1.30) is subject to substrate inhibition by acetoacetate at concentrations above 5 mM but not by D-3-hydroxybutyrate at concentrations up to 50 mM. NADH causes substrate inhibition at concentrations over 0.1 mM as does NAD. Kinetic analysis suggests that substrate inhibition by acetoacetate is due to its binding to enzyme lacking NADH, a consequence of the ordered bibi mechanism. Substrate inhibition by NADH and NAD arises from binding of these species to a secondary site. This is confirmed by kinetics which indicate that ADP and ATP compete with NAD and NADH at both sites. New analogues of acetoacetate were synthesized to test the specificity requirements of the acetoacetate binding site which has been proposed to contain a hydrogen bond donor and a cation spaced to receive acetoacetate. Both dimethoxyphosphinylacetate and methyl 2-methoxy-phosphinylacetate fulfill the structural requirements and are effective. They thus join methyl acetonylphosphonate as the only known competitive inhibitors for the acetoacetate site, confirming the proposed structure.

Amino group reactions of the sulfhydryl reagent methyl methanesulfonothioate. Inactivation of D-3-hydroxybutyrate dehydrogenase and reaction with amines in water.

Methyl methanesulfonothioate (MMTS) has been used as a sulfhydryl reagent. However, it inactivates D-3-hydroxybutyrate dehydrogenase in a manner that suggests that an amino group may have reacted with the reagent. Nuclear magnetic resonance (NMR) analysis of solutions of glycylglycine, glycine ethyl ester, and imidazole with MMTS indicates that a reaction occurs which produces what is identified by its NMR signal as the methylsulfenamide of the amine. It is suggested that caution should be used when MMTS is employed where reaction with an amine could give an undesired product.

Probing the principles of amino acid selection using the alanyl-tRNA synthetase from Escherichia coli.

The alanyl-tRNA synthetase from Escherichia coli activates cysteine, alpha-aminobutyrate and other-noncognate amino acids that are larger than alanine so slowly that no editing mechanism is required for error correction. Serine, however, is activated sufficiently rapidly that an editing mechanism is required to remove the products of misactivation. The distinction between the nominally isosteric trio of cysteine, alpha-aminobutyrate and serine by the activation site of the enzyme is attributed to the effect of small differences in size on steric repulsion, the C-O bond length being somewhat shorter than either the C-C or C-S and the van der Waals' radius of -O- being smaller than that of -S- or -CH2-. The smaller amino acid glycine is also readily activated and its reaction products rapidly removed by hydrolytic editing.

Probing the limits of protein-amino acid side chain recognition with the aminoacyl-tRNA synthetases. Discrimination against phenylalanine by tyrosyl-tRNA synthetases.

The specificity of the tyrosyl-tRNA synthetases from Escherichia coli and bacillus stearothermophilus for tyrosine compared with phenylalanine has been determined by using samples of phenylalanine which have been scrupulously freed from tyrosine by either chemical or enzymic scavenging procedures. Both kinetic measurements and product analyses give a value of 1 x 10(5)-2 x 10(5) for the preferential activation of tyrosine. Combined with the known ratio of phenylalanine to tyrosine in rapidly growing E. coli, an error rate of about approximately 5/10(4) is calculated for the misactivation of phenylalanine. Since we find no evidence for an editing mechanism and this error rate is similar to observed rates in protein synthesis, the tyrosyl-tRNA synthetases appear to have adequate amino acid selection by simple preferential binding of the correct substrate. The incremental binding energy of the phenolic hydroxyl group of tyrosine is approximately 7 kcal/mol, a value presumed close to the maximum possible because of the evolutionary pressure on tyrosyl-tRNA synthetases for maximum specificity. A summary of high incremental binding energies determined from experiments on aminoacyl-tRNA synthetase is presented.

Breath-hold 3D gadolinium-enhanced subtraction MRA in the detection of transplant renal artery stenosis.

AIMS: The purpose of this study was to assess the value of breath-hold 3D gadolinium-enhanced subtraction magnetic resonance angiography (GD-MRA) in the detection of transplant renal artery stenosis (TRAS). PATIENTS AND METHODS: Seven patients with suspected post-transplant renal artery stenosis were studied. GD-MRA was performed at 1.5T with a 3D fast spoiled gradient recalled echo (FSPGR) pulse sequence. Before injection of contrast medium, the 3D pulse sequence was performed to obtain a set of non-contrast images for subtraction purposes. Dynamic 3D imaging was performed simultaneously with the bolus injection of 40 ml of gadopentetate dimeglumine. Angiographic images were reconstructed using the Advantage Window workstation (version 2.0 GE Medical Systems) and subtraction was made with the pre-contrast image data. Any signal intensity cut-off or narrowing of more than 50% was regarded as significant stenosis. Ultrasound Doppler (USD) study was performed with both colour and spectral studies. Peak systolic velocity (PSV) of greater than 2.0 m/s and acceleration time (AT) greater than 120ms was regarded as positive for TRAS. These were then compared with the digital subtraction angiography (DSA) as the gold standard. RESULTS: A total of nine examinations performed in seven patients were included in the analysis. MRA correlated with the DSA findings in eight examinations, with one false negative. USG correlated with DSA in six examinations, with two false negative and one false positive case. CONCLUSION: In our opinion, GD-MRA is a promising and non-invasive technique in the detection of TRAS.