Mycobacterium kansasii osteomyelitis in a patient with AIDS on highly active antiretroviral therapy.

Skeletal infections with atypical mycobacteria are usually a manifestation of advanced HIV disease with most patients having CD4 counts of less than 100 cells/mm3. We report a case of Mycobacterium kansasii vertebral osteomyelitis on highly active antiretroviral therapy with a CD4 count of 320 cells/mm3 and viral load below the level of detection at the onset.

Interactions between αCaMKII and calmodulin in living cells: conformational changes arising from CaM-dependent and -independent relationships.

BACKGROUND: αCaMKII plays central and essential roles in long-term potentiation (LTP), learning and memory. αCaMKII is activated via binding with Ca²âº/CaM in response to elevated Ca²âº concentration. Furthermore, prolonged increase in Ca²âº concentration leads to the auto-phosphorylation of αCaMKII at T286, maintaining the activation of αCaMKII even after Ca²âº/CaM dissociation. Importantly, the active form of αCaMKII is thought to exhibit conformational change. In order to elucidate the relationships between the interaction of αCaMKII with CaM and the conformational change of αCaMKII, we generated molecular probes (YFP-αCaMKII with CFP-CaM and YFP-αCaMKII-CFP) and performed time-lapse imaging of the interaction with CaM and the conformational change, respectively, in living cells using FRET. RESULTS: The interaction of YFP-αCaMKII with CFP-CaM and the conformational change of YFP-αCaMKII-CFP were induced simultaneously in response to increased concentrations of Ca²âº. Consistent with previous predictions, high levels of Ca²âº signaling maintained the conformational change of YFP-αCaMKII-CFP at the time when CFP-CaM was released from YFP-αCaMKII. These observations indicated the transfer of αCaMKII conformational change from CaM-dependence to CaM-independence. Furthermore, analyses using αCaMKII mutants showed that phosphorylation at T286 and T305/306 played positive and negative roles, respectively, during in vivo interaction with CaM and further suggested that CaM-dependent and CaM-independent conformational changed forms displays similar but distinct structures. CONCLUSIONS: Importantly, these structual differences between CaM-dependent and -independent forms of αCaMKII may exhibit differential functions for αCaMKII, such as interactions with other molecules required for LTP and memory. Our molecular probes could thus be used to identify therapeutic targets for cognitive disorders that are associated with the misregulation of αCaMKII.

Solution structure of the peptidoglycan binding domain of Bacillus subtilis cell wall lytic enzyme CwlC: characterization of the sporulation-related repeats by NMR.

Bacillus subtilis CwlC is a cell wall lytic N-acetylmuramoyl-l-alanine amidase that plays an important role in mother-cell lysis during sporulation. The enzyme consists of an N-terminal catalytic domain with C-terminal tandem repeats. The repeats [repeat 1 (residues 184-219) and repeat 2 (residues 220-255)] are termed CwlCr. We report on the solution structure of CwlCr as determined by multidimensional NMR, including the use of 36 (h3)J(NC)'-derived hydrogen bond restraints and 64 residual (1)D(NH) dipolar couplings. Two tandem repeats fold into a pseudo-2-fold symmetric single-domain structure consisting of a betaalphabetabetaalphabeta-fold containing numerous contacts between the repeats. Hydrophobic residues important for structural integrity are conserved between the repeats, and are located symmetrically. We also present NMR analysis of the circularly permuted repeat mutant of CwlCr. Secondary structure content from the chemical shifts and hydrogen bonds derived from (h3)J(NC)' show that the mutant folds into a structure similar to that of the wild type, suggesting that the repeats are exchangeable. This implies that conserved hydrophobic residues are crucial for maintaining the folding of the repeats. While monitoring the chemical shift perturbations following the addition of digested soluble peptidoglycan fragments, we identified two peptidoglycan interaction sites of CwlCr at the edges of the protein symmetrically, and they are located approximately 28 A from each other.

[Fulminant myocarditis successfully treated with a left ventricular assist device: a case report].

A previously healthy 28-year-old woman was admitted under a diagnosis of acute myocarditis. Six hours after admission, circulatory support using intraaortic balloon pumping and percutaneous cardiopulmonary support were introduced, because uncontrollable ventricular arrhythmia appeared unexpectedly. Subsequently, decreased peripheral platelet count appeared, in spite of improved hemodynamics. Therefore, a left ventricular assist device was implanted and she was weaned from the percutaneous cardiopulmonary support. On the fifth postoperative day, she was successfully weaned from the left ventricular assist device with full recovery of myocardial function. Myocardial biopsy demonstrated the appearance of acute viral myocarditis. This case suggests that the left ventricular assist device might offer effective circulatory support for acute fulminant myocarditis.

Synthesis, structure, and magnetic properties of the fullerene-based ferromagnets Eu3C70 and Eu9C70.

Intercalation of C(70) with europium affords two kinds of magnetic compounds, a canted antiferromagnet Eu(x)C(70) (x approximately 3) and a ferromagnet Eu(x)C(70) (x approximately 9) with transition temperatures (T(C)) of 5 and 38 K, respectively. The Curie constants in the paramagnetic phase and the saturation moment in the ferromagnetic phase are both understood by the full moment of Eu(2+) for both systems. The structure of Eu(3)(-)(delta)C(70) (delta approximately 0.27) is pseudo-monoclinic, derived by a simple deformation of the parent face-centered cubic (fcc) structure. Eu(9)(-)(delta)C(70) (delta approximately 0.2) forms an fcc structure, in which cuboctahedral clustering of Eu(2+) ions is observed in the enhanced size octahedral holes. The observed T(C) of the Eu(9)(-)(delta)C(70) ferromagnet is comparable to or larger than those of simple binary Eu-based ferromagnets, such as Eu chalcogenides or carbides, despite the low atomic ratio of Eu in the chemical formulas. This can be understood by the short Eu(2+)-Eu(2+) distances and high coordination numbers permitted by the multiple occupation by Eu(2+) ions of the expanded octahedral interstitial sites in higher fullerene-based solids.

1H-Imidazo[4,5-c]quinoline derivatives as novel potent TNF-alpha suppressors: synthesis and structure-activity relationship of 1-, 2-and 4-substituted 1H-imidazo[4,5-c]quinolines or 1H-imidazo[4,5-c]pyridines.

Structural modification of imiquimod (1), which is known as an interferon-alpha (IFN-alpha) inducer, for the aim of finding a novel and small-molecule tumor necrosis factor-alpha (TNF-alpha) suppressor and structure-activity relationship (SAR) are described. Structural modification of a imiquimod analogue, 4-amino-1-[2-(1-benzyl-4-piperidyl)ethyl-1H-imidazo[4,5-c]quinoline (2), which had moderate TNF-alpha suppressing activity without IFN-alpha inducing activity, led to a finding of 4-chloro-2-phenyl-1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline (10) with potent TNF-alpha suppressing activity. The relation between conformational direction of 2-(4-piperidyl)ethyl group at position 1 and TNF-alpha suppressing activity is also demonstrated by NMR.

[Post-myocardial infarction ventricular aneurysm and intractable ventricular tachycardia supported by left ventricular assist device: a case report].

A 57-year-old man was admitted under a diagnosis of myocardial infarction. Cardiac catheterization revealed total occlusions of the right coronary artery and the left anterior descending artery, and ventriculography showed aneurysmal change in the anterior and septal segments. Circulatory support was introduced with intraaortic balloon pumping, but intractable ventricular tachycardia developed. Electrophysiological mapping and cryoablation to the myocardium were performed intraoperatively, and then coronary artery bypass grafting with endoventricular circular patch plasty of the left ventricle was carried out. Weaning from the cardiopulmonary bypass was attempted, but a left ventricular assist device was subsequently implanted to support the deteriorated ventricular function. The hemodynamics of the ventricle improved several days after the circulatory support was introduced, and the left ventricular assist device was removed successfully. This case suggests that the left ventricular assist device is an effective method to support recovery from serious complications after myocardial infarction.

Enhancement of J-ST-segment elevation by the glucose and insulin test in Brugada syndrome.

The effects of glucose and insulin on J-ST-segment elevation were evaluated in seven men (mean age 45 +/- 10 years) with Brugada syndrome. Six patients had been reanimated from VF and one patient had experienced syncope. The effects of intavenous (1) pilsicainide 50 mg, (2) glucose 50 g, and (3) glucose 50 g plus regular insulin 10 IU on the precordial ECG leads were examined. Pilsicainide significantly enhanced J-ST elevation in all patients and induced VF in 1 patient. A significant accentuation of the abnormal J-ST configuration was observed in all patients at a mean of 51 +/- 40 minutes after glucose and insulin infusion. Changes in blood glucose and serum potassium concentration were 111 +/- 158 mg/dL and -0.30 +/- 0.48 mEq/L, respectively. These changes were not directly related to the ECG changes. Glucose infusion without insulin caused a subtle increase in J-ST elevation. In conclusion, the administration of glucose and insulin safely unmasked or accentuation the J-ST-segment elevation in Brugada syndrome. Blood glucose and insulin concentrations may be factors modulating the circadian or day-to-day ECG variations in this syndrome.