A3-A3 anastomosis and superficial temporal artery-radial artery graft-A3 bypass to treat bilateral ACA steno-occlusive hemodynamic ischemia with cognitive and executive dysfunction: a technical note

Background

Executive functions are complex cognitive control functions that include cognitive flexibility, inhibition (self-control, self-regulation), and working memory. Bilateral frontal lobe ischemia is associated with cognitive impairment, especially in the context of dysexecutive syndrome. This report describes two patients who underwent bilateral anterior cerebral artery (ACA) reconstruction by A3-A3 anastomosis in conjunction with superficial temporal artery (STA)-radial artery (RA) graft-A3 bypass to treat bilateral ACA steno-occlusive hemodynamic ischemia accompanying cognitive and executive dysfunction.

Method

A 74-year-old woman and a 73-year-old woman were admitted to our hospital for unilateral cerebral infarction in the frontal lobe. Magnetic resonance angiogram (MRA) demonstrated severe bilateral ACA steno-occlusive pathology in both patients. Considering the presence of impaired cognitive function with dysexecutive syndrome as well as hemodynamic compromise shown by single photon emission computed tomography (SPECT), we proceeded with A3-A3 anastomosis in conjunction with STA-RA-A3 bypass. Various neuropsychiatric tests were performed before and after the surgery.

Results

We confirmed good bypass patency without periprocedural complications. One patient recovered from apallic and bedridden status and regained ambulatory condition and ability to take in an oral diet. Another patient demonstrated improved scores in several cognitive tests with some persistent executive dysfunction.

Conclusions

Bilateral ACA revascularization was technically feasible in two patients. This bypass surgery could have some positive effects in some basic cognitive function, such as memory, attention, and concentration by bilateral ACA hemodynamic improvement, although executive function, which is specific to prefrontal function, might not be reversible.     

Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c

To identify lipids with roles in tuberculosis disease, we systematically compared the lipid content of virulent Mycobacterium tuberculosis with the attenuated vaccine strain Mycobacterium bovis bacillus Calmette–Guérin. Comparative lipidomics analysis identified more than 1,000 molecular differences, including a previously unknown, Mycobacterium tuberculosis-specific lipid that is composed of a diterpene unit linked to adenosine. We established the complete structure of the natural product as 1-tuberculosinyladenosine (1-TbAd) using mass spectrometry and NMR spectroscopy. A screen for 1-TbAd mutants, complementation studies, and gene transfer identified Rv3378c as necessary for 1-TbAd biosynthesis. Whereas Rv3378c was previously thought to function as a phosphatase, these studies establish its role as a tuberculosinyl transferase and suggest a revised biosynthetic pathway for the sequential action of Rv3377c-Rv3378c. In agreement with this model, recombinant Rv3378c protein produced 1-TbAd, and its crystal structure revealed a cis-prenyl transferase fold with hydrophobic residues for isoprenoid binding and a second binding pocket suitable for the nucleoside substrate. The dual-substrate pocket distinguishes Rv3378c from classical cis-prenyl transferases, providing a unique model for the prenylation of diverse metabolites. Terpene nucleosides are rare in nature, and 1-TbAd is known only in Mycobacterium tuberculosis. Thus, this intersection of nucleoside and terpene pathways likely arose late in the evolution of the Mycobacterium tuberculosis complex; 1-TbAd serves as an abundant chemical marker of Mycobacterium tuberculosis, and the extracellular export of this amphipathic molecule likely accounts for the known virulence-promoting effects of the Rv3378c enzyme.With a mortality rate exceeding 1.5 million deaths annually, Mycobacterium tuberculosis remains one of the world''s most important pathogens (1). M. tuberculosis succeeds as a pathogen because of productive infection of the endosomal network of phagocytes. Its residence within the phagosome protects it from immune responses during its decades long infection cycle. However, intracellular survival depends on active inhibition of pH-dependent killing mechanisms, which occurs for M. tuberculosis but not species with low disease-causing potential (2). Intracellular survival is also enhanced by an unusually hydrophobic and multilayered protective cell envelope. Despite study of this pathogen for more than a century, the spectrum of natural lipids within M. tuberculosis membranes is not yet fully defined. For example, the products of many genes annotated as lipid synthases remain unknown (3), and mass spectrometry detects hundreds of ions that do not correspond to known lipids in the MycoMass and LipidDB databases (4, 5).To broadly compare the lipid profiles of virulent and avirulent mycobacteria, we took advantage of a recently validated metabolomics platform (4). This high performance liquid chromatography–mass spectrometry (HPLC-MS) system uses methods of extraction, chromatography, and databases that are specialized for mycobacteria. After extraction of total bacterial lipids into organic solvents, HPLC-MS enables massively parallel detection of thousands of ions corresponding to diverse lipids that range from apolar polyketides to polar phosphoglycolipids. Software-based (XCMS) ion finding algorithms report reproducibly detected ions as molecular features. Each feature is a 3D data point with linked mass, retention time, and intensity values from one detected molecule or isotope. All features with equivalent mass and retention time from two bacterial lipid extracts are aligned, allowing pairwise comparisons of MS signal intensity to enumerate molecules that are overproduced in one strain with a false-positive rate below 1% (4).This comparative lipidomics system allowed an unbiased, organism-wide analysis of lipids from M. tuberculosis and the attenuated vaccine strain, Mycobacterium bovis Bacillus Calmette–Guérin (BCG). BCG was chosen because of its worldwide use as a vaccine and its genetic similarity to M. tuberculosis (6). We reasoned that any features that are specifically detected in M. tuberculosis might be clinically useful as markers to distinguish tuberculosis-causing bacteria from vaccines. Furthermore, given the differing potential for productive infection by the two strains, any M. tuberculosis-specific compounds would be candidate virulence factors. Comparative genomics of M. tuberculosis and BCG successfully identified “regions of deletion” (RD) that encode genes that were subsequently proven to promote productive M. tuberculosis infection (7), including the 6-kDa early secreted antigenic target (ESAT-6) secretion system-1 (ESX-1) (8, 9). We reasoned that a metabolite-based screen might identify new virulence factors because not all functions of RD genes are known. Also, biologically important metabolites could emerge from complex biosynthetic pathways that cannot be predicted from single-gene analysis.Comparison of M. tuberculosis and BCG lipid profiles revealed more than 1,000 differences, among which we identified a previously unknown M. tuberculosis-specific diterpene-linked adenosine and showed that it is produced by the enzyme Rv3378c. Previously, Rv3378c was thought to generate free tuberculosinol and isotuberculosinol (10–12). This discovery revises the enzymatic function of Rv3378c, which acts as a virulence factor to inhibit phagolysosome fusion (13). Whereas current models of prenyl transferase function emphasize iterative lengthening of prenyl pyrophosphates using one binding pocket, the crystal structure of Rv3378c identifies two pockets in the catalytic site, establishing a mechanism for heterologous prenyl transfer to nonprenyl metabolites.     

Green Tea Consumption and Depressive Symptoms among Japanese Workers: The Furukawa Nutrition and Health Study

Although several cross-sectional studies have described an inverse association between green tea consumption and depressive symptoms, only one study has prospectively investigated this association. We investigated the cross-sectional and prospective associations between green tea consumption and depressive symptoms in a working population in Japan. Participants were 1987 workers who participated in the baseline survey for a cross-sectional association, and 916 participants who did not have depressive symptoms at baseline who responded to both the baseline and follow-up surveys for a prospective association. Green tea consumption was evaluated with a validated self-administered diet history questionnaire. Depression symptoms were evaluated with the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple logistic regression was conducted to estimate the odds ratio of depressive symptoms based on green tea consumption. In the cross-sectional analysis, green tea consumption was not associated with the prevalence of depression symptoms. Moreover, consumption at baseline was not associated with depression symptoms after 3 years; the multivariable-adjusted odds ratio of depressive symptoms for ≥2 cups/day of green tea was 1.12 (95% confidence interval 0.65–1.91) compared with <4 cups/week after adjustment for covariates including dietary factors (trend p = 0.67). Our results suggest that there is no association of consumption of green tea with symptoms of depression in Japanese.     

Muscle metabolism during exercise using phosphorus-31 nuclear magnetic resonance spectroscopy in adolescents

Very little has been reported on muscle energetics during exercise in adolescents. This is attributable to the difficulty of subjecting children to muscle biopsy. The purpose of this study was to investigate the characteristics of muscle metabolism during exercisein vivo in adolescents by comparing firstly, with adults and secondly, the differences resulting from physical activity using phosphorus-31 nuclear magnetic resonance (³¹PNMR) spectroscopy. The subjects were boys aged 12 to 15 years, comprising 21 trained boys and 23 control boys, and 6 adults controls. The ratio of phosphocreatine (PCr):(PCr + P_i), where P_i is inorganic phosphate intracellular pH at exhaustion and the time constant of PCr during recovery were measured in all the subjects using³¹PNMR. Both groups of children showed higher values of PCr:(PCr + P_i) and intracellular pH at exhaustion than did the adult control group (P < 0.01 orP < 0.05). However, no significant differences were found between the trained boys and the control boys with respect to PCr:(PCr + P_i) and intracellular pH at exhaustion. On the other hand, we found the same values for PCr time constant in all groups. This result suggested no differences of the muscle oxidative capacity between children and adults. We concluded that the adolescents, aged 12 to 15 years in both the trained and control groups, had less glycolytic ability during exercise than the adults.     

Detection of coronary plaque by computed tomography with a novel plaque analysis system, 'Plaque Map', and comparison with intravascular ultrasound and angioscopy.

BACKGROUND: Previous reports suggest that plaque may be characterized by the computed tomography (CT) number, but there is not a comprehensive method for evaluating the gray-scale CT image of the coronary artery obtained by multi-detector row CT (MDCT). METHODS AND RESULTS: Forty-five patients with acute coronary syndrome (ACS) underwent MDCT either 3-4 weeks after the onset of acute myocardial infarction (n=24) or within 1 week after percutaneous coronary intervention in patients with unstable angina (UA; n=21). The cross-sections obtained at intervals of 5 mm were converted to numerical data and a 'plaque map' was drawn using the color-based isometric line method and bird's eye view. 'Plaque map' was compared with the findings of intravascular ultrasound (IVUS) and angioscopy. Of 662 slices of 78 vessels, soft, intermediate or calcified plaque was detected in 144, 134, and 84 slices, respectively. Compared with IVUS, the sensitivities were 92%, 87%, and 89%, respectively, and compared with angioscopy, sensitivity was 80% and specificity was 87%. CONCLUSIONS: MDCT with the 'Plaque Map' system can noninvasively characterize plaque in patients with ACS.     

Combinations of cytogenetics and international scoring system can predict poor prognosis in multiple myeloma after high‐dose chemotherapy and autologous stem cell transplantation

High‐dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard therapy for newly diagnosed multiple myeloma. Combinations of recently proposed prognostic factors such as cytogenetics and international scoring system (ISS) may be useful to predict prognosis after ASCT. This study evaluated 60 consecutive patients who underwent ASCT in four institutes. The median age of patients was 57 years old. Cytogenetic analyses of bone marrow at diagnosis detected metaphase abnormalities in 9 of 51 patients and interphase abnormalities in six of 35 patients (17p13 deletion, t(4;14) and t(14;16)). Seventeen patients had ISS stage 3 at diagnosis. Twenty‐five patients who had any of these risk factors were defined as high risk. All patients were conditioned with high‐dose melphalan. With a median follow‐up of 3.4 years, overall survival and event‐free survival at 3 years were significantly worse in high‐risk patients (48% vs. 97%; P = 0.0005 and 16% vs. 37%; P = 0.038, respectively) despite the higher CR plus VGPR rate among high‐risk patients. In addition, survival at 1 year after progression was significantly worse in high‐risk patients despite salvage chemotherapy containing thalidomide (32% vs. 100%, P = 0.0001). Combinations of cytogenetics and ISS could readily predict prognosis. Quality of response is a poor surrogate marker for ultimate outcome. High‐risk patients may need more effective treatment. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Chronic Epstein-Barr Virus Infections Associated with Coronary Aneurysms

We recently reported virological studies in a patient with chronic active Epstein-Barr virus (EBV) infection in which T-lymphocytes were infected, and coronary aneurysms were detected by echocardiography. We report here the clinical features of this patient and suggest that EBV may cause coronary aneurysms and that an echocardiographic study should be performed in patients with chronic active EBV infection.