Association between the Trail Making Test and physical performance in elderly Japanese

Aim:   The Trail Making Test (TMT) is used in Western countries as an indicator of executive function, but there is little information regarding its use in Japan. Our previous initial study showed that the TMT was significantly associated with mobility-related functions among elderly Japanese living in the community and in this study, we increased the number of participants to clarify that result.
Methods:   The TMT, comprised of two parts (part A and part B), was administered to 493 subjects aged 65 years or older (164 men, 329 women). Our assessment used the time difference (ΔTMT) between parts B and A, and eight physical performance indicators: four of preventive care (usual walking speed, timed Up & Go [TUG], one-leg standing balance and handgrip strength) and four movement parameters (maximum walking speed, dual-task TUG, stair climbing and obstacle-negotiating gait).
Results:   The median ΔTMT score was 64.01 s for men and 65.56 s for women. The ΔTMT score increased with age, and there was no difference between sexes. Multinomial logistic regression analysis showed that a poor ΔTMT was related to low tertiles for all physical performances. It related to the intermediate tertile of TUG and maximum walking speed, dual-task TUG, stair climbing and obstacle-negotiating gait.
Conclusion:   The TMT reflects complex walking performance, so it can be a useful synthetic indicator for health programs promoting independence in elderly Japanese.     

Population Structure Dynamics of Mycobacterium tuberculosis Beijing Strains during Past Decades in Japan

We used 909 strains to compare the population structures of the Mycobacterium tuberculosis Beijing family between different birth-year cohorts in Japan. The results revealed that the spread of a modern sublineage that has high transmissibility is currently increasing, while the spread of an ancient sublineage, STK, has significantly decreased in younger generations.Comparative studies of the Mycobacterium tuberculosis population structure have generated interest in understanding its epidemiological relevance to human disease (2, 3, 9, 15, 21). One of the most extensively studied clades with respect to host-pathogen compatibility is the Beijing family (5, 7, 8, 16, 23), which is highly prevalent in East Asia (26). Recent studies have demonstrated the worldwide dissemination of the modern Beijing family strains (having IS6110 insertions in the NTF region) (1, 14, 17, 18) and have led to speculation about the hypervirulent features of this sublineage (4, 7, 13, 16). In contrast to the worldwide prevalence of modern Beijing strains, the ancient Beijing strains (having an intact NTF region) are highly diverse and dominant in Japan (11, 27). Studying this singularity of the Beijing strains in Japan would expand our understanding of the heterogeneity in the fitness of different sublineages. In this study, we used data from a population-based study lasting 5 years and 8 months to investigate the probable shift in the M. tuberculosis population structure during the previous decades and determine the future trend in Japan, with special attention to the modern Beijing strains.We obtained 909 M. tuberculosis isolates from newly diagnosed pulmonary tuberculosis (TB) patients between April 2002 and December 2007. These isolates accounted for approximately 70% of the new culture-positive pulmonary TB cases detected during the collection period in Kobe City. The isolates were phylogenetically classified as belonging to the Beijing clade or other clades by spoligotyping (12) and to the ancient and modern Beijing sublineages on the basis of the presence of IS6110 in the NTF region (19, 27). The ancient and modern Beijing strains were subclassified by analyzing 10 synonymous single-nucleotide polymorphisms (6, 8, 11). Molecular typing based on the variable number of tandem repeats (VNTR) method with 19 loci, which comprised the 15 loci of Supply et al. (24) and 4 hypervariable loci (QUB-11a, QUB-3232, VNTR-3820, and VNTR-4120) (10), was performed for all strains. Recent transmission was suggested by the clustering of identical VNTR profiles. The presence or absence of region of difference 181 (25) in all the Beijing strains was analyzed.Of the 909 isolates, 714 (78.5%) were classified as Beijing family strains (Table ​(Table1),1), and these included 44 Beijing-like strains. Except for the sequence type 11 (ST11) and ST26 sublineages, all the Beijing strains contained deletions in region of difference 181. All the modern strains harbored only one IS6110 insertion element. The non-Beijing family strains comprised 32 spoligotypes. The details of the genetic data of all isolates are summarized in Table S1 in the supplemental material.

TABLE 1.

Genotypic characteristics of M. tuberculosis isolates from 909 tuberculosis patients

Alpha 1 antitrypsin activity is decreased in human amnion in premature rupture of the fetal membranes

Preterm premature rupture of the membranes (PPROM) has beenconsidered to be closely associated with chorioamnionitis. However,the detailed mechanism is not well understood. Alpha 1 antitrypsin(AAT) was reported to decrease in concentration in amnioticfluid obtained from patients with PPROM. However, the originof AAT in amniotic fluid has not been clarified. In this study,we assessed the expression and localization of AAT in humanamnion, as well as its biological activity in cases with PROM.Human amniotic epithelial (hAE) cells expressed AAT. After stimulationwith oncostatin M (OSM), interleukin-6 (IL-6) or tumor necroticfactor alpha (TNF ), hAE cells increased the expression of AAT,while the expression of MMP9 was reduced by OSM and inducedby TNF . Oxidized AAT (inactivated form) was detected in theamnion with PPROM and TPROM, but not in specimens without PROM.Moreover, AAT activity was decreased in amnions from cases withPROM, regardless of gestational age. Thus, the results showedthat AAT in the amnion may function as a protective shield atinflammatory sites, and not as it loses it inhibitory activityin cases with PROM, possibly by oxidation, suggesting that itsimbalance contributes to PROM.     

Fluorescent probe-labeled lipid microsphere uptake by human endothelial cells: a flow cytometric study.

Lipid microspheres have been used as carriers of drugs such as prostaglandin E1 (lipo-PGE1) and corticosteroid (liposteroid). Lipo-PGE1 is used for the treatment of chronic arterial occlusive diseases because its activity is far greater than that of free PGE1 in vivo. To verify the fact that the drug carriers, lipid microspheres, are preferentially taken up by endothelial cells, we labeled lipid microspheres with a fluorescent probe, DiI (DiI-LM), and observed them in some in vitro models. Stoichiometric fluorescence was obtainable, and the fluorescence was stable between pH 3.3 and pH 8.9. Human umbilical vein endothelial cells and cells of a human endothelial cell line, ECV304, showed increased uptake of DiI-LM, 81% and 61%, respectively. In contrast, uptakes were less than 7% in human skin fibroblasts, 3T3 cells, and human neutrophils. Prominent perinuclear fluorescence was also observed in endothelial cells by fluorescence microscopy. DiI-LM and flow cytometric analysis will be useful for studies to elucidate the precise mechanism of the selective accumulation of lipid microspheres by cells in blood vessel walls.     

Comparative effects of N,N-disubstituted dithiocarbamates on excretion and distribution of cadmium in mice

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At 30 min after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium, and HBGD and CBGD significantly increased the urinary excretion of the metal. At 24 h after cadmium injection, BGD, HBGD, and MeOBGD significantly increased the biliary excretion of cadmium and HBGD was the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, HBGD and MeOBGD effectively depressed cadmium content in the liver and only HBGD among these chelating agents significantly reduced the cadmium content in the kidney. In another experiment, mice were injected i.p. with 109CdCl2 and three days later, they were injected with chelating agents every other day for 2 weeks. HBGD was the most effective on the fecal and urinary excretions of cadmium. The hepatic cadmium content was decreased after HBGD or MeOBGD injection. The injection of HBGD caused a much greater decrease in renal cadmium content than did BGD, CBGD, or MeOBGD. The results of this study indicated that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body, mainly through fecal excretion, without redistribution of cadmium to other tissues such as the brain, testes, and heart, more effectively than that of BGD, CBGD, or MeOBGD.     

Effects of maintenance treatment after high-dose intravenous gamma-globulin for idiopathic thrombocytopenic purpura]

High-dose intravenous immunoglobulin (IVIG) for idiopathic thrombocytopenic purpura (ITP) produces a dramatic and substantial increase in platelet count, but the increased count tends to return rapidly to its pretreatment level. We studied the effects of immunosuppressive treatment aimed at the maintenance of platelet counts following the IVIG administration in ITP. Thirty-five patients with ITP were treated with IVIG, and then thirty-two of them with an immunosuppressant (azathioprine) and a glucocorticoid (prednisolone). After IVIG, the platelet count increased significantly. With immunosuppressive therapy after IVIG, most patients had a tendency to maintain the counts. In particular, this maintaining effect was remarkable in those patients who had been responsive to the standard prednisolone therapy while non-responders to the prior prednisolone failed to maintain the counts. When prednisolone was given after IVIG, the effect of maintaining platelet counts was dose-dependent. The treatment with azathioprine and prednisolone after IVIG appears to be effective in maintenance of platelet counts.     

Development of serodiagnostic kit "HITAZYME Chlamydia Ab" for Chlamydia trachomatis infections using extracted antigen]

To develop EIA kit with low cross-reactivity for the quantitative detection of anti-chlamydial antibodies, we examined the preparation of trachomatis antigens and its specificity to mouse antisera and human sera. The chlamydial elementary body (EB) purified from C. trachomatis L2/434/Bu strain was treated by Sarkosyl, dithiothreitol and SDS by turns to obtain the soluble EB outer membrane (COMC). SDS-PAGE showed that the major components of the COMC were 96K, 60K and 39.5 KDa peptides. The reactivity of the COMC immobilized to 96 wells microtiter plate to mouse anti-serum to C. trachomatis was higher than the other two mouse anti-sera to C. psittaci and pneumoniae. In human sera, the cut off values were calculated from an average optical density plus its two-fold standard deviation obtained by the testing of 100 samples of healthy human sera. We evaluated the specificity of the kit to 17 anti-C. pneumoniae, 9 C. trachomatis and 4 C. psittaci antibodies positive patients' sera judged by the MFA method respectively. The results showed that the concordance ratio of IgG and IgA were 88%, 100% in anti-C. pneumoniae, 89%, 78% in anti-C. trachomatis and 50%, 50% in anti-C. psittaci respectively. From the results obtained in this study, we concluded that the HITAZYME method which had a very low cross-reactivity to C. pneumoniae is clinically useful in the serodiagnosis of C. trachomatis infections, even if it has a little common antigenicity with C. psittaci antigen.     

Spontaneous reflex sympathetic dystrophy (Sudeck's atrophy) syndrome associated with idiopathic thrombocytopenia.

A 37-year-old woman developed reflex sympathetic dystrophy (RSD) (Sudeck's atrophy) syndrome in the right foot. Simultaneously, she had idiopathic thrombocytopenia. There was no history of injury or bone fracture before onset of RSD. Spontaneous RSD associated with idiopathic thrombocytopenia has rarely been described. A possible relationship between the 2 conditions is discussed.     

Hospital-acquired Streptococcus pneumoniae infection

Three elderly patients were consecutively found to harbor or to become infected with intermediate-level penicillin-resistant Streptococcus pneumoniae in a hospital respiratory ward. All the isolates from the respective patients produced mucoid-type colonies on sheep blood agar plates and were found to have an identical antibiogram, indicating that those were resistant against erythromycin, clarithromycin, clindamycin and minocycline. Pulse-field gel electrophoresis of genomic DNA digested Sma I and Apa I demonstrated homology among the isolates, which may suggest person-to-person spread in a hospital setting. With this, it is an urgent to establish the institution-based infection control precautions against S. pneumoniae.     

Usefulness of massive oral nicorandil in a patient with variant angina refractory to conventional treatment

A 67-year-old man, who was previously diagnosed with vasospastic angina and treated with standard therapy, was admitted to our hospital because of recurrent chest pain refractory to sublingual nitroglycerin. Admission electrocardiography revealed ST segment elevation in II, III and aV(F), and his symptoms were relieved by intravenous bolus administration of nicorandil. He was diagnosed to have active variant angina, and remained symptomatic even after treatment with calcium antagonists and nitrates at optimal doses. Intravenous bolus administration of nicorandil was consistently effective to relieve his symptoms. Anginal attack was finally prevented by massive oral nicorandil in addition to conventional treatment.