Transcranial sonography imaging of brainstem raphe, substantia nigra and cerebral ventricles in patients with geriatric depression.

OBJECTIVES: Geriatric depression is a special condition associated with a chronic course, treatment resistance and vascular processes. However, its neurobiology has not been fully elucidated. There is no study in geriatric depression evaluating deep brain structures with transcranial sonography (TCS) which is a low-cost, non-invasive and practical tool. The present study aimed to evaluate the changes in the echogenicity of brainstem raphe (BR), substantia nigra (SN) and ventricular diameters by TCS in association with cognitive dysfunctions in patients with geriatric depression. METHODS: Echogenicity of BR and SN were assessed and transverse diameters of the third ventricle and frontal horns of the lateral ventricles were measured by TCS in 34 patients with DSM-5 major depression and 31 healthy volunteers aged 60 and older. Cognitive functions were evaluated by using Mini Mental State Examination, Montreal Cognitive Assessment Tool, Clock Drawing Test and Subjective Memory Complaints Questionnaire. RESULTS: Although depressed patients had more subjective memory complaints than controls, they had similar cognitive performances. Reduced echogenicity (interrupted/invisible echogenic line) of BR was found to be significantly higher and the ventricular diameters were larger in the depressed group. There was no difference between the groups in terms of SN echogenicity. There was no correlation between ventricular diameters and depression severity or cognitive functions. CONCLUSIONS: Results of the present study are important in terms of pointing out neurobiological changes related to geriatric depression which are in parallel with the results of the studies in younger patients with depression. However, long-term follow-up studies are required for accurate differentiation of neurocognitive disorders.

Laser-Beam-Patterned Topological Insulating States on Thin Semiconducting MoS_{2}.

Identifying the two-dimensional (2D) topological insulating (TI) state in new materials and its control are crucial aspects towards the development of voltage-controlled spintronic devices with low-power dissipation. Members of the 2D transition metal dichalcogenides have been recently predicted and experimentally reported as a new class of 2D TI materials, but in most cases edge conduction seems fragile and limited to the monolayer phase fabricated on specified substrates. Here, we realize the controlled patterning of the 1T^{'} phase embedded into the 2H phase of thin semiconducting molybdenum-disulfide by laser beam irradiation. Integer fractions of the quantum of resistance, the dependence on laser-irradiation conditions, magnetic field, and temperature, as well as the bulk gap observation by scanning tunneling spectroscopy and theoretical calculations indicate the presence of the quantum spin Hall phase in our patterned 1T^{'} phases.

No Effect of Different Stimulation Conditions on Verbal Fluency and Visuospatial Orientation in Patients with Subthalamic Nucleus Deep Brain Stimulation.

BACKGROUND: Subthalamic nucleus deep brain stimulation is an effective treatment for the symptomatic treatment of Parkinson's disease. Apart from the obvious motor benefits, some cognitive side effects have been reported, particularly in verbal fluency. OBJECTIVES: Our aim was to evaluate the effects of the stimulation on verbal fluency and visuospatial orientation with changing stimulation conditions in 35 patients with Parkinson's disease. METHODS: Patients were randomized for their stimulation conditions as 'both on', 'both off', 'right on', and 'left on' and underwent verbal fluency and visuospatial orientation tasks during their drug-on periods. Letter and categorical fluency tasks and Benton's Judgment of Line Orientation Test were used for assessment. RESULTS: Overall, 6 patients were excluded due to dementia or depression. For verbal fluency, the number of words they produced in 1 min was similar in four stimulation conditions (p > 0.05). No significant difference was found between stimulation conditions in the spatial orientation task. CONCLUSIONS: We were unable to find any significant changes in verbal fluency and visuospatial orientation task scores with different stimulation conditions. This result suggests that either stimulation has no effect on given domains or the effect is so small that more detailed batteries are required to detect the difference.

The Relationship Between Renal Function and Imaging Markers and Total Burden of Cerebral Small Vessel Disease.

BACKGROUND: Previous studies demonstrating the association between renal functions and cerebral small vessel diseases have usually focused on white matter hyperintensity in the general population or lacunar stroke patients. This study aimed to investigate the effects of renal function on imaging markers of cerebral small vessel disease and etiologic subtypes of stroke in patients with acute ischemic stroke or transient ischemic attack. MATERIALS AND METHODS: A total of 356 consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted to the Stroke Unit and underwent brain magnetic resonance imaging were evaluated. Demographic data, vascular risk factors, stroke etiology, estimated glomerular filtration rate and severity of cerebral small vessel disease markers, and total cerebral small vessel disease burden were evaluated. RESULTS: There was a significant inverse correlation between estimated glomerular filtration rate and total number of lacunes, periventricular and deep subcortical Fazekas scores, grade of enlarged perivascular spaces in the centrum semiovale, lobar and total cerebral microbleeds, and total cerebral small vessel disease burden. Impaired renal function was an independent risk factor for the presence of lacunes, deep cerebral microbleeds, and increased total burden. Renal function impairment and periventricular white matter hyperintensities were significantly associated with the etiologic subgroup of small vessel occlusion. The results were still significant after the exclusion of patients below 50 years of age. CONCLUSION: Our results indicate that there is a relationship between renal function impairment and increased total burden, as well as acute ischemic stroke/transient ischemic attack due to small vessel occlusion.

Relation between functional and cognitive impairments in remitted patients with bipolar disorder and suggestions for trials targeting cognition: An exploratory study.

BACKGROUND: Trials targeting cognition in bipolar disorder (BD) are advised to include a measure of functional capacity as key secondary or co-primary outcome to assess whether treatment efficacy on cognition translates into enhanced functional capacity. However, it is unclear which measure of functional capacity shows the strongest association with objectively-measured cognition and may thus be best suited for inclusion in cognition trials. METHODS: Participants (N = 58) with BD in partial or full remission with objective cognitive impairment and healthy controls (N = 37) were assessed with mood ratings and were given a comprehensive battery of neuropsychological tests and a questionnaire assessing subjective cognitive function, respectively. They were also assessed with performance-based, interview-based and self-reported measures of functional capacity. Associations between objective and subjective cognition and measures of functional capacity were assessed with correlation analyses. For significant correlations, multiple regression analyses were conducted to assess if the associations remained significant after adjustment for clinical and demographic variables. RESULTS: Objectively-measured cognition was directly associated with performance-based functional capacity (ß = 0.37, p < 0.01) also after adjustment for clinical and demographic variables, but not with self-reported or interview-based functional capacity (ps ≥0 .20). In contrast, subjective cognitive complaints were associated with self-reported (ß = 0.59, p < 0.01) and interview-based functional capacity (ß = 0.47, p < 0.01), but not performance-based functional capacity (ps ≥ 0.28). LIMITATIONS: The cross-sectional design and modest sample size. CONCLUSIONS: A performance-based measure of functional capacity seems most feasible for inclusion as a secondary outcome in cognition trials to capture improved functional capacity following treatment-related improvements in cognition.

Evidence for a quantum spin Hall phase in graphene decorated with Bi2Te3 nanoparticles.

Realization of the quantum spin Hall effect in graphene devices has remained an outstanding challenge dating back to the inception of the field of topological insulators. Graphene's exceptionally weak spin-orbit coupling-stemming from carbon's low mass-poses the primary obstacle. We experimentally and theoretically study artificially enhanced spin-orbit coupling in graphene via random decoration with dilute Bi2Te3 nanoparticles. Multiterminal resistance measurements suggest the presence of helical edge states characteristic of a quantum spin Hall phase; the magnetic field and temperature dependence of the resistance peaks, x-ray photoelectron spectra, scanning tunneling spectroscopy, and first-principles calculations further support this scenario. These observations highlight a pathway to spintronics and quantum information applications in graphene-based quantum spin Hall platforms.

Assessment of the Predictive Validity of Etiologic Stroke Classification.

Importance: The ability of present-day etiologic stroke classification systems to generate subtypes with discrete stroke characteristics is not known. Objective: To test the hypothesis that etiologic stroke subtyping identifies different disease processes that can be recognized through their different clinical courses. Design, Setting, and Participants: We performed a head-to-head evaluation of the ability of the Causative Classification of Stroke (CCS), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and ASCO (A for atherosclerosis, S for small-vessel disease, C for cardiac source, and O for other cause) classification systems to generate etiologic subtypes with different clinical, imaging, and prognostic characteristics in 1816 patients with ischemic stroke. This study included 2 cohorts recruited at separate periods; the first cohort was recruited between April 2003 and June 2006 and the second between June 2009 and December 2011. Data analysis was performed between June 2014 and May 2016. Main Outcomes and Measures: Separate teams of stroke-trained neurologists performed CCS, TOAST, and ASCO classifications based on information available at the time of hospital discharge. We assessed the association between etiologic subtypes and stroke characteristics by computing receiver operating characteristic curves for binary variables (90-day stroke recurrence and 90-day mortality) and by calculating the ratio of between-category to within-category variability from the analysis of variance for continuous variables (admission National Institutes of Health Stroke Scale score and acute infarct volume). Results: Among the 1816 patients included, the median age was 70 years (interquartile range, 58-80 years) (830 women [46%]). The classification systems differed in their ability to assign stroke etiologies into known subtypes; the size of the undetermined category was 33% by CCS, 53% by TOAST, and 42% by ASCO (P < .001 for all binary comparisons). All systems provided significant discrimination for the validation variables tested. For the primary validation variable (90-day recurrence), the area under the receiver operating characteristic curve was 0.71 (95% CI, 0.66-0.75) for CCS, 0.61 (95% CI, 0.56-0.67) for TOAST, and 0.66 (95% CI, 0.60-0.71) for ASCO (P = .01 for CCS vs ASCO; P < .001 for CCS vs TOAST; P = .13 for ASCO vs TOAST). The classification systems exhibited similar discrimination for 90-day mortality. For admission National Institutes of Health Stroke Scale score and acute infarct volume, CCS generated more distinct subtypes with higher between-category to within-category variability than TOAST and ASCO. Conclusions and Relevance: Our findings suggest that the major etiologic stroke subtypes are distinct categories with different stroke characteristics irrespective of the classification system used to identify them. We further show that CCS generates discrete etiologic categories with more diverse clinical, imaging, and prognostic characteristics than either TOAST or ASCO.

High frequencies of human T-lymphotropic virus type I (HTLV-I) infection and presence of HTLV-II proviral DNA in blood donors with anti-thyroid antibodies.

To investigate the relationship between human T-lymphotropic virus (HTLV) types I and II and the pathogenesis of autoimmune thyroid diseases, we examined serum anti-thyroid antibodies in 1019 blood donors with or without serum anti-HTLV-I antibody as well as proviral DNA for HTLV-II in leukocyte DNA by the polymerase chain reaction in 395 blood donors with or without anti-thyroid antibodies. The frequency of donors with anti-HTLV-I antibody who also showed anti-thyroid antibodies (7.9%) tended to be higher than that (6.3%) among donors who did not have the anti-HTLV-I antibody. The frequency of anti-thyroid antibodies in 125 young male donors aged 16-39 years with anti-HTLV-I antibody (4.8%) was significantly higher (P < 0.05) than that (0.6%) in 164 control donors without the antibody. In blood donors with anti-thyroid antibody, 25.0% of those with anti-HTLV-I antibody and 14.3% of those without the antibody had HTLV-II proviral DNA. In contrast, in donors without anti-thyroid antibody HTLV-II proviral DNA was detected in 2.3% of those with anti-HTLV-I antibody and in 0.6% of those without the antibody. Thus the detection rates in donors with anti-thyroid antibody were significantly higher (P < 0.001) than those in donors without the antibody, regardless of HTLV-I infection. These results suggest that HTLV-I infection and the presence of HTLV-II proviral DNA may be independently related to the pathogenesis of autoimmune thyroid diseases.

Graves' disease in HTLV-I carriers.

Three carriers of human T-lymphotropic virus type I (HTLV-I) with Graves' disease are reported. All three cases were complicated with uveitis, and one also showed chronic arthropathy. Anti-HLTV-I antibody was found in the serum by the particle agglutination method and western blotting, and HTLV-I proviral DNA was detected in peripheral lymphocytes by the polymerase chain reaction and Southern blotting. HTLV-I is a causal agent of adult T-cell leukemia and HTLV-I associated myelopathy/tropical spastic paraparesis, and is believed to be related to the pathogenesis of diseases such as chronic arthropathy, uveitis, chronic bronchoalveolitis, and Sjögren's syndrome. On the other hand, retrovirus infection is considered to cause autoimmune diseases. Thus, the pathogenesis of Graves' disease in the present patients might be associated with HTLV-I infection.

HLA and T-cell receptor gene polymorphisms in Guillain-Barré syndrome.

OBJECTIVE: We examined a possible involvement of genetic factors influencing the development of Guillain-Barré syndrome (GBS). METHODS: We studied T-cell receptor (TCR), alpha-chain constant (AC), and beta-chain variable (BV) gene polymorphisms using microsatellite markers and serologic HLA class I antigens, HLA-DRB1, and HLA-DQB1 alleles in 81 Japanese patients with GBS and 87 controls. RESULTS: There were no significant differences in these genetic markers between GBS patients and controls. Subgrouping of GBS patients according to recent Campylobacter jejuni infection, the presence of anti-GM1 antibody in the sera, or their combinations also failed to reveal significant associations with these genetic markers. There was, however, a tendency for an increased frequency of HLA-DRB1*0803 in the C. jejuni + GM1 + GBS group, when compared with controls. CONCLUSIONS: The data suggest that the roles of TCRAC, T-cell receptor beta-chain variable (TCRBV), HLA class I or class II in the development of GBS are not critical, and further research is necessary to clarify other genes encoded within the HLA region for genetic susceptibility to GBS.

HLA-DRB1 and tumor necrosis factor gene polymorphisms in Japanese patients with multiple sclerosis.

We studied genetic polymorphisms in the tumor necrosis factor (TNF) region as well as HLA-DRB1 of 42 patients with Western-type multiple sclerosis (MS) and 38 with Asian-type MS in Japan. The sex ratio (Female:Male) was significantly higher in Asian than in Western type MS (3.8 vs. 1.3, P = 0.038). The frequency of HLA-DRB1 * 1501 allele in the Western-type MS group increased significantly compared with the control group, while Asian-type MS and control groups showed similar distribution in the frequencies of HLA-DRB1 alleles. No significant differences existed in the TNF region, however, including TNF-a microsatellite alleles. The results suggest that MS in Asians may present two different clinical and immunogenetic manifestations.

HLAs and genes in Japanese patients with multiple sclerosis: evidence for increased frequencies of HLA-Cw3, HLA-DR2, and HLA-DQB1*0602.

The distribution of HLA-A, B, C, DR and DRB1, DQB1, DPB1 alleles was studied in 60 Japanese patients with clinically definite multiple sclerosis (MS) using serologic and genomic analysis. We found significant associations with HLA-Cw3 (p = 0.002, pc = 0.012, RR = 3.2), DR2 (p = 0.007, RR = 2.6), and DQB1*0602 (p = 0.04, RR = 4.0) in Japanese patients for the first time. The combined presence of Cw3 and DR2 gave a higher risk than each antigen alone. The reported increase in the frequency of DPw4 in Japanese MS patients [12] could not be confirmed by our genomic study. The frequencies of all of the residues in each variable region of the amino acid sequences of DQ beta and DP beta chains were not different between the MS patients and the controls. These results suggest that MS susceptibility may result from polygenic influences and from the presence of environmental factors.

Tumor necrosis factor, tumor necrosis factor receptors type 1 and 2, lymphotoxin-alpha, and HLA-DRB1 gene polymorphisms in human T-cell lymphotropic virus type I associated myelopathy.

We studied tumor necrosis factor (TNF), lymphotoxin-alpha (LT-alpha), and TNF receptors type 1 (TNFR-1) and type 2 (TNFR-2) gene polymorphisms as well as HLA class II DRB1 alleles in Japanese patients with human T-cell lymphotropic virus type I (HTLV-I) associated myelopathy (HAM) (n = 51), patients with adult T-cell leukemia/lymphoma (ATL) (n = 48), asymptomatic HTLV-I carriers (n = 50), and HTLV-I seronegative, normal controls (n = 112). There were significant differences between HAM patients and normal controls in the distributions of TNF promoter region polymophism at position --857, the LT-alpha gene NcoI polymorphism, and the T-G substitution in exon 6 of the TNFR-2 gene. The distribution of the NcoI polymorphism of the LT-alpha gene was also significantly different between HAM patients and asymptomatic HTLV-I carriers. In contrast, we failed to detect any difference in the frequency of DRB1, TNF promoter at position --1031, --863, or the TNFR-1 promoter --383 polymorphism. The results suggest that the TNF/LT-alpha gene region within the HLA class III of chromosome 6 and the TNFR-2 gene region located on chromosome 1p36 might contribute to susceptibility to HAM, and that aberrant expression or function of these cytokines and the receptor could be involved in the development of HAM.

Congenital sarcoma in the terminal ileum histologically resembling clear cell sarcoma of the kidney: a case report with an immunohistochemical study.

We report a case of a newborn female with a rare tumor, a congenital sarcoma, presenting as an abdominal mass. Laparotomy demonstrated the tumor arising from the wall of the terminal ileum. Histologically, the tumor tissue was indistinguishable from clear cell sarcoma of the kidney and was composed of proliferating cells with poorly stained cytoplasm divided into nests or cords by arborizing vasculature. Immunohistochemical staining revealed that the neoplastic cells had a phenotype similar to metanephric blastemal cells of fetal kidney, ie, positive for vimentin and CD24 but negative for cytokeratin and CD9. The results suggest that this congenital tumor may originate from primitive mesenchymal cells phenotypically related to cells present in the fetal kidney.

Neuroblastoma cell lines showing smooth muscle cell phenotypes.

Neuroblastoma is a tumor that is derived from the neural crest. Recent studies demonstrated that several human neuroblastoma cell lines exhibit at least three morphologic types: neuroblastic (N)-type, substrate-adhesive (S)-type and intermediate (I)-type cells. However, the origin of the S-type cells has not been clearly identified. In this study, the expressions of smooth muscle-specific proteins (desmin, alpha-smooth muscle actin, basic calponin and the smooth muscle myosin heavy-chain isoforms of SM1 and SM2) in three parent and four cloned neuroblastoma cell lines, composed of S-type cells, were examined by indirect immunofluorescence, Western blot and/or by reverse transcription-polymerase chain reaction (RT-PCR). Desmin was found in two of the seven cell lines, and alpha-smooth muscle actin and basic calponin were detected in all of seven of the cell lines. In three parent cell lines and one cloned cell line composed of N-type cells, none of three smooth muscle-specific proteins were detected. In smooth muscle myosin heavy-chain isoforms, SM1 was detected in two parent cell lines composed of S-type cells (MP-N-MS and KP-N-YS) by immunofluorescence, Western blot and/or by RT-PCR, whereas the SM2 isoform was detected in one parent cell line (MP-N-MS) by RT-PCR. These findings indicate that S-type cells have either the immature or mature smooth muscle cell phenotype, and neural crest cells very likely have the ability of to differentiate into smooth muscle cells in the human system.

The existence of a dispensable fibrillar layer on the wall surface of mycelial but not yeast cells of Aureobasidium pullulans.

Wall surface ultrastructure of Aureobasidium pullulans was studied by freeze-etching. Yeast cells had a smooth wall surface as in typical yeast species. Mycelial cells and chlamydospores had an extra layer on the wall surface made mostly of fibrils. The fibrils were 20 nm in diameter, and thicker than typical major fungal wall skeletal fibrils of beta-glucan and chitin. This layer was apparently easily detached from the wall proper, presumably as a result of enzymic activity or by physical means, suggesting that it is a physiologically dispensable wall component.

Cleavage of human big endothelin-1 by Candida albicans aspartic proteinase.

A Candida albicans aspartic proteinase (CAP), one of the secretory proteinases of Candida albicans, is thought to be a possible virulence factor in Candida albicans infection. Whereas endothelin-1 is found as an endothelium-derived strong vasoconstrictive peptide, it is known to have a role in the maintenance of vascular homeostasis and tissue survival. Endothelin-1 is generated from a precursor form of endothelin-1, the so-called big endothelin-1. It has recently been reported that cathepsin D, E and pepsin, which are aspartic proteinases, convert big endothelin-1 to endothelin-1. In this study, the relationship between CAP and big endothelin-1 was studied. High performance liquid chromatography analysis revealed that big endothelin-1 was cleaved into several amino acid sites by CAP, but endothelin-1 was not converted from big endothelin-1. CAP cleaved big endothelin-1 at different sites when compared with that of other known aspartic proteinases, and it suppressed endothelin-1 production through the degradation of big endothelin-1. CAP may break homeostatic mechanism of endothelin-1 in Candida albicans infectious lesions.

Significance of modes of adherence in esophageal Candida albicans.

Although esophageal candidiasis is the most common form of Candida infection in the gastro-intestinal tract, little attention has been directed toward determining the mechanism of its infection. We have already clarified the existence of four modes of adherence of Candida albicans to the esophagus; attachment, subepithelial cell insertion, cavitation, and invasion. This study was undertaken to clarify the significance of each of these modes. Scanning electron microscopic observations were made of esophageal specimens from 8-week-old rabbits infected with Candida albicans IFO 1060. In this study, attachment and subepithelial cell insertion were found to be the most frequent modes of adherence. Cavitation occurred following subepithelial cell insertion, while invasion occurred following attachment and subepithelial cell insertion. These results suggest that attachment and subepithelial cell insertion play the most important role in the initial stage of adherence. The ratios of these modes for living yeast cells were similar to those for dead yeast cells and beads. This suggests that Candida albicans can gain a foothold on the esophageal epithelium solely by physical contact, after which colonization occurs.

Esophageal Candida infection and adherence mechanisms in the nonimmunocompromised rabbit.

Candida infection of the esophagus has been reported not only in immunocompromised hosts but also in healthy individuals. However, its mechanisms of action in healthy individuals have not been clarified. Our previous study suggested that physical contact was an important factor for the adherence of Candida albicans. The aim of the present study was to test our hypothesis and clarify the adherence mechanisms. Suspensions of Candida albicans cells were given to rabbits in drinking water without the use of immunosuppressive drugs and/or antibiotics, and the esophagus was examined. Candidial lesions were observed in 14 of 15 rabbits given the suspensions held in water with and without 30% sucrose for 13 days. The number of Candida albicans cells adhering to the esophagus per square millimeter by subepithelial cell insertion was significantly larger than that adhering by attachment. These results indicate that adherence of Candida albicans to the esophagus occurs by sustained physical contact alone under a nonimmunosuppressive state, and that subepithelial cell insertion results in greater attachment on adherence. Our findings provide a clue that may help clarify the mechanism of Candida infection in healthy individuals.

Isolation and amino acid sequence of a cystatin-type cysteine proteinase inhibitor from bovine hoof.

A low molecular mass cysteine proteinase inhibitor was found and isolated from bovine hoof. Purification of the inhibitor to homogeneity was performed by carboxymethyl-papain-sepharose affinity and DE-52 ion exchange chromatographies. From 15 g of bovine hoof, 0.25 mg of cysteine proteinase inhibitor was isolated. It had 100 amino acid residues and molecular mass of 11 406 Da, and its N-terminus was blocked. The amino acid sequence of the inhibitor demonstrated high similarity with that of the family 1 group, especially bovine thymus-derived cystatin. Thus, in summary, bovine hoof contains a cystatin-type cysteine proteinase inhibitor, presumably a family 1 cystatin.