Molecular basis for SMC rod formation and its dissolution upon DNA binding.

SMC condensin complexes are central modulators of chromosome superstructure in all branches of life. Their SMC subunits form a long intramolecular coiled coil, which connects a constitutive "hinge" dimerization domain with an ATP-regulated "head" dimerization module. Here, we address the structural arrangement of the long coiled coils in SMC complexes. We unequivocally show that prokaryotic Smc-ScpAB, eukaryotic condensin, and possibly also cohesin form rod-like structures, with their coiled coils being closely juxtaposed and accurately anchored to the hinge. Upon ATP-induced binding of DNA to the hinge, however, Smc switches to a more open configuration. Our data suggest that a long-distance structural transition is transmitted from the Smc head domains to regulate Smc-ScpAB's association with DNA. These findings uncover a conserved architectural theme in SMC complexes, provide a mechanistic basis for Smc's dynamic engagement with chromosomes, and offer a molecular explanation for defects in Cornelia de Lange syndrome.

A novel 3' splice site recognition by the two zinc fingers in the U2AF small subunit.

The pre-mRNA splicing reaction of eukaryotic cells has to be carried out extremely accurately, as failure to recognize the splice sites correctly causes serious disease. The small subunit of the U2AF heterodimer is essential for the determination of 3' splice sites in pre-mRNA splicing, and several single-residue mutations of the U2AF small subunit cause severe disorders such as myelodysplastic syndromes. However, the mechanism of RNA recognition is poorly understood. Here we solved the crystal structure of the U2AF small subunit (U2AF23) from fission yeast, consisting of an RNA recognition motif (RRM) domain flanked by two conserved CCCH-type zinc fingers (ZFs). The two ZFs are positioned side by side on the ß sheet of the RRM domain. Further mutational analysis revealed that the ZFs bind cooperatively to the target RNA sequence, but the RRM domain acts simply as a scaffold to organize the ZFs and does not itself contact the RNA directly. This completely novel and unexpected mode of RNA-binding mechanism by the U2AF small subunit sheds light on splicing errors caused by mutations of this highly conserved protein.

Accuracy of Therapeutic Drug Monitoring of Teicoplanin at the Onset of Febrile Neutropenia.

Background and Objectives: Teicoplanin (TEIC) is an effective drug for patients with febrile neutropenia (FN); however, it has been reported that these patients may have increased TEIC clearance compared with patients who do not have FN. The purpose of this study was to study therapeutic drug monitoring in patients with FN when the TEIC dosing design was based on the population mean method. Materials and Methods: Thirty-nine FN patients with hematological malignancy were included in the study. To calculate the predicted blood concentration of TEIC, we used the two population pharmacokinetic (population PK) parameters (parameters 1 and 2) reported by Nakayama et al. and parameter 3, which is a modification of the population PK of Nakayama et al. We calculated the mean prediction error (ME), an indicator of prediction bias, and the mean absolute prediction error (MAE), an indicator of accuracy. Furthermore, the percentage of predicted TEIC blood concentration within 25% and 50% of the measured TEIC blood concentration was calculated. Results: The ME values were -0.54, -0.25, and -0.30 and the MAE values were 2.29, 2.19, and 2.22 for parameters 1, 2, and 3, respectively. For all of the three parameters, the ME values were calculated as minus values, and the predicted concentrations tended to be biased toward smaller values relative to the measured concentrations. Patients with serum creatinine (Scr) < 0.6 mg/dL and neutrophil counts < 100/µL had greater ME and MAE values and a smaller percentage of predicted TEIC blood concentration within 25% of measured TEIC blood concentrations compared with other patients. Conclusions: In patients with FN, the accuracy of predicting TEIC blood concentrations was good, with no significant differences between each parameter. However, patients with a Scr < 0.6 mg/dL and a neutrophil count < 100/µL showed slightly inferior prediction accuracy.

[A Case of Hepatic Undifferentiated Embryonal Sarcoma in an Adult].

A 20-year-old woman was admitted with abdominal pain and a cystic liver tumor. A hemorrhagic cyst was suspected. Contrast-enhanced computed tomography(CT)and magnetic resonance imaging(MRI)revealed a space-occupying solid mass in the right lobule. Positron emission tomography(PET)-CT revealed 18F-fluorodeoxyglucose uptake in the tumor. We performed a right hepatic lobectomy. Histopathological evaluation of the resected tumor revealed an undifferentiated embryonal sarcoma of the liver(UESL). The patient refused adjuvant chemotherapy but showed no recurrence 30 months postoperatively. UESL is a rare malignant mesenchymal tumor that occurs in infants and children. It is extremely rare and is associated with poor prognosis in adults. In this report, we described a case of adult UESL.

[A Case of Laparoscopic Resection Following Preoperative Chemoradiotherapy of a Locally Recurrent Rectal Cancer after a Prior Endoscopic Curative Resection].

A man in his seventies underwent endoscopic mucosal resection(EMR)of a rectal cancer 3 years ago. Histopathological examination showed that the specimen had been resected curatively. However, a routine follow-up colonoscopy revealed a submucosal mass on the EMR scar. Computed tomography imaging revealed a mass in the posterior wall of the rectum, with suspected invasion of the sacrum. We performed a biopsy during endoscopic ultrasonography and diagnosed a local recurrence of the rectal cancer. After preoperative chemoradiotherapy(CRT), laparoscopic low anterior resection with ileostomy was performed. Histopathological examination revealed invasion of the rectal wall from the muscularis propria to the adventitia and tissue fibrosis at the radial margin, which was devoid of cancerous cells. Subsequently, the patient received adjuvant chemotherapy with uracil/tegafur and leucovorin for 6 months. No recurrence has been reported over a postoperative follow- up period of 4 years. Preoperative CRT may be an effective treatment for locally recurrent rectal cancer after endoscopic resection.

[A Case Report of Rectal MiNEN Laparoscopic Resection].

A 74-year-old woman underwent colonoscopy for positive fecal occult blood test. A colonoscopy revealed a Type 1 tumor in the rectosigmoid region. The tumor was diagnosed as well-differentiated adenocarcinoma(tub1)by biopsy. Laparoscopic high anterior resection was performed. The final diagnosis was MiNEN(adenocarcinoma:NEC=6:4), RS, pT4a(SE), INF c, Ly1c, V1b, Pn1b, BD2, pN2a(5/28), cM0, pStage Ⅲc. All lymph node metastases were of NEC origin. This case was considered to be at high risk of recurrence and require adjuvant chemotherapy focused on NEC. She was referred to an advanced medical institution for carboplatin and etoposide therapy. MiNEN is a rare disease, and has a poor prognosis. In order to establish a therapeutic strategy of MiNEN, it is important to accumulate further cases and evidence.

Early Elevation of Cell-Free DNA After Acute Mesenteric Ischemia in Rats.

BACKGROUND: Acute mesenteric ischemia (AMI) is challenging to diagnose in the early phase. We tested the hypothesis that blood levels of cell-free DNA would increase early after AMI. In addition, proteome analysis was conducted as an exploratory analysis to identify other potential diagnostic biomarkers. METHODS: Mesenteric ischemia, abdominal sepsis, and sham model were compared in Sprague-Dawley rats. The abdominal sepsis model was induced by cecum puncture and mesenteric ischemia model by ligation of the superior mesenteric artery. Blood levels of cell-free DNA were measured 2 h and 6 h after wound closure. Shotgun proteome analysis was performed using plasma samples obtained at the 2 h timepoint; quantitative analysis was conducted for proteins detected exclusively in the AMI models. RESULTS: Blood cell-free DNA levels at 2 h after wound closure were significantly higher in the AMI model than in the sham and the abdominal sepsis models (P < 0.05). Cell-free DNA was positively correlated with the pathologic ischemia severity score (correlation coefficient 0.793-0.834, P < 0.001). Derivative proteome analysis in blood at 2-h time point revealed higher intensity of paraoxonase-1 in the AMI models than in the abdominal sepsis models; the significantly high blood paraoxonase-1 levels in the AMI models were confirmed in a separate quantitative analysis (P = 0.015). CONCLUSIONS: Cell-free DNA was demonstrated to be a promising biomarker for the early diagnosis of mesenteric ischemia in a rat model of AMI. Paraoxonase-1 may also play a role in the differential diagnosis of mesenteric ischemia from abdominal sepsis. The current results warrant further investigation in human studies.

Calcium sensing via EF-hand 4 enables thioredoxin activity in the sensor-responder protein calredoxin in the green alga Chlamydomonas reinhardtii.

Calcium (Ca2+) and redox signaling enable cells to quickly adapt to changing environments. The signaling protein calredoxin (CRX) from the green alga Chlamydomonas reinhardtii is a chloroplast-resident thioredoxin having Ca2+-dependent activity and harboring a unique combination of an EF-hand domain connected to a typical thioredoxin-fold. Using small-angle X-ray scattering (SAXS), FRET, and NMR techniques, we found that Ca2+-binding not only induces a conformational change in the EF-hand domain, but also in the thioredoxin domain, translating into the onset of thioredoxin redox activity. Functional analyses of CRX with genetically altered EF-hands revealed that EF-hand 4 is important for mediating the communication between the two domains. Moreover, we crystallized a variant (C174S) of the CRX target protein peroxiredoxin 1 (PRX1) at 2.4 Å resolution, modeled the interaction complex of the two proteins, and analyzed it by cross-linking and MS analyses, revealing that the interaction interface is located close to the active sites of both proteins. Our findings shed light on the Ca2+ binding-induced changes in CRX structure in solution at the level of the overall protein and individual domains and residues.

[A Case of Squamous Cell Carcinoma of the Lung from Gastrointestinal Perforation Due to Small Intestinal Metastasis].

An 80s male, with a medical history of hypertension, hyperuricemia, and atrial fibrillation, visited our emergency outpatient department with vomiting and diarrhea as the chief complaint in August 2017. The blood examination revealed a high level of inflammatory reaction. The plain abdominal CT revealed fluid retention contacting the small intestine and intraabdominal free gas. We diagnosed the case as a small intestinal perforation, following which we performed emergency surgery. The small intestine was perforated, and an abscess cavity was formed between the transverse mesocolon and mesentery proper. Thus, the abscess was removed, and about 30 cm of the small intestine, including the perforated site, was resected, followed by the reconstruction. The resected specimens revealed squamous cell carcinoma at the small intestinal perforated site. Lung squamous cell carcinoma was diagnosed by subsequent chest CT and immunostaining. We administered 3 courses of chemotherapy combined with carboplatin and albumin-bound paclitaxel. Although the effect was partially observed, interstitial pneumonia occurred, which was inferred to be drug-induced. The patient died in 195 days following the surgery. Herein, we reported a case of lung cancer, which was diagnosed on the detection of gastrointestinal perforation caused by a small intestinal metastasis.

[Two Cases of Laparoscopic Partial Resection of Stomach Using a Trans-Gastric Wall Approach for Submucosal Tumors].

We performed laparoscopic partial resection of the stomach with a trans-gastric wall approach for submucosal tumors. Case 1: A 67-year-old woman was referred to our hospital because of tarry stool. Upper gastrointestinal endoscopy revealed a well demarcated, round, 45mm intraluminal-type submucosal tumor with delle on the anterior wall of the gastric upper body. Case 2: An 86-year-old woman was referred to our hospital because of anemia. Upper gastrointestinal endoscopy revealed a well demarcated, round, 25mm intraluminal-type submucosal tumor on the posterior wall of the gastric upper body. Laparoscopic partial resection of the stomach with a trans-gastric wall approach was performed. The operation times were 58 minutes and 73 minutes, respectively, and blood loss was low in both cases. This operative procedure is safe and easy and allows for resection resected with a direct view for surgeons without endoscopists.

Biosynthesis of bismuth selenide nanoparticles using chalcogen-metabolizing bacteria.

Cost and energy reductions in the production process of bismuth chalcogenide (BC) semiconductor materials are essential to make thermoelectric generators comprised of BCs profitable and CO2 neutral over their life cycle. In this study, as an eco-friendly production method, bismuth selenide (Bi2Se3) nanoparticles were synthesized using the following five strains of chalcogen-metabolizing bacteria: Pseudomonas stutzeri NT-I, Pseudomonas sp. RB, Stenotrophomonas maltophilia TI-1, Ochrobactrum anthropi TI-2, and O. anthropi TI-3 under aerobic conditions. All strains actively volatilized selenium (Se) by reducing selenite, possibly to organoselenides. In the growth media containing bismuth (Bi) and Se, all strains removed Bi and Se concomitantly and synthesized nanoparticles containing Bi and Se as their main components. Particles synthesized by strain NT-I had a theoretical elemental composition of Bi2Se3, whereas those synthesized by other strains contained a small amount of sulfur in addition to Bi and Se, making strain NT-I the best Bi2Se3 synthesizer among the strains used in this study. The particle sizes were 50-100 nm in diameter, which is sufficiently small for nanostructured semiconductor materials that exhibit quantum size effect. Successful synthesis of Bi2Se3 nanoparticles could be attributed to the high Se-volatilizing activities of the bacterial strains. Selenol-containing compounds as intermediates of Se-volatilizing metabolic pathways, such as methane selenol and selenocysteine, may play an important role in biosynthesis of Bi2Se3.

The use of a fertile doubled haploid apple line for QTL analysis of fruit traits.

Apple is an economically important crop, and various approaches to genetic analysis in breeding programs have been attempted, including the production of doubled haploid (DH) lines, which are genetically homozygous. In this study, we used a DH line for QTL analyses, for the first time in a fruit tree, expecting it to simplify the analysis of the inheritance of quantitative traits and thus to enhance QTL detection power. Using an F1 population from 'Prima' × 'Apple Chukanbohon 95P6' (DH), we constructed a genetic map of 'Prima', and identified 19 QTLs for 13 traits. These QTLs had comparatively high LOD scores and explained a large part of the variation of the phenotypes. In particular, acidity, juice browning, and skin splitting clearly segregated at a 1:1 ratio, consistent with the segregation of the alleles at the detected QTLs in linkage group 16; these traits appeared to be regulated by single genes, despite general consideration that they are quantitative traits. Using this simple genetic composition of the F1 population, we concluded that the skin splitting of apple fruit has recessive inheritance, and that the allele for splitting is tightly linked with those for high acidity and low juice browning in 'Prima'.

[Two Cases of Resectable Intra-Abdominal Desmoid Tumor after Laparoscopic Gastrectomy for Gastric Cancer].

Case 1: A 52-year-old man underwent laparoscopic total gastrectomy for gastric cancer. After 2 years, a follow-up computed tomography(CT)scan showed a large, solid 10 cm-sized mass in his left upper abdomen. Under the diagnosis of a suspected mesenchymal tumor, a tumor resection with a partial resection of the upper jejunum and transverse colon was performed. Case 2: A 61-year-old man underwent laparoscopic pylorus-preserving gastrectomy for gastric cancer. After 1.5 years, follow-up CT showed a tumor of 2 cm in diameter near the greater curvature side of the upper stomach. Under the diagnosis of a suspected gastrointestinal stromal tumor(GIST), a laparoscopic partial resection of the stomach was performed. Histologically, spindle-shaped cells without atypia and rich collagen fibers were observed, and the sample was positive for b-catenin by immunostaining in both cases; from this evidence, the patients were diagnosed with desmoid tumors. Desmoid tumors have invasive proliferation characteristics, and treatment requires consideration of the balance between securing a surgical margin and increasing surgical stress.

Physical therapy intervention with a low frequency of exercise for a patient with a complicated form of hereditary spastic paraplegia: a case report.

[Purpose] Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder characterized by progressive spasticity and weakness of the lower limbs. To date, the appropriate frequency and intensity of physical therapy for patients with HSP are not well-known. We created an original rehabilitation program for a patient with a complicated form of HSP, wherein the program required low-frequency involvement to adapt to the long-term insurance system in Japan. We wanted to find out whether this program could maintain the physical functions and activities of daily living (ADL) of the patient. [Participant and Methods] A 41-year-old male diagnosed with a complicated form of HSP with decreased visual acuity and ataxia of the trunk and upper limb underwent a specific rehabilitation program that included a squatting exercise, a kneeling position exercise, and a motion exercise of taking a bath. This intervention program lasted for 20 minutes per session, with a frequency of two days per week. The patient was in the program for 12 weeks. [Results] All outcome measures, including muscle strength (grip force and quadriceps) and Barthel index, remained unchanged at the end of the intervention program. [Conclusion] The original intervention program used in this study, which had a low frequency of exercise, was effective in preventing further regression of the lower limb function of the patient with a complicated form of HSP, and in preventing a decrease in the ability of the patient to perform ADL.

Structural analysis of the STAT1:STAT2 heterodimer revealed the mechanism of Sendai virus C protein-mediated blockade of type 1 interferon signaling.

Sendai virus (SeV), which causes respiratory diseases in rodents, possesses the C protein that blocks the signal transduction of interferon (IFN), thereby escaping from host innate immunity. We previously demonstrated by using protein crystallography that two molecules of Y3 (the C-terminal half of the C protein) can bind to the homodimer of the N-terminal domain of STAT1 (STAT1ND), elucidating the mechanism of inhibition of IFN-γ signal transduction. SeV C protein also blocks the signal transduction of IFN-α/ß by inhibiting the phosphorylation of STAT1 and STAT2, although the mechanism for the inhibition is unclear. Therefore, we sought to elucidate the mechanism of inhibition of the IFN signal transduction via STAT1 and STAT2. Small angle X-ray scattering analysis indicated that STAT1ND associates with the N-terminal domain of STAT2 (STAT2ND) with the help of a Gly-rich linker. We generated a linker-less recombinant protein possessing a STAT1ND:STAT2ND heterodimeric structure via an artificial disulfide bond. Analytical size-exclusion chromatography and surface plasmon resonance revealed that one molecule of Y3 can associate with a linker-less recombinant protein. We propose that one molecule of C protein associates with the STAT1:STAT2 heterodimer, inducing a conformational change to an antiparallel form, which is easily dephosphorylated. This suggests that association of C protein with the STAT1ND:STAT2ND heterodimer is an important factor to block the IFN-α/ß signal transduction.

Structural basis of autoinhibition and activation of the DNA-targeting ADP-ribosyltransferase pierisin-1.

ADP-ribosyltransferases transfer the ADP-ribose moiety of ßNAD+ to an acceptor molecule, usually a protein that modulates the function of the acceptor. Pierisin-1 is an ADP-ribosyltransferase from the cabbage butterfly Pieris rapae and is composed of N-terminal catalytic and C-terminal ricin B-like domains. Curiously, it ADP-ribosylates the DNA duplex, resulting in apoptosis of various cancer cells, which has raised interest in pierisin-1 as an anti-cancer agent. However, both the structure and the mechanism of DNA ADP-ribosylation are unclear. Here, we report the crystal structures of the N-terminal catalytic domain of pierisin-1, its complex with ßNAD+, and the catalytic domain with the linker connecting it to the ricin B-like domains. We found that the catalytic domain possesses a defined, positively charged region on the molecular surface but that its overall structure is otherwise similar to those of protein-targeting ADP-ribosyltransferases. Electrophoretic mobility shift assays and site-directed mutagenesis indicated that pierisin-1 binds double-stranded but not single-stranded DNA and that Lys122, Lys123, and Lys124, which are found in a loop, and Arg181 and Arg187, located in a basic cleft near the loop, are required for DNA binding. Furthermore, the structure of the catalytic domain with the linker revealed an autoinhibitory mechanism in which the linker occupies and blocks both the ßNAD+- and DNA-binding sites, suggesting that proteolytic cleavage to remove the linker is necessary for enzyme catalysis. Our study provides a structural basis for the DNA-acceptor specificity of pierisin-1 and reveals that a self-regulatory mechanism is required for its activity.

Comparison of changes in the oxygenated hemoglobin level during a 'modified rock-paper-scissors task' between healthy subjects and patients with schizophrenia.

AIM: The purpose of this study, using single-event-related near-infrared spectroscopy (NIRS), was to examine the psychophysiological and social function assessment of 30 schizophrenic patients during a modified rock-paper-scissors task. METHODS: We set up a screen in front of the subjects, on which pictures of hand-gestures for rock, paper, and scissors were randomly presented. Subjects were asked to give verbal answers under the conditions of win, lose, and draw, respectively. Using the 44-channel NIRS system, we evaluated the maximum amplitude of oxygenated hemoglobin, latency, and the area based on the arithmetic mean of resulting values after the task between 30 outpatients with schizophrenia and 30 healthy subjects, and analyzed the frontal pole area, dorsolateral prefrontal region, and parietal association area as regions of interest (ROI). RESULTS: In schizophrenic patients, oxygenated hemoglobin changes (Δoxy-Hb) when losing the task showed a significantly lower level of Δoxy-Hb in ROI than controls. In addition, a significant positive correlation was observed between the Global Assessment of Functioning Scale and Δoxy-Hb in ROI, and a significant negative correlation was observed between the Negative Syndrome scale of the Positive and Negative Syndrome Scale and Δoxy-Hb in ROI. CONCLUSION: From these results, we conclude that Δoxy-Hb levels when performing the modified rock-paper-scissors task assessed using NIRS may be a useful psychophysiological marker to evaluate the cognitive and social functions of schizophrenic patients.

Characteristics of oxygenated hemoglobin concentration change during pleasant and unpleasant image-recall tasks in patients with depression: Comparison with healthy subjects.

AIM: Patients with major depressive disorder (MDD) have been reported to show cognitive impairment in attention, cognition control, and motivation. The prefrontal cortex plays an important role in the pathophysiology of depression. Neurophysiological abnormalities have been examined in MDD patients by several neuroimaging studies. However, the underlying neural mechanism is still unclear. We evaluated brain function during pleasant and unpleasant image-recall tasks using multichannel near-infrared spectroscopy (NIRS) in MDD patients. METHODS: The subjects were 25 MDD patients and 25 age- and sex-matched healthy controls. Patients were classified according to DSM-IV-TR criteria. We measured the oxygenated hemoglobin concentration change (δoxyHb) in the forehead and temporal lobe during image-recall task with pleasant (e.g., puppy) and unpleasant (e.g., snake) images using NIRS. To check whether all subjects understood the task, they were asked to draw pictures of both image tasks after NIRS measurement. RESULTS: The δoxyHb in the healthy group was significantly higher than that in the MDD group in the bilateral frontal region during the unpleasant condition. A significant negative correlation between the Hamilton Rating Scale for Depression score and δoxyHb was observed in the left frontal region during the unpleasant condition. CONCLUSION: We suggest that image-recall tasks related to emotion measured by NIRS might be a visually useful psychophysiological marker to understand the decrease in the frontal lobe function in MDD patients. In particular, we suggest that the decrease in δoxyHb in the left frontal lobe is related to the severity of depression.

Crystal structure of the human centromeric nucleosome containing CENP-A.

In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment. Centromeres specify the kinetochore formation sites on individual chromosomes, and are epigenetically marked by the assembly of nucleosomes containing the centromere-specific histone H3 variant, CENP-A. Although the underlying mechanism is unclear, centromere inheritance is probably dictated by the architecture of the centromeric nucleosome. Here we report the crystal structure of the human centromeric nucleosome containing CENP-A and its cognate α-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome, the DNA is wrapped around the histone octamer, consisting of two each of histones H2A, H2B, H4 and CENP-A, in a left-handed orientation. However, unlike the canonical H3 nucleosome, only the central 121 base pairs of the DNA are visible. The thirteen base pairs from both ends of the DNA are invisible in the crystal structure, and the αN helix of CENP-A is shorter than that of H3, which is known to be important for the orientation of the DNA ends in the canonical H3 nucleosome. A structural comparison of the CENP-A and H3 nucleosomes revealed that CENP-A contains two extra amino acid residues (Arg 80 and Gly 81) in the loop 1 region, which is completely exposed to the solvent. Mutations of the CENP-A loop 1 residues reduced CENP-A retention at the centromeres in human cells. Therefore, the CENP-A loop 1 may function in stabilizing the centromeric chromatin containing CENP-A, possibly by providing a binding site for trans-acting factors. The structure provides the first atomic-resolution picture of the centromere-specific nucleosome.

Evaluation of changes in oxyhemoglobin during Shiritori task in elderly subjects including those with Alzheimer‧s disease.

BACKGROUND: In recent years, as the prevalence of Alzheimer‧s disease (AD) has increased rapidly, demand has increased for early detection and treatment. Therefore, discovery and treatment intervention at the mild cognitive impairment stage are important. Dysfunction of the working memory is known to be conspicuously present in AD patients or mild cognitive impairment subjects from an early stage. Near-infrared spectroscopy (NIRS) is a method to measure hemoglobin concentration changes during an activation task. In the present study, we evaluated the cognitive function of elderly subjects, including those with AD, by means of NIRS. METHODS: The subjects were divided into three groups-the AD group, the intermediate group, and the healthy group (HG)-based on assement of dementia using the Hasegawa‧s Dementia Scale-Revised, Mini-Mental State Examination, and Clinical Dementia Rating. The intermediate group was divided into two groups-the high score group (HSMG) and the low score group (LSMG)-based on Hasegawa‧s Dementia Scale-Revised and Mini-Mental State Examination scores. In this study, during Shiritori tasks using single-event-related NIRS, we analyzed oxyhemoglobin changes in an area, the peak amplitude, and latency, and compared them among four groups: AD group, HSMG, LSMG, and HG. RESULT: In the AD group, the area at left channel (Ch)9, 11, and 19, the area at right Ch22, and the peak ampulitude at left Ch11 and 19 and right Ch5,12, and 22 were significantly smaller than those in HSMG and HG. Furthermore, the latency of the AD group was significantly longer than that of HSMG and HG at all region of interests. However, no significant difference was observed between the AD group and LSMG. CONCLUSION: These findings suggest that analysis of changes in oxyhemoglobin during Shiritori tasks may be a useful neuropsychological index for the early diagnosis of AD. Detailed studies will be conducted in LSMG to facilitate the early introduction of NIRS as a screening tool for cognitive impairment.