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Presents recent studies of how antibodies to the amino acid sequence Asp-Asp-Glu-Asp can inhibit transport of nuclear proteins into the nucleus. Details; Conclusions.

Abstract Background Alzheimer’s disease (AD) is the most common form of dementia. Mutations in genes such as those encoding amyloid precursor protein (APP), presenilin 1 and presenilin 2, are responsible for early-onset familial AD. Case presentation In this study, we report a 275341 G > C (Val717Leu) mutation in the APP gene in a Japanese family with early onset AD by genetic screening. This mutation has previously been detected in European families. In the Japanese family we screened, the age at onset of AD was 47.1 ± 3.1 years old (n = 9; range, 42–52). The symptoms in the affected members included psychiatric vulnerability and focal signs such as pyramidal signs, epileptic seizures, and myoclonic discharges. An MR imaging study showed relatively mild atrophic changes in the bilateral hippocampus and cerebral cortices in all affected members compared with their clinical presentations. Conclusion We conclude that the clinical features of Alzheimer’s disease can be different even when caused by the same mutation in the APP gene. Further clinical and genetic studies are required to clarify the relationship between phenotypes and genotypes.

Background: The number of dementia patients is increasing worldwide, especially in Japan, which has the world's highest ageing population. The increase in the number of older people with dementia is a medical and socioeconomic problem that needs to be prevented, but the actual situation is still not fully understood., Methods: Four cross-sectional studies on dementia were conducted in 1997, 2004, 2012, and 2016 for complete enumeration of all residents aged 65 years and older. We examined the secular trends in the prevalence of all-cause dementia, Alzheimer's disease (AD), vascular dementia (VaD), and other/unclassified dementia., Results: The age-standardised prevalence of all-cause dementia significantly increased (4.5% in 1997, 5.7% in 2004, 5.3% in 2012, 9.5% in 2016; P for trend <0.05). Similar trends were observed for AD (1.7%, 3.0%, 2.5% and 4.9%, respectively; P for trend <0.05) and other/unclassified dementia (0.8%, 1.0%, 1.0% and 2.2%, respectively; P for trend <0.05), whereas no significant change in VaD was seen (2.1%, 1.8%, 1.8%, 2.4%, respectively; P for trend = 0.77). The crude prevalence of all-cause dementia and AD increased from 1997 to 2016 among participants aged 75-79 years and ≥85 years (all P for trend <0.05). Similar trends were observed for other/unclassified dementia among participants aged ≥80 years (all P for trend <0.05), but not in VaD., Conclusions: The prevalence of dementia has increased beyond the ageing of the population, suggesting that factors in addition to ageing are involved in the increase in the number of older people with dementia. To control the increase in the number of older people with dementia, elucidation of secular trends in the incidence, mortality, and prognosis of dementia as well as the factors that promote and protect against dementia, and development of preventive strategies are necessary., (© 2022 The Authors. Psychogeriatrics published by John Wiley & Sons Australia, Ltd on behalf of Japanese Psychogeriatric Society.)

Digitized holography techniques are used to reconstruct three-dimensional (3D) images of physical objects using large-scale computer-generated holograms (CGHs). The object field is captured at three wavelengths over a wide area at high densities. Synthetic aperture techniques using single sensors are used for image capture in phase-shifting digital holography. The captured object field is incorporated into a virtual 3D scene that includes nonphysical objects, e.g., polygon-meshed CG models. The synthetic object field is optically reconstructed as a large-scale full-color CGH using red-green-blue color filters. The CGH has a wide full-parallax viewing zone and reconstructs a deep 3D scene with natural motion parallax.

Objective: Impairment of visual perception frequently occurs in Alzheimer's disease (AD) and can cause severe constraints in daily activities. The nonverbal Raven's Colored Progressive Matrices (RCPM) test consists of sets A, AB, and B and is easily performed in a short time to evaluate both visual perception and reasoning ability. The purpose of this study was to evaluate the neural basis of visual perception and reasoning ability in patients with AD using RCPM and single-photon emission computed tomography (SPECT)., Methods: Fifty patients who fulfilled the National Institute on Aging/Alzheimer's Association criteria for probable AD dementia were examined with RCPM and SPECT. All SPECTs were performed using N-isopropyl-p-[ 123 I]-iodoamphetamine. A multiple regression model was used to perform multivariate analyses of the relationships between regional cerebral blood flow (rCBF) and RCPM scores., Results: There was a significant positive correlation between RCPM total score and rCBF in the inferior parietal lobes bilaterally, the right inferior temporal gyrus, and the right middle frontal gyrus. Set A was positively correlated with rCBF in the right temporal and right parietal lobes. Set AB was positively correlated with rCBF in the right temporal, right parietal, and right frontal lobes. Set B was positively correlated with rCBF in the right parietal and right frontal lobes., Conclusion: Our findings suggest that deteriorations of specific brain regions are associated with dysfunction of visual perception and reasoning ability in AD. RCPM is another informative assessment scale of cognition for use in patients with AD. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Bromoderma is a rare skin disorder caused by bromide intake. It presents as single or multiple papillomatous nodules or plaques, and ulcers studded with small pustules on the face or limbs. The clinical features of bromoderma are similar to those of pyoderma gangrenosum. A 41-year-old Japanese woman was diagnosed with pyoderma gangrenosum 11 years prior to presentation. Pyoderma had repeatedly appeared over her entire body despite treatment. She also frequently complained of syncopal episodes. She was admitted to our hospital after loss of consciousness and an episode of generalized convulsion. Laboratory tests revealed a negative serum anion gap and hyperchloremia. Her serum bromide level was significantly elevated, suggesting bromide intoxication. The patient had a 10-year history of high serum bromide levels. After the intake of bromide-containing sedatives was stopped, there was no recurrence of pyoderma in the absence of treatment. In conclusion, this case was diagnosed as bromoderma with commercial sedative-induced bromide intoxication. Although the US Food and Drug Administration have banned the use of bromides, over-the-counter (OTC) treatments containing bromides are still used in Japan and other countries. Long-term use of OTC medicines containing bromvalerylurea may result in the development of bromoderma. If unclarified neurological or psychiatric symptoms are associated with pyoderma, we propose measurement of the patient's serum chloride concentration. Determination of hyperchloremia is helpful for the diagnosis of chronic intoxication with bromides., (© 2015 Japanese Dermatological Association.)

Objective: This aim of this study was to examine the mechanisms underlying the neuropsychiatric symptoms in dementia with Lewy bodies by investigating regional cerebral blood flow., Methods: Participants were 27 patients who fulfilled the diagnostic criteria for probable dementia with Lewy bodies. All subjects underwent single-photon emission computed tomography scans using technetium-99 m hexamethylpropyleneamine oxime. Neuropsychiatric symptoms were evaluated by neuropsychiatric inventory. Multiple regression analyses using neuropsychiatric inventory and voxel-based analyses of covariance of the regional cerebral blood flow images between subjects with or without each neuropsychiatric symptom were performed. Additionally, similar voxel-based analyses of covariance between subjects with each neuropsychiatric symptom and normal subjects were performed., Results: There were no significant correlations in any psychiatric symptoms in multiple regression analyses. All subjects had hallucination but none had euphoria. We analyzed eight neuropsychiatric symptom scores with the exception of hallucination and euphoria using voxel-based analyses of covariance. Significant differences of regional cerebral blood flow were shown in groups with agitation, disinhibition, and irritability. Subjects with agitation showed hypoperfusion in the parietal lobule, the precuneus, and the angular gyrus, and hyperperfusion in the fusiform gyrus, the lingual gyrus, and the thalamus. Subjects with disinhibition showed hypoperfusion in the left frontal gyrus. Subjects with irritability showed hyperperfusion in the right frontal gyrus. There were no significant differences in regional cerebral blood flow between subjects with any neuropsychiatric symptoms and normal subjects., Conclusion: This study reveals that dysfunction of specific brain regions is associated with various neuropsychiatric symptoms in dementia with Lewy bodies., (Copyright © 2015 John Wiley & Sons, Ltd.)

Clozapine is well-known for successful use in schizophrenic patients treatment resistant to other antipsychotics. However, even with clozapine, 25% of schizophrenic patients are not in remission. Recently, as adjunctive treatment with clozapine, electroconvulsive therapy has been reported to be an effective and safe adjunctive treatment. We report a Japanese schizophrenic woman who was not in remission with clozapine alone but with both clozapine and electroconvulsive therapy.

Aim: The purpose of this study was to compare the utility of the Rivermead Behavioural Memory Test (RBMT) and the Alzheimer's Disease Assessment Scale-Cognitive part (ADAS-Cog) for the evaluation of mild cognitive impairment (MCI) or very mild Alzheimer's disease (AD)., Methods: The discriminative abilities of RBMT and ADAS-Cog were compared in the very early stage of AD or MCI patients. Furthermore, we evaluated the difference in both RBMT score and ADAS-Cog score between different severities., Results: Evident superiority in the false negative rate was observed in RBMT over ADAS-Cog in MCI or very mild AD. In addition, 86.7% of the subjects overlooked by ADAS-Cog were correctly detected by RBMT profile score. However, the RBMT score falls in the very early stages and the range of the RBMT score is rather narrow. As a result, it is difficult to evaluate status and follow the progression in severer cases. In contrast to RBMT, the ADAS-Cog score has a wide range and can evaluate and follow the severity in more severe cases., Conclusion: RBMT is more useful than ADAS-Cog in evaluating patients with MCI or very mild AD., (© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.)

Background: Memory impairment has been proposed as the most common early sign of Alzheimer's disease (AD). The aims of this work were to evaluate the risk of progression from mild memory impairment/no dementia (MMI/ND) to clinically diagnosable AD in a community-based prospective cohort and to establish the risk factors for progression from MMI/ND to AD in the elderly., Methods: Elderly subjects aged over 65 years were selected from the participants in the first Nakayama study. MMI/ND was defined as memory deficit on objective memory assessment, without dementia, impairment of general cognitive function, or disability in activities of daily living. A total of 104 MMI/ND subjects selected from 1242 community-dwellers were followed longitudinally for five years., Results: During the five-year follow-up, 11 (10.6%) subjects were diagnosed with AD, five (4.8%) with vascular dementia (VaD), and six (5.8%) with dementia of other etiology. Logistic regression analysis revealed that diabetes mellitus (DM) and a family history of dementia (within third-degree relatives) were positively associated with progression to AD, while no factor was significantly associated with progression to VaD or all types of dementia., Conclusions: DM and a family history of dementia were significant risk factors for progression from MMI/ND to clinically diagnosable AD in the elderly in a Japanese community.

Background: Semantic dementia (SD) has been recognized as a representative of dementia with presenile onset; however, recent epidemiological studies have shown that SD also occurs in the elderly. There have been few studies about the differences of clinical profiles between early-onset SD (EO-SD) and late-onset SD (LO-SD). Age-associated changes in the brain might cause some additional cognitive and behavioural profiles of LO-SD in contrast to the typical EO-SD cases. The aim of the present study was to clarify the characteristics of neuropsychological, and behavioural and psychological symptoms of dementia (BPSD) profiles of LO-SD patients observed in screening tests in comparison with EO-SD patients and late-onset Alzheimer's disease (LO-AD) patients as controls., Methods: Study participants were LO-SD (n = 10), EO-SD (n = 15) and LO-AD (n = 47). We examined the Mini-Mental State Examination (MMSE), the Raven's Coloured Progressive Matrices (RCPM), the Short-Memory Questionnaire (SMQ), the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI)., Results: Both SD groups scored significantly lower than the LO-AD patients in 'naming' of the MMSE. In the 'construction' score of the MMSE and the RCPM score, however, the LO-SD patients as well as the LO-AD patients were significantly lower than the EO-SD patients. In the SMQ score, 'euphoria' and 'disinhibition' scores of the NPI, the SRI total and subscale scores, both SD groups were significantly higher, whereas in the 'delusion' score of the NPI, both SD groups were significantly lower than the LO-AD patients., Conclusions: Visuospatial and constructive skills of LO-SD patients might be mildly deteriorated compared with EO-SD patients, whereas other cognitive and behavioural profiles of LO-SD are similar to EO-SD. Age-associated changes in the brain should be considered when we diagnose SD in elderly patients., (© 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.)

Aim: The aim of this study was to use the Rivermead Behavioural Memory Test (RBMT) to evaluate everyday memory impairment among community-dwelling elderly who had normal cognitive function and performed daily activities normally but displayed memory impairments,and to diagnose the condition as either mild cognitive impairment or dementia., Method: Among the 1,290 community-dwelling elderly persons who participated in the study, 72 subjects scored higher than 24 on the Mini-Mental State Examination (MMSE): these subjects performed daily activities normally, but their family members reported that they showed memory impairments. Fifty-two subjects completed RBMT, Clinical Dementia Rating, and brain computed tomography, and a final diagnosis was established., Results: The mean standard profile score was 15.1+/-5.0 and mean screening score was 6.4+/-3.0. RBMT score was correlated with the MMSE score. Nine of the subjects were diagnosed with dementia and 26 of them were found to be normal. RBMT achieved 100% sensitivity and specificity with regard to the differentiation of subjects with Alzheimer's disease. However, some subjects were diagnosed with dementia even though their RBMT score was higher than the cut-off score., Conclusion: RBMT was useful in detecting memory impairments of AD subjects in community-based surveys. However, some subjects were diagnosed with dementia because of the existence of other cognitive impairments among community-dwelling elderly.

The preservation of procedural memory in individuals with schizophrenia has been confirmed by methods such as the Tower of Hanoi, pursuit rotor and mirror reading tests. However, the cognitive procedural memory of Japanese subjects with schizophrenia has never been assessed using mirror reading. To better determine the characteristics of cognitive procedural memory in schizophrenia, a Japanese version of the mirror reading task, consisting of cards with words written in Japanese katakana characters in mirror image, was administered to 18 Japanese patients with schizophrenia and 21 normal controls. The results indicated that the patients indeed learned the skill despite exhibiting lower overall performances in reading time than the controls, their scores displaying correlation with the severity of schizophrenic negative symptoms. This suggests that procedural memory for this task is retained in individuals with schizophrenia. It is important for them to use their preserved procedural memory for efficient rehabilitative efforts.

Orthodox myringoplasty was clinically compared with a simple method with fibrin glue which rapidly came into wide use after the report of Yuasa in 1989. In Okayama Saiseikai General Hospital, orthodox myringoplasty was performed in 109 ears from September 1988 to November 1995, and the simple method with fibrin glue was performed in 84 ears from May 1991 to November 1995. The results showed that 90.8% of all eardrum perforations treated by orthodox myringoplasty and 79.8% of all eardrum perforations treated by the simple fibrin glue method were successfully closed. The rate of closure with each method was low in patients with large perforations. Generally speaking the hearing prognosis with each method, hearing improvement was observed right after the operation, and the improved hearing became stable about six months later. The difference in hearing prognosis was investigated in patients with small or large perforations. In patients with large perforations, the improved hearing slightly worsened a year after treatment by orthodox myringoplasty. These results show that the simple method with fibrin glue had the advantage of good hearing prognosis over orthodox myringoplasty, while it was inferior in the rate of closure of large eardrum perforations. It was considered that a simple fibrin glue method should be devised to prevent reperforation and should be used for patients with large perforations.

By upper gastrointestinal series, a 57 years-old woman was pointed out to have scattered calcifications along the greater curvature of the stomach. On computerized tomography, the calcifications distributed in the irregularly thickened gastric wall. With a diagnosis of calcified mucinous adenocarcinoma showing Borrmann type III, total gastrectomy with splenectomy was carried out. The characteristics of this lesion were briefly presented with a review of the literature.

Six-week-old male Wistar rats were given a low fat diet containing 15% cod liver oil (FO; n = 30) or 15% safflower oil (SO; n = 30) for 6 weeks. In the polymorphonuclear leukocytes, arachidonic acid (AA) was significantly lower in the FO group than in the SO group (p < 0.001), and eicosapentaenoic acid (EPA) in the FO group was present in large amounts showing the EPA/AA ratio of 1.76. When lipopolysaccharide (LPS; 10mg/kg) was intraperitoneally injected, white blood cell counts in the blood significantly decreased in both groups (p < 0.001) compared to the controls 2 hours later, and at 4 hours, the counts in the SO group (2,033 +/- 151/mm3) were lower than in the FO group (3,189 +/- 624/mm3), (p < 0.01). In both groups, leukotriene B4 (LTB4) in the whole blood increased at 4 hours following LPS-administration compared to the controls (1,219 +/- 167.3pg/ml in the SO group and 600.0 +/- 109.0pg/ml in the FO group, p < 0.001). It should be noted that the level of LTB4 in the SO group was significantly higher than in the FO group (p < 0.001). Changes of the metabolites including decreased LTB4 production in the arachidonic cascade related to the increase of EPA may play a role in the inhibition of the decrease in white blood cell counts.

Thirty patients with adenomyomatosis of the gallbladder (AMG) were operated on between January 1983 and June 1990. They were made up 3.3% of patients who underwent cholecystectomy during the same interval. Of the 30 patients, ages ranged from 22 to 77 years (mean 52.3 years) and the male-to-female ratio was 8:7. Among the macroscopic types, 10 cases of generalized, 12 of segmental (S) and 8 of fundal (F) were noted, and the size of the affected portion in type S (0.8 +/- 0.2 cm, mean +/- SD) was significantly thinner than in other two types (p less than 0.05). Although the main symptom was abdominal pain, the majority of patients with type F had no complaints. Twenty patients (27%) were accompanied by gallstones including cholesterol stones in 60% of cases, and all six cases showing microbes in the bile had gallstones. Only six patients were diagnosed as AMG by preoperative imaging techniques. Other diagnoses comprised 15 of chronic cholecystitis and 3 of suspected gallbladder carcinoma. To identify the expanded Rokitansky-Aschoff sinuses, endoscopic retrograde cholangiography and/or ultrasonography of the abdomen were most useful. No preponderant coexistent lesion other than gallstones was noted. Levels of carcinoembryonic antigen in gallbladder bile in cases of AMG (2.5 +/- 1.5 ng/ml, mean +/- SD) were significantly lower than in gallbladder carcinoma (p less than 0.01). All the patients were easily treated with cholecystectomy, and 24 patients who have been followed up after surgery are doing well.(ABSTRACT TRUNCATED AT 250 WORDS)

Eye movements in response to visual stimuli (Benton Visual Retention Test) were examined in 22 temporal lobe epileptics (TLEs), 10 primary generalized epileptics (PGEs), and 20 normal controls. In the normal controls, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, a tendency also found in the PGEs. In TLEs with right-sided foci, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, the direction of asymmetry found in the normal controls and PGEs. However, when calculated as laterality indices (the degree of asymmetry) TLEs with right-sided foci were significantly more negative than those of both the normal controls and PGEs. In TLEs with left sided foci, the percent fixation time on the right peripheral figure tended to be higher than that on the left peripheral figure, an asymmetry which differed significantly from the normal controls, PGEs and the TLEs with right-sided foci. The results here showed that TLEs with unilateral foci had distinct eye movements which varied with the laterality of the lesion in the direction of functional overactivation of the epileptogenic hemisphere.

The present paper reports 3 cases of aphasia with small lesions in the region of the basal ganglia to discuss whether neostrial dysfunction can cause aphasic symptoms. The Standard Language Tests of Aphasia (SLTA) was used to assess the type and degree of aphasia. Two patients with infarction either in the left putamen or in the head of the left caudate nucleus showed severe disturbance only in recalling words, especially nouns. The other patient showed the same symptom, in addition to writing disturbance that developed shortly after surgical extirpation of an arteriovenous malformation (AVM) in the left caudate nuclei. The symptoms common to the 3 patients corresponded well to the "anomic aphasia" proposed by Benson. The aphasic symptoms disappeared completely or largely within several months. This easy reversibility suggests that the aphasic disorder in the three patients was caused by damage not to the basal ganglia themselves, but to the affecting axons passing through or by the nuclei.

An extremely high incidence of reappearing cyst of the pancreas (24.1%; 7 out of 29 patients) was noted in the present survey. However, reappearance could have been avoided in the majority of cases with the use of thorough pre- and peri-operative assessments of the extent of cystic lesion of the pancreas. The recurrence rate after surgical treatment for pseudocysts (13.6%; 3 out of 22 patients) was similar compared with usual recurrence rate of approximately 10 percent. If the reappearing cyst is a retention cyst or a pseudocyst, a minimally aggressive procedure should initially be considered to aid its resolution. A part of this study was reported at the 51st meeting of the Japanese Society for Clinical Surgery on November 2, 1989 at Kobe, Japan.

We studied the mechanism of transport of proteins into the nucleus using synthetic peptides containing the nuclear location signal sequence of Simian virus 40 (SV 40) large T-antigen. When chick erythrocytes containing a synthetic large T-antigen nuclear translocation signal were fused with SV 40-transformed human fibroblasts, the migration of native large T-antigen into the chick nuclei was suppressed. Migration of proteins detected by human specific antinuclear autoimmune antibody was not blocked. An analog of the nuclear location signal peptide did not inhibit entry of large T-antigen into the chick nuclei. This result suggests that the peptide blocked the migration of only native large T-antigen into the nucleus, and that the signal of the majority of nuclear proteins for nuclear transport is not the same as that of the large T-antigen. The synthetic peptide was conjugated chemically with bovine serum albumin (BSA) and introduced into the cytoplasm of cultured human cells by red blood cell ghost-mediated microinjection. The BSA-synthetic peptide conjugate was found predominantly in the nucleus within 2 h after its introduction into the cells. BSA conjugated with the cross-linking reagent alone was not transported into the nucleus. Acetylated synthetic peptide was not effective in promoting nuclear localization of BSA. Mild trypsin treatment of the BSA-synthetic peptide conjugate suppressed nuclear localization. Conjugates of the synthetic peptide with phycoerythrin (Mr about 150 kD) and with secretory IgA (Mr about 380 kD) were both found in the nucleus very shortly after their introduction into the cytoplasm. These results suggest that the synthetic peptide containing the nuclear location signal sequence provides exogenous proteins with the ability to migrate into the nucleus. But, since a conjugate of the synthetic peptide with IgM (Mr about 940 kD) did not migrate into the nucleus after its microinjection, there may be a size limit in nuclear transport of conjugated proteins.

The importance of glycoproteins located in the nuclear envelope in nuclear transport was tested by microinjection of karyophilic proteins into the cytoplasm of cultured human cells together with various lectins. Wheat germ agglutinin (WGA) blocked the nuclear transport of nucleoplasmin, a nuclear protein of Xenopus laevis oocytes, and of nonnuclear proteins conjugated with a synthetic peptide containing the nuclear localization signal sequence for simian virus 40 (SV40) large T antigen. Its inhibitory activity persisted for about 1 h after its injection into the cells and then gradually decreased. Export of at least some kinds of RNA from the nucleus seemed not to be affected by WGA even when import of the proteins into the nucleus was completely blocked (within 1 h after WGA injection). Moreover, WGA did not inhibit the passive diffusion of fluorescein isothiocyanate (FITC)-dextran (average Mr 17,900) into the nucleus. Wistaria floribunda agglutinin (WFA), concanavalin A (Con A), and lentil lectin did not block nuclear transport. These results indicate that WGA specifically blocks active protein import, but not passive diffusion of materials into the nucleus.