Search

Kazuhisa Yoshizawa,1 Masahiro Takeshima,2 Sayaka Ishino,3 Masaya Ogasawara,2 Dai Fujiwara,2 Yu Itoh,2 Aya Imanishi,2 Hidenobu Ohta,2 Kazuo Mishima2 1Department of Psychiatry, Akita Prefectural Center for Rehabilitation and Psychiatric Medicine, Daisen City, Akita, 019-2492, Japan; 2Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita City, Akita, 010-8543, Japan; 3Department of Neuropsychiatry, Sugawara Hospital, Yurihonjo City, Akita, 015-0012, JapanCorrespondence: Masahiro TakeshimaDepartment of Neuropsychiatry, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita City, Akita, 010-8543, JapanTel +81-18-884-6122Fax +81-18-884-6445Email m.takeshima@med.akita-u.ac.jpPurpose: A major depressive episode is a risk factor for venous thromboembolism (VTE) in psychiatric inpatients. However, it is unclear whether the severity of depressive symptoms or duration of the current depressive episode is associated with VTE. Further, the VTE prevalence among hospitalized patients with a major depressive episode receiving electroconvulsive therapy is unknown. This retrospective study examined factors associated with VTE among hospitalized patients with a major depressive episode and estimated the prevalence of VTE in such patients who underwent electroconvulsive therapy.Patients and Methods: Patients with a major depressive episode hospitalized in the Department of Neuropsychiatry at Akita University Hospital between January 2018 and December 2020 were included. Data from the first week of hospitalization were extracted from medical records. VTE was diagnosed based on the findings of computed tomography. To evaluate whether the severity of depressive symptoms or duration of the current depressive episode was associated with VTE, logistic regression analysis was conducted after adjusting for covariates with known VTE risk factors (antidepressants, antipsychotics, and physical comorbidities).Results: We analyzed 133 patients; of these, 14 were diagnosed with asymptomatic VTE. The severity of depressive symptoms (odds ratio: 1.220, 95% confidence interval: 1.081– 1.377, p = 0.001) was significantly associated with VTE. The prevalence of VTE among those receiving electroconvulsive therapy was 35% (7/20).Conclusion: The prevalence of VTE was 35% among patients receiving in-hospital electroconvulsive therapy for a major depressive episode. VTE should be considered for hospitalized patients with severe depressive symptoms and patients receiving in-hospital electroconvulsive therapy for a major depressive episode.Keywords: bipolar depression, depressive symptoms, electroconvulsive therapy, unipolar depression, venous thromboembolism

Masahiro Takeshima,1 Hiroyasu Ishikawa,1 Masaya Ogasawara,1 Munehiro Komatsu,2 Dai Fujiwara,1 Yu Itoh,2 Yuki Wada,3 Yuki Omori,4 Hidenobu Ohta,1 Kazuo Mishima1 1Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan; 2Department of Neuropsychiatry, Akita City Hospital, Akita, Japan; 3Department of Radiology, Akita University Graduate School of Medicine, Akita, Japan; 4Department of Neuropsychiatry, Tokyo Metropolitan Geriatric Hospital, Tokyo, JapanCorrespondence: Masahiro TakeshimaDepartment of Neuropsychiatry, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita City, Akita, 010-8543, JapanTel +81-18-884-6122Fax +81-18-884-6445Email m.takeshima@med.akita-u.ac.jpPurpose: D-dimer has the advantage of excluding venous thromboembolism (VTE) due to its high sensitivity but is disadvantageous for diagnosing VTE due to its low specificity. A method to increase the usefulness of D-dimer in the diagnosis of VTE is warranted. This study aimed to investigate the usefulness of the combination of D-dimer and soluble fibrin monomer complex (SFMC), which has been suggested as a new candidate marker for VTE, in VTE diagnosis.Patients and Methods: This prospective study in 109 subjects was performed at a psychiatric department between August 1, 2017 and December 31, 2019. Subjects’ levels of D-dimer and SFMC were measured simultaneously. Plasma levels of D-dimer and SFMC were measured using NANOPIA® D-dimer and NANOPIA® SF. Subjects with positive D-dimer (≥ 1.0 μg/mL) results underwent contrast computed tomography for confirmation of VTE within 12 hours of D-dimer measurement. A receiver operating characteristic curve analysis was performed to examine the usefulness of SFMC for the diagnosis of VTE.Results: Only 109 of the 783 subjects without symptoms suggestive of VTE participated in the study. Out of 41 subjects with positive D-dimer results, 17 subjects were diagnosed with VTE. A receiver operating characteristic curve analysis was performed to determine cutoff values. The area under the curves was 0.848 for SFMC (p< 0.001, 95% CI 0.722 to 0.974), and the optimal cutoff value was 10.0 μg/mL (sensitivity 58.8%, specificity 100%, positive predictive value 100%, negative predictive value 77.4%).Conclusion: SFMC was useful for diagnosing VTE in the psychiatric patients with positive D-dimer results.Keywords: computed tomography, D-dimer, psychiatric patients, soluble fibrin monomer complex, venous thromboembolism

SummaryRNA-binding proteins (RBPs) are essential for post-transcriptional regulation and processing of RNAs. Pathogenic missense variants in RBPs underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, inclusion body myopathy, distal myopathy, and Paget’s disease of the bone. Here, we present ten independent families with a severe, progressive, early-onset muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD), caused by heterozygous frameshift variants in the prion-like domain of hnRNPA2B1. We found that in contrast with the previously reported missense variants, the frameshift hnRNPA2B1 variants do not promote, but rather decelerate the fibrillization of the protein. Importantly, the frameshift variants harbor altered nuclear-localization sequences and exhibit reduced affinity for the nuclear-import receptor, Karyopherin-β2, which promotes their cytoplasmic accumulation in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with hnRNPA2B1 to include a severe, early-onset disease reminiscent of OPMD, caused by a distinct class of frameshift variants that alter its nucleocytoplasmic transport dynamics.

Hideto Sagara,1,2 Tetsuju Sekiryu,2 Hiroki Noji,2 Masashi Ogasawara,2 Kimihiro Imaizumi,2 Keiko Yago31The Marui Eye Clinic, Minamisoma, 2Department of Ophthalmology, School of Medicine, Fukushima Medical University. 3Northern Fukushima Medical Center, Fukushima, JapanAbstract: We present the case of a 47-year-old man who had bilateral proliferative diabetic retinopathy and neovascular glaucoma. Schirmer I test revealed tear secretions of 5 mm and 3 mm in the right and left eyes, respectively. Tear breakup times in the right and left eyes were 7 and 8 seconds, respectively. The ocular surface staining in both eyes was scored as Grade 1 as per the Oxford scheme. Retinal photocoagulation was performed for correction of the proliferative diabetic retinopathy and rubeosis iridis, which resolved with treatment. However, the intraocular pressure in the left eye could not be adequately controlled. Therefore, trabeculectomy with mitomycin C using limbal-based conjunctival flap was performed. Three hours after the surgery, the patient developed a large and diffuse filtering bleb, but no leakage occurred from the conjunctival scar. However, on the first postoperative day, leakage was noted and the conjunctiva was at the leakage point. The leakage resolved transiently, but recurred the next day. Severe keratoconjunctival epithelial failure was detected, and the patient was administrated 0.1% sodium hyaluronate eye drops six times daily. The epithelial failure improved, and many microcysts were detected on the bleb surface where the epithelial failure improved. The leakage resolved 2 days after initiation of the sodium hyaluronate eye drops. The microcysts disappeared and the bleb surface became smooth 1 month later.Keywords: trabeculectomy, bleb, bleb leak, microcyst, sodium hyaluronate

Yumi Nakano,1 Tatsuo Akechi,2 Toshiaki A Furukawa,3 Mayumi Sugiura-Ogasawara4 1Department of Psychology, School of Human Sciences, Sugiyama Jogakuen University, Nisshin, Aichi, Japan; 2Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan; 3Department of Health Promotion and Human Behavior (Cognitive-Behavioral Medicine), Kyoto University Graduate School of Medicine, Kyoto, Japan; 4Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan Objective: To examine the reduction of psychiatric symptoms using individual cognitive behavior therapy (CBT) for women who suffer from recurrent miscarriage (RM) and depression and/or anxiety. Methods: Patients with RM and a score of five or higher for K6, a self-report screening scale for depression/anxiety, were interviewed to find information about stressful situations, thoughts, and consequent behaviors that are common and potential causes of psychological distress among RM patients. We then performed individual CBT on 14 patients with RM and depression/anxiety, referring to a list from the interviews, and examined the effects of CBT by a paired t-test. Results: Fourteen women received CBT. The mean number of intervention times was 8.9 sessions (standard deviation [SD], 4.6 sessions). The average Beck Depression Inventory-Second Edition and State–Trait Anxiety Inventory–state anxiety scores, self-report screening scales for depression/anxiety, decreased from 13.6 (SD, 8.2) and 49.0 (SD, 7.1) at baseline to 5.2 (SD, 4.4) and 38.0 (SD, 10.2) posttherapy, respectively. These changes were statistically significant. Conclusion: The current preliminary open study confirmed that individual CBT was potentially useful for women with RM and depression and/or anxiety. This finding is the first step towards creating a comprehensive psychological support system for women with RM. Keywords: spontaneous abortion, psychological support, depression, anxiety

Hideto Sagara,1,2 Tomohiro Iida,2,3 Kimimori Saito,4 Hiroki Noji,2 Masashi Ogasawara,2 Hiroshi Oyamada21The Marui Eye Clinic, Fukushima, 2Department of Ophthalmology, Fukushima Medical University School of Medicine, Fukushima, 3Tokyo Women's Medical University, Tokyo, 4Matuki Eye Clinic, Fukushima, JapanBackground: Sodium hyaluronate and autologous serum eye drops are used to treat ocular surface disease (OSD) and are reported to prevent and treat late-onset bleb leaks following trabeculectomy with mitomycin C. In this study, we evaluated the efficacy of a combination of sodium hyaluronate and autologous serum eye drops and treatment for obstructive meibomian gland dysfunction as a therapy for late-onset bleb leaks after trabeculectomy with mitomycin C.Methods: This was a retrospective, interventional, nonsimultaneous study of 12 subjects (12 eyes) of mean age of 64.3 ± 18.3 years with OSD and apparent late-onset bleb leaks following trabeculectomy with mitomycin C between 1998 and 2008. We compared patients diagnosed with leakages before July 2005, who had been treated with separate eye drop solutions containing 0.1% sodium hyaluronate, 50% autologous serum, and 0.3% ofloxacin (sodium hyaluronate and autologous serum group, n = 7), with patients diagnosed from August 2005 to December 2008, who were treated with a combination of eye drops (0.1% sodium hyaluronate, 50% autologous serum, and 0.08% levofloxacin hydrate) and eyelid massage and warm compresses for obstructive meibomian gland dysfunction (combination eye drop group, n = 5).Results: Leakage was resolved in one patient (14.3%) in the separately treated sodium hyaluronate and autologous serum eye drop group and in five patients (100%) in the combination eye drop group (P = 0.015). The period after resolution of leakage with conservative treatment was 23 months in the one eye in the sodium hyaluronate and autologous serum group and 36–61 (mean 52.4 ± 10.1) months in the five eyes in the combination eye drop group.Conclusion: Late-onset bleb leaks following trabeculectomy with mitomycin C can be treated effectively using a combination of sodium hyaluronate and autologous serum eye drops, eyelid massage, and warm compresses. Furthermore, combining eye drops may improve patient adherence to the drug regimen by decreasing the frequency of administration.Keywords: ocular surface disease, bleb leak, trabeculectomy, sodium hyaluronate, autologous serum, meibomian gland dysfunction

Migaki-nishin is a Japanese term that refers to dried herring fillets. It is widely consumed in Japan due to its characteristic flavor enhancing properties. This study was conducted to investigate the changes in chemical and sensory properties of migaki-nishin during drying. Chemical analyses showed that extractive nitrogen and amount of peptides increased significantly (P < 0.05) up to the eighth day of drying and then slightly decreased by the tenth day. Glutamic acid, alanine, glycine, and histidine were the most abundant free amino acids and the largest increase was found in samples dried for 10 days. A decrease in Hunter's L* value (lightness) and increase in b* value (yellowness) as well as browning intensity suggested that nonenzymatic browning occurred in migaki-nishin during drying. Fluorescence spectrophotometric determination also revealed that Maillard reactions progressed throughout the drying period. In addition, available lysine content and free amino groups decreased significantly (P < 0.05) as drying progressed. Sensory evaluation showed that addition of water-soluble extracts to Japanese noodle soup (mentsuyu) linearly enhanced the flavor characteristics such as thickness, mouthfulness, and continuity with the increased length of drying time. These results suggest that during the drying period, proteolysis as well as Maillard reaction products increased markedly, which might contribute to the characteristic taste and flavor of migaki-nishin.

症例は74歳,男性. 54歳時,胃潰瘍にて胃幽門側切除術を施行. 1991年10月,脳梗塞で入院.便潜血反応陽性,食欲不振のため消化管精査施行.食道下部(Ei)に高分化型腺癌と印環細胞癌が併存する隆起型腫瘍を認め,腫瘍部を含み5cm以上にわたる全周性のBarrett上皮(special columnar epithelium)がみられた. Barrett食道に分化度の異なる2種の癌が発生した,きわめてまれな症例である.

Irradiated C57BL/6 (B6) and C3H mice were reconstituted with bone marrow cells from BALB/c mice. The chimaeric mice, [BALB/c----B6] and [BALB/c----C3H], developed and expressed contact sensitivity to DNFB. The in vivo responses paralleled to proliferative responses of regional lymph node cells of the chimaeras to DNBS in vitro. Furthermore, intravenous administration of DNBS rendered the chimaeras tolerant to subsequent sensitization with DNFB. The tolerance was transferred to lightly irradiated BALB/c mice by the spleen and lymph node T cells. These results represent marked contrast to our previous observations that [B6----C3H] and [B6----AKR] chimaeras were unable to develop specific unresponsiveness to stimulation with DNFB by the intravenous route. The controversial observations seen in the chimaeras prepared by BALB/c bone marrows and those prepared by B6 cells are discussed.

A monoclonal antibody, Ye-1, was generated by immunizing BALB/c mice with Yersinia enterocolitica. This antibody also reacted with all of 12 B27 positive lymphoblastoid cell lines, but only four of 31 B27 negative ones. Three of the four reactive B27 negative cell lines were B7 positive. A B27 positive cell line which has lost the B27 expression because of experimentally-induced mutation became unreactive with the Ye-1. These findings support the possibility that there is cross-reactivity between HLA-B27 antigens and Y. enterocolitica.

Synthetic tissue sites for the fourth and fifth components of complement (C4 and C5) have been investigated using allogeneic bone marrow chimaeras in mice. One group of chimaeric mice was prepared by transplanting bone marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients or vice versa, and another group was prepared by transplanting marrow cells from mice that produce high levels of C4 into irradiated recipients that are characterized by having low levels of C4 or vice versa. In such chimaeras, lymphoid cells and serum immunoglobulin allotypes were shown to be exclusively of donor origin. However, haemolytic activities of sera from the chimaeras were consistently identical with those of normal mice of the recipient strain. Similar results were obtained when the complement component levels of the sera were evaluated by double diffusion assays. C4 or C5 antigens were detected in sera of the chimaeras only when recipients were strains that are characterized by having high C4 level or were C5-sufficient mice, respectively. These findings indicate that circulating C4 or C5 complement components present in the blood are not synthesized primarily by cells that are descendants of bone marrow cells in these chimaeric mice.

Forschungsarbeit mit dem Ziel, den Verbrennungsvorgang eines intermittierenden Spritznebels im einzelnen zu untersuchen. Zu diesem Zweck wurde eine versuchsweise hergestellte Schnellkomprimierungsmaschine eingesetzt. Der Zweck dieser Maschine bestand darin, über die Hintergründe Klarheit zu schaffen und darüberhinaus den Spritznebel und das Flammenbild sichtbar zu machen, und all das, was von sich aus selbst kein Licht erzeugt, d.h. also die Spritznebelströmung sowie die in der Flamme vorhandenen Öltröpfchen und Rußteilchen usw. in die Bildfläche hereinzubekommen und damit die Voraussetzungen zu schaffen, um ein alle diese Einzelheiten enthaltendes Flammenbild zu erhalten. Bei dieser Forschungsarbeit wurde in einen heißen Hochdruckzylinder, der in eine Schnellkomprimierungsmaschine eingebaut war, jeweils nur einmal der Kraftstoff eingespritzt und dabei mittels vergrößerter Fotos, die von einer Schnellkamera aufgenommen wurden, der Verlauf der Verbrennung beobachtet.

The outer membranes of gram-negative bacteria are considered to be of importance in host-bacteria interaction, in protective immunity, and occasionally in subclassification within a species. In this study, the outer membranes of several strains of Yersinia enterocolitica and Y. pseudotuberculosis were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It was found that the appearance of the major proteins depended on the temperature at which they were solubilized in SDS. A protein was identified with the use of two-dimensional gels and preparative SDS-PAGE, which was equivalent to the "heat-modifiable protein" (protein II) of other Enterobacteriaceae species. A monoclonal antibody, 4G1, was generated against an isolated preparation of this Y. enterocolitica protein. This antibody was tested with whole cell bacterial antigens of 46 individual bacterial strains. The reactive strains included only Y. enterocolitica and Y. pseudotuberculosis. In addition, the reactivity of the 4G1 monoclonal antibody preparation could be absorbed only with Y. enterocolitica and Y. pseudotuberculosis, and not with other strains of bacteria. The reactivity of this 4G1 monoclonal antibody was also tested by the Western Blot technique. Six individual strains were tested: a Y. enterocolitica serotype 0:3, a Y. enterocolitica serotype 0:9, an Escherichia coli, a Salmonella typhimurium, a Shigella flexneri, and a Klebsiella pneumoniae. The 4G1 antibody reacted with only the proteins of the two Y. enterocolitica strains. In conclusion, the equivalent of the heat-modifiable protein was present in Y. enterocolitica and Y. pseudotuberculosis. Moreover, this protein also carried a species-specific antigenic determinant.

To assess the clinical relevance of serum growth-regulated oncogene alpha (GROalpha) levels in gynecological cancer, we investigated its concentration in distinguishing patients with cervical cancer, endometrial cancer, ovarian cancer, benign ovarian tumor and control.Preoperative serum GROalpha levels were measured in women with cervical cancer (n=46), endometrial cancer (n=39), ovarian cancer (n=124), benign ovarian tumors (n=52), and normal controls (n=38) using an enzyme-linked immunosorbent assay.Statistical analyses showed that the serum GROalpha concentration was significantly elevated in the cervical cancer, endometrial cancer and ovarian cancer patients compared with controls. Using GROalpha levels, the receiver operating characteristic (ROC) of cervical cancer (AUC approximately 0.775), endometrial cancer (AUC approximately 0.799), ovarian cancer (AUC approximately 0.749) and benign ovarian tumors (AUC approximately 0.568) vs. controls were identified.Our findings suggest that serum GROalpha measurement as a molecular marker might contribute to detection and diagnosis of gynecological cancer.

Background: Noninvasive prenatal testing (NIPT) has been performed worldwide to detect common fetal chromosomal aneuploidies. Methods: Pregnant women (n=3743) with advanced maternal age who visited Nagoya University for NIPT were enrolled in this study. The K6 mental stress scores, that is non-specific psychological distress scores were obtained by questionnaires which were administered pre-NIPT and postpartum. High K6 scores (≥10) indicate anxiety or depression. The K6 stress scores at pre-NIPT and postpartum were evaluated about the relationship between mode of conception and non-specific psychological distress using binomial logistic regression. Results: In general, 7.5% of pre-NIPT women (179/2393) and 5.1% of postpartum women (121/n) were found with high K6 scores. They also did not differ significantly based on maternal age, previous live birth, previous miscarriage, and mode of conception, i.e., natural conception, artificial insemination with husband (AIH), or assisted reproductive technology (ART). Moreover, the prenatal K6 scores were not significantly higher than those at postpartum. Conclusion: Our present data suggest that mental distress in women undergoing NIPT during pregnancy and after birth has no statistical relationship with maternal age, previous live birth, previous miscarriage, or infertility treatment, and continuous mental care may help reduce mental distress in the postpartum period.

Three strains of bacteria which induce reactive arthritis were collected: a Shigella flexneri, designated 7060; another Sh. flexneri, designated 316; and a Yersinia enterocolitica of serotype 03. Rabbit antisera were generated against each of them to test for the extent and nature of cross-reactivity among these strains. When analysed by the ELISA technique, antisera against 7060 and 316 showed strong cross-reactivity with Y. enterocolitica. In contrast, the reaction of antisera prepared against putatively non-arthritis-causing bacteria reacted several-folds less. Using immunoprecipitation, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western Blot procedures, a 92,000 MW cross-reactive antigen on the Yersinia was identified. The antigen was present on the outer membranes of the Y. enterocolitica, and enzyme digestion experiments showed that this antigen was protein in nature.

ObjectivesTo develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.MethodsThe OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.ResultsAgreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff0.37–0.48).ConclusionWe developed a provisional OGUS for potential use in clinical trials.

The endostyle is a pharyngeal organ for the internal filter feeding of urochordates, cephalochordates, and larval lamprey. This organ is also considered to be homologous to the follicular thyroid gland of higher vertebrates. Thyroglobulin (Tg) and thyroid peroxidase (TPO) are specifically expressed in the thyroid gland of higher vertebrates, and they play an important role in iodine metabolism for the synthesis of thyroid hormones. Previous histochemical observations showed that iodine-concentrating and peroxidase activities were detected in zones 7, 8, and 9 of the ascidian endostyle, suggesting that these zones contains cells that are equivalent to those in the vertebrate follicular thyroid. In order to investigate the molecular developmental mechanisms involved in the formation and function of the endostyle, with special reference to the evolution of the thyroid gland, in the present study, we isolated and characterized cDNA clones for TPO genes, CiTPO from Ciona intestinalis and HrTPO from Halocynthia roretzi. Northern blot and in situ hybridization analyses revealed that the expression of the ascidian TPO genes was restricted to zone 7, one of the elements equivalent to the thyroid. These results provide the first evidence at the gene expression level for shared function between a part of the ascidian endostyle and the vertebrate follicular thyroid gland. J. Exp. Zool. ( Mol. Dev. Evol. ) 285:158–169, 1999. © 1999 Wiley-Liss, Inc.