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Rationale: Despite accumulating evidence that psychological stress has a short-lasting detrimental effect on asthma, little is known about the way stress in childhood predisposes to adult asthma. Objectives: Using a communication box, we investigated the long-lasting effect of early psychological and physical stress on adult asthma in mice. Methods: Male BALB/c mice were exposed to either psychological stress or physical stress three times (every other day) during their fourth week of life. The mice were sensitized to ovalbumin at 8 and 10 weeks, and an ovalbumin airway challenge was conducted at the age of 11 weeks. Results: Twenty-four hours after ovalbumin challenge, both psychological and physical stress-exposed mice exhibited a significant acceleration in the number of total mononuclear cells and eosinophils and airway hyperresponsiveness compared with control mice. No differences in serum anti-OVA-specific immunoglobulin E levels were found between stress-exposed and control animals after antigen sensitization. In the psychological stress group, but not in the physical stress group, an elevation of the serum corticosterone levels during ovalbumin challenge was significantly attenuated in comparison with the control group. Moreover, pretreatment with RU-486, a glucocorticoid receptor antagonist, before ovalbumin challenge completely inhibited a psychological stress-induced exacerbation of asthma. However, pretreatment with GR-82334, a neurokinin-1 receptor antagonist, failed to affect physical stress-induced augmentation of airway inflammation. Conclusion: Early psychological and physical stresses aggravated adult asthma via hyporesponsiveness of the hypothalamic-pituitary-adrenal axis during antigen challenge and via a pathway(s) distinct from the hypothalamic-pituitary-adrenal axis or neurokinin-1 receptors. [ABSTRACT FROM AUTHOR]

Exposure to 600 rad of X-irradiation 3 h after primary immunization with chicken erythrocytes (CRBC) abolished the production of antibodies and the generation of killer T cells, but scarcely affected the induction of delayed footpad reactions. Exposure to irradiation 3 h after secondary immunization reduced only slightly the generation of killer T cells and reduced slightly or substantially the production of antibodies. Delayed reactions persisted for long periods after elicitation in irradiated, boosted mice. Cross-reactivity between CRBC and quail erythrocytes (QRBC) was very weak with respect to the tyrotoxicity, antibody and delayed reaction raised after primary immunization. Those raised after secondary immunization with the homologous antigen showed some degrees of cross-reactivity to another antigen. The booster with QRBC in CRBC-primed mice augmented the response to CRBC with respect to the induction of cytotoxicity and delayed footpad reaction, but only weakly affected the response with respect to the production of antibody. Therefore, effector cells of cytotoxicity and delayed footpad reaction showed greater degrees of cross-reactivity than antibody-producing cells during an anamnestic response. The cross-reactive response raised after secondary immunization was radioresistant with respect to cytotoxicity and delayed footpad reaction but radiosensitive with respect to antibody production. Cytotoxicity to immunizing antigen was inhibited by the unlabelled homologous antigen. Cytotoxicity to a cross-reacting antigen was inhibited by the same cross-reacting antigen and also by an immunizing antigen. There may exist heterogeneous populations of cytotoxic lymphocytes with different abilities to recognize antigens. [ABSTRACT FROM AUTHOR]

Direct cytotoxicity raised at an early interval after immunization with chicken erythrocytes (CRBC) has been ascribed to θ-positive, immunoglobulin (Ig)-bearing lymphocytes. Cytotoxicity of such effector cells was not affected by trypsinization. Cytotoxity was reduced by the treatment of effector cells with anti-IgG serum and complement or by the addition of anti-IgG serum to culture medium for cytotoxicity test. When the effector cells were treated with trypsin before cytotoxicity test, such procedures with anti-IgG serum did not affect their cytotoxicity, Ig molecules on cytotoxic T lymphocytes may not be an essential element for antigen recognition. This explanation may he supported by the fact that cytotoxicity against CRBC could be raised in 600 tad irradiated, thymus-cell transferred mice in the absence of antibody production. [ABSTRACT FROM AUTHOR]

Immune responses were examined after immunization with chicken erythrocytes (CRBC) in mice, Cytotoxicity of spleen cells was assessed by the release of 51Cr from labelled target cells. (1) At early stages (day 4–7) after primary intraperitoneal immunization, direct cytotoxicity of spleen cells was raised efficiently in C57BL/6 and AKR mice, but not in C3H,/He, SL and DDD mice. Delayed hypersensitivity and antibody production were raised to almost the same extent in all the strains at such periods. (2) Effector cells in direct cytotoxicity were θ-positive and IgG-positive, and glass-nonadherent and Nylon wool column-adherent. Effector cells in antibody-dependent cell-mediated cytotoxicity in the presence of antibody to CRBC were eliminated by treatment with anti-IgG serum, but not by treatment with anti-θ serum. (3) Cytotoxicity and antibody production were raised efficiently after intraperitoneal or intravenous immunization, but not after footpad immunization. On the other hand, delayed hypersensitivity developed most efficiently after footpad immunization. [ABSTRACT FROM AUTHOR]

The effect of neonatal thymectomy at various times after birth (Tx-1, Tx-7) on effector and suppressor I cells responsible for cell-mediated cytotoxicity (CMC) for allogeneic antigens was deter- mined. Following in-vitro primary mixed lymphocyte cultures, in the absence of T-cell growth factor (TCGF), alloreactive CMC was not detected in spleen cells of Tx-1 mice, but was detected in spleen cells of Tx-7 mice at as high levels as in those of sham-operated mice. However, in the presence of TCGF, as much alloreactive CMC was detected in spleen cells of Tx-1 mice as in those of Tx-7 mice. Furthermore, TCGF production was not detected in spleen cells of Tx-1 mice but was detected in those of Tx-7 mice. In in-vivo experiments, inhibition of allogeneic tumour growth and CMC in spleen cells showed the same pattern as in in-vitro experiments. These results sup- port the concept that the reduction of CMC in Tx-I mice might be due to a defect in helper function (TCGF-producing capacity) rather than to a defect in cytotoxic T lymphocytes and/or cytotoxic T lymphocyte precursors. Alloreactive suppressor T cells could not be induced in spleen cells of Tx-1 mice but were induced in spleen cells of Tx-7 mice. Therefore, it was suggested that alloreactive suppressor T cells require the presence of the thymus for 7 days after birth in their development. [ABSTRACT FROM AUTHOR]

Effects of thymectomy at various times after birth on cytotoxicity, delayed footpad reaction and antibody production were examined in 6 week old mice immunized intraperitoneally with chicken erythrocytes. Cytotoxicity and antibody production were abolished by thymectomy within 3 days after birth. Mice thymectomized at 5 days of age or later showed appreciable degrees of cytotoxicity and antibody production. On the other hand, a delayed footpad reaction could be elicited even in mice thymectomized within 24 h after birth, although the degree of the reaction was reduced by such a treatment. Therefore, T cells responsible for delayed hypersensitivity were less thymus-dependent and required the presence of the thymus for a shorter period in their development that those responsible for cytotoxicity or antibody production. [ABSTRACT FROM AUTHOR]

While immunization with allogeneic spleen cells did not generate positive cytotoxic activity, it produced accelerated rejection of subsequent turnout grafts carrying the same H-2 antigen. No augmented generation of cytotoxicity was dctectable by 51Cr-release assay in the host spleen cells, even in the presence of accelerated rejection of turnout allografts. However, augmented cytotoxicity was generated in mixed lymphocyte culture and in peritoneal lymphocytes after an intraperitoneal boost. These results indicate that while immunization with allogeneic spleen ceils does not generate mature cytotoxic T lymphocytes (CTL) detectable by the present assay, it may produce premature CTL that rapidly differentiate into mature CTT, after direct contact with antigen at the site of graft rejection. The inability to generate a high degree of cytotoxicity in the spleen cells may be ascribed to the early development or CTL at the rejection site. The relationship between accelerated rejection of allogeneic tumour grafts and delayed-type hypersensitivity reactions is also discussed. [ABSTRACT FROM AUTHOR]

Effects of whole body irradiation with 600 rad on delayed hypersensitivity, direct cytotoxicity and antibody production were examined in mice immunized with chicken erythrocytes (CRBC) or sheep erythrocytes (SRBC) in saline. Delayed footpad reactions to CRBC were not affected by the exposure to irradiation 3 h before or after antigenic stimulation. On the other hand, direct cytotoxic activities in spleen cells and antibody titres to CRBC were reduced by such exposures. Additionally, delayed footpad reactions to SRBC were not affected by the exposure to irradiation. Generation of effector cells responsible for delayed footpad reactions proved to be resistant to irradiation. [ABSTRACT FROM AUTHOR]

Abstract Background The prevention of serious physical complications in anorexia nervosa (AN) patients is important. The purpose of this study is to clarify which physical and social factors are related to the necessity for urgent hospitalization of anorexia nervosa (AN) patients in a long-term starvation state. We hypothesized that the change of longitudinal BMI, body composition and social background would be useful as an index of the necessity for urgent hospitalization. Methods AN patients were classified into; urgent hospitalization, due to disturbance of consciousness or difficulty walking(n = 17); planned admission (n = 96); and outpatient treatment only groups (n = 136). The longitudinal BMI pattern and the clinical features of these groups were examined. In the hospitalization groups, comparison was done of body composition variation and the social background, including the educational level and advice from family members. Results After adjusting for age and duration of illness, the BMI of the urgent hospitalization group was lower than that of the other groups at one year before hospitalization (P < 0.01) and decreased more rapidly (P < 0.01). Urgent hospitalization was associated with the fat free mass (FFM) (P < 0.01). Between the groups, no considerable difference in social factors was found. Conclusions The longitudinal pattern of BMI and FFM may be useful for understanding the severity in AN from the viewpoint of failure of the homeostasis system.

Abstract Background Previous studies have shown the short-term or intermediate-term practice of yoga to be useful for ameliorating several mental disorders and psychosomatic disorders. However, little is known about the long-term influences of yoga on the mental state or stress-related biochemical indices. If yoga training has a stress-reduction effect and also improves an individual's mental states for a long time, long-term yoga practitioners may have a better mental state and lower stress-related biochemical indices in comparison to non-experienced participants. This study simultaneously examined the differences in mental states and urinary stress-related biochemical indices between long-term yoga practitioners and non-experienced participants. Methods The participants were 38 healthy females with more than 2 years of experience with yoga (long-term yoga group) and 37 age-matched healthy females who had not participated in yoga (control group). Their mental states were assessed using the Profile of Mood States (POMS) questionnaire. The level of cortisol, 8-hydroxydeoxyguanosine (8-OHdG) and biopyrrin in urine were used as stress-related biochemical indices. Results The average self-rated mental disturbance, tension-anxiety, anger-hostility, and fatigue scores of the long-term yoga group were lower than those of the control group. There was a trend toward a higher vigor score in the long-term yoga group than that in the control group. There were no significant differences in the scores for depression and confusion in the POMS between the two groups. The urine 8-OHdG concentration showed a trend toward to being lower in the long-term yoga group in comparison to the control group. There were no significant differences in the levels of urine biopyrrin or cortisol. Conclusions The present findings suggest that long-term yoga training can reduce the scores related to mental health indicators such as self-rated anxiety, anger, and fatigue.

Abstract Objective To examine relationships between a mother's stress-related conditions and parenting attitudes and their children's asthmatic status. Methods 274 mothers of an asthmatic child 2 to 12 years old completed a questionnaire including questions about their chronic stress/coping behaviors (the "Stress Inventory"), parenting attitudes (the "Ta-ken Diagnostic Test for Parent-Child Relationship, Parent Form"), and their children's disease status. One year later, a follow-up questionnaire was mailed to the mothers that included questions on the child's disease status. Results 223 mothers (81%) responded to the follow-up survey. After controlling for non-psychosocial factors including disease severity at baseline, multiple linear regression analysis followed by multiple logistic regression analysis found chronic irritation/anger and emotional suppression to be aggravating factors for children aged < 7 years; for children aged 7 and over, the mothers' egocentric behavior was a mitigating factor while interference was an aggravating factor. Conclusions Different types of parental stress/coping behaviors and parenting styles may differently predict their children's asthmatic status, and such associations may change as children grow.

Abstract A case of benign mixed tumor of the soft tissue in a 64-year-old Japanese male is presented. He noticed a painless, elastic hard mass sized 3 cm in the right knee, which gradually grew larger and harder in the last 5 years. Magnetic resonance imaging demonstrated a mass lesion embedded in the subcutaneous tissue with low and high signal intensity at T1- and T2-weighted images, respectively. Tl-201 scintigraphy showed an early uptake of Tl-201 within the lesion at 10 minutes after injection, which was slightly decreased but still continued at 2 hours later. The patient underwent a resection of tumor, and the pathological diagnosis was a benign mixed tumor of soft tissue without high vascularity, characterized by histological features similar to pleomorphic adenomas in the salivary glands. Immunohistochemical study proved expression of Na+/K+-ATPase of tumor cells. Overexpression of Na+/K+-ATPase of the tumor might be responsible for the early uptake of Tl-201, and poor vascular structure in this tumor might lead to continuous accumulation. The Tl-201 scintigraphic features of mixed tumor of soft tissue are assessed to resemble those of malignant soft tissue tumors.

Abstract Background This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes. Methods Participants were 304 patients with type 2 diabetes who were treated as outpatients at diabetes clinics. All participants were assessed for HbA1c and completed the following self-report psychological inventories: 1) Diabetes Treatment Satisfaction Questionnaire (DTSQ), 2) Problem Areas in Diabetes Survey (PAID), 3) Well-being Questionnaire 12 (W-BQ12), 4) Self-Esteem Scale (SES), 5) Social Support Scale, and 6) Self-Efficacy Scale. HbA1c was again measured one year later. The relationships between the psychosocial variables obtained by analysis of the psychological inventories and baseline or one-year follow-up HbA1c were determined. Results Baseline HbA1cwas significantly correlated with age, diet treatment regimen, number of microvascular complication of diabetes, and the total scores of DTSQ, W-BQ12, PAID, SES and the Self-Efficacy Scale. Hierarchical stepwise multiple regression revealed that significant predictors of baseline HbA1c were total DTSQ and PAID scores, along with age, diet treatment regimen, and number of microvascular complication of diabetes after adjustment for demographic, clinical and other psychosocial variables. Two hundred and ninety patients (95.4% of 304) were followed and assessed one year after baseline. Hierarchical stepwise multiple regression analysis showed the significant predictors of follow-up HbA1c to be total DTSQ and PAID scores, along with age and diet treatment regimen. However, the correlation between baseline and follow-up HbA1c was so high that the only other variable to retain significance was diet treatment regimen once baseline HbA1c was included in the regression of follow-up HbA1c. Conclusion The DTSQ and the PAID predicted both current and future HbA1c to a similar and significant degree in patients with type 2 diabetes.

Abstract Objective To examine the validity and reliability of a Japanese version of the Symptom Checklist 90 Revised (SCL-90-R (J)). Methods The English SCL-90-R was translated to Japanese and the Japanese version confirmed by back-translation. To determine the factor validity and internal consistency of the nine primary subscales, 460 people from the community completed SCL-90-R(J). Test-retest reliability was examined for 104 outpatients and 124 healthy undergraduate students. The convergent-discriminant validity was determined for 80 inpatients who replied to both SCL-90-R(J) and the Minnesota Multiphasic Personality Inventory (MMPI). Results The correlation coefficients between the nine primary subscales and items were .26 to .78. Cronbach's alpha coefficients were from .76 (Phobic Anxiety) to .86 (Interpersonal Sensitivity). Pearson's correlation coefficients between test-retest scores were from .81 (Psychoticism) to .90 (Somatization) for the outpatients and were from .64 (Phobic Anxiety) to .78 (Paranoid Ideation) for the students. Each of the nine primary subscales correlated well with their corresponding constructs in the MMPI. Conclusion We confirmed the validity and reliability of SCL-90-R(J) for the measurement of individual distress. The nine primary subscales were consistent with the items of the original English version.

Abstract Background In Japan and Asia, few studies have been done of physical and sexual abuse. This study was aimed to determine whether a history of childhood physical abuse is associated with anxiety, depression and self-injurious behavior in outpatients with psychosomatic symptoms. Methods We divided 564 consecutive new outpatients at the Department of Psychosomatic Medicine of Kyushu University Hospital into two groups: a physically abused group and a non-abused group. Psychological test scores and the prevalence of self-injurious behavior were compared between the two groups. Results A history of childhood physical abuse was reported by patients with depressive disorders(12.7%), anxiety disorders(16.7%), eating disorders (16.3%), pain disorders (10.8%), irritable bowel syndrome (12.5%), and functional dyspepsia(7.5%). In both the patients with depressive disorders and those with anxiety disorders, STAI-I (state anxiety) and STAI-II (trait anxiety) were higher in the abused group than in the non-abused group (p < 0.05). In the patients with depressive disorders, the abused group was younger than the non-abused group (p < 0.05). The prevalence of self-injurious behavior of the patients with depressive disorders, anxiety disorders and pain disorders was higher in the abused groups than in the non-abused groups (p < 0.005). Conclusion A history of childhood physical abuse is associated with psychological distress such as anxiety, depression and self-injurious behavior in outpatients with psychosomatic symptoms. It is important for physicians to consider the history of abuse in the primary care of these patients.

Abstract Background Anorexia nervosa often requires inpatient treatment that includes psychotherapeutic intervention in addition to physical and nutritional management for severe low body weight. However, such patients sometimes terminate inpatient treatment prematurely because of resistance to treatment, poor motivation for treatment, unstable emotions, and problematic behaviors. In this study, the psychopathological factors related to the personality of anorexic patients that might predict discontinuation of inpatient treatment were investigated using the Minnesota Multiphasic Personality Inventory (MMPI). Methods Subjects were 75 consecutive anorectic inpatients who received cognitive behavioral therapy with a behavior protocol governing privileges in a university hospital based general (not psychiatric) ward. The MMPI was done on admission for all patients. A comparison was done of patients who completed the process of inpatient treatment, including attainment of target body weight (completers), and patients who dropped out of inpatient treatment (dropouts). Results: No significant differences between completers (n = 51) and dropouts (n = 24) were found in the type of eating disorder, age of onset, duration of illness, age, or BMI at admission. Logistic regression analysis found the MMPI scales schizophrenia (Sc), hypomania (HYP), deviant thinking and experience, and antisocial attitude to be factors predicting completion or dropout. Conclusion Dropouts have difficulty adapting to inpatient treatment protocols such as our behavior protocol governing privileges because they have social and emotional alienation, a lack of ego mastery (Sc), emotional instability (HYP) and an antisocial attitude. As a result, they have decreased motivation for treatment, leave the hospital without permission, attempt suicide, or shoplift, which leads them to terminate inpatient treatment prematurely. Treatments based on cognitive behavioral therapy with a behavior protocol governing privileges should be carefully adopted for anorectic patients who exhibit the psychopathological elements identified in this study.

Abstract Background The construct validity of alexithymia and its assessment using the 20-item Toronto Alexithymia Scale (TAS-20) in Japan is unknown. Low reliability has been found for the third factor of the TAS-20 in some cultures, and the factor structure for psychosomatic disorder patients has not been adequately investigated. Although alexithymia most likely has certain developmental aspects, this has infrequently been investigated. Methods The newly-developed Japanese TAS-20 was administered to a normative sample (n = 2,718; 14–84 y.o.), along with the NEO Five-Factor Inventory (NEO-FFI) for cross validation. Psychosomatic patients (n = 1,924, 12–87 y.o.) were tested to evaluate the factor structure in a clinical sample. College students (n = 196) were used for a test-retest study. Internal reliability and consistency were assessed, and the factorial structure was evaluated using confirmatory and exploratory factor analyses for both the normative and the clinical samples. The correlations between the TAS-20 and the NEO-FFI factor scores were evaluated. Age-related and gender differences in the TAS-20 were explored using analysis of variance in the normative sample. Results The original three-factor model of the TAS-20 was confirmed to be valid for these Japanese samples, although a 4-factor solution that included negatively keyed items (NKI) as an additional factor was more effective. Significant correlations of the TAS-20 with the NEO-FFI were found, as has been previously reported. Factor analyses of the normative and patient samples showed similar patterns. The TAS-20 total, difficulty in identifying feelings (DIF), and difficulty in describing feelings (DDF) scores were high for teenagers, decreased with age, and from 30s did not change significantly. In contrast, externally oriented thinking (EOT) scores showed an almost linear positive correlation with age. DIF scores were higher for females, while EOT scores were higher for males, without any interaction between gender and age differences. Conclusion The original three-factor concept of the TAS-20 was generally supported for practical use. Age-related differences in TAS-20 scores indicate developmental aspects of alexithymia. Alexithymia is made up of two components with different developmental paths: DIF/DDF and EOT.

Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas composed of myofibroblastic and fibroblastic cells, accompanied by inflammatory cell infiltration. Many IMTs exhibit clonal rearrangement of anaplastic lymphoma kinase (ALK). We herein report a 56-year-old woman with uterine IMT harboring a thrombospondin-1::ALK fusion that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Laboratory data before systemic therapy indicated increased interleukin-6 and severe leukocytosis. The patient was treated with lorlatinib; however, the response duration was approximately two months. Similar case reports need to be compiled and evaluated to elucidate the efficacy of lorlatinib in post-allo-HSCT IMT with ALK rearrangement.

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected the treatment system of medical institutions across the world. Studies of the populations and patients have reported mental health problems caused by the pandemic. However, there are few large-scale studies that have examined the effects of the COVID-19 on diseases from the perspective of psychosomatic medicine. The purpose of this study was to examine changes made to the psychosomatic treatment system of Japan during the COVID-19 pandemic and the impact of the pandemic on patients with diseases treated in psychosomatic medicine., Methods: We conducted a nationwide questionnaire survey of members of the Japanese Society of Psychosomatic Medicine and the Japanese Society of Psychosomatic Internal Medicine from December 24, 2021 to January 31, 2022., Results: Of the 325 respondents, 23% reported restrictions in initial outpatient admissions, 66% implemented telemedicine, 46% reported a decrease in outpatient admissions, and 31% working in facilities with inpatient units reported decreased inpatient admissions. To reduce in-person visits, 56% of the respondents decreased the frequency of patient visits and 66% introduced telemedicine. Seventy-eight percent of the respondents reported that the COVID-19 pandemic affected the onset or exacerbation of diseases treated in psychosomatic medicine, including psychosomatic disorders, anxiety disorders, mood disorders, adjustment disorders, and eating disorders., Conclusions: This study revealed that the COVID-19 pandemic might have affected the practice of psychosomatic treatment in Japan and that various alternative measures were taken to prevent infection. In addition, although the items in this study were not compared to pre-pandemic data, the COVID-19 pandemic, it could have significant psychosocial effects on Japanese patients requiring psychosomatic care. Furthermore, respondents believed that numerous psychosocial factors were behind the impact of the COVID-19 pandemic on patients with diseases treated in psychosomatic medicine., (© 2023. The Author(s).)

Pericytic tumors are subclassified as myopericytomas, myofibromas, angioleiomyomas, and glomus tumors according to the current World Health Organization classification. These pericytic tumors form a continuous morphologic spectrum, including those with combined morphology. However, to our knowledge, no widely accepted criteria for classifying tumors with combined morphology are available. Recent studies have identified platelet-derived growth factor receptor-beta (PDGFRB) gene mutations in a subset of myofibromas, myopericytomas, and myopericytomatoses but not in angioleiomyomas. NOTCH receptor 3 (NOTCH3) mutations have been reported in a subset of infantile myofibromatosis. To assess their potential role in classifying pericytic tumors, we investigated PDGFRB and NOTCH3 mutations in 41 pericytic tumors of variable morphology, including some combined forms. Our results show these mutations to be present in a variety of pericytic tumors, such as myopericytomas (PDGFRB, 3/11; NOTCH3, 4/11), myopericytomatoses (1/2; 1/2), myofibromas (3/6; 0/6), angioleiomyomas (2/13; 3/13), and glomus tumors (5/9; 1/9). Point mutations were identified in 3 tumors in PDGFRB exon 12 (Y562C, S574F, and G576S), 12 tumors in PDGFRB exon 14 (M655I, H657L, and N666K), and 9 tumors in NOTCH3 exon 25 (A1480S/T, D1481N, G1482S, T1490A, E1491K, G1494S, and V1512A). All PDGFRB mutations and NOTCH3 G1482S, T1490A, and G1494S mutations were classified as "deleterious/damaging" by ≥4 of 6 pathogenicity prediction tools in silico. Five-mutation-positive tumors, including 1 myopericytoma-angioleiomyoma, 2 myopericytomatoses-myofibroma, 1 myofibroma-myopericytoma and 1 angioleiomyoma-myopericytoma, were of combined morphology. Therefore, we found PDGFRB and NOTCH3 mutations to be detectable in a much wider variety of pericytic tumors than previously reported and confirmed myopericytomas, myofibromas, angioleiomyomas, and glomus tumors as members harboring PDGFRB or NOTCH3 mutations. Our results thus suggest that PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic tumor family., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Therapeutic antibodies sometimes elicit anti-drug antibodies (ADAs) that can affect efficacy and safety. Engineered antibodies that contain artificial amino acid sequences are potentially highly immunogenic, but this is currently difficult to predict. Therefore, it is important to efficiently assess immunogenicity during the development of complex antibody-based formats. Here, we present an in vitro peripheral blood mononuclear cell-based assay that can be used to assess immunogenicity potential within 3 days. This method involves examining the frequency and function of interleukin (IL)-2-secreting CD4 + T cells induced by therapeutic antibodies. IL-2-secreting CD4 + T cells seem to be functionally relevant to the immunogenic potential due to their proliferative activity and the expression of several cytokines. The rates of the donors responding to low and high immunogenic proteins, mAb1, and keyhole limpet hemocyanin were 1.3% and 93.5%, respectively. Seven antibodies with known rates of immunogenicity (etanercept, emicizumab, abciximab, romosozumab, blosozumab, humanized anti-human A33 antibody, and bococizumab) induced responses in 1.9%, 3.8%, 6.4%, 10.0%, 29.2%, 43.8%, and 89.5% of donors, respectively. These data are comparable with ADA incidences in clinical settings. Our results show that this assay can contribute to the swift assessment and mechanistic understanding of the immunogenicity of therapeutic antibodies.

Video 1Underwater EMR for establishing diagnosis of diffuse infiltrative gastric cancer., (© 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

Angiomyofibroblastoma and superficial myofibroblastoma are distinctive benign mesenchymal tumors occurring in the female lower genital tract. Despite their significant overlapping clinicopathologic features, including the presence of bland-looking spindle or oval cells with myofibroblastic or myoid differentiation, the tumors have been regarded as separate entities. Although subepithelial, hormone-sensitive mesenchymal cells of the female lower genital tract are considered as their potential common progenitor cells, their potential kinship or pathogenetic similarities remain elusive. Based on the identification of a novel RNA sequencing-based MTG1-CYP2E1 fusion transcript in an angiomyofibroblastoma index case, we investigated an additional ten samples of the tumor and its site-specific histological mimics, including eight superficial myofibroblastomas, four deep angiomyxomas, four cellular angiofibromas, three fibroepithelial stromal polyps, and eight non-site-specific mesenchymal tumors occurring in the female lower genital tract. Using reverse transcription-polymerase chain reaction, we showed that the MTG1-CYP2E1 fusion transcripts were consistently detectable in angiomyofibroblastomas (5/5, 100%) and often in superficial myofibroblastomas (3/5, 60%) but were not detected in the other examined site-specific or non-site-specific mesenchymal tumors. Our immunohistochemical experiments showed that CYP2E1, an isoenzyme belonging to the cytochrome P450 superfamily, exhibited increased positivity in tumors with MTG1-CYP2E1 than was observed in fusion-negative tumors (RR = 6.56, p = 0.001). The results of our study provide further evidence supporting the assertion that angiomyofibroblastoma and superficial myofibroblastoma represent phenotypic variants of site-specific mesenchymal tumors and share a common oncogenic mechanism., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background: Pictorial Representation of Illness and Self Measure (PRISM) is a tool that can be used to visualize and evaluate the burden of suffering caused by an illness. The aim of this study was to identify which aspects of the burden of chronic pain patients are associated with Self/illness separation (SIS), an indicator of the magnitude of suffering. We also examined the effectiveness of PRISM for evaluating changes in the relationships between patients and their medical care and significant others due to our inpatient treatment., Methods: Seventy-two patients with chronic pain who were outpatients or admitted to the Department of Psychosomatic Medicine completed PRISM, depression and anxiety scales, and three types of pain-related self-assessment questionnaires (Brief Pain Inventory, Short-form McGill Pain Questionnaire, and Pain Catastrophizing Scale). Outpatients were queried at the time of outpatient visits and inpatients at the time of admission. In addition to PRISM disks related to illness, we asked each patient to place disks related to things important to them and their medical care. Of the inpatients, 31 did PRISM at the time of discharge. Among the reported important factors, which significant other was placed at the time of admission and discharge was evaluated. The distances of self/medical care separation (SMcS) and self/significant others separation (SSoS) were measured., Results: Of the 21 scales measured, 10 showed a significant correlation with SIS. Factor analysis of these 10 scales extracted three factors, Life interferences, Negative affects, and Pain intensity. The SMcS and SSoS distances were shorter at discharge than at admission., Conclusions: PRISM for patients with chronic pain is an integrated evaluation method that reflects three aspects of pain. By adding medical care and significant others to the usual method of placing only illness on the sheet it became possible to assess changes in the quality of interpersonal relationships., (© 2021. The Author(s).)

A 60-year-old woman presented with multiple lung and bone metastases with unknown primary cancer. Chest CT images showed multiple pulmonary cysts, predominantly of the middle and lower lobes. She also had a history of pneumothorax. Four years after chemotherapy and radiation therapy, multiple hypervascular tumors eventually developed in the bilateral kidneys, suggesting the possibility of Birt-Hogg-Dubé (BHD) syndrome. Genetic testing revealed a folliculin mutation, which confirmed the diagnosis of BHD syndrome. When we encounter cancer of unknown primary with multiple pulmonary cysts in a patient with a history of pneumothorax, thorough imaging of the kidneys and genetic testing for BHD syndrome is necessary.