Chemotherapy-Induced Oesophageal Stricture in a Child with Osteosarcoma: A Case Report

Treatment with a combination of chemotherapy and radiotherapy is known to be associated with oesophageal stricture in both children and adults with malignancies. However, oesophageal stricture resulting from chemotherapy alone is a rare complication, with few reports on it. We experienced a rare paediatric case of oesophageal stricture caused by chemotherapy for osteosarcoma of the left distal femur. After completion of the chemotherapy course, the patient showed dysphagia caused by the oesophageal stricture and underwent balloon dilatation for the oesophageal stricture. After balloon dilatation, he was able to ingest solid foods, and the oesophagus was normal without any strictures at the last follow-up (20 months after ballooning). Therefore, oesophageal stricture should be considered as a complication of treatment with chemotherapy alone in children with malignancies

Blood pressure in heart failure management and prevention

Hypertension is a leading cause of heart failure and other cardiovascular diseases. Its role in the pathogenesis of heart failure with reduced ejection fraction (HFrEF) differs from that in heart failure with preserved ejection fraction (HFpEF). Moreover, rigorous blood pressure control may reduce the incidence of heart failure. However, once heart failure develops, prognosis is affected by blood pressure, which may differ between patients with and without heart failure. Therefore, the association between guideline-directed medical therapy (GDMT) for heart failure and its uptitration must be considered for blood pressure management and should not be overlooked. Heart failure medications affect the blood pressure and efficacy per baseline blood pressure value. This review discusses the potential mechanisms by which hypertension leads to HFrEF or HFpEF, the impact of hypertension on incident heart failure, and the recommended approaches for blood pressure management in patients with heart failure. </p

Xanthogranulomatous inflammation of the perimetrium with infiltration into the uterine myometrium in a postmenopausal woman: a case report

BACKGROUND: Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to the normal tissue of affected organs. Although xanthogranulomatous endometritis and xanthogranulomatous salpingitis of the female genital tract has been described previously, to the best of our knowledge, this is the first report of xanthogranulomatous inflammation with infiltration into the uterine myometrium from the perimetrium without endometritis. CASE PRESENTATION: A 68-year-old Japanese woman with intermittent lower abdominal pain and low-grade fever who was initially treated with antibiotics underwent hysterectomy due to abscess formation in the posterior wall of the myometrium and perimetrium (the outer serosal layer of the uterus). Histopathological findings revealed that the abscess was caused by xanthogranulomatous inflammation with the granulation tissue and chronic inflammatory cells that consisted of focal and sheets of foam cells. The inflammation destroyed the perimetrial elastic lamina, and the myometrium was deeply infiltrated by the xanthoma cells. Neither endometritis nor salpingitis was coexistent with the xanthogranulomatous inflammation. CONCLUSION: The patient was diagnosed as xanthogranulomatous inflammation, most likely arising from the perimetrium. Our findings suggest that the perimetrium, as well as the endometrium and adnexae, is one of the origins of xanthogranulomatous inflammation in female genital tract

Clinicopathological Significance of Loss of ARID1A Immunoreactivity in Ovarian Clear Cell Carcinoma

Recent genome-wide analysis has demonstrated that somatic mutations in ARID1A (BAF250) are the most common molecular genetic changes in ovarian clear cell carcinoma (OCCC). ARID1A mutations, which occur in approximately half of OCCC cases, lead to deletion of the encoded protein and inactivation of the putative tumor suppressor. In this study, we determined the significance of loss of ARID1A immunoreactivity with respect to several clinicopathological features in a total of 149 OCCCs. First, we demonstrated that ARID1A immunohistochemistry showed concordance with the mutational status in 91% of cases with 100% sensitivity and 66% specificity. Specifically, among 12 OCCC cases for which ARIDA mutational status was known, ARIDIA immunoreactivity was undetectable in all 9 cases harboring ARID1A mutations and was undetectable in one of 3 cases with wild-type ARID1A. With respect to the entire cohort, ARID1A immunoreactivity was undetectable in 88 (59%) of 149 OCCCs. There was no significant difference between ARID1A negative and positive cases in terms of histopathologic features, age, clinical stage, or overall survival. In conclusion, this study provides further evidence that mutations in ARID1A resulted in loss of ARID1A protein expression in OCCC, although no significant differences between ARID1A positive and negative cases were observed with respect to any clinicopathological features examined

Disorganization of intercalated discs in dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a primary myocardial disease, the pathology of which is left ventricular or biventricular dilation and impaired myocardial contractility. The clinical and pathological diagnosis of DCM is difficult, and other cardiac diseases must be ruled out. Several studies have reported pathological findings that are characteristic of DCM, including cardiomyocyte atrophy, nuclear pleomorphism, and interstitial fibrosis, but none of these findings are DCM-specific. In this study, we examined the morphological differences in the intercalated discs (ICDs) between three groups of patients, a DCM group, a chronic heart failure group, and a control group. A total of 22 autopsy cases, including five DCM cases, nine CHF cases and eight control cases, were retrieved from the archives of the Department of Pathology at Akita University, Japan. The morphological differences were examined using multiple methods: macroscopic examination, light microscopy, immunohistochemistry, electron microscopy, and gene expression analyses. We observed disorganized ICDs, clearly illustrated by N-cadherin immunostaining in the DCM group. Reduction of N-cadherin immunostaining intensity and ICD scattering was DCM-specific. The results suggest that disorganized ICDs contribute to the development of DCM, and that N-cadherin immunostaining is useful for determining the presence of disorganized ICDs and for the pathological diagnosis of DCM

TIMP3 promotes the maintenance of neural stem-progenitor cells in the mouse subventricular zone

Adult neural stem cells (NSCs) in the mouse subventricular zone (SVZ) serve as a lifelong reservoir for newborn olfactory bulb neurons. Recent studies have identified a slowly dividing subpopulation of embryonic neural stem-progenitor cells (NPCs) as the embryonic origin of adult NSCs. Yet, little is known about how these slowly dividing embryonic NPCs are maintained until adulthood while other NPCs are extinguished by the completion of brain development. The extracellular matrix (ECM) is an essential component of stem cell niches and thus a key determinant of stem cell fate. Here we investigated tissue inhibitors of metalloproteinases (TIMPs)—regulators of ECM remodeling—for their potential roles in the establishment of adult NSCs. We found that Timp2, Timp3, and Timp4 were expressed at high levels in slowly dividing NPCs compared to rapidly dividing NPCs. Deletion of TIMP3 reduced the number of adult NSCs and neuroblasts in the lateral SVZ. In addition, overexpression of TIMP3 in the embryonic NPCs suppressed neuronal differentiation and upregulated the expression levels of Notch signaling relating genes. These results thus suggest that TIMP3 keeps the undifferentiated state of embryonic NPCs, leading to the establishment and maintenance of adult NSCs

Millimeter Observations of the Type II SN2023ixf: Constraints on the Proximate Circumstellar Medium

We present 1.3 mm (230 GHz) observations of the recent and nearby Type II supernova, SN2023ixf, obtained with the Submillimeter Array (SMA) at 2.6-18.6 days after explosion. The observations were obtained as part the SMA Large Program POETS (Pursuit of Extragalactic Transients with the SMA). We do not detect any emission at the location of SN2023ixf, with the deepest limits of $L_\nu(230\,{\rm GHz})\lesssim 8.6\times 10^{25}$ erg s$^{-1}$ Hz$^{-1}$ at 2.7 and 7.7 days, and $L_\nu(230\,{\rm GHz})\lesssim 3.4\times 10^{25}$ erg s$^{-1}$ Hz$^{-1}$ at 18.6 days. These limits are about a factor of 2 times dimmer than the mm emission from SN2011dh (IIb), about an order of magnitude dimmer compared to SN1993J (IIb) and SN2018ivc (IIL), and about 30 times dimmer than the most luminous non-relativistic SNe in the mm-band (Type IIb/Ib/Ic). Using these limits in the context of analytical models that include synchrotron self-absorption and free-free absorption we place constraints on the proximate circumstellar medium around the progenitor star, to a scale of $\sim 2\times 10^{15}$ cm, excluding the range $\dot{M}\sim {\rm few}\times 10^{-6}-10^{-2}$ M$_\odot$ yr$^{-1}$ (for a wind velocity, $v_w=115$ km s$^{-1}$, and ejecta velocity, $v_{\rm eje}\sim (1-2)\times 10^4$ km s$^{-1}$). These results are consistent with an inference of the mass loss rate based on optical spectroscopy ($\sim 2\times 10^{-2}$ M$_\odot$ yr$^{-1}$ for $v_w=115$ km s$^{-1}$), but are in tension with the inference from hard X-rays ($\sim 7\times 10^{-4}$ M$_\odot$ yr$^{-1}$ for $v_w=115$ km s$^{-1}$). This tension may be alleviated by a non-homogeneous and confined CSM, consistent with results from high-resolution optical spectroscopy.Comment: Submitte

Saizu: A Very Big Loanword in Japanese

The tradition of student-centered active learning for development of critical thinking at Miyazaki International College provides valuable opportunities for discovery in the classroom. This brief paper outlines the results of one such student project in LL3141, Topics in Linguistics, taught by Debra J Occhi in fall semester of 2013. Students were inspired to undertake this research while reading and discussing Language Contact Meets Cognitive Linguistics: A Case of Getto-suru in Japanese (Horie & Occhi 2001). This paper reviews those findings, presents issues students found especially relevant about loanword behavior discussed in Olah (2007) and about English made in Japan (wasei eigo, discussed in Miller 1997), lists noun loanwords found in Japanese-English dictionaries, presents and analyzes instances of use of the loanword saizu (from English “size”)

Digital quantitative analysis of mast cell infiltration in interstitial cystitis

AimsTo evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique. MethodsBladder biopsy specimens from 31 patients with Hunner type IC and 38 patients with non-Hunner type IC were analyzed. Bladder biopsy specimens from 37 patients without IC, including 19 non-specific chronic cystitis (non-IC cystitis) specimens and 18 non-inflamed bladder (normal bladder) specimens, were used as controls. Mast cell tryptase-, CD3-, CD20-, and CD138-immunoreactive cells were quantified using digital image analysis software to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and lymphoplasmacytic cell densities were counted independently in the entire lamina propria and detrusor areas and compared among the four groups. ResultsIn the lamina propria, there were no significant differences in mast cell and lymphoplasmacytic cell densities between Hunner type IC and non-IC cystitis or between non-Hunner type IC and normal bladder specimens. In the detrusor, the mast cell densities were not significantly different among the four groups. Mast cell density was correlated with lymphoplasmacytic cell density, but not with clinical parameters. ConclusionsMast cell density is not significantly different between IC specimens and non-IC control specimens with a similar degree of background inflammation. The intensity of mast cell infiltration generally correlated with that of lymphoplasmacytic cells. We conclude that mast cell count is of no value in the differential diagnosis between IC and other etiologies

Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice

新型コロナウイルスを中和するアルパカ抗体 --マウス実験で有効性を確認--. 京都大学プレスリリース. 2023-02-17.BACKGROUND: SARS-CoV-2 Omicron variants are highly resistant to vaccine-induced immunity and human monoclonal antibodies. METHODS: We previously reported that two nanobodies, P17 and P86, potently neutralize SARS-CoV-2 VOCs. In this study, we modified these nanobodies into trimers, called TP17 and TP86 and tested their neutralization activities against Omicron BA.1 and subvariant BA.2 using pseudovirus assays. Next, we used TP17 and TP86 nanobody cocktail to treat ACE2 transgenic mice infected with lethal dose of SARS-CoV-2 strains, original, Delta and Omicron BA.1. RESULTS: Here, we demonstrate that a novel nanobody TP86 potently neutralizes both BA.1 and BA.2 Omicron variants, and that the TP17 and TP86 nanobody cocktail broadly neutralizes in vitro all VOCs as well as original strain. Furthermore, intratracheal administration of this nanobody cocktail suppresses weight loss and prolongs survival of human ACE2 transgenic mice infected with SARS-CoV-2 strains, original, Delta and Omicron BA.1. CONCLUSIONS: Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice