Computed tomographic characteristics of testicular teratoma in a cat.

A 5-year-old intact male mixed-breed cat weighing 4.5 kg was referred to our hospital with a left testicular mass. CT revealed mild heterogeneous contrast enhancement and calcification in the testicular mass. A well-defined, contrast-enhancing, multiloculated mass with fluid-filled areas was extended from the testicular mass in the scrotum to the caudal aspect of the left kidney. The abdominal mass extended to the right crus of the diaphragm, and the gastrointestinal tract was compressed dorsally. Histopathology was consistent with teratoma. Characteristic CT findings in a feline testicular teratoma may include calcification and cystic areas.

Liposome-encapsulated progesterone efficiently suppresses B-lineage cell proliferation.

Progesterone suppresses several ancient pathways in a concentration-dependent manner. Based on these characteristics, progesterone is considered a candidate anticancer drug. However, the concentration of progesterone used for therapy should be higher than the physiological concentration, which makes it difficult to develop progesterone-based anticancer drugs. We previously developed liposome-encapsulated progesterone (Lipo-P4) with enhanced anticancer effects, which strongly suppressed triple-negative breast cancer cell proliferation in humanized mice. In this study, we aimed to clarify whether Lipo-P4 effectively suppresses the proliferation of B-lineage cancer cells. We selected six B-cell lymphoma and two myeloma cell lines, and analyzed their surface markers using flow cytometry. Next, we prepared liposome-encapsulated progesterone and examined its effect on cell proliferation in these B-lineage cancer cells, three ovarian clear cell carcinoma cell lines, two prostate carcinoma cell lines, and one triple-negative breast cancer adenocarcinoma cell line. Lipo-P4 suppressed the proliferation of all cancer cell lines. All B-lineage cell lines, except for the HT line, were more susceptible than the other cell types, regardless of the expression of differentiation markers. Empty liposomes did not suppress cell proliferation. These results suggest that progesterone encapsulated in liposomes efficiently inhibits the proliferation of B-lineage cells and may become an anticancer drug candidate for B-lineage cancers.

Iatrogenic cerebral amyloid angiopathy in older adults.

BACKGROUND AND PURPOSE: An increasing number of cases of iatrogenic cerebral amyloid angiopathy (CAA) have now been reported worldwide. Proposed diagnostic criteria require a history of medical intervention with potential for amyloid-ß transmission, for example those using cadaveric dura mater or requiring instrumentation of the brain or spinal cord. Clinical presentation occurs after an appropriate latency (usually three or four decades); to date, most patients with iatrogenic CAA have had 'early-onset' disease (compared to sporadic, age-related, CAA), as a consequence of childhood procedures. RESULTS: We describe five cases of possible iatrogenic CAA in adults presenting in later life (aged 65 years and older); all had prior neurosurgical interventions and presented after a latency suggestive of iatrogenic disease (range 30-39 years). Use of cadaveric dura mater was confirmed in one case, and highly likely in the remainder. CONCLUSION: The presentation of iatrogenic CAA in older adults widens the known potential spectrum of this disease and highlights the difficulties of making the diagnosis in this age group, and particularly in differentiating iatrogenic from sporadic CAA. Increased vigilance for cases presenting at an older age is essential for furthering our understanding of the clinical phenotype and broader implications of iatrogenic CAA.

Noonan Syndrome-related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review.

Noonan syndrome-related myeloproliferative disorder (NS/MPD) and juvenile myelomonocytic leukemia (JMML) are rare MPDs that occur in young children. We herein report a case of NS/MPD with neonatal onset. The patient had a characteristic appearance and high monocyte count in the peripheral blood and bone marrow. Genetic testing showed the E139D mutation in PTPN11 ; however, the patient did not meet all the diagnostic criteria for JMML, and we thus diagnosed him with NS/MPD. Eight other cases of NS/MPD with neonatal onset are also summarized. The initial presentation varied, and the prognosis was considered poor compared with previous reports of NS/MPD.

Fibrinogen Aα-chain amyloidosis outbreaks in Japanese squirrels (Sciurus lis): a potential disease model.

Fibrinogen Aα-chain amyloidosis is a hereditary systemic amyloidosis characterized by glomerular amyloid depositions, which are derived from the fibrinogen Aα-chain variant in humans. Despite its unique pathology, the pathogenic mechanisms of this disease are only partially understood. This is in part because comparative pathological studies on fibrinogen Aα-chain amyloidosis are currently unavailable as there is a lack of reported cases in animals other than humans. In this study, mass spectrometry-based proteomic analyses of Japanese squirrels (Sciurus lis) that died in five Japanese zoos showed that they developed glomerular-associated fibrinogen Aα-chain amyloidosis with an extremely high incidence rate (29/38 cases, 76.3%). The condition was found to be age-dependent in the Japanese squirrels, with 89% of individuals over 4 years of age affected. Mass spectrometry revealed that the C-terminal region of the fibrinogen Aα-chain was involved in amyloidogenesis in Japanese squirrels as well as humans. No gene variations were identified between amyloid-positive and amyloid-negative squirrels, which contrasted with the available data for humans. The results indicate that fibrinogen Aα-chain amyloidosis is a senile amyloidosis in Japanese squirrels. The results have also provided comparative pathological support that the amyloidogenic C-terminal region of the fibrinogen Aα-chain is involved in the characteristic glomerular pathology, regardless of the animal species. This study elucidates the potential causes of death in Japanese squirrels and will contribute to future comparative pathological studies of fibrinogen Aα-chain amyloidosis. © 2023 The Pathological Society of Great Britain and Ireland.

Cystatin C as a Potential Blood Biomarker for Sarcoidosis: A Case Report.

Sarcoidosis is a multi-organ medical condition that is characterized by the formation of granulomas. We aimed to identify a correlation between each sarcoidosis blood biomarker and cystatin C (Cys-C) in sarcoidosis patients. We report a case of a 60-year-old man with sarcoidosis. The correlation between his Cys-C and each blood biomarker level and that between each blood biomarker and serum creatinine levels were determined using linear regression. Serum Cys-C correlated with each blood biomarker of sarcoidosis, while creatinine did not. These findings suggest that Cys-C is a potential blood biomarker for sarcoidosis.

Simultaneous bilateral spontaneous pneumothorax in a patient with anorexia nervosa.

Anorexia nervosa causes various complications accompanying weight loss and malnutrition. Although bilateral spontaneous pneumothorax (SBSP) is uncommon, caution is needed in anorexia nervosa because this complication can be fatal. We encountered a 17-year-old girl with SBSP from emphysematous pulmonary changes due to anorexia nervosa. She was hospitalized with SBSP during treatment for anorexia nervosa. Chest tube drainage was started on admission, but no improvement was achieved. Surgery was therefore performed. Lung lesions on surgical specimens demonstrated malnutrition-induced emphysematous changes, a risk factor for SBSP. Attention should be paid to the occurrence of SBSP during the clinical course of anorexia nervosa.

IPC prediction of patent documents using neural network with attention for hierarchical structure.

International patent classifications (IPCs) are assigned to patent documents; however, since the procedure for assigning classifications is manually done by the patent examiner, it takes a lot of time and effort to select some IPCs from about 70,000 IPCs. Hence, some research has been conducted on patent classification with machine learning. However, patent documents are very voluminous, and learning with all the claims (the part describing the content of the patent) as input would run out of the necessary memory, even if the batch size is set to a very small size. Therefore, most of the existing methods learn by excluding some information, such as using only the first claim as input. In this study, we propose a model that considers the contents of all claims by extracting important information for input. In addition, we focus on the hierarchical structure of the IPC, and propose a new decoder architecture to consider it. Finally, we conducted an experiment using actual patent data to verify the accuracy of the prediction. The results showed a significant improvement in accuracy compared to existing methods, and the actual applicability of the method was also discussed.

Indications for Percutaneous Drainage in Patients with Huang Class 3B Emphysematous Pyelonephritis: A Case Report and Literature Review.

Emphysematous pyelonephritis (EPN) is a severe urinary tract infection common in patients with diabetes. Nephrectomy is recommended when the Huang classification is ≥3B. We herein report a case in which nephrectomy was avoided using antimicrobial agents and percutaneous drainage (PCD). A 59-year-old man was diagnosed with EPN (Huang classification 3B). The causative bacteria were Escherichia coli. Despite high-risk factors, EPN was cured with kidney preservation and PCD because the emphysema and abscess were not extensive. Thus, PCD should be considered in patients with Huang Class 3B EPN and high-risk factors if emphysema and abscess are not extensive.

Reconstruction of convex urethral stoma in a cat with prepubic urethrostomy.

An intact, male mixed-breed cat approximately 3 months of age was referred to Iwate University Veterinary Teaching Hospital with dysuria that developed after a traffic accident. At the initial visit, a cystostomy tube was placed as a temporal urinary diversion. Antegrade urethrography revealed severe stenosis of the intrapelvic urethra. A prepubic urethrostomy (PPU) with formation of a convex urethral stoma was performed 22 days after the first visit. Twenty-four months after surgery, the cat could urinate smoothly in a standing position, although a small amount of intermittent leakage was observed immediately after getting up. There was no evidence of peristomal dermatitis. Therefore, the formation of a convex urethral stoma may effectively prevent peristomal dermatitis in cats who undergo PPU.

Ventral onlay graft urethroplasty using bladder mucosa in a cat with a urethral stricture.

A 3-year-old, 4.0 kg, intact male domestic shorthair cat presented with postoperative dysuria following urethral resection and anastomosis for urethral rupture. Retrograde urethrography revealed a stricture in the pelvic urethra. Urethroplasty with bladder mucosa was performed following a bilateral pubic-ischial osteotomy. The bladder wall was resected to harvest an appropriately sized bladder mucosa graft. The graft was placed over the urethral defect in patch fashion and stabilized with interrupted sutures. The cat was able to urinate normally with no evidence of lower urinary tract signs 2 year postoperatively. Therefore, urethroplasty with an onlay bladder mucosa graft may be a feasible alternative to prepubic or subpubic urethrostomy for the treatment of pelvic urethral stricture in cats.

Molecular design of near-infrared (NIR) fluorescent probes targeting exopeptidase and application for detection of dipeptidyl peptidase 4 (DPP-4) activity.

Monitoring the activities of proteases in vivo is an important requirement in biological and medical research. Near-infrared (NIR) fluorescent probes are particularly useful for in vivo fluorescence imaging, due to the high penetration of NIR and the low autofluorescence in tissue for this wavelength region, but most current NIR fluorescent probes for proteases are targeted to endopeptidase. Here, we describe a new molecular design for NIR fluorescent probes that target exopeptidase by utilizing the >110 nm blueshift of unsymmetrical Si-rhodamines upon amidation of the N atom of their xanthene moiety. Based on this molecular design, we developed Leu-SiR640 as a probe for leucine amino peptidase (LAP). Leu-SiR640 shows a one order of magnitude larger fluorescence increment (669-fold) upon reaction with LAP than existing NIR fluorescent probes. We similarly designed and synthesized EP-SiR640, a NIR fluorescent probe that targets dipeptidyl peptidase 4 (DPP-4). We show that this probe can monitor DPP-4 activity not only in living cells but also in mouse organs and tumors. This probe could also detect esophageal cancer in human clinical specimens, based on the overexpression of DPP-4 activity.

Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts.

Background: Combining a fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (B-EOS) may be a useful strategy for administration of biologics such as anti-IgE or anti-IL-5 to patients with type 2 inflammatory-predominant severe asthma and is important to be elucidated considering the increasing use of biologics. Methods: This cross-sectional study analyzed the clinical data from 114 adult patients with severe asthma, who were treated at Saitama Medical University Hospital. The eligible patients were stratified into four subgroups defined by thresholds of FeNO and blood eosinophil (B-EOS) counts to detect sputum eosinophilia, using the receiver operating characteristic curve analysis. A total of 75 patients with optimal samples were stratified into four subtypes defined by thresholds of sputum eosinophilia and neutrophilia. Clinical characteristics, pattern of biologics, and distribution of sputum subtypes were analyzed in the stratified subclasses according to the FeNO and B-EOS thresholds. The asthma exacerbation (AE)-free time of the FeNO/B-EOS subgroups and any biologics treatment including anti-IgE or anti-IL-5 use were examined using the Kaplan-Meier method. The hazard ratios (HRs) for AE-free time were examined using the Cox proportional hazard model. Results: The optimal cutoff values for prediction of sputum eosinophilia were defined as ≥2.7% wherein for FeNO as ≥27 ppb and B-EOS as ≥265/µL were considered. The high-FeNO subgroups showed significant high total IgE, compared with the low FeNO. The high-FeNO/high-B-EOS and the high-FeNO/low-B-EOS subgroups showed the largest prevalence of mepolizumab and benralizumab use among the other FeNO/B-EOS, respectively. The high-FeNO/low-B-EOS showed the largest frequency of AEs, high HR, and the shortest AE-free time, among the other FeNO/B-EOS. The sputum eosinophil-predominant subtype was the great majority in the high FeNO/high B-EOS. A diverse distribution of sputum leukocyte-predominant subtype was observed in the other FeNO/B-EOS. The subsequent AE-free time and its HR were comparable among the biologics use groups. Conclusion: The strategy of classifying severe asthma based on the combination of FeNO and B-EOS proposes particular refractory type 2 severe asthma and underlying airway inflammation as a feasible trait for optimal biologics use.

Diffuse FDG uptake in the bilateral lungs: hypersensitivity pneumonitis supported by low-dose CT findings.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease resulting from an immune-mediated response in susceptible and sensitized individuals to various inhaled antigens in the environment. Imaging diagnosis is usually based on high-resolution CT findings. Here, we present a 49-year-old man with a history of diffuse large B-cell lymphoma presented with fever and occasional cough. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed diffuse FDG uptake in the bilateral lungs. Expiratory low-dose CT simultaneously performed in PET scanning revealed centrilobular nodules and air trapping in ground glass opacities (GGO). Our imaging diagnosis was acute hypersensitivity pneumonitis (HP). Based on the results of his clinical course, blood laboratory tests, and bronchoscopy, he was diagnosed with acute HP. Diffuse pulmonary FDG uptake can be seen in the patients with acute HP. In addition, expiratory low-dose CT findings of centrilobular nodules and air trapping in GGO may be helpful for accurate diagnosis of acute HP.

Effect of manuka honey on human immunodeficiency virus type 1 reverse transcriptase activity.

Manuka honey (MkH), derived from New Zealand manuka tree (Leptospermum scoparium), is considered a therapeutic agent owing to its antibacterial, antioxidant, antifungal, antiviral, anti-inflammatory, and wound healing activities. In this study, the inhibitory effect of five honey types, including MkH, on HIV-1 RT activity was evaluated, using an RT assay colorimetric kit, according to the manufacturer's instructions with slight modifications. MkH exerted the strongest inhibitory effect in a dose-dependent manner, with a half maximal inhibitory concentration (IC50) of approximately 14.8 mg/mL. Moreover, among the MkH constituents, methylglyoxal (MGO) and 2-methoxybenzoic acid (2-MBA) were determined to possess anti-HIV-1 RT activity. MGO and 2-MBA in MkH were identified by High Performance Liquid Chromatography (HPLC) and Liquid Chromatograph - Mass Spectrometry (LC-MS/MS). The findings suggest that the inhibitory effect of MkH on the HIV-1 RT activity is mediated by multiple constituents with different physical and chemical properties.

[Investigation of the safety and usefulness of a renal biopsy for older elderly patients ≥75 years old].

AIM: We herein report the safety and usefulness of a kidney biopsy in older elderly patients (≥75 years old). METHODS: A retrospective observational study was conducted in older elderly patients who had received a renal biopsy at the Department of Nephrology, Shimane University Hospital, from January 1, 2008, to December 31, 2018. The native renal biopsy results of 52 later-stage elderly patients were analyzed (29 men and 23 women). RESULTS: The most common indication for a renal biopsy was nephrotic syndrome (n = 22), followed by rapidly progressive glomerulonephritis (n = 12) and asymptomatic urinary abnormalities (n = 12). The most common pathological diagnosis was membranous nephropathy (n = 12), followed by ANCA-associated nephritis (n= 8), minimal change nephrotic syndrome (6 case), membranoproliferative glomerulonephritis (n = 5), IgA nephropathy (n = 4), and diabetic nephropathy (n = 3). The concordance rate between the clinical and pathological diagnoses was 53.8%. The only complication of the renal biopsy was hemorrhaging requiring blood transfusion (1 patient; 1.9%). The hemoglobin level decreased by 0.5±0.05 d/dL after the biopsy. CONCLUSION: The rate of serious complications associated with a renal biopsy was comparable to that in previous reports in younger patient. Renal biopsies can therefore be safely performed even in older elderly patients. The concordance rate of the clinical and pathological diagnoses was about 50%. Therefore, renal biopsies should be performed in older elderly patients when necessary.

A Remarkable Elevation in the Procalcitonin Levels Due to Diabetic Ketoacidosis in a Hemodialysis Patient.

Procalcitonin (PCT), a marker of the inflammatory response during infections, can be elevated by diabetic ketoacidosis (DKA). A male patient in his 50s with diabetic nephropathy on hemodialysis presented with vomiting and a reduced level of consciousness and was diagnosed with DKA. His PCT level was markedly elevated, but bacterial cultures (blood, urine, and stool) were negative. The PCT level decreased after DKA improvement. In this patient, DKA probably enhanced the PCT levels. As DKA can increase the PCT levels, an elevation of the PCT levels in DKA patients may not be indicative of infectious diseases, and non-infectious causes of DKA should therefore be considered.

Relationship between airway inflammation and airflow limitation in elderly asthmatics.

BACKGROUND: The prevalence of asthma in elderly population has been increasing. Previous studies have demonstrated clinical characteristics of elderly asthmatics (EA). However, little is known regarding the influence of immunological change on the physiological status of EA. OBJECTIVE: We investigated the relationship between inflammatory mediators and the pulmonary function (PF) of EA. METHODS: Eligible adult asthmatics recruited from the Allergy Center of Saitama Medical University Hospital were classified into a non-EA group (<40 years old, n = 15) and an EA group (≥60 years old, n = 43). Sputum induction and PF tests were performed. Concentrations of an eosinophil-derived neurotoxin (EDN) and neutrophil elastase (NE) in sputum supernatants were measured by enzyme-linked immunosorbent assay and a fluorometric assay using a commercial assay kit, respectively. Cell counts and EDN and NE concentrations in sputum were compared between the 2 groups. The association among those parameters and PF were analyzed in each group. RESULTS: The EA group had a significantly higher severe asthmatics proportion (p = 0.01), a lower current smokers proportion (p = 0.002), lower sensitization rate to aeroallergens (p = 0.012), several PFs deterioration (p < 0.0001) and lower total IgE levels (p = 0.001) than the non-EA group. Sputum neutrophil counts and NE concentrations were significantly higher in the EA group than those in the non-EA group (median neutrophil: 4.11 vs. 2.74 ×105/mL, p = 0.03; NE: 2.0 vs.1.6 µg/mL, p < 0.05, respectively), whereas sputum eosinophil counts and EDN concentrations were not. Sputum EDN concentrations were significantly positively correlated with sputum neutrophil counts (r = 0.39, p = 0.031) and NE concentrations (r = 0.57, p < 0.0001) only in the EA group. Eosinophil-related parameters were negatively correlated with several PFs in the 2 groups. Neutrophil-related parameters were negatively correlated with PFs only in the non-EA group. CONCLUSION: This study determines that in EA, persistent active eosinophilic airway inflammation is accompanied by advanced neutrophilic inflammation, which may contribute to deteriorated PF. This distinct airway inflammation may increase the severity of asthma in EA.