The immunoreactive signature of monocyte-derived dendritic cells from patients with Down syndrome.

The clinical spectrum of Down syndrome (DS) ranges from congenital malformations to premature aging and early-onset senescence. Excessive immunoreactivity and oxidative stress are thought to accelerate the pace of aging in DS patients; however, the immunological profile remains elusive. We investigated whether peripheral blood monocyte-derived dendritic cells (MoDCs) in DS patients respond to lipopolysaccharide (LPS) distinctly from non-DS control MoDCs. Eighteen DS patients (age 2~47 years, 12 males) and 22 controls (age 4~40 years, 15 males) were enrolled. CD14-positive monocytes were immunopurified and cultured for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and IL-4, yielding MoDCs in vitro. After the LPS-stimulation for 48 hours from days 7 to 9, culture supernatant cytokines were measured by multiplex cytokine bead assays, and bulk-prepared RNA from the cells was used for transcriptomic analyses. MoDCs from DS patients produced cytokines/chemokines (IL-6, IL-8, TNF-α, MCP-1, and IP-10) at significantly higher levels than those from controls in response to LPS. RNA sequencing revealed that DS-derived MoDCs differentially expressed 137 genes (74 upregulated and 63 downregulated) compared with controls. A gene enrichment analysis identified 5 genes associated with Toll-like receptor signaling (KEGG: hsa04620, p = 0.00731) and oxidative phosphorylation (hsa00190, p = 0.0173) pathways. MoDCs obtained from DS patients showed higher cytokine or chemokine responses to LPS than did control MoDCs. Gene expression profiles suggest that hyperactive Toll-like receptor and mitochondrial oxidative phosphorylation pathways configure the immunoreactive signature of MoDCs in DS patients.

Embolization of pseudoaneurysms in the ureteral branch of the renal artery.

BACKGROUND: Although transcatheter arterial embolization for pseudoaneurysms is already well-established, ureteral artery pseudoaneurysm embolization is extremely rare. The present case shows a successful transcatheter arterial embolization for pseudoaneurysms in the ureteral branch of the renal artery due to ureteral invasion from gastric cancer. CASE PRESENTATION: A 57-year-old female presented with gross hematuria after treatments for poorly differentiated gastric adenocarcinoma. A contrast-enhanced computed tomography revealed pseudoaneurysms around the right ureter with a massive hematoma in the right ureter and bladder. The diagnosis was ureteral branch pseudoaneurysms resulting from possible retroperitoneal invasion due to pelvic lymph node metastasis of gastric cancer. Transcatheter arterial embolization was performed using gelatin particles, successfully controlling her hematuria without complications. CONCLUSIONS: Ureteral branch artery embolization, although extremely rare, may be an effective and safe treatment option.

Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells.

Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14high cells expressed interleukin (IL) -1ß after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1ß production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.

Prevention of New Metastatic Lesions by Eribulin Monotherapy Is Associated with Better Prognosis in Patients with Metastatic Breast Cancer.

BACKGROUND: Eribulin therapy has been reported to prolong overall survival (OS) but not progression-free survival, probably because it prevents the development of metastatic lesions; however, this effect has not yet been confirmed. METHODS: We reviewed the medical charts of 50 patients with metastatic breast cancer who underwent eribulin monotherapy at our hospital between 2014 and 2019. Patients were divided into two groups, namely, those who discontinued eribulin because of disease progression due to development of new lesions (NL group) and those who discontinued eribulin for other reasons, such as lesion growth and unacceptable side effects (non-NL group). Survival times were estimated for both groups and we investigated if eribulin-mediated suppression of new metastasis increased OS. RESULTS: Median OS for all patients, from eribulin initiation, was 14.4 months (range 1.2-60.1), whereas it was 4.6 months (range 1.7-24.7) in the NL group and 16.8 months (range 1.2-60.1) in the non-NL group. OS was significantly poorer in the NL group than in the non-NL group (p < 0.05). CONCLUSION: Eribulin monotherapy-mediated suppression of new metastatic lesions results in a better prognosis in patients with metastatic breast cancer.

Well-differentiated Astroblastoma with Both Focal Anaplastic Features and a Meningioma 1 Gene Alteration.

A 6-year-old female was incidentally found to have a brain tumor. Magnetic resonance imaging (MRI) demonstrated a gadolinium-enhanced mass in the left parietal lobe. We performed gross total resection with the assistance of fluorescent guidance by 5-aminolevulinic acid (5-ALA). A histological examination of the tumor specimen showed well-differentiated astroblastic features with focal anaplasia. Fluorescence in situ hybridization (FISH) revealed meningioma 1 (MN1) gene alteration and supported our diagnosis. She received local radiotherapy and oral temozolomide followed by maintenance temozolomide chemotherapy, and the tumor was well controlled without any neurological deficit for 27 months. Our case is considered to be valuable since it describes a patient who is diagnosed to have a well-differentiated astroblastoma with both focal anaplastic features and MN1 gene rearrangement. A larger study is warranted to establish evidence supporting the diagnosis and treatment of astroblastoma with molecular characteristic features. MN1 alteration will be a diagnostic marker for astroblastoma in the future.

[Phyllodes Tumor of the Breast Occurring near Postoperative Fibroadenoma Scar-A Case Report].

We report the case of a phyllodes tumor of the breast occurring near a postoperative scar of fibroadenoma of the breast. The patient was a 41-year-old female who had a lump in the left breast, and underwent surgical resection of the tumor 5 years ago at another hospital.The pathological diagnosis of the tumor was fibroadenoma, and surgical margin was negative. The patient underwent ultrasonography every year at the treatment hospital.Five years later, the patient noticed a tumor in her left breast and visited our hospital.The tumor was 30mm in diameter and situated near the postoperative scar.A core needle biopsy for breast tumor led to the diagnosis of a phyllodes tumor.Surgical resection was performed with 5mm margins, and pathological analysis of the surgical specimen revealed a benign phyllodes tumor.The surgical margins were not involved.One year and 6 months after surgery, no metastases or recurrence were reported.

[Breast Papilloma with Rapid Growth Difficult to Distinguish from Carcinoma-A Case Report].

We report a case of papilloma of the breast with rapid growth in a 39-year-old female who had a lump in the left breast. The follow-up for the breast tumor was performed at another hospital.Three years after her first visit, 3 tumors measuring 1.8 cm, 0.5 cm, and 0.3 cm in diameter were detected. The patient visited our hospital to diagnose these tumors. We performed core needle biopsy for the tumor, and the pathological diagnosis was benign papilloma.After 1 year, the tumor grew to 3.0 cm in diameter, and we repeated the core needle biopsy. The pathological diagnosis remained as benign papilloma; however, the ultrasonography and MRI results showed that the tumor was malignant.Surgical resection was performed for the tumors, and pathological analysis of the surgical specimen revealed 3 benign papillomas with no involvement of the surgical margin.Six years after surgery, no recurrence was reported.

Early Recovery of Height Velocity in Prepubertal Children With Acute Lymphoblastic Leukemia Treated by a Short Intensive Phase Without Cranial Radiation Therapy.

PURPOSE: There have been few reports on height disturbance in childhood acute lymphoblastic leukemia (ALL) patients treated without cranial radiation therapy (CRT). Our study aimed to clarify the critical period of growth in pediatric patients who were treated by the Japan Childhood Leukemia Study (JACLS) ALL-02 protocol, which involved short-term intensive treatment without CRT. PATIENTS AND METHODS: A retrospective, cohort study was conducted for prepubertal children with B-precursor ALL who were diagnosed from July 2002 to November 2011 and treated by the JACLS ALL-02 protocol at Oita University Hospital. The heights were chronologically measured at pretreatment, after the intensive phase (INT), at the end of treatment (END), and at 1 to 5 year(s) posttreatment (POST 1 to 5). RESULTS: Nine boys and 4 girls were enrolled. Z score of the height was reduced at INT and END. Delta Z scores of the height and Z score of height velocity were reduced from pretreatment to INT, and they demonstrated an early recovery during maintenance treatment in INT to END. CONCLUSIONS: Early recovery of delta Z scores of the height and Z score of height velocity was observed during the INT to END period. The shortened intensive phase without CRT may result in an adequate height in prepubertal ALL patients.

[Clinical Evaluation of Immunosuppressive Acidic Protein in the Serum of Patients with Inflammatory Breast Recurrence].

Inflammatory breast recurrence after breast conserving surgery often compromises patient quality of life(QOL)and is associated with a poor prognosis. For this type of recurrence, the immunological situation of the patient is uncertain. We evaluated the clinical significance of immunosuppressive acidic protein(IAP)in the serum of patients with inflammatory breast recurrence during treatment. We collected serum from 3 patients at three different time points: the pre-treatment phase, recurrence phase, and the post-treatment phase. IAP was then measured from these multiple serum samples. There was a significant difference between serum IAP values in the pre-treatment and recurrence phases. The recurrence phase had a mean IAP value that was higher than the pre-treatment phase. The IAP values were indicative of the disease condition. These results suggest that serum IAP is a useful quantification of the immunological condition of patients with inflammatory breast recurrence.

Three-Quarters Adrenalectomy for Infantile-Onset Cushing Syndrome due to Bilateral Adrenal Hyperplasia in McCune-Albright Syndrome.

BACKGROUND: Bilateral adrenalectomy is performed in cases with infantile-onset Cushing syndrome due to bilateral adrenal hyperplasia in McCune-Albright syndrome (MAS) because severe Cushing syndrome with heart failure and liver dysfunction can have a lethal outcome. This procedure can completely ameliorate hypercortisolism, although lifetime steroid replacement therapy and steps to prevent adrenal crisis are necessary. Recently, the efficacy of unilateral adrenalectomy has been reported in adult cases of bilateral macronodular adrenal hyperplasia, but there is no consensus regarding the appropriate surgical treatment for bilateral adrenal hyperplasia in MAS. OBJECTIVE: A 6-month-old girl presented with café-au-lait spots, short stature, central obesity, a moon face, and hypertension. Endocrinological tests and imaging studies led to the diagnosis of ACTH-independent Cushing syndrome due to bilateral adrenal hyperplasia induced by MAS. "Three-quarters adrenalectomy", namely right-sided total adrenalectomy and left-sided half adrenalectomy, was carried out. An activating mutation of the GNAS1 gene (p.Arg201Cys) was identified in the adrenal tissues. Since the operation, our patient has been in a state of clinical remission for more than 2 years. CONCLUSION: Our original surgical intervention, three-quarters adrenalectomy, may be a new treatment option for Cushing syndrome associated with MAS.

Reversible cerebral vasoconstriction syndrome manifesting as focal seizures without a thunderclap headache: A pediatric case report.

We report a pediatric case of reversible cerebral vasoconstriction syndrome with focal seizures without a thunderclap headache. A 7-year-old girl had a mild acute headache with nausea after swimming. She subsequently developed hemi-convulsions followed by right hemiplegia. Brain magnetic resonance angiography revealed generalized vasoconstriction of the main cerebral peripheral arteries. Her hemiplegia was spontaneously resolved within 6h. Over the next 24h she suffered from recurrent and transient headaches, which recurred on days 3 and 5. Follow-up magnetic resonance angiography on day 3 documented the multifocal narrowing of the main cerebral arteries, which was observed to have diminished at 12weeks after her initial presentation. She did not have any headaches or neurological deficits after day 5. This case indicates that reversible cerebral vasoconstriction syndrome should be considered in children with focal seizures even when they do not present with thunderclap headaches. The timely and appropriate evaluation by magnetic resonance angiography and imaging is essential for diagnosing reversible cerebral vasoconstriction syndrome.

Central retinal vein occlusion in a pediatric patient with SLE and antiphospholipid antibodies without anti-cardiolipin or anti-ß2 glycoprotein I antibodies.

BACKGROUND: Antiphospholipid antibody syndrome is characterized by venous and/or arterial thrombosis, and is found in patients with systemic lupus erythematosus. Its diagnosis requires the presence of both clinical and laboratory findings, such as positive anti-cardiolipin and anti-ß2 glycoprotein I antibodies and lupus anticoagulant. However, cardiolipin is a minor component of the vascular endothelial cells in human, and phosphatidylcholine and phosphatidylethanolamine are major components. CASE PRESENTATION: A 15-year-old female suddenly developed massive left intraretinal hemorrhaging due to central retinal vein occlusion. She also had a butterfly rash, and her laboratory findings revealed positive serum anti-nuclear antibodies and decreased serum complement. During this episode, she was diagnosed with systemic lupus erythematosus. Although she was negative for serum anti-cardiolipin IgG and anti-ß2 glycoprotein I antibodies as well as lupus anticoagulant, her serum anti-phosphatidylcholine, anti-phosphatidylethanolamine, anti-phosphatidylinositol and phosphatidylserine IgG antibodies levels were increased. CONCLUSION: Pediatric cases of central retinal vein occlusion are rare. Even in patients without anti-cardiolipin or anti-ß2 glycoprotein I antibodies and lupus anticoagulant, there is the potential for the development of antiphospholipid antibody-related thrombosis.

[Physics properties of non-helical scan using 320-row multi detector computed tomography].

Recently, clinical applications utilizing 320-row multi detector computed tomography (320MDCT) have increased, and the physical image properties of 320MDCT have been more concerned. We evaluated the spatial resolution in scan plane and z-direction, image noise and low-contrast sensitivity of non-helical mode (320NH), 640 slices mode by a double slice reconstruction technology (640DS), and 64-row helical mode (64HE) by using a 320MDCT. The spatial resolution in z-direction was evaluated by the section sensitivity profile (SSP) measurement with the micro coin phantom and the contrast transfer ratio (CTR) with the 0.5-mm comb phantom. The in-plane spatial resolution of 320NH was uniform over all the slice positions. The spatial resolution in z-direction decreased from the cathode side toward the anode side. The image noise of the anode side was higher than that of the cathode side. The contrast to noise ratio as index of the low contrast sensitivity was uniform over all the slice position. The CTR of 320NH fluctuated in the z-position, and the fluctuation was improved by 640DS except for the center of rotation.