Bilateral Optic Neuritis and Hypophysitis With Diabetes Insipidus 1 Month After COVID-19 mRNA Vaccine: Case Report and Literature Review.

Either optic neuritis (neuropathy) or hypopituitarism has been known to occur separately after COVID-19 vaccination. In this report, we describe the rare combination of hypophysitis and optic neuritis which occurred after COVID-19 vaccination. A 74-year-old woman began to have thirst, polydipsia, and polyuria, and was diagnosed as central diabetes insipidus 1 month after the fourth COVID-19 mRNA vaccine. Head magnetic resonance imaging (MRI) disclosed the thickened pituitary stalk and enlarged pituitary gland with high contrast enhancement as well as the absence of high-intensity signals in the posterior pituitary lobe on the T1-weighted image, leading to the diagnosis of lymphocytic hypophysitis. She was well with desmopressin nasal spray until further 2 months later, when she developed bilateral optic neuritis, together with gait disturbance, intention tremor of the upper extremities, urinary retention, constipation, abnormal sensation in the distal part of the lower extremities, and moderate hemiplegia on the left side. Autoantibodies, including anti-aquaporin 4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG), were all negative. She showed multifocal spinal cord lesions on MRI and oligoclonal bands in the cerebrospinal fluid obtained by spinal tap, and so underwent steroid pulse therapy with methylprednisolone in the tentative diagnosis of multiple sclerosis, resulting in visual acuity recovery and alleviation of neurological symptoms. In the literature review, the combination of optic neuritis and hypophysitis, mostly with diabetes insipidus, was reported in 15 patients as case reports before the years of COVID-19 pandemic. The COVID-19 vaccination would trigger the onset of hypophysitis and optic neuritis in this patient.

[Primary effusion lymphoma-like lymphoma transformed to diffuse large B-cell lymphoma].

A rare kind of malignant lymphoma, called primary effusion lymphoma (PEL) is associated with human herpesvirus 8 (HHV-8), and characterized by lymphomatous effusion in the bodily cavities. Although the initial clinical presentation of primary effusion lymphoma-like lymphoma (PEL-LL) is similar to that of PEL, PEL-LL is HHV-8 negative and has a favorable prognosis. A PEL-LL diagnosis was made after an 88-year-old man was admitted to our hospital with a pleural effusion. His disease regressed after effusion drainage. He demonstrated disease progression to diffuse large B-cell lymphoma after two years and ten months. Our example demonstrates that aggressive B-cell lymphoma can develop from PEL-LL.

[MIC2 (CD99) as a diagnostic marker for TdT-negative B lymphoblastic lymphoma].

Lymphoblastic lymphoma (LBL) is a rare hematologic malignancy that originates from immature lymphocytes and usually expresses terminal deoxynucleotidyl transferase (TdT). Here, we report a case of TdT-negative B-LBL. A 71-year-old male patient presented to a hospital with shortness of breath. His chest computed tomography showed a mediastinal mass. Tumor cells did not express TdT but expressed MIC2, which led to LBL diagnosis. MIC2 is a useful marker for LBL diagnosis.

Interaction of Nerve Growth Factor ß with Adiponectin and SPARC Oppositely Modulates its Biological Activity.

Both adiponectin and secreted protein, acidic and rich in cysteine (SPARC) inhibit platelet-derived growth factor-BB (PDGF-BB)-induced and basic fibroblast growth factor (FGF2)-induced angiogenic activities through direct and indirect interactions. Although SPARC enhances nerve growth factor (NGF)-dependent neurogenesis, the physical interaction of NGFß with adiponectin and SPARC remains obscure. Therefore, we first examined their intermolecular interaction by surface plasmon resonance method. NGFß bound to immobilized SPARC with the binding constant of 59.4 nM, comparable with that of PDGF-BB (24.5 nM) but far less than that of FGF2 (14.4 µM). NGFß bound to immobilized full length adiponectin with the binding constant of 103 nM, slightly higher than those of PDGF-BB (24.3 nM) and FGF2 (80.2 nM), respectively. Treatment of PC12 cells with SPARC did not cause mitogen-activated protein kinase (MAPK) activation and neurite outgrowth. However, simultaneous addition of SPARC with NGFß enhanced NGFß-induced MAPK phosphorylation and neurite outgrowth. Treatment of the cells with adiponectin increased AMP-activated protein kinase (AMPK) phosphorylation but failed to induce neurite outgrowth. Simultaneous treatment with NGFß and adiponectin significantly reduced cell size and the number of cells with neurite, even after silencing the adiponectin receptors by their siRNA. These results indicate that NGFß directly interacts with adiponectin and SPARC, whereas these interactions oppositely regulate NGFß functions.

Calcium-dependent phospholipid scramblase activity of TMEM16 protein family members.

BACKGROUND: TMEM16A and 16B work as Cl(-) channel, whereas 16F works as phospholipid scramblase. The function of other TMEM16 members is unknown. RESULTS: Using TMEM16F(-/-) cells, TMEM16C, 16D, 16F, 16G, and 16J were shown to be lipid scramblases. CONCLUSION: Some TMEM16 members are divided into two Cl(-) channels and five lipid scramblases. SIGNIFICANCE: Learning the biochemical function ofTMEM16family members is essential to understand their physiological role. Asymmetrical distribution of phospholipids between the inner and outer plasma membrane leaflets is disrupted in various biological processes. We recently identified TMEM16F, an eight-transmembrane protein, as a Ca(2+)-dependent phospholipid scramblase that exposes phosphatidylserine (PS) to the cell surface. In this study, we established a mouse lymphocyte cell line with a floxed allele in the TMEM16F gene. When TMEM16F was deleted, these cells failed to expose PS in response to Ca(2+) ionophore, but PS exposure was elicited by Fas ligand treatment. We expressed other TMEM16 proteins in the TMEM16F(-/-) cells and found that not only TMEM16F, but also 16C, 16D, 16G, and 16J work as lipid scramblases with different preference to lipid substrates. On the other hand, a patch clamp analysis in 293T cells indicated that TMEM16A and 16B, but not other family members, acted as Ca(2+)-dependent Cl(-) channels. These results indicated that among 10 TMEM16 family members, 7 members could be divided into two subfamilies, Ca(2+)-dependent Cl(-) channels (16A and 16B) and Ca(2+)-dependent lipid scramblases (16C, 16D, 16F, 16G, and 16J).

Diet-induced obesity disrupts ductal development in the mammary glands of nonpregnant mice.

Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin.