Osteosarcomatosis involving craniofacial bones presenting with cranial nerve palsies

Osteosarcomatosis (also known as multifocal osteosarcoma or multiple sclerotic osteosarcoma) is a rare condition, characterized by multiple skeletal lesions at initial presentation. We describe a case of osteosarcomatosis involving craniofacial bones presenting with cranial nerve palsies. In addition, a brief review of the literature is given, with a discussion of this highly aggressive form of osteosarcoma.     

Inhibition of autophagy by chloroquine makes chemotherapy in nasopharyngeal carcinoma more efficient

Objectives

A combination of platinum-based chemotherapy and radiotherapy is the standard treatment for nasopharyngeal carcinoma (NPC). However, the efficacy of chemotherapy has reached a plateau. Many autophagy studies suggest that autophagy can either promote or suppress to cancer progression. Thus, a role of autophagy in the acquisition of chemoradioresistance has recently been a notable event. Therefore, we examined the relationship between autophagy and chemotherapy in NPC.

Urinary Transthyretin as a Biomarker in ATTRv Val50Met Amyloidosis

Transthyretin (TTR), the precursor protein for amyloidogenic TTR (ATTR) amyloidosis, forms tetramers and escapes glomerular filtration by binding with thyroxine and retinol-binding protein. However, variant TTRs are unstable as tetramers, so monomeric TTR has become the precursor protein of amyloid deposits, via protein misfolding. The aim of the study was to evaluate the utility of urinary TTR in the diagnosis of ATTRv amyloidosis. Urinary samples from healthy volunteers, ATTRv V50M amyloidosis patients, and asymptomatic carriers of the ATTRv V50M gene were analysed using ELISA. To analyse the different forms of TTR secreted to the urine, we performed Western blotting and mass spectrometry. Urinary TTR concentrations were significantly higher in the ATTRv V50M amyloidosis patients than they were in the healthy volunteers and asymptomatic carriers of the gene. Although the TTR concentrations were negligible in the healthy volunteers, they were correlated with disease progression and urinary albumin concentrations in the ATTRv V50M amyloidosis patients. The Western blotting and mass spectrometry revealed the presence of monomeric wild-type and variant TTRs in the urine. Urinary TTR concentrations may become a more sensitive biomarker of ATTRv progression than albumin.     

Miller Fisher Syndrome Following Vaccination against SARS-CoV-2

After BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination, a 30-year-old man developed bilateral lateral gaze palsy, diplopia, absent tendon reflexes, and ataxic gait. Serum anti-GQ1b and anti-GT1a immunoglobulin G (IgG) antibodies were strongly positive. Based on those findings, he was diagnosed with Miller Fisher syndrome (MFS). Intravenous immunoglobulin therapy was administered, and his symptoms fully recovered within approximately 3 months. To the best of our knowledge, this is the first report to describe the development of MFS after COVID-19 mRNA vaccination.     

Possible Cerebral Vasculitis in a Case with Rheumatoid Arthritis

Cerebral rheumatoid vasculitis (CRV) is a rare, fatal, and diagnostically challenging disorder. We herein report an 81-year-old woman with a 4-year history of rheumatoid arthritis who presented with a fever, progressive disturbance of consciousness, high level of rheumatoid factor, and hypocomplementemia. The enhancement of the perforating branches in the left middle cerebral artery led us to suspect CRV. A brain biopsy could not be performed. After we intensified steroid therapy, the size of the cerebral lesions temporarily decreased. However, recurrence in the left frontal lobe occurred one month later, and the patient subsequently died. Early intensive treatments may be needed for CRV.     

Dab1‐mediated colocalization of multi‐adaptor protein CIN85 with Reelin receptors,ApoER2 and VLDLR,in neurons

Reelin‐Dab1 signaling is indispensable for proper positioning of neurons in mammalian brain. Reelin is a glycoprotein secreted from Cajal‐Reztuis cells in marginal zone of cerebral cortex, and its receptors are Apolipoprotein E receptor 2 (ApoER2) or very low density lipoprotein receptor (VLDLR) expressed on migrating neurons. When Reelin binds to ApoER2 or VLDLR, an adaptor protein Dab1 bound to the receptors undergoes Tyr phosphorylation that is essential for Reelin signaling. We reported previously that Cdk5‐p35 phosphorylates Dab1 at Ser400 and Ser491 and the phosphorylation regulates its binding to CIN85, which is an SH3‐containing multiadaptor protein involved in endocytic downregulation of receptor‐tyrosine kinases. However, the interaction of CIN85 with Dab1 has not been addressed in neurons. We examined here a possibility that CIN85 has a role in Reelin signaling. We found nonpho‐sphorylated Dab1‐mediated colocalization of CIN85 with ApoER2. The colocalization of CIN85 with ApoER2 was increased in neurons stimulated with Reelin repeats 3‐6, an active Reelin fragment. The stimulation recruited CIN85 to domains in plasma membrane where it colocalized with ApoER2 and Dab1 and then to EEA1‐labeled early endosomes in the cytoplasm. In addition, Tyr phosphorylation of Dab1 strengthened the binding to CIN85. These results suggest that CIN85 participates in Reelin signaling through the binding to Dab1.     

Role of spinal metabotropic glutamate receptors in regulation of lower urinary tract function in the decerebrate unanesthetized rat

Biomarker levels in cerebrospinal fluid (CSF) may serve as surrogate markers for treatment efficacy in clinical trials of disease-modifying drugs against Alzheimer's disease (AD). A prerequisite, however, is that the marker is sufficiently stable over time in individual patients. Here, we tested the stability of the three established CSF biomarkers for AD, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181)) and the 42 amino acid isoform of beta-amyloid (Abeta42), over 6 months in a cohort of AD patients on stable treatment with acetylcholinesterase (AChE) inhibitors. Fifty-three patients completed the study, 29 men and 24 women, mean age (+/-S.D.) 76.1+/-7.9 years. Mean levels of CSF biomarkers were very stable between baseline and endpoint, with coefficients of variation (CVs) of 4.4-6.1%. Intra-individual biomarker levels at baseline and endpoint were also highly correlated with Pearson r-values above 0.95 (p<0.0001), for all three markers. We conclude that T-tau, P-tau and Abeta42 concentrations in CSF are remarkably stable over a 6-month period in individual AD patients. This suggest that these biomarkers may have a potential to identify and monitor very minor biochemical changes induced by treatment, and thus support their possible usefulness as surrogate markers in clinical trials with drug candidates with disease-modifying potential, such as secretase inhibitors, Abeta immunotherapy and tau phosphorylation inhibitors.     

Clinical significance of small, dense LDL cholesterol in patients with hyperlipidemia and type 2 diabetes

We investigated the serum levels of small, dense LDL-cholesterol (sd LDL-C) in patients with hyperlipidemia and type 2 diabetes. An analytical assay was used to determine the levels of sd LDL-C, employing a filter method using a separating agent of polyanion and divalent cation natures. Reference intervals of sd LDL-C in normal healthy subjects (n=113) ranged from 8.0 to 42.0 mg/dl. We found a strong correlation between the levels of sd LDL-C and both the ratio of LDL-C/apolipoprotein B and the LDL migration index. The LDL migration index was analyzed using polyacrylamide gel disk electrophoresis. The levels of sd LDL-C in patients with types IIa, IIb and IV hyperlipidemia were significantly higher than those in normal subjects and in patients with normal lipidemia. The levels of sd LDL-C in patients with type IIb were higher than those with types IIa and VI. Examination of patients with polydisperse LDL showed that the levels of nodular and disrupted type sd LDL-C were higher than the levels of symmetry type sd LDL-C. Moreover, the levels of sd LDL-C in patients with type 2 diabetes were higher than those in normal subjects. A high level of sd LDL-C in patients with type 2 diabetes was found to be an indicator of possible complications of hyperlipidemia and lessly related to glycemic control. Therefore, the determination of sd LDL-C levels can be useful in the diagnosis of patients with hyperlipidemia and polydisperse LDL and in patients with type 2 diabetes with complications of hyperlipidemia and atherosclerosis.