Primary age-related tauopathy (PART) is characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. In the present study, we analyzed the distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART, Alzheimer's disease (AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages > 0 and ≤ IV, and a Thal phase of 0 (no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus, stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.
Aged ; Aged, 80 and over ; Aging ; metabolism ; pathology ; Brain ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Inclusion Bodies ; pathology ; Male ; Middle Aged ; Neurofibrillary Tangles ; metabolism ; pathology ; Neurons ; metabolism ; pathology ; Severity of Illness Index ; Tauopathies ; metabolism ; pathology

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A, resulting in the accumulation of glycosphingolipids within the lysosomes of various cell types. It has a wide spectrum of clinical phenotypes, and renal failure is a serious complication. Fabry disease is confirmed either by measurement of α-galactosidase A activity or by genetic testing for GLA mutations. Renal biopsy findings on light microscopy, specifically enlarged podocytes with foamy cytoplasm, and osmiophilic inclusion bodies in the cytoplasm in all types of renal cells on electron microscopy, are characteristic of this disease. The predominant differential diagnosis is iatrogenic phospholipidosis in association with certain drugs that can cause cellular injuries indistinguishable from Fabry disease. Here, we report the case of a 10-year-old boy with microscopic hematuria who underwent a renal biopsy that showed morphological findings consistent with Fabry disease, although the patient had neither a GLA mutation nor a history of drug consumption. Six years later, spontaneous regression of this renal pathology was observed in a second renal biopsy examination.
Biopsy* ; Child* ; Cytoplasm ; Diagnosis, Differential ; Fabry Disease* ; Genetic Testing ; Glycosphingolipids ; Hematuria* ; Humans ; Inclusion Bodies ; Lysosomes ; Male* ; Microscopy ; Microscopy, Electron ; Pathology ; Phenotype ; Podocytes ; Renal Insufficiency

OBJECTIVETo investigate histopathology and proteinopathy in the spinal cord of patients with common neurodegenerative diseases.

METHODSSpinal cord tissues from clinically and neuropathologically confirmed neruodegnerative diseases were enrolled in this study, including 3 cases of multiple system strophy, 4 cases of amyotrophic lateral sclerosis, 5 cases of Alzheimer's disease (AD, included 2 cases of AD combined with Parkinson's disease), 2 cases of progressive supranuclear palsy, 1 case of dementia with lewy body and 1 case of corticobasal degeneration from 1955 to 2013 at Chinese People's Liberation Army General Hospital. Four normal control cases were also included. Routine HE and Gallyas-Braak staining, and immunohistochemical stainings for anti-PHF tau (AT8), anti-α-synuclein, anti-TDP-43 and anti-ubiquitin were performed.

RESULTSExamination of the spinal cord in 3 cases with multiple system strophy revealed severe neuron loss in the intermediolateral nucleus of thoracic segment and Onuf's nucleus of the sacral segment, along with moderate neuron loss in the anterior horn of the cervical segment and mild myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments. Large amount of argentophilic, ubiquitin and synuclein positive oligodendroglial cytoplasmic inclusions were found widely distributed in the anterior horn and the anterior funiculus and anterolateral funiculus of the full spinal cord. Severe neuron loss and several morphological changes with gliosis in the anterior horn and severe loss of myelin in the anterior funiculus and anterolateral funiculus of the full spinal cord were observed in 4 cases of amyotrophic lateral sclerosis, 2 of which were found with Bunina bodies in neurons of the anterior horn. Three amyotrophic lateral sclerosis cases had ubiquitin-positive neuronal inclusions and TDP-43 positive neuronal and glial inclusions in the anterior horn at cervical and lumbar segments. A few argentophilic, tau positive neurofibrillary tangles (NFTs) and neuropil threads in the anterior horn at cervical and lumbar segments were found in 4 AD cases. Examination of spinal cord in 2 cases with Parkinson's disease combined with AD and 1 case with dementia with lewy body revealed severe neuron loss in the intermediolateral nucleus of thoracic segment, and a few synuclein positive lewy bodies and neuritis were also observed. There was mild neuron loss in the anterior horn at cervical and lumbar segments, along with some argentophilic, tau positive globous NFTs and many argentophilic, tau positive neutrophil threads were observed in 2 progressive supranuclear palsy cases and 1 corticobasal degeneration case.

CONCLUSIONEach common neurodegenerative diseases of the spinal cord including multiple system strophy, amyotrophic lateral sclerosis and Parkinson's disease has its own specific histopathology and proteinopathy characteristics.

Alzheimer Disease ; pathology ; Amyotrophic Lateral Sclerosis ; pathology ; DNA-Binding Proteins ; metabolism ; Humans ; Immunohistochemistry ; Inclusion Bodies ; pathology ; Neurodegenerative Diseases ; pathology ; Neurofibrillary Tangles ; pathology ; Neurons ; pathology ; Parkinson Disease ; pathology ; Spinal Cord ; pathology ; Ubiquitin ; metabolism ; alpha-Synuclein ; metabolism

A 63-year-old man presented with a 1.5-year history of progressive personality changes. Clinical evaluations revealed severe frontal dysfunction and bilateral frontal atrophy/glucose hypometabolism. He was diagnosed as probable behavioral variant frontotemporal dementia. He continued to decline, and died at the age of 66. At autopsy, numerous tau-positive gilial threads and coiled bodies were observed in the white matter. Tau-positive astrocytic plaques and neuronal cytoplasmic inclusions were also seen in cerebral cortices, which were compatible with corticobasal degeneration.
Autopsy* ; Cerebral Cortex ; Coiled Bodies ; Frontotemporal Dementia* ; Humans ; Inclusion Bodies ; Middle Aged ; Neurons ; Pathology*

A 63-year-old man presented with a 1.5-year history of progressive personality changes. Clinical evaluations revealed severe frontal dysfunction and bilateral frontal atrophy/glucose hypometabolism. He was diagnosed as probable behavioral variant frontotemporal dementia. He continued to decline, and died at the age of 66. At autopsy, numerous tau-positive gilial threads and coiled bodies were observed in the white matter. Tau-positive astrocytic plaques and neuronal cytoplasmic inclusions were also seen in cerebral cortices, which were compatible with corticobasal degeneration.
Autopsy* ; Cerebral Cortex ; Coiled Bodies ; Frontotemporal Dementia* ; Humans ; Inclusion Bodies ; Middle Aged ; Neurons ; Pathology*

This study is to optimize the preparation process of fusion protein Fv-LDP which was expressed in the form of inclusion body and consisted of lidamycin apoprotein LDP and single-chain Fv antibody (scFv) directed against type IV collagenase. The preparation and the dissolution of inclusion body, the immobilized metal affinity chromatography of the target protein and the renaturization by stepwise dialysis were optimized by single-factor analysis or orthogonal design. In addition, the refolded fusion protein Fv-LDP was refined by Sephadex G-75 chromatography followed by fluorescence-activated cell sorter (FACS)-based saturation binding assay to measure its antigen-binding activity. After optimization of the process, the purity of fusion protein Fv-LDP existed in the inclusion body was 63.9% and the corresponding solubility was 95.7%; Under denaturing conditions, the purity of fusion protein Fv-LDP was more than 95% after the purification process. The percentage of monomeric fusion protein Fv-LDP was 60% after the refolding process, while it was further refined to 85% which was 5.6-fold higher than that of the initial refolding condition. The refined fusion protein Fv-LDP could bind to human lung adenocarcinoma PAa cells and human hepatoma BEL-7402 cells with the dissociation constants (Kd) of 0.176 micromol x L(-1) and 0.904 micromol x L(-1), respectively. The preparation process of fusion protein Fv-LDP has been successfully optimized, which provides the experimental basis for the production and future development of fusion protein Fv-LDP, and might serve as a relatively practical system for the preparation of other scFv-based proteins expressed in the form of inclusion body.
Adenocarcinoma ; metabolism ; pathology ; Aminoglycosides ; chemistry ; metabolism ; Antibiotics, Antineoplastic ; chemistry ; metabolism ; Apoproteins ; chemistry ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Collagenases ; immunology ; Enediynes ; chemistry ; metabolism ; Escherichia coli ; chemistry ; metabolism ; Humans ; Inclusion Bodies ; chemistry ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Lung Neoplasms ; metabolism ; pathology ; Protein Binding ; Recombinant Fusion Proteins ; chemistry ; metabolism ; Single-Chain Antibodies ; chemistry ; metabolism

OBJECTIVETo investigate the effect of Yisui Shengxue Granule (, YSSXG), a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H (HbH) disease.

METHODSTwenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin (Hb), red blood cells (RBCs), and reticulocyte percent (Ret)] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy (TEM); activities of antioxidant defense enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (Cat)] and erythrocyte membrane malondialdehyde (MDA) concentrations were determined.

RESULTSIn patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment (P<0.01). Measured values of Ret from the second to the third months after treatment were significantly lower than before treatment (P<0.05 and P<0.01, respectively). Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity (P<0.01), a decrease in Cat activity (P<0.01), and no significant differences in GSHPx activity (P>0.05) or MDA concentration (P>0.05). However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels (P<0.01) both before and after treatment.

CONCLUSIONSYSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of β-globin chains.

Adolescent ; Adult ; Catalase ; metabolism ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Erythrocyte Membrane ; drug effects ; metabolism ; ultrastructure ; Erythrocytes ; drug effects ; enzymology ; pathology ; ultrastructure ; Female ; Glutathione Peroxidase ; metabolism ; Humans ; Inclusion Bodies ; drug effects ; ultrastructure ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; drug effects ; Superoxide Dismutase ; metabolism ; Young Adult ; alpha-Thalassemia ; blood ; drug therapy ; pathology

Calcium-Binding Proteins ; metabolism ; Diagnosis, Differential ; Female ; Fibroma ; metabolism ; pathology ; surgery ; Humans ; Inclusion Bodies ; pathology ; Infant ; Microfilament Proteins ; metabolism ; Skin Neoplasms ; metabolism ; pathology ; surgery ; Soft Tissue Neoplasms ; pathology ; Tendons ; pathology ; Toes ; Vimentin ; metabolism

OBJECTIVETo compare the clinical, pathological, laboratory test and follow-up data between familial and sporadic patients with distal myopathy with rimmed vacuoles (DMRV) and discuss the characteristics of this disorder in Chinese population.

METHODSThe clinical and pathological features, laboratory data and follow-up results of 33 sporadic and 4 familial cases of pathologically confirmed DMRV were summarized and compared retrospectively.

RESULTSThe patients age, onset age, or disease duration showed no significant difference between sporadic and familial cases; the onset pattern and affected muscle groups were also similar, but the sporadic cases showed more frequent dysmorphic features than the familial cases. The patients showed mild to moderate elevation of the muscle enzymes by one to three folds, and the familial patients had more significant elevation than the sporadic ones. No correlation was found between the disease duration and the level of muscle enzymes. The pathological findings were similar between the cases, and Gomori staining showed rimmed vacuoles and inclusion bodies without inflammatory cell infiltration. Follow-up results of 29 cases showed no significant difference between the two groups. The disease was slowly progressive and severely affected the quality of life of the patients, but did not produce obvious effect on the life expectancy.

CONCLUSIONThe clinical, pathological and laboratory data of Chinese DMRV patients are basically similar to those of Japanese cases. Sporadic cases tend to show more dysmorphic features than the familial ones, and occasional sporadic cases have early disease onset in early childhood.

Adult ; Asian Continental Ancestry Group ; Distal Myopathies ; classification ; genetics ; pathology ; Female ; Humans ; Inclusion Bodies ; pathology ; Male ; Pedigree ; Retrospective Studies ; Vacuoles ; pathology ; Young Adult

Reports of combined candidal and herpetic esophagitis in immunocompetent states are rare and sporadic. A 44-year-old previously healthy lady presented with a one week history of progressive dysphagia, odynophagia and fever. Esophagogastroduodenoscopy (EGD) showed extensive desquamation of the entire esophagus except for distal 4 cm. Histopathological examination revealed ulcerated and inflamed squamous epithelium with the margin of ulcer showing a few overhanging squamous cells with dense eosinophilic cytoplasm, multinucleated and faceted nuclei with glassy chromatin, and an occasional Cowdry type A intranuclear inclusion bodies. Few candidal spores were seen in the underlying stroma. Intravenous acyclovir, fluconazole and pantoprazole were initiated. Oral analgesics were given for pain relief. She was treated for a total of 14 days. She showed significant improvement and was tolerating oral intake after discharge. The patient was asymptomatic with no evidence of recurrence at a 2-month follow-up.
Adult ; Antifungal Agents ; therapeutic use ; Antiviral Agents ; therapeutic use ; Candidiasis ; diagnosis ; drug therapy ; microbiology ; Esophagitis ; diagnosis ; drug therapy ; microbiology ; virology ; Esophagus ; microbiology ; pathology ; virology ; Female ; Herpes Simplex ; diagnosis ; drug therapy ; virology ; Humans ; Inclusion Bodies, Viral ; Spores, Fungal ; Treatment Outcome