Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease

Kidney tissues from cats with naturally occurring chronic kidney disease (CKD) and adult and senior cats without CKD were assessed to determine whether telomere shortening and nitrosative stress are associated with senescence in feline CKD. The histopathologic assessment of percent global glomerulosclerosis, inflammatory infiltrate, and fibrosis was performed. Senescence and nitrosative stress were evaluated utilizing p16 and iNOS immunohistochemistry, respectively. Renal telomere length was evaluated using telomere fluorescent in situ hybridization combined with immunohistochemistry. CKD cats were found to have significantly increased p16 staining in both the renal cortex and corticomedullary junction compared to adult and senior cats. Senior cats had significantly increased p16 staining in the corticomedullary junction compared to adult cats. p16 staining in both the renal cortex and corticomedullary junction were found to be significantly correlated with percent global glomerulosclerosis, cortical inflammatory infiltrate, and fibrosis scores. p16 staining also correlated with age in non-CKD cats. Average telomere length was significantly decreased in CKD cats compared to adult and senior cats. CKD cats had significantly increased iNOS staining compared to adult cats. Our results demonstrate increased renal senescence, telomere shortening, and nitrosative stress in feline CKD, identifying these patients as potential candidates for senolytic therapy with translational potential.

Neuronal intranuclear inclusion disease presented with recurrent vestibular migraine-like attack: a case presentation

Background Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder characterized by dementia, tremor, episodic encephalopathy and autonomic nervous dysfunction. To date, vestibular migraine (VM)-like attack has never been reported in cases with NIID. Here, we describe an 86-year-old patient with NIID who presented with recurrent vertigo associated with headache for more than 30 years. Case presentation An 86-year-old Chinese woman with vertigo, headache, weakness of limbs, fever, and disturbance of consciousness was admitted to our hospital. She had suffered from recurrent vertigo associated with headache since her 50 s,followed by essential tremor and dementia. On this admission, brain magnetic resonance imaging revealed high intensity signals along the corticomedullary junction on diffusion weighted imaging (DWI). Peripheral neuropathy of the extremities was detected through electrophysiological studies. We diagnosed NIID after detecting eosinophilic intranuclear inclusions in the ductal epithelial cells of sweat glands and identifying an abnormal expansion of 81 GGC repeats in the 5’UTR of NOTCH2NLC gene. Conclusions VM-like attack may be associated with NIID.

Differential Location of NKT and MAIT Cells within Lymphoid Tissue

Natural Killer T (NKT) cells and Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells that express semi-invariant αβ T cell receptors (TCRs) through which they recognise CD1d and MR1 molecules, respectively, in complex with specific ligands. These cells play important roles in health and disease in many organs, but their precise intra-organ location is not well established. Here, using CD1d and MR1 tetramer staining techniques, we describe the precise location of NKT and MAIT cells in lymphoid and peripheral organs. Within the thymus, NKT cells were concentrated in the medullary side of the corticomedullary junction. In spleen and lymph nodes, NKT cells were mainly localised within T cell zones (TCZ), although following in vivo activation with the potent NKT-cell ligand α-GalCer, they expanded throughout the spleen. MAIT cells were clearly detectable in Vα19 TCR transgenic mice and were rare but detectable in lymphoid tissue of non-transgenic mice. In contrast to NKT cells, MAIT cells were more closely associated with the B cell zone (BCZ) and red pulp (RP) of the spleen. Accordingly, we have provided an extensive analysis of the in situ localisation of NKT and MAIT cells and suggest differences between the intra-organ location of these two cell types.

The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease

The clinical manifestations of neuronal intranuclear inclusion disease (NIID) are heterogeneous, and the premortem diagnosis is mainly based on skin biopsy findings. Abnormal GGC repeat expansions in NOTCH2NLC was recently identified in familial and sporadic NIID. The comparison of diagnostic value between abnormal GGC repeat expansions of NOTCH2NLC and skin biopsy has not been conducted yet. In this study, skin biopsy was performed in 10 suspected adult NIID patients with clinical and imaging manifestations, and GGC repeat size in NOTCH2NLC was also screened by repeat primed-PCR and GC-rich PCR. We found that five cases had ubiquitin-immunolabelling intranuclear inclusion bodies by skin biopsy, and all of them were identified with abnormal GGC repeat expansions in NOTCH2NLC, among whom four patients showed typical linear hyperintensity at corticomedullary junction on DWI. Five (5/10) NIID patients were diagnosed by combination of NOTCH2NLC gene detection, skin biopsy or combination of NOTCH2NLC, and typical MRI findings. The diagnostic performance of NOTCH2NLC gene detection was highly consistent with that of skin biopsy (Kappa = 1). The unexplained headache was firstly reported as a new early phenotype of NIID. These findings indicate that NOTCH2NLC gene detection is needed to be a supplement in the diagnose flow of NIID and also may be used as an alternative method to skin biopsy especially in Asian population.

Neuronal intranuclear inclusion disease with mental abnormality: a case report

Background Neuronal intranuclear inclusion disease (NIID) is a chronic progressive neurodegenerative disease that is characterized by the discovery of eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. In this paper, we report a case of an adult-onset neuronal intranuclear inclusion disease presenting with mental abnormality in China. Case presentation A 62-year-old woman presented with mental abnormality and forgetfulness for 3 months before she was admitted to our hospital. There were prodromal symptoms of fever before she had the mental disorder. Encephalitis was first suspected, and the patient underwent lumbar puncture and brain magnetic resonance imaging (MRI). A cerebrospinal fluid (CSF) examination indicated normal pressure, a normal white blood cell count, and slightly elevated protein and glucose levels. Coxsackie B virus, enterovirus, and cytomegalovirus tests showed normal results. Bacterial culture and Cryptococcus neoformans test results were negative. The contrast-enhanced MRI of the brain was normal. The brain diffusion-weighted imaging (DWI) showed a symmetrically distributed strip-shaped hyperintensity signal of the corticomedullary junction in the bilateral frontal, parietal, and temporal lobes. We considered the diagnosis of the NIID, and therefore, skin biopsy was performed. The electron microscopy revealed that intranuclear inclusions in the nucleus of fibrocytes existed and were composed of filaments. Conclusions NIID is a rare neurodegenerative disease with diverse clinical manifestations. In clinical work, when a patient presents with abnormal mental behavior and exhibits hyperintensity signals on DWI images of the corticomedullary junction, it is crucial to consider the diagnosis of NIID.

Histogenesis of human fetal kidney from 14 weeks to 36 weeks: a study

Background: The knowledge of fetal human Kidney morphology and developmental anatomy is very important for prenatal diagnosis of disorders such as Wilm’s tumor, hydronephroses and congenital malformation etc.Methods: The study was carried out on 40 kidneys procured from 20 spontaneously aborted fetuses (11males and 9 females) ranging from 14wks-36wks of gestation, after confirming their age through CRL they were grouped and then processed to form slides and stained with haemtoxylin and eosin and seen under light microscope.Results: All kidneys were lobulated at early gestational age and became fused by 36 wks. Corticomedullary junction and preformed collecting tubules were seen clearly by 18wks. Well differentiated PCT and DCT were formed by 19-23 wks. Well-formed pyramids by 28 wks and medullary rays by 29 weeks were clearly distinguished. Loop of Henle developed and distinguished by 28 wks. Increased vascularity was seen by 32-36 wks. Nephrogenic zone and undifferentiated mesenchyme decreased and matured glomeruli increased by 36 wks.Conclusions: The present study gave emphasis to the development of each component in medulla and cortex of kidney.

Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress

T cell egress from the thymus is essential for adaptive immunity and involves chemotaxis along a sphingosine-1-phosphate (S1P) gradient. Pericytes at the corticomedullary junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)–mediated metabolism. Although SPL is robustly expressed in thymic epithelial cells (TECs), in this study, we show that deleting SPL in CD11c+ dendritic cells (DCs), rather than TECs or other stromal cells, disrupts the S1P gradient, preventing egress. Adoptive transfer of peripheral wild-type DCs rescued the egress phenotype of DC-specific SPL knockout mice. These studies identify DCs as metabolic gatekeepers of thymic egress. Combined with their role as mediators of central tolerance, DCs are thus poised to provide homeostatic regulation of thymic export.