The significance and usefulness of immunohistochemically quantitated cutaneous nerves in the evaluation of diabetic neuropathy was examined in biopsied skins of the calf from healthy subjects (n = 12) and non‐insulin dependent diabetic patients (n = 32) with diabetic sensory neuropathy. Skin samples were immunostained with antibodies against protein gene product (PGP) 9.5, a pan‐axonal marker. A quantitative analysis to determine nerve fiber (NF) number and nerve lengths (NLs) was performed on nerve fibers of the epidermis and the dermis and on nerves surrounding sweat glands. Nerve function tests were performed on the biopsied sites and erythrocyte aldose reductase level was determined by enzyme‐linked immunosorbent assay. Numbers of epidermal NFs, NLs of epidermis and dermis and NL around sweat glands were significantly decreased in diabetic patients compared with control subjects (P<0.001, P<0.001, P < 0.01, P < 0.01, respectively). NL of epidermis showed a significant correlation with NL of dermis (P < 0.01). Sural nerve conduction velocity was significantly correlated with NL of dermis (P < 0.05). Patients with higher AR level (> 10.8 (average in 555 diabetic patients) ng/mgHb) possessed a shorter NL of dermis NFs than those with lower AR level (> 10.8) (P < 0.05). These findings suggest that the quantitation of cutaneous nerves in biopsied skin samples provides important information about diabetic neuropathy and may improve the understanding of the pathophysiology of sensory nerve terminals in diabetic neuropathy.
We herein report a sporadic Creutzfeldt-Jakob disease (sCJD) patient followed from the presymptomatic phase to death. A 67-year-old woman had abnormal hyperintense cortical lesions on diffusion-weighted magnetic resonance imaging (MRI) one year before the onset. The levels of 14-3-3 protein and total tau protein, and findings from a real-time quaking-induced conversion test were normal at first but became abnormal after disease onset. Although there are four reports of presymptomatic sCJD identified by MRI, this is the first case report in which all three biomarkers had been assessed before and after the disease onset. MRI might be the most sensitive modality for detecting presymptomatic sCJD patients.
Transient receptor potential melastatin 8 (TRPM8) is a member of the transient receptor potential superfamily of Ca2+ channels. The aim of the present study was to clarify TRPM8 expression in reactive lymphoid tissues and mature B-cell neoplasms. Reactive and neoplastic lymphoid tissues were used to evaluate TRPM8 expression by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). TRPM8+ cells were frequently detected in the follicular light zone and marginal zone of reactive lymphoid tissues. Double immunostaining revealed that TRPM8+ cells co-expressed cluster of differentiation (CD) 38, CD79a, CD138, interferon regulatory factor 4/melanoma associated antigen (mutated) 1, B cell CLL/lymphoma 6 and transmembrane activator and CAML interactor. TRPM8+ neoplastic cells were frequently detected in plasma cell myeloma. The positive band of TRPM8 mRNA was confirmed by RT-PCR in cases of myeloma. The present study is, to the best of our knowledge, the first to demonstrate the expression of TRPM8 in reactive lymphoid tissues and mature B-cell neoplasms, revealing that TRPM8 is frequently expressed in pre-plasmablasts, plasmablasts, plasma cells and mature B-cell lymphomas that are likely to differentiate into plasma cells.
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