Mouse model of paraquat-poisoned lungs and its gene expression profile

Paraquat (PQ)-induced pulmonary toxicity is characterized by initial development of pulmonary edema, infiltration of inflammatory cells, and damage to the alveolar epithelium, which may progress to severe fibrosis. However, the exact role of PQ in the progression of the pathogenesis has not been clearly established. To understand the mechanism of PQ in pulmonary toxicity, we developed an animal model of PQ-induced lung injury by intranasal instillation of PQ solution using C57Black/6J mice. Twenty microliters of PQ solution (0.01, 0.01, and 0.04 mg/mouse) was applied through the nares, and the same amount of vehicle was applied in control mice. The pathological progression of lung pathology in our mouse model was very similar to that of patients suffering from PQ poisoning. The lungs of some animals exposed to PQ showed acute fulmination, resulting in death from 5 days post-exposure, but others showed a more protracted injury, resulting in typical pulmonary fibrosis at 3 weeks. Using this PQ-poisoned mouse model, we examined the gene expression at the initial destructive phase (within 5 days) that fibrosis has not completely developed. We prepared RNAs after 6h, 24h, and 5 days and examined the changes of the expression levels for 45 selected genes. The genes showing >2-fold increase at 6h or a time-dependent decrease during this experimental period may be the early markers for the destructive phase. These genes are Mt1, Mt2, Hmox1, Gcl, GR, IL-6, IL-13, Txn1, Fas, FasL, Lpin2, Mmp1a, Mmp12, Sfp-B, Sfp-D, CAT, EC-SOD, GST, and Pltp. On the other hand, the genes involved in the development of fibrosis, such as procollagen, Fn1, Eln, SMA, and Mmp9, Timp1 were significantly increased on day 5, not at 6h nor at 24h, after PQ treatment (the late marker). The genes showing a significant increase (Mmp3 and Mmp8) or decrease (VEGFA) at 24h and 5 days and not at 6h may be also the late markers. These changes in gene expression, which are equalled to functional activities of proteins, will be the targets for future studies focused on the development on PQ-induced pulmonary damage.     

Establishment of standard values for the latency, interval and amplitude parameters of tibial nerve somatosensory evoked potentials (SEPs).

OBJECTIVE: To establish standard values for tibial nerve somatosensory evoked potentials (SEPs). METHODS: We examined SEPs following left tibial nerve stimulation in 65 normal subjects of various ages, and performed multiple regression analysis using height, age, (age-20)(2) and gender as predictor variables. We objectively selected the latency or interval parameters with less intersubject variability as the standard parameters for evaluation. RESULTS: Among 3 cortical bipolar derivations investigated, the Cz'-Cc lead gave a more constant and stable P38 component than the Cz'-Fz or Ci-Cc lead. The latencies of the N8o (N8 onset) of the popliteal potential, P15 (P15 peak) in the contralateral iliac crest-ipsilateral greater trochanter lead, N21, N30 and P38o/P38 in the Cz'-Cc lead, as well as the intervals between these components were selected as standard parameters. P15 was easily identified in all of the subjects and is expected to be a new parameter to evaluate the proximal segment of the tibial nerve. The amplitudes of P15 and the other components were also evaluated. We present nomograms for the normal limit values of each parameter. CONCLUSIONS: We present a thorough set of standard values for tibial SEPs where the subject factors were fully considered, and which is easily applicable to clinical practice.     

Impairment of an event-related potential correlate of memory in schizophrenia: effects of immediate and delayed word repetition.

OBJECTIVE: We investigated the nature of the memory impairment in schizophrenia using an event-related potential (ERP). METHODS: Visual ERPs were recorded while 20 schizophrenics and 20 controls performed semantic categorization tasks with incidental word repetitions. Participants responded to occasional target words. Half of the non-target words were repeated immediately after initial presentation (lag 0) or after 5 intervening words (lag 5). RESULTS: In both groups, ERPs to words at lag 0 were more positive than those to non-repeated words, though this positive-going effect was attenuated in the schizophrenics, especially around 400-500 ms. The effect at lag 5 was smaller and shorter than that at lag 0 but was comparable between groups. Attenuation of the N400 peak occurred for word repetition at lag 0 in controls but not in schizophrenics, whereas a peak increment in the late positive component induced by word repetition at both lags was observed in both groups. CONCLUSIONS: Findings indicate that patients with schizophrenia have a deficit in a brain process modulating ERP correlates of memory, when words are repeated immediately. This deficit might be related to an abnormal N400 priming effect in schizophrenia.     

Presence of basal lamina-like substance with anchoring fibrils within the amyloid deposits of primary localized cutaneous amyloidosis

The dermal-epidermal (DE) junction areas of skin specimens obtained from 16 patients with either lichen amyloidosis or macular amyloidosis were studied. In the dermal papillae where amyloid was deposited, elastic fibers frequently were absent, but periodic acid-Schiff reaction after diastase digestion was homogenously positive. Ultrastructural studies revealed that a basal lamina-like substance with anchoring fibrils was present between and within amyloid deposits. By indirect immunofluorescence technique using an anti-basement membrane zone antiserum obtained from a patient with bullous pemphigoid, specific linear fluorescence occurred at the DE junction, and in a reticular pattern in dermal papillae. It seemed that apoptotic keratinocytes of the epidermis brought down basal lamina and fine fibrous components attached to it when these cells dropped down to the papillary dermis and became the source of amyloid. These findings support the hypothesis that epidermal keratinocyte degeneration plays an important role in the histogenesis of cutaneous amyloidoses.     

A new comprehensive ultrasonic diagnostic method for celiac artery compression syndrome that hybridizes “arterial compression hook sign” and peak systolic velocity

PurposeDiagnosing celiac artery compression syndrome (CACS) is based on an imaging finding of celiac artery compression (CAC), but the diagnostic criteria are inconsistent. The study aim was to devise an ultrasonographic screening method to effectively diagnose CAC in occult CACS.MethodsThe subjects were 61 patients with suspected CACS who underwent ultrasonography at our hospital from May 2017 to December 2019 and were divided into the following two groups: the “arterial compression hook sign”-positive group (n = 15, mean age: 26.6 ± 16.4 years, six males, nine females) and -negative group (n = 41, mean age: 32.5 ± 18.6 years, 12 males, 34 females). We used B-mode and advanced dynamic flow to detect arterial compression hook sign and pulse Doppler to measure expiration peak systolic velocity (EPSV) and inspiration PSV (IPSV).ResultsThe EPSV was significantly higher in the arterial compression hook sign-positive group (304.7 ± 47.4 cm/s) than in the -negative groups (158.2 ± 38.7 cm/s), (p < 0.001). Receiver operating characteristic curve analysis was performed to calculate the EPSV cutoff value for presence of CAC, which was 226 cm/s (sensitivity: 0.957, specificity: 1.000, AUC: 0.997, 95% confidence interval: 0.99–1). The IPSV was lower in the positive group than in the negative group in all cases (EPSV − IPSV range: 68–199 cm/s).ConclusionOur results showed that if arterial compression hook sign determined by B-mode ultrasound, EPSV > 226 cm/s, and IPSV decreases by ≥ 68 cm/s, then CAC can be detected with high specificity.Graphic abstract      

Synovial chondromatosis of the temporomandibular joint with intracranial extension

A 52-year-old man presented with an extremely rare case of synovial chondromatosis in the temporomandibular joint (TMJ) with extension into the middle cranial fossa manifesting as swelling and exacerbation of pain. He had a long history of right TMJ disorders. Computed tomography and magnetic resonance imaging showed a mass in the right TMJ with extension into the intracranial part through the destroyed temporal skull base. The preoperative diagnosis was chondrosarcoma or osteosarcoma. The patient underwent surgery via combined trans-zygomatic temporal skull base and pre-auricular approaches and the mass was totally removed. Histological examination found an enormous number of closely packed loose bodies of various sizes, consisting of hyaline chondrocytes. The histological diagnosis was synovial chondromatosis. This rare lesion is difficult to discriminate from chondrosarcoma, so total removal is essential for correct diagnosis and cure.