Timeframe Analysis of Novel Synthetic Cannabinoids Effects: A Study on Behavioral Response and Endogenous Cannabinoids Disruption.

This study investigates the impact of SCs consumption by assessing the effects of three novel synthetic cannabinoids (SCs); MDMB-CHMINACA, 5F-ADB-PINACA, and APICA post-drug treatment. SCs are known for their rapid onset (<1 min) and prolonged duration (≥5 h). Therefore, this research aimed to assess behavioral responses and their correlation with endocannabinoids (ECs) accumulation in the hippocampus, and EC's metabolic enzymes alteration at different timeframes (1-3-5-h) following drug administration. Different extents of locomotive disruption and sustained anxiety-like symptoms were observed throughout all-encompassing timeframes of drug administration. Notably, MDMB-CHMINACA induced significant memory impairment at 1 and 3 h. Elevated levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were detected 1 h post-MDMB-CHMINACA and 5F-ADB-PINACA administration. Reduced mRNA expression levels of fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) (AEA and 2-AG degrading enzymes, respectively), and brain-derived neurotrophic factor (BDNF) occurred at 1 h, with FAAH levels remaining reduced at 3 h. These findings suggest a connection between increased EC content and decreased BDNF expression following SC exposure. Cognitive disruption, particularly motor coordination decline and progressive loss manifested in a time-dependent manner across all the analyzed SCs. Our study highlights the importance of adopting a temporal framework when assessing the effects of SCs.

[Surgical Therapy of Slipping Rib Syndrome].

We have operated on two cases of slipped ribs syndrome( SRS). Both patients were men in their 40s with a history of right thoracic trauma who were referred to us because of unexplained lower thoracic pain. The left rib was positive for hooking maneuver (lift test), and dynamic ultrasonography showed narrowing of the intercostal space, which led to the diagnosis of SRS. in the first case, the tip of the ninth rib cartilage was excised, and the ninth and tenth rib cartilages were sutured and fixed with No.2 fiber wire in two places with Z sutures. In the second case, the tip of the ninth rib cartilage was excised, the eighth and ninth ribs and the ninth and tenth ribs were fixed with No.2 fiber wire with Z sutures as in the first case, and a 0.7 mm thick poly-L-lactide (PLLA) plate was added between the eighth and tenth rib cartilages. In both cases, the postoperative course was good and the pain disappeared. SRS should be recognized as a disease and surgical treatment should be used as therapy.

Identification of genes responsible for absorbing palladium ion in Escherichia coli.

The capability of Escherichia coli BW25113 to adsorb palladium (Pd) ions in a single-gene-knockout library was investigated using high-throughput screening. The results revealed that compared to BW25113, nine strains promoted Pd ion adsorption, whereas 22 strains repressed. Although further studies are required because of the first screening results, our results will provide a new perspective for improving the biosorption.

Improvement of Imaging Conditions to Improve the Detection Rate of Head and Neck Cancer by Positron Emission Tomography/Computed Tomography Examination.

Positron emission tomography (PET)/computed tomography (CT) has improved sensitivity and resolution using silicon photomultiplier as a photosensor. Previously, only a fixed setting was available for the shooting time of 1 bed, but now, the shooting time can be changed for each bed. Time can be shortened or extended depending on the target area. A few studies reported on image reconstruction conditions for head and neck cancer in whole-body PET/CT examinations. Thus, this study aimed to optimize the imaging conditions of the head and neck region during whole-body imaging. A cylindrical acrylic container with a 200 mm diameter was used to simulate the head and neck area using a PET/CT system equipped with a semiconductor detector. Spheres of 6-30 mm in diameter were enclosed in the 200 mm diameter cylindrical acrylic vessel. Radioactivity in 18F solution (Hot:BG ratio 4:1) was enclosed in a phantom following the Japanese Society of Nuclear Medicine (JSNM) guidelines. Background radioactivity concentration was 2.53 kBq/mL. List mode acquisition of 1,800 s was collected at 60-1,800 s with the field of view of 700 mm and 350 mm. The image was reconstructed by resizing the matrix to 128 × 128, 192 × 192, 256 × 256, and 384 × 384, respectively. The imaging time per bed in the head and neck should be at least 180 s, and the reconstruction conditions should be a field of view (FOV) of 350 mm, matrix sizes of ≥ 192, and a Bayesian penalized likelihood (BPL) reconstruction with a ß-value of 200. This allows detection of > 70% of the 8-mm spheres in the images.

[Thoracoscopic Right Upper Lobectomy in a Patient with a Right Aortic Arch:Report of a Case].

It has been reported that the recurrent nerve may not be recognized during mediastinal lymph node dissection in surgery for right upper lobe lung cancer associated with the right aortic arch. In the present case, a 66-year-old man underwent thoracoscopic right upper lobectomy for right upper lobe lung cancer associated with the right aortic arch. The gap between the superior vena cava and descending aortic arch was narrow, and the vagus nerve ran between the superior vena cava and the aorta. The recurrent laryngeal nerve was able to confirm. The vagus nerve ran the hilum of lung back side from arch of azygos vein on the peripheral side. The morphology of the right aortic arch varies from case to case, and if the vagus nerve and recurrent nerve are difficult to identify, the nerve may be hidden by the superior vena cava. If the nerve cannot be recognized, the space between the superior vena cava and the aorta should be dissected and confirmed. In addition, taping the vagus nerve and observing it from the caudal to the cephalic side may be useful for the recurrent nerve that turns to the mediastinum. In this case, magnification of the thoracoscope is extremely useful.

LAPTM4α is targeted from the Golgi to late endosomes/lysosomes in a manner dependent on the E3 ubiquitin ligase Nedd4-1 and ESCRT proteins.

Lysosome-associated protein transmembrane 4α (LAPTM4α) is a four transmembrane-spanning protein primarily localized in endosomes and lysosomes and has several putative lysosomal targeting signals at its C-terminal cytoplasmic domain, including tyrosine-based motifs (YxxΦ) and PY motifs (L/PxxY). LAPTM4α has been previously shown to be ubiquitinated by the E3 ubiquitin ligase Nedd4-1 through binding to its PY motifs and sorted to lysosomes, however, the molecular mechanisms underlying the localization of LAPTM4α to endosomes/lysosomes have not yet been fully elucidated. In the present study, we show that LAPTM4α binds Nedd4-1 in a manner dependent on PY motifs, while the PY motifs and Nedd4-1 are not necessarily required for LAPTM4α ubiquitination. The binding of LAPTM4α with Nedd4-1, however, is necessary for an effective sorting of LAPTM4α from the Golgi to late endosomes/lysosomes. An unexpected finding is that LAPTM4α is localized in the lumen, but not in the limiting membrane, of late endosomes, and degraded in lysosomes over time. Interestingly, we further found that siRNA knockdown of endosomal sorting complexes required for transport (ESCRT) components that mediate sorting of ubiquitinated membrane proteins into intralumenal vesicles (ILVs) of endosomes selectively blocks the transport of LAPTM4α to endosomes. Collectively, these results suggest that trafficking of LAPTM4α from the Golgi to endosomes is promoted by the interaction with Nedd4-1, which further requires ESCRT components. Furthermore, our findings highlight a novel function for ESCRT proteins in mediating protein and/or vesicle trafficking from the Golgi to endosomes/lysosomes.

An expanded genetic code facilitates antibody chemical conjugation involving the lambda light chain.

Most of the currently approved therapeutic antibodies are of the immunoglobulin gamma (IgG) κ isotype, leaving a vast opportunity for the use of IgGλ in medical treatments. The incorporation of designer amino acids into antibodies enables efficient and precise manufacturing of antibody chemical conjugates. Useful conjugation sites have been explored in the constant domain of the human κ-light chain (LCκ), which is no more than 38% identical to its LCλ counterpart in amino acid sequence. In the present study, we used an expanded genetic code for site-specifically incorporating Nε-(o-azidobenzyloxycarbonyl)-l-lysine (o-Az-Z-Lys) into the antigen-binding fragment (Fab) of an IgGλ, cixutumumab. Ten sites in the LCλ constant domain were found to support efficient chemical conjugation exploiting the bio-orthogonal azido chemistry. Most of the identified positions are located in regions that differ between the two light chain isotypes, thus being specific to the λ isotype. Finally, o-Az-Z-Lys was incorporated into the Fab fragments of cixutumumab and trastuzumab to chemically combine them; the resulting bispecific Fab-dimers showed a strong antagonistic activity against a cancer cell line. The present results expand the utility of the chemical conjugation method to the whole spectrum of humanized antibodies, including the λ isotype.

Adenine-related compounds modulate UDP-glucuronosyltransferase (UGT) activity in mouse liver microsomes.

Adenine-related compounds are allosteric inhibitors of UDP-glucuronosyltransferase (UGT) in rat liver microsomes (RLM) and human UGT isoforms treated with detergent or pore-forming peptide, alamethicin.To clarify whether the same is true beyond species, the effects of adenine-related compounds on 4-methylumbelliferone (4-MU) glucuronidation were examined using detergent-treated mouse liver microsomes (MLM).Brij-58 treatment of MLM increased the Vmax and the Michaelis constant, Km, of 4-MU. This study was performed using Brij-58-treated MLM as an enzyme source. ATP- and ADP-inhibited 4-MU glucuronidation. In contrast, AMP caused a 1.5-fold increase in glucuronidation. Oxidised forms, NAD+ and NADP+, potently inhibited 4-MU glucuronidation, whereas the reduced forms, NADH and NADPH, did not. Furthermore, the IC50 values of ATP, ADP, NAD+, and NADP+ were approximately 15 µM.In our previous study, ATP was the strongest inhibitor of UGT activity in RLM. However, in this study, the above-mentioned compounds inhibited 4-MU UGT in a comparable and non-competitive manner. Furthermore, AMP antagonised the inhibitory effects of ATP and ADP.These results suggest that ATP, ADP, NAD+, and NADP+ are common endogenous inhibitors of UGT beyond species.

Ablation of Selenbp1 Alters Lipid Metabolism via the Pparα Pathway in Mouse Kidney.

Selenium-binding protein 1 (Selenbp1) is a 2,3,7,8-tetrechlorodibenzo-p-dioxin inducible protein whose function is yet to be comprehensively elucidated. As the highly homologous isoform, Selenbp2, is expressed at low levels in the kidney, it is worthwhile comparing wild-type C57BL mice and Selenbp1-deficient mice under dioxin-free conditions. Accordingly, we conducted a mouse metabolomics analysis under non-dioxin-treated conditions. DNA microarray analysis was performed based on observed changes in lipid metabolism-related factors. The results showed fluctuations in the expression of numerous genes. Real-time RT-PCR confirmed the decreased expression levels of the cytochrome P450 4a (Cyp4a) subfamily, known to be involved in fatty acid ω- and ω-1 hydroxylation. Furthermore, peroxisome proliferator-activated receptor-α (Pparα) and retinoid-X-receptor-α (Rxrα), which form a heterodimer with Pparα to promote gene expression, were simultaneously reduced. This indicated that reduced Cyp4a expression was mediated via decreased Pparα and Rxrα. In line with this finding, increased levels of leukotrienes and prostaglandins were detected. Conversely, decreased hydrogen peroxide levels and reduced superoxide dismutase (SOD) activity supported the suppression of the renal expression of Sod1 and Sod2 in Selenbp1-deficient mice. Therefore, we infer that ablation of Selenbp1 elicits oxidative stress caused by increased levels of superoxide anions, which alters lipid metabolism via the Pparα pathway.

[Pulmonary Partial Resection for a Lung Foreign Body( Watermelon Seed):Report of a Case].

We experienced a case of a foreign body in the lung with granuloma by aspiration of watermelon seeds. A 72-year-old woman who had been diagnosed as having lung foreign body was admitted to our hospital for the treatment of the pulmonary shadow caused by the granuloma. A foreign body could not be identified by bronchoscopy, and the thoracoscopic partial resection of right S4 was performed. The postoperative course was uneventful, and the patient was discharged from our hospital on the second day after the operation.

Lysosomal integral membrane protein LGP85 (LIMP-2) is ubiquitinated at the N-terminal cytoplasmic domain.

LGP85/LIMP-2 is a type III transmembrane glycoprotein of lysosomes, which traverses the membrane twice with an N-terminal uncleaved signal sequence and C-terminal hydrophobic domain. In addition to functioning as a receptor for a lysosomal enzyme ß-glucocerebrosidase and for several enteroviruses, LGP85 plays a key role in the biogenesis and maintenance of endosomal/lysosomal compartments (ELCs). Our previous studies have demonstrated that overexpression of rat LGP85 into COS cells results in the enlarged ELCs, from where membrane trafficking is impaired. We show here that rat LGP85 is polyubiquitinated at the N-terminal short cytoplasmic domain that comprises of only three amino acid residues, alanine, arginine, and cysteine. Replacement of either arginine or cysteine with alanine within the N-terminal cytoplasmic domain did not influence the ubiquitination of LGP85, thereby indicating that ubiquitin (Ub) is conjugated to the α-NH2 group of the N-terminal alanine residue. Furthermore, we were able to define a domain necessary for ubiquitination in a region ranging from the amino acids 156 to 255 within the lumenal domain of LGP85. This is the first report showing that the integral lysosomal membrane protein LGP85 is ubiquitinated.

Hetero-oligomer formation of mouse UDP-glucuronosyltransferase (UGT) 2b1 and 1a1 results in the gain of glucuronidation activity towards morphine, an activity which is absent in homo-oligomers of either UGT.

UDP-Glucuronosyltransferase (UGT, Ugt) is a major drug metabolizing enzyme family involved in the glucuronidation and subsequent elimination of drugs and small lipophilic molecules. UGT forms homo- and hetero-oligomers that enhance or suppress UGT activity. In our previous study, we characterized mouse Ugt1a1 and all the Ugt isoform belonging to the Ugt2b subfamily and revealed that mouse Ugt2b1 and Ugt1a1 cannot metabolize morphine. Mouse Ugt2b1 had been believed to function similarly to rat UGT2B1, which plays a major role in morphine glucuronidation in rat liver. Thus, in this study, we hypothesized that hetero-oligomerization with another Ugt isoform may affect Ugt2b1 catalytic ability. We co-expressed Ugt1a1 and Ugt2b1 in a baculovirus-insect cell system, and confirmed hetero-oligomer formation by co-immunoprecipitation. As reported previously, microsomes singly expressing Ugt1a1 or Ugt2b1 were inactive towards the glucuronidation of morphine. Interestingly, in contrast, morphine-3-glucuronide, a major metabolite of morphine was formed, when Ugt2b1 and Ugt1a1 were co-expressed. This effect of hetero-oligomerization of Ugt1a1 and Ugt2b1 was also observed for 17ß-estradiol glucuronidation. This is the first report demonstrating that UGT acquires a novel catalytic ability by forming oligomers. Protein-protein interaction of Ugts may contribute to robust detoxification of xenobiotics by altering the substrate diversity of the enzymes.

Investigation of the Endoplasmic Reticulum Localization of UDP-Glucuronosyltransferase 2B7 with Systematic Deletion Mutants.

UDP-Glucuronosyltransferase (UGT) plays an important role in the metabolism of endogenous and exogenous compounds. UGT is a type I membrane protein, and has a dilysine motif (KKXX/KXKXX) in its C-terminal cytoplasmic domain. Although a dilysine motif is defined as an endoplasmic reticulum (ER) retrieval signal, it remains a matter of debate whether this motif functions in the ER localization of UGT. To address this issue, we generated systematic deletion mutants of UGT2B7, a major human isoform, and compared their subcellular localizations with that of an ER marker protein calnexin (CNX), using subcellular fractionation and immunofluorescent microscopy. We found that although the dilysine motif functioned as the ER retention signal in a chimera that replaced the cytoplasmic domain of CD4 with that of UGT2B7, UGT2B7 truncated mutants lacking this motif extensively colocalized with CNX, indicating dilysine motif-independent ER retention of UGT2B7. Moreover, deletion of the C-terminal transmembrane and cytoplasmic domains did not affect ER localization of UGT2B7, suggesting that the signal necessary for ER retention of UGT2B7 is present in its luminal domain. Serial deletions of the luminal domain, however, did not affect the ER retention of the mutants. Further, a cytoplasmic and transmembrane domain-deleted mutant of UGT2B7 was localized to the ER without being secreted. These results suggest that UGT2B7 could localize to the ER without any retention signal, and lead to the conclusion that the static localization of UGT results from lack of a signal for export from the ER.

Evaluation of flexor pollicis longus tendon attrition using color Doppler imaging after volar plate fixation for distal radius fracture.

PURPOSE: Early diagnosis of attritional wear of the flexor pollicis longus (FPL) tendon is essential in preventing subsequent tendon rupture. There are currently few objective methods of assessing FPL attrition. We hypothesized that color Doppler imaging could visibly detect FPL tendon attrition, and analyzed our results. METHODS: We evaluated ultrasound imaging of the contact between the FPL tendon and a volar locking plate using the real-time B-mode and Doppler waveforms of the FPL tendon using the continuous Doppler wave mode in 40 patients who underwent fixation of the distal volar locking plate for distal radius fracture. Twenty out of 40 patients underwent plate removal surgery after ultrasound evaluation. We also assessed the relationship between the Doppler waveforms and attrition of the FPL tendon in these 20 patients. RESULTS: Based on the ultrasound findings (n = 40), we divided Doppler waveforms of the FPL tendon into three categories: type 1, spindle wave; type 2, spindle wave with spike; and type 3, spike wave. There were 23, 11, and six patients with type 1, 2, and 3 waveforms in the affected hand, respectively. There were 37 patients with type 1, three with type 2, and no patient with type 3 waveforms in the contralateral wrist. Of the 20 patients who underwent plate removal, five had type 3 waveforms. We found tendon fraying or partial tears in three of these five patients. In addition, all five patients showed changes to type 1 or 2 waveforms after plate removal. None of the other 15 patients with type 1 or 2 waveforms had any tendon injuries during plate removal. CONCLUSIONS: Spike Doppler waveform can indicate abnormal findings, and may be a useful method to predict tendon attrition, because of its visibility. DIAGNOSTIC STUDY: Level III evidence.

Antitumor effects of minodronate, a third-generation nitrogen-containing bisphosphonate, in synergy with γδT cells in human glioblastoma in vitro and in vivo.

Nitrogen-containing bisphosphonates (N-BPs), which prevent bone resorption, exert direct and γδT cell (GDT)-mediated antitumor effects against several tumor cell types, including glioblastoma (GBM). However, limited information is available regarding the antitumor effects of N-BPs in GBM. Specifically, the antitumor effects of minodronate (MDA), a third-generation N-BP, in GBM are yet unclear. This study aimed to investigate the antitumor effects of MDA in GBM in vitro and in vivo. We performed growth inhibition and apoptosis detection assays using the GBM cell lines U87MG and U138MG. Apoptosis inhibition assays were also conducted. In vivo xenograft assays were performed in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Sug)/Jic mice subcutaneously implanted with U87MG and U138MG cells. Growth inhibition and apoptosis detection assays demonstrated that MDA inhibited GBM cell growth via apoptosis, which was markedly enhanced by ex vivo expanded GDT. A pan-caspase inhibitor, z-VAD-fmk, inhibited MDA-induced U138MG apoptosis and MDA/GDT-induced U87MG and U138MG apoptosis. But z-VAD-fmk increased MDA-induced U87MG apoptosis. MDA/GDT-mediated apoptosis was blocked by the anti-T cell receptor (TCR) Vγ9, mevalonate pathway inhibitor, granzyme B inhibitor, and antitumor necrosis factor (TNF)-α. In vivo xenograft assays showed that combined intraperitoneal administration of MDA/GDT induced antitumor effects on unestablished U87MG-derived subcutaneous tumors. MDA exerted direct and GDT-mediated anti-GBM apoptotic effects in a caspase-dependent manner. GDT recognized MDA-exposed GBM cells via TCRVγ9 and induced apoptosis via granzyme B and TNF-α release. Because MDA elicited anti-GBM effects in synergy with GDT in vivo, a combination of MDA and ex vivo-generated GDT could be an effective treatment in patients with GBM.

Intracellular Dynamics and Fate of a Humanized Anti-Interleukin-6 Receptor Monoclonal Antibody, Tocilizumab.

Tocilizumab (TCZ), a humanized anti-interleukin-6 (IL-6) receptor (IL-6R) monoclonal antibody, abrogates signal transducer protein gp130-mediated IL-6 signaling by competitively inhibiting the binding of IL-6 to the receptor, and shows clinical efficacy in autoimmune and inflammatory diseases. Despite accumulating evidence for therapeutic efficacy, the behavior and fate of TCZ at the cellular level remain largely unknown. To address this, we evaluated the endocytosis and intracellular trafficking of IL-6R in HeLa cells. The results of our study provide evidence that IL-6R is constitutively internalized from the cell surface by ligand or TCZ binding and the expression of gp130 in an independent manner and is targeted via endosomes without being significantly directed to the recycling pathway to, and degraded in, lysosomes. Furthermore, the cytoplasmic tail of IL-6R is required for constitutive endocytosis of the receptor, which is mediated by the clathrin and AP-2 complex. We further demonstrate that FcRn, whose function is to regulate the serum persistence of IgG, is confined primarily to early/recycling endosomes and rapidly transits between these compartments and late endosomes/lysosomes without being degraded. Importantly, the expression of FcRn induces the segregation of TCZ from IL-6R, resulting in extensive colocalization of TCZ and FcRn in IL-6R-depleted endosomal compartments. Collectively, our results suggest that FcRn can accelerate the retrieval of the internalized TCZ, not only from endosomes but also from lysosomes. Our findings provide new insight into the mechanism by which the antibody internalized into cells is rescued from lysosomal degradation and into how its serum levels are maintained.

Membrane-associated RING-CH (MARCH) 8 mediates the ubiquitination and lysosomal degradation of the transferrin receptor.

The transferrin receptor (TfR) mediates the uptake of transferrin (Tf)-bound iron from the plasma into the cells of peripheral tissues. The TfR continuously recycles between the plasma membrane and early/recycling endosomes. TfR expression is tightly controlled by the intracellular iron concentration through the regulation of TfR mRNA stability. However, much less is known about the mechanism by which TfR is degraded in cells. Previously, we reported a correlation between TfR ubiquitination and its iron-induced lysosomal degradation. The identification and characterization of a specific ubiquitin ligase for TfR is important in understanding the mechanism of iron homeostasis. Here, we show that membrane-associated RING-CH (MARCH) 8 ubiquitinates TfR and promotes its lysosomal degradation. Similar to other RING-type ubiquitin ligases, the RING-CH domain of MARCH8, which is located in the N-terminal cytoplasmic domain, is essential for the ubiquitination and downregulation of TfR. MARCH8 specifically recognizes the transmembrane domain of TfR and mediates ubiquitination of its cytoplasmic domain. In addition, the six-amino-acid sequence located in the C-terminal domain of MARCH8, which is highly conserved among different species, is required for the downregulation of TfR. Finally, and most importantly, TfR expression was markedly increased by siRNA-mediated knockdown of endogenous MARCH8. These findings demonstrate that the endogenous level of MARCH8 regulates TfR protein turnover through the downregulation and ubiquitination of TfR.

Visualization of vascular structure of spinal hemangioblastoma using intraoperative indocyanine green videoangiography and temporary feeder occlusion.

BACKGROUND AND PURPOSE: To more safely resect pathological lesions during spinal vascular lesion surgery, it is most important to understand local abnormal hemodynamics in detail. New devices or techniques that make out intraoperative local hemodynamics have been awaited. To introduce a resourceful method, we present a case of spinal hemangioblastoma for which temporary arterial occlusion during near-infrared intraoperative indocyanine green (ICG) videoangiography gives useful assessment of the main and minor feeders easily. METHODS: A 36-year-old female suffered progressive paresthesia of both lower extremities for 12 months and gait disturbance for 2 weeks. A neurological examination revealed T10 myelopathy. Magnetic resonance imaging (MRI) of the thoracic spine showed an intramedullary tumor at the T8 level and severe spinal cord edema with a flow void in the extended dorsal spinal veins. Spinal angiography showed a hemangioblastoma at the T8 level, with two main feeders and minor feeders. RESULTS: She underwent total resection of the tumor by a posterior approach. During the intraoperative ICG videoangiography, temporary arterial occlusion of the two main feeders and FLOW(®)800 analysis enabled clear understanding of the vasculature, especially of the two minor feeders. At the 9-month follow-up, her neurological manifestation was partially resolved, and post-operative MRI showed total removal of the tumor and disappearance of the spinal cord edema. CONCLUSIONS: Temporary clipping of the main feeders during intraoperative ICG videoangiography is very useful for easily determining the minor feeding arteries, and helpful for maintaining normal perfusion of the spinal cord in spinal hemangioblastoma surgery. Furthermore, the FLOW 800 analysis, especially the false color-coded variation, increased our understanding of the hemodynamics.

Sonographic evaluation of effects of the volar plate on trigger finger.

BACKGROUND: We evaluated trigger fingers ultrasonographically and clarified differences between fingers with and without continuous locking or snapping symptoms according to the thicknesses of the A1 pulley, flexor tendon and volar plate. METHODS: We evaluated 26 trigger fingers, divided into two groups: Group 1, 14 fingers with locking or snapping; and Group 2, 12 fingers without such symptoms. We also evaluated 26 contralateral fingers as controls (Control 1 and 2 groups). We compared each group to the respective control group according to thickness of the A1 pulley and volar plate, and cross-sectional area of the flexor tendon. In addition, nine fingers with locking or snapping and treated using corticosteroid injection were evaluated according to symptoms and sonographic findings 3-4 weeks after treatment. RESULTS: Thickness of the A1 pulley and cross-sectional area of the flexor tendon were greater in both Groups 1 and 2 than in controls. Thickness of the volar plate was greater in Group 1 than in Control 1, although no significant difference was seen between Group 2 and Control 2. In Group 1, eight of the nine fingers showed an alleviation of locking or snapping symptoms with corticosteroid injection, and sonographic findings showed that thickness of the volar plate was significantly decreased with corticosteroid injection, in addition to reduced thickness of the A1 pulley. CONCLUSION: In addition to thickening of the A1 pulley, thickening of the volar plate may represent an important contributor to continuous snapping or locking symptoms.

Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components.

Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5-genes essential for autophagosome formation-was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.