Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis

We have reported that normal human salivary gland-derived epithelial cells exclusively express keratinocyte growth factor receptor (KGFR). In the process of malignant transformation of human salivary gland tumors, KGFR gene expression disappeared concomitantly with the de novo expression of the fibroblast growth factor receptor 1 (FGFR1) and FGFR4 genes. In the present study, we introduced wild-type KGFR cDNA or chimeric KGFR/FGFR1 cDNA, which encoded the extracellular domain of KGFR and the intracellular domain of FGFR1, into the HSY human salivary adenocarcinoma cell line. The KGFR tyrosine kinase suppressed the activity of FGF receptor substrate 2 (FRS2) and inhibited the growth of HSY by inducing differentiation and apoptosis in vitro and in vivo. Our results provided significant insight into the mechanism of KGFR tumor suppression and suggest that KGFR gene therapy might be a viable method of inhibiting human salivary adenocarcinoma growth.     

Three‐Dimensional Visualization of Developing Neurovascular Architecture in the Craniofacial Region of Embryonic Mice

Recent studies have highlighted the mechanism of vascular and axonal guidance to ensure proper morphogenesis and organogenesis. We aimed to perform global mapping of developing neurovascular networks during craniofacial development of embryonic mice. To this end, we developed histology‐based three‐dimensional (3D) reconstructions using paraffin‐embedded serial sections obtained from mouse embryos. All serial sections were dual‐immunolabeled with Pecam1 and Pgp9.5/Gap43 cocktail antibodies. All immunolabeled serial sections were digitized with virtual microscopy to acquire high spatial resolution images. The 3D reconstructs warranted superior positional accuracy to trace the long‐range connectivity of blood vessels and individual cranial nerve axons. It was feasible to depict simultaneously the details of angiogenic sprouting and axon terminal arborization and to assess quantitatively the locoregional proximity between blood vessels and cranial nerve axons. Notably, 3D views of the craniofacial region revealed the following: Branchial arch arteries and blood capillary plexi were formed without accompanying nerves at embryonic day (E) 9.5. Cranial nerve axons began to grow into the branchial arches, developing a labyrinth of small blood vessels at E10.5. Vascular remodeling occurred, and axon terminals of the maxillary, mandibular, chorda tympani, and hypoglossal nerve axons had arborized around the lateral lingual swellings at E11.5. The diverged patterning of trigeminal nerves and the arterial branches from the carotid artery became congruent at E11.5. The overall results support the advantage of dual‐immunolabeling and 3D reconstruction technology to document the architecture and wiring of the developing neurovascular networks in mouse embryos. Anat Rec, 298:1824–1835, 2015. © 2015 Wiley Periodicals, Inc.     

Contribution of abdominal muscle strength to various activities of daily living of stroke patients with mild paralysis

[Purpose] The trunk muscles frequently become weak after stroke, thus impacting overall activities of daily living. However, activities of daily living items closely related with trunk strength remain unclear. This study aimed to clarify the influence of trunk muscle weakness on activities of daily living items. [Subjects] The subjects were 24 stroke patients who fulfilled the following inclusion criteria: first stroke and the absence of severe paralysis, marked cognitive function deterioration, unilateral spatial neglect or apathy. [Methods] According to abdominal strength, the 24 patients were divided into a nonweakness group and a weakness group. For the assessment, we used the stroke impairment assessment set, the Berg balance scale, a simple test for evaluating hand function, grip strength, and functional independence measure scale scores and the results were compared between the groups. [Results] The Berg balance scale score and scores for dressing, toilet use, transfer to bed, and walk items of the functional independence measure were significantly lower in the weakness group than in the nonweakness group. [Conclusion] Our results suggest that weakness of the abdominal muscles adversely impacts the balance of patients with mild stroke as well as their ability to dress, use a toilet, transfer, and walk. Trunk training, including abdominal muscle exercises, can effectively improve the performance of these activities of daily living items.Key words: Stroke, Activities of daily living, Abdominal muscles     

Effect of early mobilization on discharge disposition of mechanically ventilated patients

[Purpose] The purpose of this study was to clarify the benefits of early mobilization for mechanically ventilated patients for their survival to discharge to home from the hospital. [Subjects and Methods] Medical records were retrospectively analyzed of patients who satisfied the following criteria: age ≥ 18 years; performance status 0–2 and independent living at their home before admission; mechanical ventilation for more than 48 h; and survival after mechanical ventilation. Mechanically ventilated patients in the early mobilization (EM) group (n = 48) received mobilization therapy, limb exercise and chest physiotherapy, whereas those in the control group (n = 60) received bed rest alone. Univariate and multivariate logistic regression analyses were performed to identify clinical variables associated with discharge disposition. [Results] Early mobilization was a positive independent factor and the presence of neurological deficits was a negative factor contributing to discharge to home. Among patients surviving mechanical ventilation without neurological deficits, the rate of discharge to home was significantly higher among patients in the EM group that in the control group (76% vs. 40%). [Conclusion] Early mobilization can improve the rate of discharge to home of patients requiring mechanical ventilation because of non-neurological deficits.Key words: Mechanical ventilation, Early mobilization, Physiotherapy     

Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C

We aimed to examine the relationship between renal dysfunction and anaemia that may develop during combination therapy involving pegylated interferon, ribavirin and telaprevir (PEG‐IFN/RBV/TVR) for the treatment of chronic hepatitis C. Sixty‐eight patients with genotype 1b high viral loads were treated with PEG‐IFN/RBV/TVR. Peg‐IFN and RBV doses were administered according to body weight. TVR was prescribed at 2250 mg/day for 44 patients and at 1500 mg/day for 24 patients who had low haemoglobin level (<12 g/dL). When anaemia had developed, the RBV dose was decreased. The serum TVR concentration at day 8 was measured, and the serum RBV concentration was measured serially. The estimated glomerular filtration rate (eGFR) was estimated to assess renal function. At week 1, serum TVR concentration was not correlated with a decrease in eGFR; however, the TVR dose, on a weight basis (mg/kg), and eGFR were correlated (r = 0.2691; P = 0.0265). Moreover, there was a negative correlation between eGFR and RBV serum concentration (r = −0.3694; P = 0.0025), and the serum RBV concentration and decrease in the haemoglobin were significantly correlated from week 1 to week 8. In triple therapy, the TVR dose per weight is correlated with a decline in renal function. Thus, the serum concentration of RBV increases, with a concomitant decrease in haemoglobin. It is important to adjust the doses of TVR and RBV to avoid excessive serum RBV levels and the development of severe anaemia, to achieve a good clinical effect.