No abstract

Hepatocyte growth factor (HGF) is a humoral mediator of epithelial-mesenchymal interactions, acting on a variety of epithelial cells as mitogen, motogen, and morphogen. Exogenous HGF acts as a hepatotrophic factor and a renotrophic factor during experimental injury. To investigate whether HGF has a pulmotrophic function, human recombinant HGF was administered to C57BL/6 mice with severe lung injury by bleomycin (BLM). Low dose simultaneous and continuous administration of HGF (50 micrograms/mouse/7 d) with BLM (100 mg/mouse/7 d) repressed fibrotic morphological changes at 2 and 4 wk. Ashcroft score showed a significant difference in lung fibrosis with and without HGF at 4 wk (3.7 +/- 0.4 versus 4.9 +/- 0.3, p < 0.05). Furthermore, either simultaneous or delayed administration of high dose HGF (280 micrograms/mouse/14 d) equally repressed fibrotic changes by BLM when examined at 4 wk (Ashcroft score: 2.6 +/- 0.4 and 2.4 +/- 0.2 versus 4.1 +/- 0.2, p < 0.01). Hydroxyproline content in the lungs was significantly lower in mice with either simultaneous or delayed administration of high dose HGF as compared to those administered BLM alone (121.8 +/- 8.1% and 113.2 +/- 6.2% versus 162.7 +/- 4.6%, p < 0.001). These findings indicate that exogenous HGF acts as a pulmotrophic factor in vivo and prevents the progression of BLM-induced lung injury when administered in either a simultaneous or delayed fashion. HGF may be a potent candidate to prevent or treat lung fibrosis.

Background: Prospective trials of active surveillance for asymptomatic papillary microcarcinoma (T1aN0M0) since the 1990s have shown progression rates of only 5-10%. Late rescue surgery after progression had no deleterious effects on mortality and morbidity. The 2015 American Thyroid Association guidelines approved active surveillance for very low-risk papillary thyroid carcinoma (PTC) as an alternative method to immediate surgery. However, there is no study that evaluates long-term active surveillance for T1b tumors. Methods: A prospective trial of active surveillance with 360 very low-risk PTC (T1aN0M0) patients has been conducted since 1995. Of the 392 T1bN0M0 patients, 61 selected active surveillance over surgery and eventually participated in this trial, while the remaining 331 patients underwent surgery. To find an appropriate management strategy for patients with T1bN0M0 PTC, the outcomes of active surveillance for T1bN0M0 to T1aN0M0 PTC were investigated and compared, and the outcomes of surgery for T1bN0M0 PTC were studied. Results: After a mean of 7.4 years of active surveillance, 29 (8%) T1aN0M0 tumors and four (7%) T1bN0M0 tumors had increased in size ( p = 0.69). Development of lymph node metastasis was seen in three (0.8%) patients and two (3%) patients, respectively ( p = 0.10). No significant difference in progression rate was seen between groups. Among T1bN0M0 tumors, weak calcification and rich vascularity were risk factors for tumorsize increase, and younger age was a predictor for the development of lymph node metastasis. Mean initial tumor size was significantly greater in T1bN0M0 patients who underwent immediate surgery (14.5 -2.8 mm) than it was in patients who chose observation (11.7 -1.1 mm; p < 0.0001). No postoperative recurrence was seen in patients with tumor <15 mm in diameter. Conclusions: Active surveillance is an option for selected patients with T1bN0M0 PTC.

We investigated immunohistochemical localization of V2 vasopressin receptor along the nephron using a specific polyclonal antibody. Staining was observed in some of thick ascending limbs and all of principal and inner medullary collecting duct (IMCD) cells. Not only basolateral but also luminal membrane was stained in collecting ducts, especially in terminal IMCD (tIMCD).To learn the functional role of luminal V2 receptor in tIMCD, we studied the luminal effects of arginine vasopressin (AVP) on osmotic water permeability (Pf), urea permeability (Pu), and cAMP accumulation using isolated perfused rat tIMCD. In the absence of bath AVP, luminal AVP caused a small increase in cAMP accumulation, Pf and Pu, confirming the presence of V2 receptor in the lumen of tIMCD. In contrast, luminal AVP inhibited Pf and Pu by 30-65% in the presence of bath AVP by decreasing cAMP accumulation via Vla or oxytocin receptors and by an unknown mechanism via V2 receptors in the luminal membrane of tIMCD.These data show that V2 receptors are localized not only in the basolateral membrane but also in the luminal membrane of the distal nephron. Luminal AVP acts as a negative feedback system upon the basolateral action of AVP in tIMCD. (J. Clin. Invest. 1995. 96:1768-1778

The mechanical properties of tendon autografts used in reconstruction of the anterior cruciate ligament (ACL) are reduced after surgery. Previous studies showed that growth factors such as transforming growth factor-(31 (TGF-(31) and epidermal growth factor (EGF) can stimulate fibroblast proliferation and increase collagen and noncollagenous protein synthesis by these cells. These factors might be useful, therefore, in preventing graft deterioration after transplantation or accelerating mechanical restoration of the deteriorated graft. The purpose of our study, therefore, was to clarify the effects of TGF-(31 and EGF on biomechanical properties using an in situ freeze-thaw ACL model in the rabbit. A total of 142 rabbits underwent the freeze-thaw treatment in the right ACL and were then divided into four groups. Group I served as a freeze-thaw, but otherwise untreated control. In Group 11, a delivery vehicle (fibrin sealant) alone was applied. In Group 111, 4-ng TGF-PI and 100-ng EGF mixed with the vehicle were applied, In Group IV, higher doses (2-pg TGF-(31 and 50-pg EGF) of growth factors were mixed with the vehicle. The groups were compared at 6 and 12 weeks on the basis of mechanical properties, water content, and histological and ultrastructural observations. The crosssectional area of Group 111 (average, 7.1 mm') was significantly less than that of Groups I, TI, and IV (9.0, 8.2, and 9.4 mm2, respectively) at 12 weeks. The tensile strength of Group I11 (62.2 MPa) was significantly greater than that of Groups I, 11, and IV (35.6, 43.7, and 36.9 MPa, respectively) at 12 weeks, while the water content of Group 111 (70.7'%,) was significantly lower than that of Group I (75.2%). No other significant differences occurred among Groups I, 11, and IV. A unirnodal distribution of collagen fibril diameters was noted in Groups I and 11, while a bimodal pattern was found in Group 111. This study demonstrated that low-dose application of TGF-P1 and EGF significantly inhibited not only the increased water content and cross-sectional area, but also the decreased tensile strength caused by the freeze-thaw treatment, while a high dose of TGF-PI and EGF does not have the same beneficial effects.