Cyclic stretch upregulates interleukin-8 and transforming growth factor-beta1 production through a protein kinase C-dependent pathway in alveolar epithelial cells

OBJECTIVE: Positive-pressure mechanical ventilation can injure the lung, causing oedema and alveolar inflammation, which is termed 'ventilator-induced lung injury' (VILI). We postulated that cyclic stretch upregulates the release of cytokines, which may cause lung damage, and explored which cytokines were released after cyclic stretch in type II alveolar epithelial cells (A549). METHODOLOGY: To test this hypothesis, A549 cells were cultured on a silicoelastic membrane and interleukin (IL)-1beta, IL-8, granulocyte-macrophage colony stimulating factor, activin, transforming growth factor (TGF)-beta1, insulin-like growth factor-2 and tumour necrosis factor-alpha mRNA and protein were assessed after stimulation of the cells by cyclic stretch. RESULTS: Cyclic stretch induced activation of protein kinase C and resulted in the release of IL-8 and TGF-beta1 from A549 cells. CONCLUSIONS: The release of IL-8 and TGF-beta1 from alveolar epithelial cells may be a contributing factor in alveolitis associated with VILI.     

Involvement of large tenascin-C splice variants in breast cancer progression

Alternative splicing of fibronectin-like type III (FNIII) repeats of tenascin-C (Tn-C) generates a number of splice variants. The distribution of large variants, typical components of provisional extracellular matrices that are up-regulated during tumor stroma remodeling, was here studied by immunoblotting and immunohistochemistry using a monoclonal antibody against the FNIII B domain (named 4C8MS) in a series of human breast cancers. Large Tn-C variants were found at only low levels in normal breast tissues, but were highly expressed at invading sites of intraductal cancers and in the stroma of invasive ductal cancers, especially at invasion fronts. There was a positive correlation between the expression of large Tn-C variants and the cell proliferation rate determined by immunolabeling of the Ki-67 antigen. Of the Tn-C recombinant fragments (all FNIII repeats or mFNIII FL, the conserved FNIII domain only, the epidermal growth factor-like domain, and the fibrinogen-like domain) which were expressed by CHO-K1 cells transfected with mouse Tn-C cDNAs, only the mFNIII FL enhanced in vitro migration and mitotic activity of mammary cancer cells derived from a Tn-C-null mouse. Addition of 4C8MS blocked the function of mFNIII FL. These findings provide strong evidence that the FNIII alternatively spliced region has important roles in tumor progression of breast cancer.     

Thyroid-stimulating hormone receptor levels and binding affinity in the thyroid gland of growth-retarded mice

Growth-retarded (grt/grt) mice are congenitally primary hypothyroid. Our previous study indicated that thyroid-stimulating hormone (TSH) responsiveness was defective in the grt/grt thyroid gland. We now report additional studies of impaired grt/grt thyroid function. Semiquantitative RT-PCR confirmed that TSH receptor (TSHR) mRNA expression in the grt/grt thyroid was significantly decreased compared with +/+ thyroids. Scatchard analysis revealed that grt/grt and +/+ mice have only one type of TSH binding site. grt/grt thyroids had fewer TSH binding sites, although this did not apparently affect the affinity of TSH for its receptor. The present data suggest that reduced TSHR levels or defects in TSHR signaling could be one of the possible defective sites in the grt/grt thyroid gland.     

Association of working conditions and lifestyle with increased serum gamma-glutamyltransferase: a follow-up study

BACKGROUND: This study investigated the association of working conditions and lifestyle with the development of increased serum gamma-glutamyltransferase (GGT) in Japanese workers. METHODS: A follow-up study was carried out on workers of a telecommunication enterprise who received their first annual health check-up between 1992 and 1996, when they were between 40 and 54 years of age. Workers who had high serum GGT (> or =60 IU/L in males, > or =30 IU/L in females), a past history of disease, or current illness at their first check-up were excluded from the analysis. In total, the study included 15,586 workers. The association between working conditions and lifestyle and development of increased serum GGT (> or =60 IU/L in males, > or =30 IU/L in females) was investigated by pooled logistic regression analyses. RESULTS: In males, body mass index, consumption of alcohol (<2 times/week, 2-5 times/week, >5 times/week), smoking (<20 cigarettes/day, > or =20 cigarettes/day), rarely taking three meals a day, marked preference for salty meals, and little preference for vegetables were positively associated with the development of increased serum GGT. Preferences for fatty meals (marked, moderate) were negatively associated with the development of increased serum GGT. In females, age and BMI were positively associated with the development of increased serum GGT. CONCLUSIONS: Applying a new statistical analysis to this retrospective cohort study of 5 years, we revealed the health influences of alcohol consumption, smoking and eating habits on increased serum GGT. On the other hand, this study indicated that shift work or other working conditions are not significant risk factors for increased serum GGT.     

Receptor protein tyrosine phosphatase sigma inhibits axonal regeneration and the rate of axon extension

Transgenic mice lacking receptor protein tyrosine phophatase-sigma (RPTPsigma), a type IIa receptor protein tyrosine phosphatase, exhibit severe neural developmental deficits. Continued expression of RPTPsigma in the adult suggests that it plays a functional role in the mature nervous system. To determine if RPTPsigma might influence axonal regeneration, the time course of regeneration following facial nerve crush in wild-type and RPTPsigma (-/-) mice was compared. Mice lacking RPTPsigma exhibited an accelerated rate of functional recovery. Immunocytochemical examination of wild-type neurons in cell culture showed RPTPsigma protein in the growth cone. To determine if RPTPsigma affects the ability of a neuron to extend an axon, the rate of axon growth in neuronal cultures derived from wild-type and RPTPsigma (-/-) embryonic mice was compared. RPTPsigma did not affect the rate of axon initiation, but the rate of axon extension is enhanced in neurons obtained from RPTPsigma (-/-) mice. These findings indicate that RPTPsigma slows axon growth via a mechanism intrinsic to the neuron and identify a role for RPTPsigma regulating axonal regeneration by motoneurons.     

Unenhanced CT findings of vascular compromise in association with intussusceptions in adults

OBJECTIVE: The purpose of this study was to evaluate unenhanced CT findings for predicting the degree of vascular compromise in intussusception observed at surgery. MATERIALS AND METHODS: The imaging studies, clinical records, and surgical and pathologic findings in 25 patients with intussusception were reviewed retrospectively. We evaluated six CT findings based on the abnormalities of each component of intussusception. Presence or absence of these findings was compared with the degree of vascular compromise as observed on pathologic examination, such as edema, ischemia, or necrosis. RESULTS: The hypodense layer was observed in 16 of 18 intussusceptions with various degrees of vascular compromise. A fluid collection surrounded by the returning wall, which was revealed to correspond to trapped peritoneal fluid, was observed in eight of nine intussusceptions with ischemia or necrosis. A gas collection surrounded by the returning wall was observed in two of four intussusceptions with necrosis. Free peritoneal fluid coexisted with a fluid collection surrounded by the returning wall in all the intussusceptions except one. Bowel obstruction was observed in six of nine intussusceptions with ischemia or necrosis. The maximum wall thickness was not related to the degree of vascular compromise. CONCLUSION: The CT findings of a hypodense layer in the returning wall, fluid collection in the space surrounded by the returning wall, and gas collection in the space surrounded by the returning wall can be useful in predicting the degree of vascular compromise in intussusception.     

Effect of dexamethasone therapy on pulmonary function in chronic lung disease: A comparison of disease types

BACKGROUND: In the present study, we investigated the effect of dexamethasone (DEX) therapy on extubation and pulmonary function in patients with chronic lung disease (CLD) who required long-term mechanical ventilation. In addition, we compared the effects of DEX therapy among CLD types. METHODS: Twenty-two CLD patients who were ventilator dependent for 28 days or longer received DEX therapy for the purposes of extubation. A tapering dose of DEX, starting from 0.5 mg/kg per day, was administered for 7 days. Pulmonary function was measured at initiation of administration and 4 days after initiation. We evaluated static respiratory system compliance (Crs) and static respiratory system resistance (Rrs) adjusted by bodyweight. Chronic lung disease types were categorized according to the classification of the Ministry of Health and Welfare Research Project. We compared the effect of DEX therapy among CLD types. RESULTS: Dexamethasone therapy was started at a mean (+/-SD) 45 =/- 11 days after birth and 32.1 +/- 1.3 weeks of postconceptional age in infants with a mean bodyweight of 939 +/- 153 g. After DEX therapy, extubation was successful in all 22 patients. Following DEX administration, Crs was significantly increased from 0.69 +/- 0.13 to 1.17 +/- 0.21 mL/cm H2O per kg. In contrast, Rrs did not show any clear changes. Comparing CLD types, no difference was observed for Crs and Rrs in each disease type. CONCLUSIONS: Dexamethasone was administered to CLD patients requiring long-term mechanical ventilation for the purposes of extubation and extubation was successful in all patients. It was found that Crs was increased in all patients following DEX, regardless of CLD type. The increase in Crs following DEX administration may have been related to successful extubation.