IPS-1 is crucial for DAP3-mediated anoikis induction by caspase-8 activation.

Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, a process known as anoikis. We have shown that DAP3 is critical for anoikis induction. However, the mechanism for anoikis induction mediated by DAP3 is still unclear. Here, we show that interferon-beta promoter stimulator 1 (IPS-1) binds DAP3 and induces anoikis by caspase activation. Recently, IPS-1 has been shown to be critical for antiviral immune responses, although there has been no report of its function in apoptosis induction. We show that overexpression of IPS-1 induces apoptosis by activation of caspase-3, -8, and -9. In addition, IPS-1 knockout mouse embryonic fibroblasts were shown to be resistant to anoikis. Interestingly, IPS-1 expression, recruitment of caspase-8 to IPS-1, and caspase-8 activation were induced after cell detachment. Furthermore, DAP3-mediated anoikis induction was inhibited by knockdown of IPS-1 expression. Therefore, we elucidated a novel function of IPS-1 for anoikis induction by caspase-8 activation.

Gas-driven subharmonic waves in a vibrated two-phase granular material.

Vibrated powders exhibit striking phenomena: subharmonic waves, oscillons, convection, heaping, and even bubbling. We demonstrate novel rectangular profile subharmonic waves for vibrated granular material, that occur uniquely in the two-phase case of grains, and a fluid, such as air. These waves differ substantially from those for the gas-free case, exhibit different dispersion relations, and occur for specific shaking parameters and air pressure, understandable with gas-particle flow models. These waves occur when the gas diffusively penetrates the granular layer in a time comparable to the shaker period. As the pressure is lowered towards P =0, the granular-gas system exhibits a Knudsen regime. This instability provides an opportunity to quantitatively test models of two-phase flow.

CCN family 2/connective tissue growth factor (CCN2/CTGF) stimulates proliferation and differentiation of auricular chondrocytes.

OBJECTIVES: CCN family 2/connective tissue growth factor (CCN2/CTGF) is an atypical growth factor for growth plate chondrocytes. It plays an important role in their proliferation and differentiation in vitro, but does not stimulate hypertrophy or calcification of articular chondrocytes. We herein report for the first time that CCN2/CTGF promotes growth and differentiation of auricular chondrocytes and maintains their molecular phenotype in vitro and in vivo. METHODS: Auricular chondrocytes were isolated from rabbit auricular cartilage by trypsin-collagenase treatment, and treated with human recombinant CCN2/CTGF or infected with adenovirus harboring the ccn2/ctgf gene. Cell proliferation was measured by [(3)H] thymidine incorporation and MTS assay, and changes in gene expression of auricular chondrocyte markers were monitored by real-time polymerase chain reaction, Northern hybridization, and histological analysis. For in vivo studies, auricular chondrocytes were cultured as pellets and implanted subcutaneously after treatment of recombinant human CCN2/CTGF. Ectopically formed cartilage was subjected to histological analysis. Cell death was monitored by in situ TUNEL analysis. RESULTS: CCN2/CTGF stimulated proliferation, differentiation and synthesis of elastin and proteoglycans of rabbit primary auricular chondrocytes in a dose-dependent manner. CCN2/CTGF caused a 2.5-fold increase in the expression of elastin in comparison to the control, resulting in enhanced deposition of elastin fibers in a monolayer culture of auricular chondrocytes. Mineralization was not induced; in contrast, CCN2/CTGF stimulated expression of matrix gla protein which is known to impair mineralization. Furthermore, pretreatment of pellets of auricular chondrocytes with CCN2/CTGF and subcutaneous implantation significantly enhanced the growth of ectopic auricular cartilage pieces expressing phenotypic markers of auricular chondrocytes including type II and X collagen. Notably, chondrocyte apoptosis was impaired by CCN2/CTGF. CONCLUSIONS: These findings show that CCN2/CTGF may be a suitable agent for promoting differentiation and growth of auricular chondrocytes, while preventing mineralization and apoptosis, and suggests that CCN2/CTGF may be useful for the repair or reconstruction of elastic cartilage.

A repetitive, steady mouth opening induced an osteoarthritis-like lesion in the rabbit temporomandibular joint.

Although excessive mechanical stress is assumed to be one of the factors contributing to pathogenesis of temporomandibular joint (TMJ) osteoarthritis (OA), no pure mechanical-stress-induced OA model has been developed without surgical manipulation or puncture of the joint cavity. The purpose of this study was to establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive, forced jaw-opening, 3 hrs/day for 5 days, was applied with the use of a general anesthesia protocol. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes, and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the repetitive, forced-jaw-opening period. These results suggest that the repetitive, forced-jaw-opening protocol without surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and this OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.

Low-speed impact craters in loose granular media.

We report on craters formed by balls dropped into dry, noncohesive, granular media. By explicit variation of ball density rho(b), diameter D(b), and drop height H, the crater diameter is confirmed to scale as the 1/4 power of the energy of the ball at impact: D(c) approximately equal (rho(b)D(3)(b)H)(1/4). Against expectation, a different scaling law is discovered for the crater depth: d approximately equal (rho(3/2)(b)D(2)(b)H)(1/3). The scaling with properties of the medium is also established. The crater depth has significance for granular mechanics in that it relates to the stopping force on the ball.

Effects of tamoxifen on the breast in the luteal phase of the menstrual cycle.

OBJECTIVES: The effect of tamoxifen on cyclic mastalgia and on chemoprophylaxis against breast cancer is little known, mainly due to the difficulties in studying the normal human gland. We proposed to evaluate the mitotic index and the nuclear volume of the lobule of women medicated with tamoxifen only during the luteal phase of the menstrual cycle in order to observe the effect of tamoxifen on the normal human mammary gland. METHODS: Twenty-four premenopausal women with fibroadenoma diagnosed via biopsy were studied. The phase of the cycle was determined by the date of menstruation and serum progesterone level in the luteal phase (> or = 3 ng/ml). The patients admitted to the study and were given written informed consent to participate in the investigation, which was previously approved of by the hospital Ethics Committee. Patients were divided at random into two groups: Group I consisted of 12 untreated women (control) and Group II consisted of 12 patients treated with 20 mg/day tamoxifen for 10 consecutive days beginning on the 13th day of the menstrual cycle. In both groups, the patients were submitted to biopsies of the nodule and of a 1-cm3 fragment of adjacent mammary parenchyma between the 23rd and 26th day of the cycle. The mitotic index (number of mitoses/1000 nuclei counted) and mean nuclear volume (mean of 10 nuclear volumes for each case) were measured. RESULTS: No mitosis was observed in Group II. There was a reduction in the mean nuclear volume in Group II (Mann-Whitney test). CONCLUSIONS: Tamoxifen, when administered only during the luteal phase of the menstrual cycle, significantly reduces the nuclear volume and mitotic activity of the epithelium. This data demonstrates an antagonistic action of tamoxifen on estrogen even when administered for short periods of time.

[Pathway of the radial artery located with a small-caliber Doppler probe for arterial cannulation in pediatric patients].

The pathway of the radial artery of 23 patients, ranging in age from 17 days to 10 years, was located with a small-caliber Doppler probe, 1.5 mm in diameter, and the artery was punctured along the pathway traced on the skin surface. In all patients the arterial pathway, including its branch and diameter, was shown clearly. In 11 patients, ranging in weight from 5 to 24 kg, the artery was greater than 0.5 mm in diameter and was cannulated easily. In another 4 patients, all less than 3 kg in weight, the artery under the thin skin layer was cannulated successfully in three of them. However, among the remaining 8 patients, ranging in weight from 3 to 5 kg, cannulation was successful in only two cases. The thick tissue layer, including the skin and the subcutaneous layer over the small artery, was thought to interfere with the accurate location of the artery in the other six patients. Nevertheless, the arterial pathway traced on the skin surface facilitated successful percutaneous cannulation by another method in these six. Visualization of the arterial pathway by the small-caliber Doppler probe was thought to be helpful for percutaneous cannulation, with or without another cannulation method.

[Severe bronchospasm induced by extracorporeal circulation for cardiac surgery].

Cardiac surgery was performed on a 50-yr-old man suffering from mitral valve stenosis. He has no history of allergic disease or bronchial asthma. Mitral valve was replaced uneventfully under extracorporeal circulation, and ventilation with pure oxygen was tried. But the lung was so stiff that the bag of anesthetic circuit could not be squeezed by hand. Fiberoptic bronchoscopy revealed no obstruction in endotracheal tube or bronchial tree. A presumptive diagnosis of severe bronchospasm was made, and partial extracorporeal circulation was maintained. Soon after aggressive bronchodilator therapy, there was noticeable improvement in pulmonary compliance, and the patient was removed from bypass uneventfully. No further recurrence of bronchospasm was seen in the intra- or postoperative period. Although the exact causes for bronchospasm in our case are not clear, we concluded that severe bronchospasm was induced by extracorporeal circulation. Possible etiologies and the management of patients with this problem are reviewed.

Glucagon response to arginine in growth hormone deficient children before and after treatment with growth hormone and in children with non-endocrine short stature.

In order to assess the role of growth hormone in the modulation of alpha cell function, the plasma pancreatic glucagon response to intravenous arginine (0.5 g/kg) was determined in thirty-two children with non-endocrine short stature and in eighteen growth hormone deficient children. 60 min after arginine infusion, the growth hormone deficient children had significantly higher (P less than 0.05) plasma glucagon values than the children with non-endocrine short stature. Following short-term growth hormone therapy (2 iu qd or bid for 5 days) in eleven of these growth hormone deficient children, plasma pancreatic glucagon response to arginine was diminished, and there was a significantly (P less than 0.02) more rapid return to basal values than in the untreated group. The same trends persisted after long-term growth hormone therapy (2 iu three times per week for 12-30 months) in ten children but were not statistically significant. We conclude that growth hormone may play a role in modulating plasma pancreatic glucagon response. The persistent glucagon response to arginine noted in growth hormone deficient children might reflect a greater gluconeogenic stress imposed upon these children during fasting or decreased catabolism of glucagon in the growth hormone deficient state.

Metabolic response to fasting in experimental intrauterine growth retardation induced by surgical and nonsurgical maternal stress.

Experimental intrauterine growth retardation was produced by two groups of neonatal rats by maternal sham surgery or by maternal obligatory exercise during the last 5 days of gestation (forced swim). Both experimental groups of neonates had lower plasma glucose and higher plasma insulin levels than controls after a 4-hour fast. Fetal stunting may be produced by a variety of maternal stresses in the rat and may be associated with alterations in the hormonal and glycemic response to fasting. Studies of the metabolic effects of experimental intrauterine growth retardation must be interpreted with caution if control animals have been subjected to intrauterine stress.