Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses

BACKGROUND: Calponin is a calmodulin-and actin-binding protein expressed in smooth muscle. It promotes actin polymerization and inhibits actin-activated myosin ATPase activity. Despite the molecular and functional characterization of calponin in vitro, the physiological role of calponin in vivo has not been clarified. RESULTS: We investigated the in vivo function of smooth muscle calponin (also called basic calponin or calponin h1) by generating mice carrying a targeted mutation in both alleles of the calponin gene. Mice lacking basic calponin expression displayed enhanced ectopic bone formation in vivo, induced by recombinant human bone morphogenetic protein-2 (rhBMP-2), and an augmentation of the degree of osteoblastic differentiation of embryonic mesenchymal cells when they were stimulated by rhBMP-2. Basic calponin messenger RNA was shown to be expressed in developing and healing bone tissues, and in undifferentiated MC3T3-E1 osteoblasts. An examination of the skeletons of mutated mice showed an early onset of cartilage formation and ossification, and increased postnatal bone formation characterized by an increase in the number of activated periosteal osteoblasts. Bone fracture healing was accelerated in mutated mice. CONCLUSION: This is the first demonstration of animals with enhanced BMP responsiveness in host cells, suggesting that endogenous basic calponin may play a negative role in an osteogenic programme.     

The mode of action of AKD-2C, an antifungal antibiotic from Streptomyces sp. OCU-42815

The mechanism of the antifungal action of AKD-2C was studied by using Torulaspora delbrueckii IFO 1621 as a model. AKD-2C slightly inhibited the incorporation of radioactive precursors into protein, RNA and lipid, but not into DNA. On the other hand, AKD-2C greatly enhanced the leakage of K+ ions from treated cells and showed a potent effect on liposomal glucose leakage. Using electron microscopic studies, though drastic morphological changes were not observed, an increase in cell membrane irregularities and swelling of the mitochondria caused by AKD-2C were demonstrated. These results suggest that the antifungal action of AKD-2C is due to effects on the yeast cell membrane.     

Changes in tissue and blood polyamines during N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder carcinogenesis in rats

(BACKGROUND): Polyamine are recognized as cell growth factors. We studied in order to determine whether alterations in the levels of tissue and blood polyamines were useful biochemical markers for bladder tumor. (METHODS): The concentrations of three polyamines, diamine, spermidine and spermine, in urinary bladder and blood were determined during N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis in male F344 rats. At 5 weeks of age, rats were given 0.05% BBN in the drinking water for 20 weeks. (RESULTS): BBN induced bladder hyperplasia in 4 of 5 rats at 8 weeks, papillomas in 2 of 5 rats at 12 weeks, and transitional cell carcinoma in all the rats by 20 weeks. The levels of total polyamine in both bladder and blood of the rats during 12-20 weeks were significantly higher than those of the control animals given water alone. The elevation of total polyamine was mainly due to the increase of spermidine of the three polyamines, which was coincident with the incidence of bladder tumors. (CONCLUSION): The results indicated that the polyamines are excellent biochemical markers for bladder tumors.     

In-situ X-ray observation of phase transformation of rhombohedral boron nitride under static high pressure and high temperature

In-situ X-ray diffraction study for phase transformation of rhombohedral boron nitride (rBN) to a denser phase was performed under static high pressure (HP) and high temperature (HT) up to 9 GPa and 1600 °C. It was found that the layer stacking sequence of rBN structure began to change at less than 1 GPa, and the phase transformation to wurtzite structure (wBN) was observed at 6–7 GPa and room temperature. After conversion to wBN, further transformation to the zincblend type cubic structure (cubic BN) at 8 GPa and 1400 °C was observed, which is quenchable and the P-T conditions yielding cBN form were similar to that from hexagonal boron nitride. The observed behavior of the phase transformation of rBN by using in-situ X-ray diffraction study is well consistent with the results obtained from the quenching experiment from HP/HT by using belt type HP apparatus.

No structural change was observed at 600°C isothermal compression up t0 8GPa, while wBN formation was observed at room temperature compression at 7 GPa. This variation of the transformation behavior under HT isothermal compression may essentially be caused by the reduction of shear stress which affects the rotation and/or slip of hexagonal plane of rBN under HP.     

High-speed InGaP/GaAs heterojunction bipolar transistors withburied SiO2 using WSi as the base electrode

High-speed InGaP/GaAs heterojunction bipolar transistors (HBT's) with a small emitter area are described. WSi is used as the base electrode to fabricate HBT's with a narrow base contact width and a buried SiO₂ structure. An HBT with an emitter area of 0.8×5 μm exhibited an f_T of 105 GHz and an f_max of 120 GHz. These high values are obtained due to the reduction of C_BC by using buried SiO₂ with a narrow base contact width, indicating the great potential of GaAs HBT's for high-speed and low-power circuit applications     

Degradation of tensile strength of Ni–Ti superelastic alloy due to hydrogen absorption in methanol solution containing hydrochloric acid

Degradation of tensile strength of a Ni–Ti superelastic alloy due to hydrogen absorption has been studied in methanol solution containing 0.1 mass % hydrochloric acid (HCl). The amount of absorbed hydrogen from the solution was measured by thermal desorption analysis (TDA). Hydrogen desorption of immersed specimens appeared in the temperature range from 100 to 600 °C. The amounts of absorbed hydrogen of immersed specimens were in the range of 50–500 mass ppm when immersed in the solution for 8–120 h. Tensile strength of immersed specimens decreased abruptly up to immersion time of 24 h. In the immersion time range from 24 to 120 h, the tensile strength was coincident with the critical stress for martensite transformation. It was concluded that the degradation of tensile strength of a Ni–Ti superelastic alloy is caused by hydrogen absorption in methanol solution containing HCl.     

Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma

Recently, the N-terminal fragment of proatrial natriuretic peptide (N-terminal proANP) has been proposed as a marker of chronic congestive heart failure. In this study, we established a two-step immunoradiometric assay using monoclonal antibodies and synthetic N-terminal proANP (1-67) as a standard. It allows us to measure plasma N-terminal proANP in only 4 h without prior extraction. The detection limit of this assay was 15 pmol/L for a 100 microL sample of plasma. Within-run CVs ranged from 1.7% to 2.9% and between-run CVs ranged from 4.2% to 5.1%. The dilution curves of plasma samples showed good linearity and analytical recovery was 89-104%. The mean (+/-SD) N-terminal proANP in plasma of 33 healthy subjects was 188 (+/-71) pmol/L and 1030 (+/-411) pmol/L in 25 patients with heart failure. Our immunoradiometric assay is rapid and precise enough for routine determination of N-terminal proANP in human plasma.     

Ataxia-telangiectasia in the Japanese population: identification of R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two being relatively common mutations

Postmenopausal uterine bleeding is an indication to sample the endometrium for diagnostic purposes. The endometrial brush cytologies of 20 advanced postmenopausal women collected at the time of hysterectomy in order to benchmark the expected morphology of postmenopausal endometrial brushings were reviewed. No women had symptoms or gross findings of primary endomyometrial disease. Endometrium was collected at the surgical pathology laboratory using the Tao Brush and CytoRich Fixative System. After formalin fixation of the uterus, the entire endometrium was embedded for routine histology. Sixteen endometrial brushings and matched endometrial sections showed endometrial atrophy, one brushing showed many ciliated epithelial cells, and three brushings showed focal (less than 10%) epithelial-cell atypia. In two atypias, abnormal endometrial epithelial-cell sheets contained enlarged, clear nuclei with nuclear notches and grooves resembling papillary thyroid cancer. One case showed no histological counterpart to this finding. The other case showed thickening of the pericornual fundic endometrium with cystic glands. The third case with epithelial atypia showed abnormal endometrial-cell sheets with nuclei resembling atypical hyperplasia or type I endometrial adenocarcinoma; corresponding endometrial tissue sections showed rare, irregular glands and back-to-back gland clusters with equivalent nuclear features. Atypical epithelium may be found in atrophic uteri in the absence of gross endometrial thickening. This may be a common event related either to de novo intraepithelial dysplasia in a noncycling endometrium or to hyperplasia that has partly regressed with estradiol withdrawal. This study shows that, in addition to endometrial intraepithelial carcinoma (EIC), isolated atypical glands with morphological and immunohistochemical features of atypical hyperplasia or type I endometrial adenocarcinoma may be found in grossly normal advanced postmenopausal endometrium of asymptomatic patients. This atypical epithelium is readily apparent in endometrial brush preparations, but requires serial sectioning of the endometrium to be demonstrated histologically. We have not established the natural history of this lesion, and in the absence of EIC or gross endometrial thickening indicative of atypical hyperplasia, we do not know whether this degree of epithelial atypia should be an indication for hysterectomy.