Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and disease."

Recombinant human alpha 1-antitrypsin (rAAT) was expressed and secreted from transgenic rice cell suspension cultures in its biologically active form. This was accomplished by transforming rice callus tissues with an expression vector, p3D-AAT, containing the cDNA for mature human AAT protein. Regulated expression and secretion of rAAT from this vector was achieved using the promoter, signal peptide, and terminator from a rice alpha-amylase gene Amy3D. The Amy3D gene of rice is tightly controlled by simple sugars such as sucrose. It was possible, therefore, to induce the expression of the rAAT by removing sucrose from the cultured media or by allowing the rice suspension cells to deplete sucrose catabolically. Although transgenic rice cell produced a heterogeneous population of the rAAT molecules, they had the same N-terminal amino acids as those found in serum-derived (native) AAT from humans. This result indicates that the rice signal peptidase recognizes and cleaves the novel sequence between the Amy3D signal peptide and the first amino acid of the mature human AAT. The highest molecular weight band seen on Western blots (AAT top band) was found to have the correct C-terminal amino acid sequence and normal elastase binding activity. Staining with biotin-concanavalin A and avidin horseradish peroxidase confirmed the glycosylation of the rAAT, albeit to a lesser extent than that observed with native AAT. The rAAT, purified by immunoaffinity chromatography, had the same association rate constant for porcine pancreatic elastase as the native AAT. Thermostability studies revealed that the rAAT and native AAT decayed at the same rate, suggesting that the rAAT is correctly folded. The productivity of rice suspension cells expressing rAAT was 4.6-5.7 mg/g dry cell. Taken together, these results support the use of rice cell culture as a promising new expression system for production of biologically active recombinant proteins.

Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring (UN offspring) showed an increase in systolic blood pressure (8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery (16 wk, P < 0.05) and cardiac cardiomegaly (16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen (P < 0.05) and endothelin-1 (P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles (16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.

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Pc 1 pulsation sources, •. _ p , __, 2790, 1975. proton energies, J. Atmos. Terr. Phy•s., 41, Fukunishi, H., Occurrence of sweepers in the 293, 1979. evening sector following the onset of magne-Jacobs, J. A., and T. Watanabe, Theoretical notes Fukunishi et al.: Classification of Hydromagnetic Emissions 9039 on whistlers and periodic emissions in the hy-tion region by a statistical analysis of ground dromagnetic regime, Planet. Space Sci., 1__5, 'based observations, Planet. Space Sci., 2__•, 799, 1967. 993, 1975. Kangas, J., T. Pikkarainen, Yu. Golikov, L. Saito, T., Geomagnetic pulsations, Space Sci. Baransky, V. A. Troitskaya, and V. Sterlikova, R. ev.., 10, 319, 1969.

The Cretaceous accretionary complexes of the Idonnappu Zone in the Urakawa area are divided into five lithological units, four of which contain greenstone bodies. The Lower Cretaceous Naizawa Complex consists of two lithologic units. The Basaltic Unit (B‐Unit) is a large‐scale tectonic slab of greenstone, consisting of depleted tholeiite similar to that of the Lower Sorachi Ophiolite (basal forearc basin ophiolite) in the Sorachi‐Yezo Belt. The Mixed Unit of Naizawa Complex (MN‐Unit) contains oceanic island‐type alkaline greenstones which occur as slab‐like bodies and faulted blocks with tectonically dismembered trench‐fill sediments. Repeated alternations of the two units in the Naizawa Complex may have been formed by the collision of seamounts with forearc ophiolitic body (Lower Sorachi Ophiolite) in the trench. The Upper Cretaceous Horobetsugawa Complex structurally underlies the Naizawa Complex in its original configuration, and it also contains greenstone bodies. Greenstones in the MH‐Unit occur as blocks and sedimentary clasts in a clastic matrix, and exhibit depleted tholeiite and oceanic‐island alkaline basalt/tholeiite chemistry. This unit is interpreted as submarine slide and debris flow deposits. Greenstones in the PT‐Unit occur at the base of several chert‐clastic successions. Most of the greenstones are severely sheared and show normal‐type mid‐ocean ridge basalt composition. The PT‐Unit greenstones are considered to have been derived from abyssal basement peeled off during accretion. The different accretion mechanism of the greenstones in the Naizawa and Horobetsugawa complexes reflects temporal changes in subduction zone conditions. Seamount accretion and tectonic erosion were dominant in the Early Cretaceous, due to highly oblique subduction of the old oceanic crust and minimal sediment supply. Whereas, thick sediments with minor mid‐ocean ridge basalt and olistostrome accreted in the Late Cretaceous, due to near‐orthogonal subduction of young oceanic crust with voluminous sediment supply.

Adenocarcinomas arising from adenomyosis uteri are rare. This study reports four such cases and characterizes them clinically and microscopically. In all four patients, the endometrial cytology was negative, and MR imaging and ultrasound sonography did not detect the tumors preoperatively. The histological subtypes of the four tumors were endometrioid (one grade 1, one grade 3), serous, and clear cell. In three cases, the adenocarcinomas were present exclusively in the myometrium, and a transition between the carcinomas and the adenomyotic glands was observed in all cases. The eutopic endometrium was normal except in one case in which there was a small focus of invasive carcinoma. In two of four cases, pelvic or paraaortic lymph node metastases were present. In the carcinomas, ER immunoreactivity was not found in any tumor and PR positivity was found in only one tumor. In contrast, p53 immunopositivity was found in three of four carcinomas. Adenocarcinomas arising from adenomyosis are difficult to diagnose preoperatively, and their aggressive behavior in some cases seems to be related to the histological subtype.

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