The repression of the reverse-oriented transcription from the adenovirus terminus by NFI in competition with TFIID

AbstractNuclear factor 1 (NFI) represses the transcription which is promoted by the cloned adenovirus (Ad) type 5 DNA replication origin and is reverse-oriented with respect to the direction of the replication. The mechanism of this repression by NFI was investigated. In the cell-free transcription system, the repression was observed only when NFI was present during the formation of the transcription initiation complex. From the results of DNase I protection experiments, it was indicated that NFI bound to its binding site in the Ad replication origin prevents TFIID from proper binding to the adjacent AT-rich region and consequently represses the transcription

Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy

Predominant or codominant immunoglobulin (Ig) A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN). Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were found to be well associated with the development of IgAN. Several therapeutic strategies based on corticosteroids or other immunosuppressive agents have been shown to at least partially suppress the progression of IgAN. On the other hand, several case reports of kidney transplantation or acquired IgA deficiency uncovered a remarkable ability of human kidney to remove mesangial IgA deposition, resulting in the long-term stabilization of kidney function. Continuous exposure to circulating immune complexes containing aberrantly glycosylated IgA1 and sequential immune response seems to be essential in the disease progression of IgAN. Removal of mesangial IgA deposition may be a challenging, but fundamental approach in the treatment of IgAN

C3 glomerulopathy and current dilemmas

C3 glomerulopathy (C3G) is a recently identified disease entity caused by dysregulation of the alternative complement pathway, and dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are its components. Because laboratory detection of complement dysregulation is still uncommon in practice, “dominant C3 deposition by two orders greater than that of immunoglobulins in the glomeruli by immunofluorescence”, as stated in the consensus report, defines C3G. However, this morphological definition possibly includes the cases with glomerular diseases of different mechanisms such as post-infectious glomerulonephritis. In addition, the differential diagnosis between DDD and C3GN is often difficult because the distinction between these two diseases is based solely on electron microscopic features. Recent molecular and genetic advances provide information to characterize C3G. Some C3G cases are found with genetic abnormalities in complement regulatory factors, but majority of cases seem to be associated with acquired factors that dysregulate the alternative complement pathway. Because clinical courses and prognoses among glomerular diseases with dominant C3 deposition differ, further understanding the background mechanism, particularly complement dysregulation in C3G, is needed. This may resolve current dilemmas in practice and shed light on novel targeted therapies to remedy the dysregulated alternative complement pathway in C3G

Report on the method for determining the location of the polar vortex boundary region

To determine the boundary region of the polar vortex objectively using the PV distribution on isentropic surfaces, the equivalent latitude(Eql) of the polar vortex boundary was calculated using a slightly modified form of the technique of E.R. Nash et al.(J. Geophys. Res., 101D, 9471, 1996). Using the NCEP/NCAR reanal- ysis data, the Eql of the polar vortex boundary region in the winter of 1999/2000 was calculated, and compared with the ozone mixing ratio in the lower stratosphere over Eureka observatory(80°N , 86°W ). The results indicate that this method determines the boundary region of the polar vortex well

Angiotensin-Converting-Enzyme Inhibitor, Lisinopril, Reduces Lipopolysaccharide-Induced Expression of Splenic Interleukin-6 mRNA in Dehydrated Rats

Angiotensin II (ANG II) has been shown to have proinflammatory properties. To investigate whether ANG II is involved in the lipopolysaccharide (LPS)-induced production of a pyrogenic/proinflammatory cytokine, interleukin-6 (IL-6), we examined the effects of an angiotensin-converting-enzyme (ACE) inhibitor, lisinopril, on LPS-induced fever and on the expression of IL-6 mRNA in the spleen of dehydrated rats (in which the secretion of ANG II increases). The results showed that the ACE inhibitor significantly inhibited LPS-induced fever as well as the splenic expression of IL-6 mRNA in dehydrated rats. It is suggested that endogenous ANG II may be involved in the production of IL-6 that occurs in response to LPS, and thereby contribute to the LPS-induced febrile response in dehydrated rats

Apparent stratospheric ozone loss rate over Eureka in 1994/95, 1995/96, and 1996/97 inferred from ECC ozonesonde observations

Many ECC-type ozonesondes were launched at the Canadian Arctic Eureka observatory(80°N , 86°W ), one of the most northern stations in the Arctic, during winters from 1993/94 to 2001/02, and the temporal evolutions of the vertical ozone profiles were obtained in detail. The lower stratospheric temperature over Eureka was very low inside the polar vortex and the largest ozone loss was observed in 1999/2000, as reported in a previous paper. Similarly, Eureka was often or persistently inside the vortex in the lower stratosphere(around the 470K isentropic surface level) in the winters of 1994/95, 1995/96, and 1996/97. Very low temperatures were observed inside the vortex in the lower stratosphere over Eureka, as indicated by detection of PSCs by Mie lidar. Observations of tracers(N_2O, total reactive nitrogen species(NOy), and others) inside the vortex during these winters using an ER-2 aircraft and balloons indicated that the effect of air parcel mixing across the vortex edge was minimal, based on the tracer-tracer relationship(e.g., Y. Kondo et al.; J. Geophys. Res., 104D, 8215, 1999). Therefore, significant decreases of the in-travortex ozone mixing ratio in the lower stratosphere were considered to be chemical ozone losses due to chlorine activation of PSCs following diabatic descent. The apparent ozone loss rate inside the vortex over Eureka was estimated for each year. The rates ranged from 0.01 to 0.03ppmv/day, less than that observed in 1999/2000(0.04ppmv/day). The observations were conducted at a single station; however, the apparent ozone loss rate over Eureka inside the vortex each year agrees with loss rates obtained in other studies

BMP7 dose‐dependently stimulates proliferation and cadherin‐11 expression via ERK and p38 in a murine metanephric mesenchymal cell line

BMP7 is expressed in ureteric buds and cap mesenchyme of the fetal kidney, mediating branching morphogenesis and survival and priming of metanephric mesenchyme. Although dose‐dependent effects of BMP7 in collecting duct cells have been reported, studies in metanephric mesenchymal cells are lacking. We examined the effects of BMP7 on MAP kinase activation, proliferation, and expression of cadherins in a metanephric mesenchymal cell line MS7 by thymidine incorporation, immunoblot analysis, and quantitative real‐time PCR. The levels of phosphorylated ERK (P‐ERK) and phosphorylated p38 (P‐p38) were not altered at 10 min, 1 h, and 6 h with low‐dose BMP7 (0.25 nmol/L), but were increased at 24 h. At 24 h, P‐ERK was increased with low‐dose BMP7, but not by intermediate‐ (1 nmol/L) or high‐dose (10 nmol/L) BMP7, whereas p38 was activated by intermediate‐dose BMP7. Cell proliferation of MS7 was significantly increased by low‐ and intermediate‐dose BMP7 and decreased by high‐dose BMP7. A p38 inhibitor SB203580 5 μmol/L or a MEK inhibitor PD98059 5 μmol/L abolished BMP7‐stimulated proliferation. Expression of cadherin‐11, an adhesion molecule known to promote cell migration and compaction, was upregulated by intermediate‐dose BMP7. BMP7‐induced cadherin‐11 expression was inhibited by cotreatment with SB203580 and PD98059. Finally, in metanephroi cultured with siRNA for cadherin‐11, the number and thickness of cap mesenchyme were reduced. In conclusion, BMP7 exerts differential effects depending on the concentration; it may expand mesenchymal cells in the stroma where BMP7 concentration is low and may upregulate cadherin‐11 promoting condensation around the tip of ureteric buds

Peritoneal keratin granuloma associated with endometrioid adenocarcinoma of the uterine corpus

We present a 69-year-old woman with a chief complaint of postmenopausal bleeding. She was diagnosed as having an endometrioid adenocarcinoma by biopsy, and underwent a total abdominal hysterectomy. At the time of surgery, granulation tissue-like nodules were found on the peritoneal serosa of the uterus. In the intraoperative cytology of peritoneal washing, atypical cells were noted. The intraoperative frozen section of the peritoneal nodule revealed granulation tissue with proliferating mesothelial cells. Microscopic examination of the permanent section showed keratin granulomas without viable adenocarcinoma cells on the serosal surface of the ovaries, fallopian tubes and broad ligaments. Postoperative chemotherapy was administered. She has been alive with no evidence of recurrence for 6 months postoperatively. It should be noted that the prognosis of cases in peritoneal keratin granuloma without viable cancer cells is favorable, and that the histological examination is essential for its diagnosis