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The ovarian hormone 17β-estradiol (E2) exerts profound neuroprotective actions against ischemia-induced brain damage in rodent models of global and focal ischemia. This review focuses on the neuroprotective efficacy of post-ischemic administration of E2 and non-feminizing estrogen analogs in the aging brain, with an emphasis on studies in animals subjected to a long-term loss of circulating E2. Clinical findings from the Women's Health Initiative study as well as data from animal studies that used long-term, physiological levels of E2 treatment are discussed in this context. We summarize major published findings that highlight the effective doses and timing of E2 treatment relative to onset of ischemia. We then discuss recent findings from our laboratory showing that under some conditions the aging hippocampus remains responsive to E2 and some neuroprotective non-feminizing estrogen analogs even after prolonged periods of hormone withdrawal. Possible membrane-initiated signaling mechanisms that may underlie the neuroprotective actions of acutely administered E2 are also discussed. Based on these findings, we suggest that post-ischemic treatment with high doses of E2 or certain non-feminizing estrogen analogs may have great therapeutic potential for treatment of brain damage and neurodegeneration associated with ischemia.

Growing evidence indicates that chronic exposure to Bisphenol A (BPA) may disrupt normal brain function and behavior mediated by gonadotropin-releasing hormone (GnRH) pathways. Previous studies have shown that low dose BPA (200 ng/ml) exposure during embryogenesis altered development of extra-hypothalamic GnRH3 systems and non-reproductive locomotor behavior in medaka. Effects of parental low-dose BPA exposure on the development of GnRH3 systems and locomotor behavior of offspring are not well known. This study examines whether the neurophysiological and behavioral effects of BPA in parents (F0 generation) are carried over to their offspring (F1 generation) using stable transgenic medaka embryos/larvae with GnRH3 neurons tagged with green fluorescent protein (GFP). Parental fish were exposed to BPA (200 ng/ml) for either life-long or different developmental time windows. Fertilized F1 eggs were collected and raised in egg/fish water with no environmental exposure to BPA. All experiments were performed on F1 embryos/larvae, which were grouped based on the following parental (F0) BPA exposure conditions – (i) Group 1 (G1): through life; (ii) G2: during embryogenesis and early larval development [1–14 days post fertilization (dpf)]; (iii) G3: during neurogenesis (1–5 dpf); and (iv) G4: during sex differentiation (5–14 dpf). Embryos from unexposed vehicle treated parents served as controls (G0). G1 embryos showed significantly reduced survival rates and delayed hatching time compared to other groups, while G4 embryos hatched significantly earlier than all other groups. At 3 dpf, the GnRH3-GFP intensity was increased by 47% in G3 embryos and decreased in G4 embryos by 59% compared to controls. At 4 dpf, G1 fish showed 42% increased intensity, while GFP intensity was reduced by 44% in G3 subjects. In addition, the mean brain size of G1, G3 and G4 embryos were smaller than that of control at 4 dpf. At 20 dpf, all larvae from BPA-treated parents showed significantly decreased total movement (distance covered) compared with controls, with G2 and G3 fish showing reduced velocity of movement. While at 20 dpf no group differences were seen in the soma diameter of GnRH3-GFP neurons, a 34% decrease in SV2 expression, a marker for synaptic transmission, in G1 larvae was observed. These data suggest that parental BPA exposure during critical windows of embryonic development or chronic treatment affects next-generation offspring both in embryonic and larval brain development as well as larval behavior.

Acute effects of bisphenol (BPA), an environmental chemical, on estradiol (17α or β-E2)-dependent recognition memory and dendritic spines in the medial prefrontal cortex and hippocampus were investigated in adult female rats. Ovariectomized rats received BPA 30 min before or immediately after a sample trial (viewing objects), and retention trials were performed 4 h later. Retention trials tested discrimination between old and new objects (visual memory) or locations (place memory). When given immediately after the sample trial, BPA, 1–400 μg/kg, did not alter recognition memory, but 1 and 40 μg/kg BPA, respectively, blocked 17β-E2-dependent increases in place and visual memory. When ovariectomized rats were tested with 17α-E2, 1 μg/kg BPA blocked place memory, but up to 40 μg did not block visual memory. BPA, given to cycling rats at 40 μg/kg, blocked visual, but not place, memory during proestrus when 2 h intertrial delays were given. Spine density was assessed at times of memory consolidation (30 min) and retention (4 h) after 17β-E2 or BPA + 17β-E2. In prefrontal cortex, BPA did not alter E2-dependent increases. In the hippocampus, BPA blocked E2 increases in basal spines at 4 h and was additive with E2 at 30 min. Thus, these novel data show that doses of BPA, below the current Environmental Protection Agency safe limit of 50 μg/kg, rapidly alter neural functions dependent on E2 in adult female rats.

BACKGROUND/AIMS Because of the notion that pancreatic and duodenal homeobox 1 (PdX-1)-positive cells are pancreatic stem cells that contribute to the differentiation and proliferation of exocrine cells, we examined PdX-1-associated changes in the morphology of rat pancreatic acinar cells that occur between the late fetal and early neonatal periods. METHODS Light and electron microscopy and PdX-1 and MIB-5 immunohistochemistry were used to examine pancreatic tissues obtained from fetal rats 22 days postconception (dpc), from newborn rats 48 and 72 hours after natural birth, and from rats 7 days after natural birth. RESULTS At 22 dpc, the cytoplasm of the acinar cells was large and eosinophilic due to accumulation of dense and numerous zymogen granules. Zymogen granules, rough endoplasmic reticulum, and other organelles were distributed throughout the cytoplasm. At 48 hours, i.e., just after feeding, the cytoplasm appeared smaller, less eosinophilic, and vacuolated. Electron microscopic examination showed cleaved nuclei and fewer zymogen granules. Expression of both PdX-1 and MIB-5 was increased at 48 hours. At 72 hours, acinar cell cytoplasm was decreased in size. At 7 days, the acinar cells were larger, biphasic distribution of zymogen granules was seen on the eosinophilic apical side, and rough endoplasmic reticulum and other ergastoplasms were seen on the basophilic basal side, typical of mature pancreatic acinar cells. Expression of PdX-1 and MIB-5 was markedly decreased in acinar cells. CONCLUSION Our findings indicate dynamic PdX-1-associated morphologic change from fetal to mature pancreatic acinar cells between 48 and 72 hours after birth.

Effects of estradiol benzoate (EB), ERα-selective agonist, propyl pyrazole triol (PPT) and ERβ-selective agonists, diarylpropionitrile (DPN) and Compound 19 (C-19) on memory were investigated in OVX rats using object recognition (OR) and placement (OP) memory tasks. Treatments were acute (behavior 4 h later) or sub chronic (daily injections for 2 days with behavior 48 h later). Objects were explored in sample trials (T1), and discrimination between sample (old) and new object/location in recognition trials (T2) was examined after 2–4 h inter-trial delays. Subjects treated sub chronically with EB, DPN, and C-19, but not PPT, discriminated between old and new objects and objects in old and new locations, suggesting that, at these doses and duration of treatments, estrogenic interactions with ERβ contribute to enhancements in recognition memory. Acute injections of DPN, but not PPT, immediately after T1, also enhanced discrimination for both tasks (C19 was not investigated). Effects of EB, DPN and PPT on anxiety and locomotion, measured on elevated plus maze and open field, did not appear to account for the mnemonic enhancements. Monoamines and metabolites were measured following DPN treatment in subjects that did not receive behavioral testing. DPN was associated with alterations in monoamines in several brain areas: indexed by the metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), or the MHPG/norepinephrine (NE) ratio, NE activity was increased by 60–130% in the prefrontal cortex (PFC) and ventral hippocampus, and NE activity was decreased by 40–80% in the v. diagonal bands and CA1. Levels of the dopamine (DA) metabolite, homovanillic acid (HVA), increased 100% in the PFC and decreased by 50% in the dentate gyrus following DPN treatment. The metabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), was increased in the PFC and CA3, by approximately 20%. No monoaminergic changes were noted in striatum or medial septum. Results suggest that ERβ mediates sub chronic and acute effects of estrogens on recognition memory and that memory enhancements by DPN may occur, in part, through alterations in monoaminergic containing systems primarily in PFC and hippocampus.

Acute effects of estrogens on mnemonic processes were examined at the behavioral and neurochemical levels. 17beta-estradiol and 17alpha-estradiol influences on memory consolidation were assessed using object placement (OP) and object recognition (OR) tasks. Subjects received treatment immediately after a sample trial (exploring two novel objects), and memory of objects (OR memory) or location of objects (OP memory) was tested 4h later. Both isomers of estradiol enhanced memory. For spatial memory, 15 and 20 microg/kg of 17beta-estradiol facilitated OP, while lower and higher doses were ineffective. 17alpha-estradiol had a similar pattern, but a lower dose was effective. When treatment was delayed until 45 min after a sample trial, memory was not enhanced. For non-spatial memory, OR was facilitated at 5 microg/kg of 17beta-estradiol and at 1 and 2 microg/kg of 17alpha-estradiol and, similar to OP, lower and higher doses were ineffective. These data demonstrate that beneficial effects of estrogens are dose, time and task dependent, and the dose-response pattern is an inverted U. Because monoamines are known to have contributions to memory, brains were removed 30 min after treatment for measurements of dopamine (DA), norepinephrine (NE), serotonin (5-HT), and metabolites. Estrogen elevated 5HT, NE metabolite MHPG, turnover ratio of NE to MHPG, and DA metabolite DOPAC levels in the prefrontal cortex, while NE and MHPG were decreased in the hippocampus. Thus, acute estrogens exert rapid effects on memory consolidation and neural function, which suggests that its mnemonic effects may involve activation of membrane associated estrogen receptors and subsequent signaling cascades, and that monoamines may contribute to this process.

We report on a 45-year-old woman with intimal sarcoma of the pulmonary artery. She presented with a chief complaint of shortness of breath. Computed tomography (CT) of the chest showed an intraluminal hypoattenuated area extending from the main pulmonary artery into the right main pulmonary artery and bilateral lobar pulmonary arteries. She underwent resection of the lobulated mass from the pulmonary artery. The tumor was diagnosed as an intimal sarcoma. Although she received chemotherapy with amrubicin and carboplatin when the tumor recurred, the tumor enlarged. After radiotherapy was performed, CT of the chest showed shrinkage of the tumor and the regression of consolidation and ground-glass opacity. Radiotherapy and chemotherapy are treatment option for patients with pulmonary artery sarcoma.

Aged F344 female rats (21 months) showed decreased performance, as compared to young rats (4 months), on an object recognition memory task. Golgi impregnation measured dendritic spine density of pyramidal neurons in the prefrontal cortex (layer II-III), a brain area important for recognition memory. Densities of spines in aged rats were 16% lower in tertiary, apical dendrites, but not significantly different in secondary basal dendrites. Concurrent measures of memory and spine density in the young and aged subjects show that age-related declines in recognition memory are associated with decreased cortical spine density.

Accumulating evidence indicates that chronic low dose exposure to Bisphenol A (BPA), an endocrine disruptor, may disrupt normal brain development and behavior mediated by the gonadotropin-releasing hormone (GnRH) pathways. While it is known that GnRH neurons in the hypothalamus regulate reproductive physiology and behavior, functional roles of extra-hypothalamic GnRH neurons remain unclear. Furthermore, little is known whether BPA interacts with extra-hypothalamic GnRH3 neural systems in vulnerable developing brains. Here we examined the impact of low dose BPA exposure on the developing GnRH3 neural system, eye and brain growth, and locomotor activity in transgenic medaka embryos and larvae with GnRH3 neurons tagged with GFP. Fertilized eggs were collected daily and embryos/larvae were chronically exposed to 200ng/ml of BPA, starting at 1 day post fertilization (dpf). BPA significantly increased fluorescence intensity of the GnRH3-GFP neural population in the terminal nerve (TN) of the forebrain at 3dpf, but decreased the intensity at 5dpf, compared with controls. BPA advanced eye pigmentation without affecting eye and brain size development, and accelerated times to hatch. Following chronic BPA exposure, 20dpf larvae showed suppression of locomotion, both in distance covered and speed of movement (47% and 43% reduction, respectively). BPA-induced hypoactivity was accompanied by decreased cell body sizes of individual TN-GnRH3 neurons (14% smaller than those of controls), but not of non-GnRH3 neurons. These novel data demonstrate complex neurobehavioral effects of BPA on the development of extra-hypothalamic GnRH3 neurons in teleost fish.

A 40-year-old pregnant woman admitted into hospital to treat hypertension (HT) and gestational diabetes at 19 weeks of gestation. She contracted enterocolitis due to the foodborne pathogen Yersinia enterocolitica (YE) at 22 weeks of gestation. Hypoalbuminemia and ascites developed due to prolonged intractable diarrhea and vomiting. Since 25 weeks of gestation, marked albuminuria appeared and blood pressure gradually elevated. Fetal growth was found to be retarded. Cesarean section for non-reassuring fetal status was performed at 27 weeks 2 days, delivering a 641 gr boy (-2.9 SD from averaged neonatal body weights compatible with the gestational weeks, Apgar score 3/8 at1/5min.). Gastrointestinal symptoms and ascites resolved within 1 week of delivery. This represents the first report of YE infection seriously affecting perinatal prognosis.

Background Biphasic pulmonary blastoma is a rare malignant neoplasm of debatable histogenesis. Although well described histologically, it is scarcely mentioned in the cytologic literature. Case A 78-year-old man reporting intermittent hemoptysis was admitted to the hospital. Chest radiography revealed a right-sided pulmonary mass. Cytologic examination of tumor specimens revealed 2 types of malignant cells. The smears were highly cellular, with a necrotic background. The stromal cells had predominantly round to ovoid or spindle-shaped nuclei and scant cytoplasm, and the nucleoli had slightly irregular borders with coarsely aggregated chromatin. The epithelial cells were arranged in sheets and glandular configurations. The cytoplasm of these cells was finely vacuolated or foamy, with indistinct cellular boundaries; eccentrically located nuclei were hyperchromatic and had irregularly shaped nucleoli. The cell block preparation showed a distinctly biphasic malignant tumor with the classic morphologic features of pulmonary blastoma. Conclusion A preoperative diagnosis ofpulmonary blastoma is difficult to obtain by cytopathologic methods. A diagnosis of biphasic pulmonary blastoma should be considered whenever epithelial cells and a separate population of stromal cells are seen in a pulmonary exfoliative cytology specimen.

I have studied about the each purpose of the two Encouragement Acts for the Marriage issued in 1724 and 1763 by tracing back to the Laws for the Military Houses ("Buke shohatto") restricting the range of social status of Daimyo's partner in life.The Act of 1724 recognizes with some reservations that Daimyo takes a concubine as his wife, and the Act of 1763 permits the free remarriage though the first marriage is restrained strictly in the marriage range by "Buke shohatto".The system of the hostage and "Sankin kotai" is the basic policy of Tokugawa Shogunate in order to control the Daimyos.It seems that the Act of 1724 aims at reinforcing the hostage system, whereas shortening the stay in Edo under "Sankin kotai" system.However, as a result of my research on the actual conditions, there are no documents or records showing that Daimyo actually took a concubine as his wife.This means that in this period the institution of social position is more important than the new hostage system.It seems that the purpose of the Act of 1763 is a relaxation of the restricted marriage range.This supposition is supported practically by the investigation on the actual conditions of the marriages of Daimyos.

A case of carcinosarcoma of the urinary bladder in a 2-year-old girl is reported. The tumor, measuring 34 x 20 x 18 mm, was located in the peri-trigone area of the urinary bladder with polypoid features. Histologic examination revealed transitional cell carcinoma at the tumor surface with downward invasion. Concurrently, a sarcomatous area was found beneath the carcinoma, with these two different malignant components sharing on apparent transition without distinct boundaries. Sarcomatous components included immature round cells focally showing rhabdoid features. No rhabdomyomatous component was observed. Immunohistochemistry disclosed vimentin and cytokeratin-double positive cells at the transposition between carcinoma and sarcomatous components. In addition, ultrastructural analysis revealed that the epithelial cells had a distinct junctional complex, and the sarcomatous cells occasionally had a meshwork of cytoplasmic intermediate filaments, indicating bidirectional cytodifferentiation to epithelial and mesenchymal elements. The extremely young age at which this case of carcinosarcoma occurred suggests that the tumor may be of mesodermal stem cell origin.

Reactions of FeIII(NO3)3·9H2O with 0.5 equivalent of 2-hydroxypropane-1,3-diamine-N,N,N′,N′-tetraacetic acid (H5dhpta) and an excess of amino acid [glycine (Gly) or L-alanine (L-Ala)] in water with the pH adjusted to ca. 5 by a solution of NaOH gave pale green crystals formulated as Na[Fe4(dhpta)2(µ-O)(µ-OH)(O2CCHRNH3)2] (R = H 1 or CH3 2) in moderate yields. The tetrairon(III) complexes were characterized by elemental analyses, IR and 57Fe Mossbauer spectra, variable-temperature magnetic susceptibility, and X-ray crystallographic and absorption analyses. The structure of 2·6H2O was determined by X-ray crystallography to comprise a (µ-oxo)(µ-hydroxo)bis(µ-alkoxo)bis(µ-carboxylato)tetrairon(III) cluster core bridged by two dhpta and two amino acid ligands. Two identical dinuclear iron(III) units [Fe(1)Fe(2) and Fe(3)Fe(4)] are each co-ordinated by a pentadentate dhpta ligand. The Fe(1) and Fe(4) are then bridged by the carboxylate of an amino acid and an oxo group, with the Fe(2) and Fe(3) similarly linked. The central two oxo groups are protonated to form a strongly hydrogen bonded (O–H–O)3– bridge [O· · ·O 2.426(4) A]. The average Fe· · ·Fe distance for the µ-alkoxo dinuclear units is 3.692 A (intradimer) and that for the bis(µ-carboxylato)(µ-oxo/hydroxo)diiron units is 3.463 A (interdimer), both being in accord with the corresponding values from EXAFS analyses. The two L-alanine moieties are in zwitterionic form and act as interdimer bridging ligands with the carboxylate groups. The Na+ counter cation is well packed between the tetrairon(III) complex anions, resulting in an infinite chain aggregation. The 57Fe Mossbauer spectrum for 2·6H2O clearly demonstrated that the four iron sites are equivalent, being in a high-spin octahedral iron(III) state. The variable-temperature magnetic susceptibility measurement for 2·6H2O showed modest antiferromagnetism with an interdimer coupling constant (J) of –42.3 cm–1 and an intradimer coupling constant (J′) of –20.8 cm–1.

Intraductal neoplasms of the pancreas are generally referred to as intraductal papillary mucin-producing neoplasms (IPMNs), according to the WHO classification system. Herein, we report that morphologic and immunohistochemical features of intraductal tubular carcinoma (ITC) are quite different from those of intraductal papillary mucinous carcinoma (IPMC).We analyzed histogenesis and differentiation of ITC by light microscopy and immunohistochemistry.Histologically, ITC was characterized as an intraductal nodular appearances with a monotonous tubular growth pattern without papillary projection. ITC showed de novo-like appearance without sequential progression usually observed in IPMC, suggesting that ITC is a homogeneous neoplasm. Cuboidal tumor cells in ITC resembled normal pancreatic duct epithelia, and the characteristic growth pattern of ITC replaced that of normal pancreatic duct epithelium. Immunohistochemically, ITC cells were positive for MUC-1 on the apical side of the cell membrane. In contrast to ITC cells, IPMC cells were negative for MUC-1, and ductal adenocarcinoma cells were strongly positive for MUC-1, as was the stroma around the cancer. The immunohistochemical staining pattern of DUPAN-2 resembled that of MUC-1. Interestingly, localization of MUC-1 and DUPAN-2 staining in ITC cells was similar to that in normal pancreatic ductules. ITC cells were negative for MUC-2 and MUC-5AC. In contrast, most IPMC cells were positive for MUC-2 and MUC-5AC.Based on our histologic and immunohistochemical findings, the intraductal pancreatic neoplasm (IPN) can be classified into 2 groups: IPN with gastrointestinal differentiation and IPN with pancreatic duct differentiation. Our present data indicated that ITC cells may arise directly from duct epithelia without progression and possessed pancreatic duct differentiation. On the basis of our data, we suggest that classification of pancreatic neoplasms in the WHO and The Armed Forces Institute of Pathology (AFIP) systems should be reconsidered.

A resected case of adenoneurofibroma of the colon: is it a new entity of the colonic tumor?

The crystal structure of the syndiotactic polystyrene-toluene molecular compound was studied by X-ray diffraction. The crystal data are as follows: monoclinic system, space group P21/a (no. 14), a = 17.58, b = 13.26 , c(chain axis) = 7.71 A, γ = 121.2 °, eight monomer units (two chains) and two toluene molecules per unit cell, the molar ratio of monomer: toluene being 4:1. The polymer chains take a twofold helical structure of (-TTGG-)2 conformation, and the packing of the polymer chains enables each toluene molecule to occupy an isolated hole between the benzene rings of adjacent polymer chains. The molecular compounds with benzene, chlorobenzene, p-xylene, 1,2,4-trichlorobenzene and so on are isomorphous to the toluene molecular compound. These molecular compounds are commonly transformed on heating between 120 and 150°C to another crystalline phase free from the guests, in which the polymer chains retain the helical structure.

Syndiotactic polystyrene was found to form a molecular compound with iodine as well as with a variety of organic compounds. The iodine molecular compound with uniaxial orientation was obtained by immersing amorphous polystyrene (obtained by quenching the melt into ice-water followed by stretching) into molten iodine at 120–130°C. The crystal structure of the iodine molecular compound is isomorphous to that of the molecular compound with toluene. The crystal data are as follows: monoclinic, space group P 2 1 a , a = 17.29, b = 12.85, c ( chain axis ) = 7.79 A , γ = 120.3° (c-unique), and there are eight monomer units (two chains) in the unit cell. The polymer chains take a (-TTGG-)2 twofold helical structure and it is expected, from the viewpoint of the crystal symmetry and the size of the hole, that two iodine molecules occupy one isolated hole formed between the polymer chains. However, in spite of several attempts to prepare the molecular compound, not all the holes contained iodine. The sample used for X-ray structure analysis was estimated to contain about 70% of the expected iodine content. On annealing in the range 130–150°C, the X-ray reflection intensities changed, indicating escape of iodine to some extent. However, the pure helical form free from the guest molecule was not obtained, in contrast to the case of molecular compounds with organic compounds; on annealing at temperatures higher than 160°C the iodine molecular compound was directly transformed to the planar form I.

The features of the crystallization of syndiotactic polystyrene were investigated by X-ray diffraction, differential thermal analysis, thermogravimetry and density measurements. This polymer exhibits polymorphism: there are principally four distinct crystalline phases. Melt-crystallization yields a planar zigzag form. As-cast samples from solutions with a variety of solvents are molecular compounds with the solvents used, in which the polymer chains assume a twofold helical conformation of type ( TTGG ) 2 . On annealing the molecular compounds at moderate temperatures below ∼130°C, they are transformed in common, by removal of the solvent molecules, to a ( TTGG ) 2 twofold helical form free from solvents. On annealing at higher temperatures, the helical form is transformed to a planar zigzag form, which is distinguished from the melt-crystallized planar zigzag form in terms of the mode of molecular arrangement.

Biphasic pulmonary blastoma is a rare malignant neoplasm of debatable histogenesis. Although well described histologically, it is scarcely mentioned in the cytologic literature.A 78-year-old man reporting intermittent hemoptysis was admitted to the hospital. Chest radiography revealed a right-sided pulmonary mass. Cytologic examination of tumor specimens revealed 2 types of malignant cells. The smears were highly cellular, with a necrotic background. The stromal cells had predominantly round to ovoid or spindle-shaped nuclei and scant cytoplasm, and the nucleoli had slightly irregular borders with coarsely aggregated chromatin. The epithelial cells were arranged in sheets and glandular configurations. The cytoplasm of these cells was finely vacuolated or foamy, with indistinct cellular boundaries; eccentrically located nuclei were hyperchromatic and had irregularly shaped nucleoli. The cell block preparation showed a distinctly biphasic malignant tumor with the classic morphologic features of pulmonary blastoma.A preoperative diagnosis ofpulmonary blastoma is difficult to obtain by cytopathologic methods. A diagnosis of biphasic pulmonary blastoma should be considered whenever epithelial cells and a separate population of stromal cells are seen in a pulmonary exfoliative cytology specimen.

Primary varicella infection in immunocompetent adults is very rare, but it has a high mortality rate because of serious complications. We describe a case of varicella infection in a previously healthy young adult complicated with acute respiratory distress syndrome (ARDS), rhabdomyolysis, acute hepatitis and disseminated intravascular coagulation (DIC). Acyclovir was administered for varicella infection and the ARDS was successfully treated with steroidpulse therapy, hemofiltration and a mechanical respiratory support with a positive end-expiratory pressure. Early administration of antiviral agents and extensive management were thought to be necessary for such patients with severe complications.

Cathepsin D (CD) is an aspartyl lysosomal protease, and the prognostic value of CD expression has been studied in a variety of tumors, however, its role in early adenocarcinomas remains unclear.We evaluated the expression of CD in a series of colorectal adenomas with severe dysplasia containing foci of early carcinoma and compared the results to several histopathological and immunohistochemical features.Adenomas were obtained by endoscopic polypectomy from 33 patients. Twenty-four of the 33 adenomas contained well-differentiated adenocarcinomas and nine adenomas contained moderately differentiated adenocarcinomas.Positive CD expressions were observed in 25% of well-differentiated adenocarcinomas and in 66.7% of moderately differentiated adenocarcinomas (p0.05). Of the 12 adenocarcinomas with positive CD expression, four had positive CD expression in their adenomas (p0.01), 6 showed positive Ki-67 expression in their adenomas (NS), and 10 had positive p53 expression in their adenomas (p0.05). No significant association was seen between the level of CD expression and adenoma size.The expression of CD in adenocarcinoma correlated significantly with differentiation, and with the levels of CD and p53 expression in the adenomas of the polyp.

A 56-year-old woman who had undergone excision of the gallbladder because of a choledochal cyst had a tumorous lesion of the pancreas identified by upper abdominal ultrasonography, but an operation was not carried out, because there was no apparent increase in the cystic mass and no elevation of serum tumor markers. In October 2001, she was admitted to our hospital to check for malignancy because of elevated levels of the tumor marker Dupan-2. Abdominal enhanced computed tomography and upper abdominal ultrasonography revealed a large multilocular cystic mass in the body to tail of the pancreas. Endoscopic retrograde cholangiopancreatography showed elongation of the common duct that communicates with the common bile duct and the main pancreatic duct, indicating an anomalous arrangement of the biliary and pancreatic duct system. No apparent communications between the cystic mass and the main pancreatic duct were observed. In January 2002, the patient underwent a spleen-preserving distal pancreatectomy, and histopathological and immunohistochemical examinations led to the diagnosis of pancreatic mucinous cystadenoma with ovarian-like stroma. The mucinous cystadenoma was detected 17 years after the operation for the choledochal cyst. To the best of our knowledge, no documented case reports of mucinous cystadenoma of the pancreas associated with a choledocal cyst have been reported to date. We present here the first case report of pancreatic mucinous cystadenoma occurring in the body to tail of the pancreas, associated with a choledocal cyst.

The zucker diabetic fatty (ZDF-fa/fa) rat is one of the attractive models for type II diabetes based on impaired glucose tolerance caused by the inherited insulin-resistance gene fa. Characterization of nephropathy in this model may provide useful insights into the mechanism of the progression of diabetic nephropathy. The present study analyzed the pathophysiology of diabetes and nephropathy, including the process of glomerulosclerosis in this model by biochemical and morphometric analyses. In addition, we conducted studies in podocytes in culture to examine the direct effects of high glucose on podocytes. ZDF-fa/fa rats showed overt diabetes despite hyperinsulinemia as early as 3 months of age. Blood glucose levels increased further with a considerable decrease of insulin levels at 5 months. Glomerular filtration rate (GFR) was significantly elevated until 3 months, but fell to the level seen in lean rats by 7 months. Proteinuria started to rise during the period of increased GFR, and increased further after GFR had fallen to within the normal range. Renal fibronectin, collagen iv, and vascular endothelial growth factor mRNA levels were increased at 7 months. Glomerulosclerosis commenced as early as 5 months of age, and was associated with glomerular hypertrophy and mild mesangial expansion with evidence of accentuated podocyte injury, as revealed by increased expression of desmin. Electron microscopy suggested that degeneration of podocytes and the development of tuft adhesions were responsible for the glomerular sclerosis in this model. In addition, glomeruli from the diabetic rats showed up-regulation of the cyclin kinase inhibitors, p21 and p27. Further studies suggested that the increase in p27 expression was predominantly caused by podocytes, because predominant immunolocalization of p27 in podocytes in diabetic rats and high glucose medium induced cell hypertrophy accompanied by p27 up-regulation in differentiated podocyte cell lines. In conclusion, progressive diabetic nephropathy in ZDF-fa/fa rats is associated with evidence of podocyte injury. High concentrations of ambient glucose induced podocyte hypertrophy and stress in vitro, suggesting that the podocyte is a likely target of the diabetic milieu.

Subsequent loss of the proliferated bile ductules in fulminant hepatitis in childhood—isn't it caused by apoptosis?

The reacion of L-alanine (L-ala) with Fe(NO3)2·9H2O in the presence of H5dhpta (1,3-diamino-2-hydroxypropane-N,N,N′,N′-tetraacetic acid) and base (NaOH) affords the novel tetranuclear complex Na[Fe4(dhpta)2(O)(OH)(L-ala)2]·6H2O having L-alaninato bridges and an (Fe4(O2H))9+ core whose crystal structure and magnetic properties were determined.