Stromal cell-derived factor-1 (SDF1)-dependent recruitment of bone marrow-derived renal endothelium-like cells in a mouse model of acute kidney injury.

Ischemic acute kidney injury (AKI) is the most key pathological event for accelerating progression to chronic kidney disease through vascular endothelial injury or dysfunction. Thus, it is critical to elucidate the molecular mechanism of endothelial protection and regeneration. Emerging evidence indicates that bone marrow-derived cells (BMCs) contribute to tissue reconstitution in several types of organs post-injury, but little is known whether and how BMCs contribute to renal endothelial reconstitution, especially in an early-stage of AKI. Using a mouse model of ischemic AKI, we provide evidence that incorporation of BMCs in vascular components (such as endothelial and smooth muscle cells) becomes evident within four days after renal ischemia and reperfusion, associated with an increase in stromal cell-derived factor-1 (SDF1) in endothelium and that in CXCR4/SDF1-receptor in BMCs. Notably, anti-CXCR4 antibody decreased the numbers of infiltrated BMCs and BMC-derived endothelium-like cells, but not of BMC-derived smooth muscle cell-like cells. These results suggest that reconstitution of renal endothelium post-ischemia partially depends on a paracrine loop of SDF1-CXCR4 between resident endothelium and BMCs. Such a chemokine ligand-receptor system may be attributable for selecting a cellular lineage (s), required for renal vascular protection, repair and homeostasis, even in an earlier phase of AKI.

Crocetin, a carotenoid from Gardenia jasminoides Ellis, protects against hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats.

Crocetin is a natural carotenoid dicarboxylic acid that is found in the fruit of Gardenia jasminoides Ellis (Cape Jasmine) and in the stamen and pistil of Crocus sativus L. (saffron). It is used worldwide as an important spice, food colorant, and herbal medicine. In the current investigation, we have examined the cardiovascular effects of crocetin using stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs (6 weeks old) were classified into three groups: a control group and two crocetin groups (25 and 50 mg/kg/day). The animals were given crocetin for 3 weeks. Body weights in each group were not significantly different during the treatment period, but the increase in systolic blood pressures observed with age was significantly moderated by crocetin. Thrombogenesis, assessed using a He-Ne laser technique in pial vessels, was significantly decreased. Antioxidant activity, assessed by measuring urinary 8-hydroxy-2'-deoxyguanosine levels, together with urinary nitric oxide (NO) metabolite levels, was increased significantly after treatment. Acetylcholine-induced vasodilation was measured using the aorta and indicated that endothelial function was significantly improved by crocetin. These results strongly suggest that the antihypertensive and antithrombotic effects of crocetin were related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species.

Decreases in podocin, CD2-associated protein (CD2AP) and tensin2 may be involved in albuminuria during septic acute renal failure.

Podocytes have a peculiar structure constituting slit diaphragm (SD) and foot process (FP), and play essential roles in the glomerular filtration barrier. There is now ample evidence that SD- and FP-associated molecules, such as podocin and CD2-associated protein (CD2AP), are down-regulated during albuminuria of chronic kidney disease. However, it is still unclear whether these molecules are altered during acute renal failure (ARF) with albuminuria. Using lipopolysaccharide (LPS)-treated mice as a model of septic ARF, we provide evidence that the expression of SD- and FP-associated molecules becomes faint, along with albuminuria. In the LPS-treated mice, urinary albumin levels gradually increased, associated with the elevation of blood urea nitrogen levels, indicating the successful induction of albuminuria during septic ARF. In this pathological process, glomerular podocin expression became faint, especially at 36 hr post-LPS challenge (i.e., a peak of albuminuria). Likewise, LPS treatment led to a significant decrease in CD2AP, an anchorage between podocin and F-actin. With regard to this, tensin2 is a novel molecule that stabilizes F-actin extension. Interestingly, glomerular tensin2 expression levels were also decreased during the albuminuric phase, associated with losses of glomerular F-actin and synaptopodin under septic states. As a result, there were some lesions of podocytic FP effacement, as shown by electron microscopy. Based on these data, we emphasize the importance of concomitant decreases in podocin, CD2AP and tensin2 during septic ARF-associated proteinuria.

Decreased preference for sucrose in rats fed a low protein diet and its intensification by zinc-deficiency.

This study examined whether protein concentrations in the diet of rats fed adequate Zn or deficient Zn affect their preference for disaccharides of sucrose and maltose. Sucrose and maltose were used as a source of carbohydrate and the selection patterns of rats were analyzed for 28 d by a two-choice selection method. Diets provided as a set of two either Zn-adequate or Zn-deficient diets containing 10, 20 and 40% protein each were changed in position daily. For the first 24 h, both the control Zn-adequate and Zn-deficient rats preferred sucrose to maltose and then gradually selected the maltose diet. Protein in the diet affected the selection of the disaccharides for both the control and Zn-deficient rats. The decrease order of the ratio of consumed sucrose to maltose over 28 d was 10% > 20% > 40% protein diet group, and Zn-deficiency emphasized the decrease. These results suggest that sucrose has a stronger taste effect than maltose in rats, but that the selection of sucrose is decreased by the post-ingestive effect which is stimulated in low-protein and Zn-deficient diets.

Type 2a sodium-phosphate co-transporter serves as a histological predictor of renal dysfunction and tubular apical damage in the kidneys of septic mice.

Acute renal failure (ARF) occurs in septic patients and is histologically characterized by tubular apical damages, including brush border breakdown. Nevertheless, little information is available to identify the apical injury at a molecular level. Type 2a Na-phosphate (Pi) co-transporter (NaPiT2a) is constitutively expressed by brush borders of proximal tubules under a healthy condition. Therefore, we investigated if NaPiT2a could be used as a negative marker to predict the renal dysfunction, using an animal model of septic ARF. After the treatment of lipopolysaccharide (LPS), mice manifested the tubular apical injury and renal dysfunction, as evidenced by the increase in blood urea nitrogen (BUN) levels. Immunohistochemical examination revealed that the expression of NaPiT2a by renal proximal tubules became faint, being reciprocal to the development of tubular hypoxia during sepsis. Inversely, the loss in apical NaPiT2a was restored in a regenerating stage, associated with the recovery from renal hypoxia. Overall, there was a negative correlation between the NaPiT2a expression and BUN levels or tubular injury scores in septic mice. Our data indicate that the loss of NaPiT2a is a reliable marker for predicting the progression of septic ARF, while local hypoxia might be involved in the decrease of NaPiT2a expression.

Change to a preference for maltose from sucrose over days in Zn-deficient rats selecting from maltose and sucrose diets.

This paper describes a preference for two disaccharides in the diets of Zn-adequate and Zn-deficient rats. Maltose and sucrose were used as a source of carbohydrate in the diet and the selection patterns of rats were analyzed for 28 d by a two-choice selection method. Diets provided as a set of two either Zn-adequate or Zn-deficient diets were changed in position daily. Control Zn-adequate and Zn-deficient rats both exclusively selected the sucrose diet at days 1 and 2, after onset of the feeding experiment, and then gradually selected the maltose-diet. After changing their preference from sucrose to maltose, the Zn-adequate control rats selected widely from both the maltose and sucrose diets, while the Zn-deficient rats exclusively and continuously selected the maltose diet from the two diets over the experimental period. The level of selection of sucrose-diet on day 28 had a correlation with the intestinal sucrase activity in the control rats. The sum of daily maltose and sucrose diet intake in rats fed a Zn-deficient diet showed a characteristic variation with the cyclic period of 3.6+/-0.2 d. The daily body-weight change of rats fed a Zn-deficient diet was well synchronized with their own food intake cycle. The day before changing preference from sucrose to maltose in rats fed a Zn-deficient diet represented a trough in their own food intake and body-weight cycles. These results suggest that one sign of a change in preference from sucrose to maltose in Zn-deficient rats is caused by a stage of negative energy balance.

Modulation of maltose preference by selection from dextrin, maltose and glucose diets in zinc-deficient rats.

This study examined whether the chain length of glucose in the diet could affect the selection of foods by Zn-adequate and Zn-deficient rats. Dextrin, maltose and glucose were used as sources of carbohydrate in the diet and the selection patterns of the rats were analyzed for 28 d by a 3-choice selection. Diets provided as a set of three either Zn-adequate or Zn-deficient diets were rotated daily. The Zn-adequate control rats selected widely from the three diets throughout the 28 d. In contrast, rats fed a Zn-deficient diet selected exclusively and continuously the dextrin diet or dextrin and glucose diets from the three diets over the experimental periods. The average daily total food intakes of rats fed a Zn-deficient diet were very significantly decreased. The selections of dextrin, maltose and glucose diets in the 3-choice methods of the control rats were 5.7+/-1.6(b), 5.8+/-2.0(b) and 2.7+/-0.9(a) g/d, respectively (p<0.05), and those of the Zn-deficient rats were 6.4+/-2.5(c), 0.8+/-1.3(a) and 2.6+/-1.4(b) g/d, respectively (p<0.05). The ratios of the selected maltose-diet in the Zn-adequate control and the Zn-deficient rats were 40.8+/-13.8 and 9.0+/-15.6%, respectively (p<0.01) and those of the dextrin-diet were 40.3+/-11.4 and 63.0+/-22.3%, respectively (p<0.05). The decreased preference for the maltose-diet in the Zn-deficient rats may reflect the increased selection of the dextrin-diet.

Reduced alpha4beta1 integrin/VCAM-1 interactions lead to impaired pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice.

Mice with a targeted gene disruption of Fut8 (Fut8(-/-)) showed an abnormality in the transition from pro-B cell to pre-B cell, reduced peripheral B cells, and a decreased immunoglobulin production. Alpha 1,6-fucosyltransferase (FUT8) is responsible for the alpha 1,6 core fucosylation of N-glycans, which could modify the functions of glycoproteins. The loss of a core fucose in both very late antigen 4 (VLA-4, alpha4beta1 integrin) and vascular cell adhesion molecule 1 (VCAM-1) led to a decreased binding between pre-B cells and stromal cells, which impaired pre-B cells generation in Fut8(-/-) mice. Moreover, the B lineage genes, such as CD79a, CD79b, Ebf1, and Tcfe2a, were downregulated in Fut8(-/-) pre-B cells. Indeed, the frequency of preBCR(+)CD79b(low) cells in bone marrow pre-B cells in Fut8(-/-) was much lower than that in Fut8(+/+) cells. These results reveal a new role of core fucosylated N-glycans in mediating early B cell development and functions.

Carbohydrate binding specificity of a fucose-specific lectin from Aspergillus oryzae: a novel probe for core fucose.

The alpha1,6-fucosyl residue (core fucose) of glycoproteins is widely distributed in mammalian tissues and is altered under pathological conditions. A probe that specifically detects core fucose is important for understanding the role of this oligosaccharide structure. Aleuria aurantia lectin (AAL) and Lens culimaris agglutinin-A (LCA) have been often used as carbohydrate probes for core fucose in glycoproteins. Here we show, by using surface plasmon resonance (SPR) analysis, that Aspergillus oryzae l-fucose-specific lectin (AOL) has strongest preference for the alpha1,6-fucosylated chain among alpha1,2-, alpha1,3-, alpha1,4-, and alpha1,6-fucosylated pyridylaminated (PA)-sugar chains. These results suggest that AOL is a novel probe for detecting core fucose in glycoproteins on the surface of animal cells. A comparison of the carbohydrate-binding specificity of AOL, AAL, and LCA by SPR showed that the irreversible binding of AOL to the alpha1,2-fucosylated PA-sugar chain (H antigen) relative to the alpha1,6-fucosylated chain was weaker than that of AAL, and that the interactions of AOL and AAL with alpha1,6-fucosylated glycopeptide (FGP), which is considered more similar to in vivo glycoproteins than PA-sugar chains, were similar to their interactions with the alpha1,6-fucosylated PA-sugar chain. Furthermore, positive staining of AOL, but not AAL, was completely abolished in the cultured embryo fibroblast (MEF) cells obtained from alpha1,6-fucosyltransferase (Fut8) knock-out mice, as assessed by cytological staining. Taken together, these results suggest that AOL is more suitable for detecting core fucose than AAL or LCA.

Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts.

Fucosylated alpha-fetoprotein (AFP) is a highly specific tumor marker for hepatocellular carcinoma (HCC). However, the molecular mechanism by which serum level of fucosylated AFP increases in patients with HCC remains largely unknown. Here, we report that the fucosylation of glycoproteins could be a possible signal for secretion into bile ducts in the liver. We compared oligosaccharide structures on glycoproteins in human bile with those in serum by several types of lectin blot analyses. Enhanced binding of biliary glycoproteins to lectins that recognize a fucose residue was observed over a wide range of molecular weights compared with serum glycoproteins. A structural analysis of oligosaccharides by two-dimensional mapping high performance liquid chromatography and matrix-assisted laser desorption ionization time-of flight mass spectrometry confirmed the increases in the fucosylation of biliary glycoproteins. Purification followed by structural analysis on alpha1-antitrypsin, alpha1-acid glycoprotein and haptoglobin, which are synthesized in the liver, showed higher fucosylation in bile than in serum. To find direct evidence for fucosylation and sorting signal into bile ducts, we used alpha1-6 fucosyltransferase (Fut8)-deficient mice because fucosylation of glycoproteins produced in mouse liver was mainly an alpha1-6 linkage. Interestingly, the levels of alpha1-antitrypsin and alpha1-acid glycoprotein were quite low in bile of Fut8-deficient mice as compared with wild-type mice. An immunohistochemical study showed dramatic changes in the localization of these glycoproteins in the liver of Fut8-deficient mice. Taken together, these results suggest that fucosylation is a possible signal for the secretion of glycoproteins into bile ducts in the liver. A disruption in this system might involve an increase in fucosylated AFP in the serum of patients with HCC.

Down-regulation of trypsinogen expression is associated with growth retardation in alpha1,6-fucosyltransferase-deficient mice: attenuation of proteinase-activated receptor 2 activity.

Alpha1,6-fucosyltransferase (Fut8) plays important roles in physiological and pathological conditions. Fut8-deficient (Fut8-/-) mice exhibit growth retardation, earlier postnatal death, and emphysema-like phenotype. To investigate the underlying molecular mechanism by which growth retardation occurs, we examined the mRNA expression levels of Fut8-/- embryos (18.5 days postcoitum [dpc]) using a cDNA microarray. The DNA microarray and real-time polymerase chain reaction (PCR) analysis showed that a group of genes, including trypsinogens 4, 7, 8, 11, 16, and 20, were down-regulated in Fut8-/- embryos. Consistently, the expression of trypsinogen proteins was found to be lower in Fut8-/- mice in the duodenum, small intestine, and pancreas. Trypsin, an active form of trypsinogen, regulates cell growth through a G-protein-coupled receptor, the proteinase-activated receptor 2 (PAR-2). In a cell culture system, a Fut8 knockdown mouse pancreatic acinar cell carcinoma, TGP49-Fut8-KDs, showed decreased growth rate, similar to that seen in Fut8-/- mice, and the decreased growth rate was rescued by the application of the PAR-2-activating peptide (SLIGRL-NH2). Moreover, epidermal growth factor (EGF)-induced receptor phosphorylation was attenuated in TGP49-Fut8-KDs, which was highly associated with a reduction of trypsinogens mRNA levels. The addition of exogenous EGF recovered c-fos, c-jun, and trypsinogen mRNA expression in TGP49-Fut8-KDs. Again, the EGF-induced up-regulation of c-fos and c-jun mRNA expression was significantly blocked by the protein kinase C (PKC) inhibitor. Our findings clearly demonstrate a relationship between Fut8 and the regulation of EGF receptor (EGFR)-trypsin-PAR-2 pathway in controlling cell growth and that the EGFR-trypsin-PAR-2 pathway is suppressed in TGP49-Fut8-KDs as well as in Fut8-/- mice.

Demonstration of the expression and the enzymatic activity of N-acetylglucosaminyltransferase IX in the mouse brain.

We recently reported on a brain-specific beta1,6-N-acetylglucosaminyltransferase IX (GnT-IX, also referred to as GnT-VB), a GnT-V homologue, which acts on alpha-linked mannose of N-glycans and O-mannosyl glycans. To distinguish functions of GnT-IX with GnT-V, we examined the distribution of GnT-IX and GnT-V transcripts in mouse tissues by Northern blot analysis. The two enzymes were differentially expressed as has previously been observed in human tissues. GnT-IX transcripts were restricted to the cerebrum, cerebellum, thymus and testis, whereas GnT-V transcripts were expressed ubiquitously in mouse tissues. To investigate the localization of these enzymes in mouse tissues in more detail, a polyclonal antibody against GnT-IX was prepared. The antibody specifically recognized GnT-IX, but not GnT-V, in the Golgi apparatus, as confirmed by the use of GnT-IX and GnT-V transfectants. In agreement with the Northern blot analysis data, an immunohistochemical study showed substantial expression of GnT-IX in the brain, while no expression was observed in the liver. Moreover, to exclude GnT-V contamination, we performed an enzymatic assay for GnT-IX using a Mgat5 (GnT-V)-null mouse brain as an enzyme source and found the enzymatic activities do, in fact, exist in mouse brain. The reaction product was confirmed by high performance liquid chromatography and mass spectrometry. These results demonstrate, for the first time, that GnT-IX protein is actually expressed and may function as a glycosyltransferase in the brain.

Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice.

The core fucosylation (alpha1,6-fucosylation) of glycoproteins is widely distributed in mammalian tissues, and is altered under pathological conditions. To investigate physiological functions of the core fucose, we generated alpha1,6-fucosyltransferase (Fut8)-null mice and found that disruption of Fut8 induces severe growth retardation and death during postnatal development. Histopathological analysis revealed that Fut8(-/-) mice showed emphysema-like changes in the lung, verified by a physiological compliance analysis. Biochemical studies indicated that lungs from Fut8(-/-) mice exhibit a marked overexpression of matrix metalloproteinases (MMPs), such as MMP-12 and MMP-13, highly associated with lung-destructive phenotypes, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, as well as retarded alveolar epithelia cell differentiation. These changes should be consistent with a deficiency in TGF-beta1 signaling, a pleiotropic factor that controls ECM homeostasis by down-regulating MMP expression and inducing ECM protein components. In fact, Fut8(-/-) mice have a marked dysregulation of TGF-beta1 receptor activation and signaling, as assessed by TGF-beta1 binding assays and Smad2 phosphorylation analysis. We also show that these TGF-beta1 receptor defects found in Fut8(-/-) cells can be rescued by reintroducing Fut8 into Fut8(-/-) cells. Furthermore, exogenous TGF-beta1 potentially rescued emphysema-like phenotype and concomitantly reduced MMP expression in Fut8(-/-) lung. We propose that the lack of core fucosylation of TGF-beta1 receptors is crucial for a developmental and progressive/destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema.

Prevalence of Helicobacter pylori infection, endoscopic gastric findings and dyspeptic symptoms among a young Japanese population born in the 1970s.

BACKGROUND: With the prevalence of Helicobacter pylori (H. pylori) infection rapidly decreasing in Japan, endoscopic findings and dyspeptic symptoms need to be re-evaluated. METHODS: In a health check-up program, endoscopy was performed on 530 young Japanese subjects (371 men and 159 women) born in the 1970s. Helicobacter pylori infection was evaluated using serology and a rapid urease test. Endoscopic gastritis was classified according to the Sydney classification system, in addition to nodular gastritis. Dyspeptic symptoms were also recorded before endoscopy. RESULTS: Of the 530 subjects, 87 (16.4%) were H. pylori positive. Of the 443 H. pylori-negative subjects, 349 (78.8%) were considered to have endoscopically normal gastric mucosa. However, of the 87 H. pylori-positive subjects, only 19 (21.8%) tested normal (P < 0.001). The prevalence of several types of gastritis was significantly higher in H. pylori-positive subjects compared with H. pylori-negative subjects: atrophic gastritis (37.9% vs 1.1%, P < 0.001), flat erosive gastritis (29.9% vs 7.2%, P < 0.001), rugal hyperplastic gastritis (12.6% vs 0.0%, P < 0.001), and nodular gastritis (13.8% vs 0.0%, P < 0.001). Other types of gastritis were not related to H. pylori status. The prevalence of subjects with dyspeptic symptoms was significantly higher in H. pylori-positive subjects compared with H. pylori-negative ones (28.7% vs 6.5%, P < 0.001). CONCLUSION: It is suggested that in consideration of its recent low prevalence and the slow increase in its infection, the prevalence of H. pylori-related gastritis will gradually decrease in Japan. Further studies will be required to ascertain if there is a need for H. pylori eradication in this young population.

Acid-suppressive efficacy of a reduced dosage of rabeprazole: comparison of 10 mg twice daily rabeprazole with 20 mg twice daily rabeprazole, 30 mg twice daily lansoprazole, and 20 mg twice daily omeprazole by 24-hr intragastric pH-metry.

Rabeprazole achieves more potent acid suppression than other proton pump inhibitors. Therefore it is administered at reduced as well as high dosages in eradication therapy for Helicobacter pylori; however, there is incomplete assessment of the efficacy of a reduced dosage of rabeprazole as might be employed in therapy. In this study, we evaluated acid-suppressive efficacy of a reduced dosage of rabeprazole on day 7 by 24-hr pH-metry in 10 healthy male cytochrome P-450 2C19 extensive metabolizers without Helicobacterpylori infection and compared the results with those of high dosages of rabeprazole, lansoprazole, and omeprazole. Median intragastric pH value, pH >3 holding time ratio (pH>3HT), pH>4HT, pH>5HT, pH>6HT, and pH>7HT for 24 hr with rabeprazole, 10 mg twice daily, were not significantly different from those of rabeprazole, 20 mg twice daily, lansoprazole, 30 mg twice daily, and omeprazole, 20 mg twice daily. In conclusion, for acid-suppressive efficacy, a reduced dosage of rabeprazole is comparable to high dosages of rabeprazole, lansoprazole, and omeprazole.

Effect of fasting on methionine adenosyltransferase expression and the methionine cycle in the mouse liver.

The effect of fasting on mouse liver methionine adenosyltransferase (MAT I/ III) expression and the regulation of methionine metabolism were investigated. The mRNA level, protein level, and activity of MAT I/III were increased by fasting for 10 or 16 h. In spite of the increase of MAT I/III activity, S-adenosylmethionine, the product of methionine due to MAT I/III, decreased. S-Adenosylhomocysteine, which is made from S-adenosylmethionine by its coupling to methyltransferase, increased as a result of fasting for 16 h. These results suggest that the total methylation reactions using S-adenosylmethionine are stimulated in the fasting mouse liver. However, the DNA methylation level was not changed by fasting for 16 h. Glutathione, which is made by the transsulfuration pathway from homocysteine, decreased due to fasting. Regulation of supplementation of S-adenosylmethionine may occur in the fasting mouse because MAT I/III activity increases and the flow to glutathione is decreased.

Gastric acidity in patients with follicular gastritis is significantly reduced, but can be normalized after eradication for Helicobacter pylori.

BACKGROUND: Follicular gastritis is thought to be caused by Helicobacter pylori infection. However, the pathophysiology of it remains unclear. MATERIALS AND METHODS: We assessed gastric acidity in 15 patients with follicular gastritis, aged 20-37 years, using a 24-hour intragastric pH-metry, as well as by histologic and serologic evaluations; and compared it with that in other age-matched groups: 18 cases of H. pylori-positive antrum-predominant gastritis, 12 of pangastritis, and 24 H. pylori-negative normals. In eight cases with follicular gastritis, it was re-assessed 6 months after the eradication therapy for H. pylori. RESULTS: During nighttime, the percentage of time with intragastric pH above 3.0 in follicular gastritis was significantly higher than that in normals (p<.0001), and in antrum-predominant gastritis (p<.001), but was comparable with that in pangastritis. In the daytime period, this parameter in follicular gastritis was significantly higher than that in normal (p<.001), in antrum-predominant gastritis (p<.001), and in pangastritis (p<.05). Marked mononuclear cell and neutrophil infiltration but no apparent glandular atrophy were observed in both the antrum and corpus. Serum pepsinogen I/II ratio was significantly lower in follicular gastritis than that in normals (p<.0001) and in antrum-predominant gastritis (p<.001), whereas serum gastrin was significantly higher than that in normals (p<.0001), in antrum-predominant gastritis (p<.01) and in pangastritis (p<.05). After eradication for H. pylori, all of the parameters in follicular gastritis were altered to the same ranges as those in normals. CONCLUSIONS: In follicular gastritis, gastric acidity is significantly reduced, but can be normalized by eradication of H. pylori. It can thus be speculated that inflammatory cytokines or H. pylori-infection-induced prostaglandins might strongly inhibit gastric acid secretion in follicular gastritis.

Preference for glucose in Zn-deficient rats selecting from glucose and fructose diets.

Glucose and fructose selection patters of rats were analyzed for 28 d by a 2-choice selection in either Zn-adequate or Zn-deficient status. In this paper, we describe the following serial studies: (1) For the first 24 h, rats fed a Zn-deficient diet preferred a fructose-diet compared with a glucose-diet. On and after the third day, rats fed both Zn-adequate and Zn-deficient diets preferred the glucose-diet. (2) Throughout the experimental period, many of the rats fed a Zn-adequate and Zn-deficient diet continuously selected one diet. (3) Some of the rats fed a Zn-adequate and Zn-deficient diet suddenly changed preference for the glucose-diet or the fructose-diet. (4) The sum of daily glucose- and fructose-diet intake in rats fed a Zn-deficient diet showed a characteristic variation with the cyclic period of 3.9 +/- 0.4 d.

Gastric acid normosecretion is not essential in the pathogenesis of mild erosive gastroesophageal reflux disease in relation to Helicobacter pylori status.

In the pathogenesis of gastroesophageal reflux disease (GERD), gastric acid is considered to be one of the most important factors, but little is known about the degree of gastric acid secretion in GERD patients. In this study, we evaluated it in GERD patients and control subjects by 24-h intragastric pH, and serological and histological investigations, in relation to Helicobacter pylori (H. pylori) status. In H. pylori-negative GERD patients gastric acid secretion was similar to that in H. pylori-negative control subjects. In H. pylori-positive GERD patients, in particular, mild GERD patients, it decreased significantly compared to that in H. pylori-negative control subjects, but the degree of decrease was smaller than in H. pylori-positive control subjects. Results of serological and histological evaluation were supportive. In conclusion, in some GERD patients, gastric acid secretion was significantly decreased. Increased or maintained gastric acid secretion was not essential in the pathogenesis of mild GERD.

Repeated streptozotocin injections cause early onset of glomerulosclerosis in mice.

Diabetic nephropathy (DN), a major cause of end-stage chronic renal failure, is histologically characterized by glomerulosclerosis. To investigate the molecular mechanisms of DN, it is important to establish a stable model of glomerulosclerosis in mice, because genomic manipulation techniques (such as gene destruction or transgene insertion) are well established in rodent species. In this study, we found that repeated administrations of streptozotocin led to early onset of glomerular sclerotic lesions in C57BL/6 mice, accompanied with renal dysfunction. During the natural course of DN, glomerular endothelial cells decreased at 10 weeks after the start of streptozotocin-injections, whereas myofibroblastic mesangial cells became evident. Our results provide an animal tool to elucidate the molecular mechanisms of DN, for example to investigate vascular pathology in diabetic glomerular diseases.