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PubMed1999

Localized wedge-shaped defects of retinal nerve fiber layer and disc hemorrhage in glaucoma.

OBJECTIVE: To evaluate frequencies of localized wedge-shaped defects of the retinal nerve fiber layer (RNFL) in eyes with and without disc hemorrhage in normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG). This study also aims to define a topographic correlation between disc hemorrhage and localized RNFL defects in POAG. DESIGN: Cross-sectional study. PARTICIPANTS AND CONTROLS: The authors studied 83 eyes of 83 patients with NTG (male/female = 23/60; age, 58.8+/-12.9 years) and 20 eyes of 20 patients with POAG (male/female = 9/11; age, 61.6+/-11.4 years); subjects in both groups had developed new disc hemorrhage at the time of enrollment. The authors randomly selected 45 eyes of 45 patients with NTG (male/female = 20/25; age, 62.0+/-9.3 years) and 24 eyes of 24 patients with POAG (male/female = 13/11; age, 56.3+/-14.5 years) with no history of disc hemorrhage during the follow-up period of more than 2 years. METHODS: Visual field in the patients with POAG was matched to that of the patients with NTG regarding global indices for both the hemorrhage and the nonhemorrhage groups. Localized wedge-shaped defects of RNFL were identified by scanning laser ophthalmoscopy using an argon-blue laser. MAIN OUTCOME MEASURES: The frequency of localized RNFL defects and the relationship between the locations of disc hemorrhages and localized RNFL defects were determined. RESULTS: Localized wedge-shaped defects of RNFL occurred significantly more often in the hemorrhage group than in the nonhemorrhage group in both NTG (Fisher's exact probability test, P < 0.0001) and POAG (P < 0.05) patients. Regardless of the presence of disc hemorrhage, there was no significant difference in the frequency of localized RNFL defects between patients with NTG and those with POAG. Most disc hemorrhages were present in the vicinity of the border between localized RNFL defects and relatively healthy-looking RNFL in both patients with POAG and those with NTG. CONCLUSION: Disc hemorrhage is associated with localized damage of RNFL in both NTG and POAG.

Cross-Sectional Studies↗
PubMed1976

Cardiac myosin from pig heart ventricle. Purification and enzymatic properties.

A method is described for the preparation of high purity myosin from the left ventricle of pig heart. The purified myosin was free from nucleic acid, actin, tropomyosin, troponin, the 150,000 molecular weight protein and other contaminants. Analyses of subunits in the purified myosin were carried out on 3.5% acrylamide gel with 0.1% SDS. Of the total protein present in myosin, 11.3% was in the light chains; light chain 1 (LC1), 5.9% and light chain 2 (LC2), 5.4%. Urea gel electrophoresis of the purified myosin showed three closely spaced bands corresponding to the 20,000 dalton, the charge-modified 20,000 dalton and the phosphorylated 20,000 dalton components. The properties of the Ca2+-activated and K+-activated ATPases [EC 3.6.1.3] of the purified myosin were also studied. The Km values were 27 and 55 muM and the Vmax values were 0.263 and 0.317 mumole P1/mg/min for the Ca2+-activated and K+-activated ATPases, respectively. The pH-activity profiles and the effects of SH modification were of the skeletal myosin type except that the activities were lower.

Adenosine Triphosphatases↗
PubMed1998

Dermatologists' attitudes toward independent nonphysician electrolysis practice.

BACKGROUND: Dermatologists' attitudes toward independent electrolysis practice by nonphysicians has historically ranged from the critical to the praiseworthy. It is hypothesized that dermatologists' attitudes toward independent electrolysis practice by nonphysicians is related to physicians' perception of licensing requirements for independent nonphysician electrologists (INE). METHODS: Nine hundred and thirty-seven fellows of the American Academy of Dermatology (AAD) residing in the Southern United States were anonymously surveyed about independent electrolysis practice by nonphysicians. The results of the survey were analyzed using the Pearson chi-square test. RESULTS: Dermatologists who perceived that licensing was required for INE were significantly more likely to refer patients to INE for hair removal (P = 0.001) and prescribe EMLA cream (lidocaine 2.5% and prilocaine 2.5%) to patients requesting it for electrolysis performed by INE (P = 0.001). However, those dermatologists who had electrolysis services available in their practice settings (15.1%) were significantly less likely to refer patients to INE (P = 0.001) and to prescribe EMLA cream to patients seeking electrolysis from INE (P = 0.034). Only 5.7% of responding dermatologists supported the use of hair removal lasers by INE. CONCLUSION: Dermatologists' attitudes toward INE generally appear to be positively related to perceived licensure requirements for INE, but these positive attitudes do not extend to independent laser use by nonphysician electrologists for hair removal.

Allied Health Personnel↗
PubMed2006

[Screening method for the determination of 199 pesticides in agricultural products by gas chromatography/ion trap mass spectrometry (GC/MS/MS)].

A screening method is described for determining 200 pesticides, except dimethipin, divided into four groups by means of gas chromatography/tandem mass spectrometry (GC/MS/MS) using an ion trap mass spectrometer equipped with automated gain control (AGC). The quantitation limit for 194 pesticides was 0.01 mg/kg on a crop basis, except for allidochlor, dimethoate, hexythiazox, methamidophos and triadimenol. The calibration curve of each pesticide was linear in the range of 0.04-5.0 microg/mL. One hundred and ninety-nine pesticides were added to matrix of potato, spinach, cabbage, apple, orange, soybean and unpolished rice at twice the limits of quantitation. The recoveries of 194 pesticides from all crops were satisfactory (50-150%) for screening purposes. Although some pesticides in apple and orange were not determined by selected ion monitoring (SIM) analysis at the limits of quantitation, all of them were identified by ion-trap GC/MS/MS at the same concentration. Thus, the ion trap GC/MS/MS technique is useful for the screening of residual pesticides present at low levels in agricultural products.

Brassica↗
PubMed1999

Swelling and flow properties of tubular poly(vinyl alcohol) gels.

Swelling and flow properties of tubular poly(vinyl alcohol) (PVA) hydrogels prepared with the cooling method were investigated using an inflation testing method. When the tubular hydrogel in liquid paraffin was inflated by using liquid paraffin as a pressure transmitting medium, namely in the case that the liquids inside and outside the gel are both liquid paraffin (P/P combination), the gel showed a slight volume change determined by Poisson's ratio of the gel. When the gel in water was inflated by liquid paraffin (P/W combination), the gel swelled to large extent compared with the case of P/P. The hydrogel in W/W combination, namely in the situation that the gel was immersed in water and also inflated by water, showed a very large volume change if the comparison was done at the same pressure. The origin of the volume change in P/P, P/W and W/W combinations is discussed. The volume change in P/P was governed by the Poisson ratio as a material constant (mu 0) of the PVA gels, and the gels swelled by the change in the application of pressure (or deformation) in P/W. The volume change in W/W was closely related to the flow of solvent in the gel.

Gels↗
PubMed2007

Sequential assessment of the intrahepatic expression of epidermal growth factor and transforming growth factor-beta1 in hepatofibrogenesis of a rat cirrhosis model.

Responses of the liver to chronic injury include inflammation, regeneration and fibrosis, which finally lead to cirrhosis. The cause of liver cirrhosis appears to be impaired proliferative capability of hepatocytes caused by continuous hepatic damage, and subsequent accumulation of extracellular matrix produced by hepatic stellate cells (HSCs). Epidermal growth factor (EGF) and transforming growth factor-beta1 (TGF-beta1) play a crucial role in hepatocyte proliferation and hepatofibrogenesis, respectively. However, sequential analyses of the intrahepatic expression of EGF and TGF-beta1 in the course of cirrhosis development have not been examined fully. In the present study, liver cirrhosis was produced in rats by intraperitoneal administration of dimethylnitrosamine (DMN), and intrahepatic mRNA expression levels of proliferating cell nuclear antigen (PCNA), EGF and TGF-beta1 were quantitatively estimated by a real-time reverse transcription-polymerase chain reaction method. Histological and semiquantitative densitometric examination of liver sections revealed that the accumulation of extracellular matrix components was increased according to the period of DMN treatment. Histological examination of liver sections of rats treated with DMN for 4 and 6 weeks revealed pre-cirrhosis and cirrhosis, respectively. Intrahepatic mRNA expression levels of PCNA and EGF correlated well. Expression levels of both molecules were increased significantly during the course of cirrhosis development, but decreased significantly at the time of complete cirrhosis manifestation. In contrast, intrahepatic TGF-beta1 expression was increased significantly according to the period of DMN treatment, and reached a peak at the time of cirrhosis manifestation. These results suggest that proliferative capability of hepatocytes was impaired by continuous liver damage due, in part, to the decrease of a hepatocyte mitogen EGF, and that increased intrahepatic TGF-beta1 activated HSCs to retrieve space lost by hepatocyte destruction, resulting in complete cirrhosis manifestation.

Animals↗
PubMed1989

[Innervation of the mitral valve in normal and prolapsed mitral valves].

To evaluate the relationship between mitral valve prolapse (MVP) and autonomic nerve dysfunction, clinical and immunohistochemical studies were performed. I. Clinical study Autonomic function tests and supine bicycle exercise were performed in 60 patients with MVP, 41 under 35 years of age and 19 of 35 years and older, and the results were compared with those of 31 normal controls, 19 under 35 years of age and 12 of 35 years and older. Case with positive response on postural stress and cold pressor tests were more frequent in both MVP groups than those of controls. Plasma nor-adrenaline levels were higher in the MVP groups than in the control groups during exercise. Our clinical observation suggested that autonomic dysfunction, particularly sympathetic hyperactivity, probably is present in MVP irrespective of age. II. Immunohistochemical study In 23 mitral valves (15 of normal controls and eight of MVP), three normal tricuspid, three normal aortic and three normal pulmonic valves, immunohistochemical localizations of S-100 protein, glial fibrillary acidic protein (GFAP) and neurofilament protein (NFP) were examined to detect the distribution of all nerve endings, choline acetyltransferase (ChAT) to detect the distribution of cholinergic nerve fibers, and neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) to detect the distribution of afferent nerve fibers, using the avidin-biotin peroxidase complex (ABC) method. The distribution of adrenergic nerve fibers was examined by fluorescence with the glyoxylic acid method. In normal valves, S-100 protein was mainly demonstrated in the base and body of the valve cusp. It was very scanty in the tip, and was only found in the coaptation zone that is, the layer of the atrialis or along the boundary between the atrialis and the spongiosa in the atrioventricular valves. The distribution of S-100 protein in the prolapsed mitral valve was the same as that of the normal valve except for the lack of S-100 protein in the degenerated portion. The distribution of GFAP, NFP, ChAT, NPY, CGRP and adrenergic fluorescence were the same as that of S-100 protein in both the normal and prolapsed mitral valves. It is suggested that the above-mentioned anatomical distribution of the nerve in the mitral valve is closely related to the dysfunction of the autonomic nerve system in the condition of mitral valve prolapse, because the body of the mitral valve is rich in nerve endings and this area is most easily influenced by the mechanical stimulation due to abnormal coaptation.

Adult↗
PubMed2006

Impaired insulin secretion in vivo but enhanced insulin secretion from isolated islets in pancreatic beta cell-specific vascular endothelial growth factor-A knock-out mice.

AIMS/HYPOTHESIS: Endothelial cells are considered to be essential for normal pancreatic beta cell function. However, there have been no reports showing their importance for beta cell function. MATERIALS AND METHODS: Using mice with disrupted vascular endothelial growth factor-A gene specifically in beta cells, we investigated the relation between islet vascular structure and beta cell function. RESULTS: Mice with disrupted vascular endothelial growth factor-A gene specifically in beta cells had reduced islet vascular density with impaired formation of endothelial fenestration. While their fasting glucose and body weight were comparable with control mice, their glucose- and tolbutamide-induced rapid insulin release were impaired, thus resulting in glucose intolerance. On the other hand, glucose and KCl enhanced the levels of insulin secreted from islets isolated from these mice. In addition, the production of soluble N-ethylmaleimide-sensitive factor attachment protein receptors in the islets was increased. Insulin content and expression of insulin I and pancreas duodenum homeobox 1 mRNA in the islets were also increased. CONCLUSIONS/INTERPRETATION: Our results indicate that an abnormal quality and quantity of blood vessels due to reduced expression of vascular endothelial growth factor-A in beta cells could be a cause of impaired insulin secretion without impairment of beta cell function.

Animals↗
PubMed2006

Effect of tourniquet application on deep vein thrombosis after total knee arthroplasty.

INTRODUCTION: There is a great deal of controversy about the effect of tourniquets on development of deep vein thrombosis (DVT) after total knee arthroplasty (TKA). PATIENTS AND METHODS: We investigated the incidence of postoperative DVT after TKA with or without the use of a tourniquet. The patients were 48 consecutive patients undergoing primary ipsilateral cemented TKA for osteoarthritis. Group A (21 patients) underwent the operation without a tourniquet, and Group B (27 patients) underwent the operation with a tourniquet. Ultrasonography to assess DVT was performed before and after the operation. RESULTS: Group B had less intraoperative and total blood loss than Group A. Postoperative DVT was detected in 81.3% of all cases, and symptomatic pulmonary embolism occurred in 1.7%. Most of DVT was found in the calf vein. There was no significant difference in the incidence of postoperative DVT between the two groups. CONCLUSION: We conclude that the use of a tourniquet is beneficial, because it decreases perioperative blood loss and does not increase the risk of DVT. The incidence of DVT after TKA is considerably high with or without use of a tourniquet. Therefore, prevention and early detection of DVT are important for prevention of fatal pulmonary thromboembolism.

Aged↗
PubMed2003

Mast cells and tubulointerstitial fibrosis in patients with ANCA-associated glomerulonephritis.

BACKGROUND: To elucidate the role of mast cells (MCs) in the pathogenesis of crescentic glomerulonephritis, we investigated the immunohistochemical localization of MCs in the kidney and the correlation between MC localization and tubulointerstitial lesions in biopsy specimens and serum stem cell factor (SCF) levels in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis. METHODS: Thirteen patients with ANCA-associated glomerulonephritis were enrolled in this study. Clinical parameters, such as serum creatinine and urinary protein excretion, were obtained from each patient at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining, using the labelled streptavidin bio-tin (LSAB) method. Monoclonal antibodies to human tryptase, alpha-smooth-muscle actin, and CD68 were used as primary antibodies. Ten cortical interstitial fields were randomly selected at an original magnification of x400 and assessed using a computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed as the percentage of the area stained with Masson trichrome in ten cortical interstitial fields. The measurement of serum SCF levels was performed by using an enzyme-linked immunoassay. RESULTS: In all of the control subjects, a few tryptase-positive MCs were observed in the glomeruli and interstitium. In contrast, sparse MCs were observed in the interstitium, but not in the glomeruli of diseased kidneys. The number of interstitial MCs in the tubulointerstitial lesions was positively correlated with the degree of interstitial fibrosis. Moreover, a significant positive correlation was observed between the number of interstitial MCs and the serum SCF concentration (r = 0.85; P = 0.001). CONCLUSIONS: Our findings suggest that MC infiltration induced by SCF in interstitial tissues seems to be associated with tubulointerstitial fibrosis in human ANCA-associated glomerulonephritis.

Anti-Glomerular Basement Membrane Disease↗
PubMed2005

Aging is associated with decreased pancreatic acinar cell regeneration and phosphatidylinositol 3-kinase/Akt activation.

BACKGROUND & AIMS: The effects of aging on pancreatic acinar cell proliferation have not been clearly defined. Phosphatidylinositol 3-kinase (PI3K)-mediated phosphorylation of Akt is a critical step for proliferation of various cell types and insulin secretion from pancreatic endocrine cells; however, its role in acinar cell proliferation is not known. The purpose of this study was to (1) delineate the effects of aging on pancreatic regeneration after partial pancreatectomy (Px) and (2) define the involvement of the PI3K/Akt pathway in pancreatic regeneration. METHODS: Following partial Px, pancreatic regeneration and activation of the PI3K pathway were compared in young and aged mice. Activation of the PI3K/Akt pathway was evaluated by Akt phosphorylation (pAkt). The role of the PI3K pathway in pancreatic regeneration after partial Px was assessed by effects of a pharmacologic PI3K inhibitor wortmannin or small interfering RNA (siRNA) to the p85alpha regulatory subunit. To confirm further the critical role of the PI3K/Akt pathway in pancreatic acinar cell proliferation, IGF-1-mediated cell proliferation was determined in cultured acinar cells pretreated with wortmannin or p85alpha siRNA. RESULTS: Pancreatic regeneration and pAkt expression after partial Px were significantly decreased with aging. Treatment with wortmannin or p85alpha siRNA reduced pancreatic regeneration after partial Px. The IGF-1-mediated cell proliferation in vitro was completely blocked by wortmannin or p85alpha siRNA but not by the MEK/ERK inhibitor PD98059. CONCLUSIONS: PI3K/Akt activation plays a critical role in the regeneration of pancreatic acini after resection. Furthermore, pancreatic regeneration is markedly attenuated in the aged pancreas most likely because of decreased PI3K/Akt activation.

Aging↗
PubMed2001

High concentrations of glucose induce synthesis of argpyrimidine in retinal endothelial cells.

PURPOSE: To determine if high concentrations of glucose applied to cultured bovine retinal endothelial cells (BRE cells) would result in production of intracellular methylglyoxal (MG), and consequently, the synthesis of MG-derived advanced glycation end products (AGEs). METHODS: BRE cells were incubated with 30 mM D-glucose or 30 mM L-glucose for 7 days. Cells incubated with medium that had 5-mM glucose served as controls. Cells were lysed and the lysate was centrifuged to get a supernatant and a pellet fraction. We measured argpyrimidine, a MG-derived fluorescent AGE in the two fractions by a competitive ELISA using a monoclonal antibody. RESULTS: BRE cells incubated with 30 mM D-glucose produced significantly higher (P < 0.05) levels of intracellular MG than control cells or cells incubated with 30 mM L-glucose. Incubation with 30 mM D-glucose significantly (P < 0.05) enhanced the synthesis of argpyrimidine in both supernatant and pellet fractions when compared to control cells. Immunofluorescence studies confirmed results obtained by ELISA and showed higher levels of argpyrimidine in cells incubated with 30 mM D-glucose. CONCLUSION: These results suggest that MG-mediated protein modification can occur in elevated glucose, and might contribute to endothelial cell changes associated with diabetic retinopathy.

Animals↗
PubMed2006

Clinicopathologic study on pancreatic groove carcinoma.

OBJECTIVES: Pancreatic groove carcinoma usually presents with duodenal stenosis. This report describes the clinicopathologic features of 5 cases. METHODS: All the clinical and radiological features were reviewed retrospectively and analyzed to identify correlations with the histological findings. RESULTS: Vomiting was an initial symptom in all cases, but obstructive jaundice was not inevitable until the disease progresses. Hypotonic duodenography demonstrated severe postbulbar stenosis. Pathological findings of biopsy specimens showed no evidence of malignancy at the early stage. Computed tomography revealed a hypovascular mass. Magnetic resonance imaging indicated a hypointense mass on T1-weighted images and an isointense to slightly hyperintense mass on T2 images. Macroscopically, the stenosis seemed to be the result of a hard yellowish-white tumor invading the duodenal wall. Histopathologically, an adenocarcinoma arising from the groove infiltrated the submucosal layer of the duodenum circumferentially. No cancer cells were found in the mucosa at the early stage. The intrapancreatic common bile duct was involved at the advanced stage. CONCLUSIONS: We believe that these features resulted from the anatomical characteristics of the groove involvement and that the string stricture of the duodenum resulted from invasion of the groove tumor into the submucosal layer around the wall.

Aged↗
PubMed2004

Tenascin-C concentration in synovial fluid correlates with radiographic progression of knee osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a major cause of disability and represents the most common disease in the aging population. Although the course of the disease is generally assessed using standard radiographic images, biochemical markers may be employed to detect the disease and determine the degree of severity. We developed an enzyme linked immunosorbent assay (ELISA) system using a monoclonal antibody specific for the large-splice variants of tenascin-C (TN-C) and examined whether TN-C in synovial fluid (SF) is an adequate biochemical marker of OA progression. METHODS: SF samples were obtained from knees of 74 patients with OA and 16 without OA. Based on the radiographic grading of the OA severity, the knees were divided into 3 groups: mild, moderate, and severe OA. Expression of TN-C splice variants was examined using immunoblotting. TN-C concentrations were determined by ELISA. RESULTS: Western blotting showed the presence of large TN-C variants in SF from severe OA. TN-C levels were 5-fold higher in OA samples compared to subjects without OA (p < 0.0001). TN-C levels were not different between control cases and mild OA, but increased significantly in moderate (p = 0.0244) and severe OA (p < 0.0001). After adjusting TN-C levels for age, body mass index, and sex, TN-C levels correlated with radiographic progression of knee OA (R2 = 0.404, p < 0.0001). CONCLUSION: TN-C, including the large-variant subunits, is a useful biochemical marker for OA progression in the later stages of disease.

Adolescent↗
PubMed1993

[In vitro susceptibility to fluconazole of fungal strains freshly isolated from child patients with deep-seated mycoses].

The susceptibility to fluconazole (FLCZ) were evaluated for 40 strains of 8 yeast species and 4 strains of 3 Aspergillus species, all of which were isolated from clinical specimens during clinical trials of FLCZ in child patients performed from January 1991 to January 1993 in this country. The in vitro activity of FLCZ against yeast isolates and Aspergillus isolates were measured using the microdilution method with semisolid SAAMF (synthetic amino acid medium fungal) agar and the macrodilution method with Eagle MEM (minimum essential medium), respectively, using amphotericin B (AMPH) and flucytosine as the reference drugs. Out of all yeast species tested, Candida albicans and Candida tropicalis were the most susceptible to FLCZ with geometric mean (GM)-MICs of < 0.4 microgram/ml that were far less than the corresponding values for AMPH or flucytosine. On the other hand, FLCZ showed the lowest activity against Candida krusei and Candida glabrata with GM-MICs of approximately 10 micrograms/ml that were slightly higher than those for AMPH. The susceptibilities to FLCZ of Candida parapsilosis, Candida pelliculosa (anamorph of Hansenula anomala), Candida famata, and Trichosporon cutaneum were intermediate. Antifungal activities of FLCZ and the 2 reference drugs against aspergilli were determined on the basis of the amount of total protein recovered from drug-treated cultures relative to that from drug-free control cultures. Fifty percent and 90% inhibitory concentrations of FLCZ against 2 isolates of Aspergillus fumigatus were 6.25-25 micrograms/ml and 50 micrograms/ml, respectively. Against this and 2 other species of Aspergillus, AMPH appeared more highly active than FLCZ.

Amphotericin B↗
PubMed2006

Physiological roles of AQP7 in the kidney: Lessons from AQP7 knockout mice.

The aquaporin7 (AQP7) water channel is known to be a member of the aquaglyceroporins, which allow the rapid transport of glycerol and water. AQP7 is abundantly present at the apical membrane of the proximal straight tubules in the kidney. In this paper, we review the physiological functions of AQP7 in the kidney. To investigate this, we generated AQP7 knockout mice. The water permeability of the proximal straight tubule brush border membrane measured by the stopped flow method was reduced in AQP7 knockout mice compared to wild-type mice (AQP7, 18.0+/-0.4 x 10(-3 )cm/s vs. wild-type, 20.0+/-0.3 x 10(-3) cm/s). Although AQP7 solo knockout mice did not show a urinary concentrating defect, AQP1/AQP7 double knockout mice showed reduced urinary concentrating ability compared to AQP1 solo knockout mice, indicating that the contribution of AQP7 to water reabsorption in the proximal straight tubules is physiologically substantial. On the other hand, AQP7 knockout mice showed marked glycerol in their urine (AQP7, 1.7+/-0.34 mg/ml vs. wild-type, 0.005+/-0.002 mg/ml). This finding identified a novel pathway of glycerol reabsorption that occurs in the proximal straight tubules. In two mouse models of proximal straight tubule injury, the cisplatin-induced acute renal failure (ARF) model and the ischemic-reperfusion ARF model, an increase of urine glycerol was observed (pre-treatment, 0.007+/-0.005 mg/ml; cisplatin, 0.063+/-0.043 mg/ml; ischemia, 0.076+/-0.02 mg/ml), suggesting that urine glycerol could be used as a new biomarker for detecting proximal straight tubule injury.

Acute Kidney Injury↗
PubMed2001

A critical role for IL-7R signaling in the development of Helicobacter felis-induced gastritis in mice.

BACKGROUND & AIMS: Interleukin (IL)-7 is a critical cytokine in the development of T and B cells and is involved in gastrointestinal pathophysiology. The aim of this study was to investigate the involvement of IL-7 receptor (IL-7R) signaling in Helicobacter-induced gastritis. METHODS: C57BL/6 mice (n = 40) were inoculated with H. felis. Twenty mice were injected intraperitoneally with neutralizing IL-7R antibody (A7R34) every seventh day for 3 months. Histology, serum anti-H. felis antibody, and gene expression of IL-7, IL-7R, and proinflammatory cytokines in the gastric mucosa were evaluated. RESULTS: Seventeen of 20 (85%) infected mice without A7R34 developed severe atrophic gastritis, whereas there was no gastritis in A7R34-treated infected mice. There was no difference in the serum levels of anti-H. felis antibody between the 2 groups. IL-7, IL-7R, IL-1alpha, tumor necrosis factor alpha, and interferon gamma messenger RNA expressions were up-regulated in control infected mice, whereas only IL-7 messenger RNA was up-regulated in A7R34-treated infected mice. Immunohistochemistry indicated positive cytoplasmic staining of IL-7 in the gastric epithelial cells. CONCLUSIONS: These data suggest a critical role for IL-7 receptor signaling in the development of Helicobacter-induced gastritis in mice.

Animals↗
PubMed2003

Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma.

PURPOSE: Akt has been implicated in the pathogenesis and progression of numerous human malignant tumors because Akt regulates many key effector molecules involved in controlling the balance of survival and apoptosis. Elevated Akt activation has been demonstrated in various types of malignant tumors. In the current study we evaluated Akt activation in renal cell carcinoma and investigated its association with pathological features and clinical outcome. MATERIALS AND METHODS: Akt activation was evaluated by immunohistochemistry using antiphospho-specific Akt antibody, which recognizes only activated Akt, in 48 patients with renal cell carcinoma. High immunostaining tumors were defined as tumors with increased staining intensity compared with adjacent nonneoplastic kidney tissue and low immunostaining tumors were defined as tumors with equivalent or decreased staining intensity. The association of Akt activation status with clinicopathological features was analyzed. RESULTS: Of 48 patients examined 18 (37.5%) demonstrated high antiphospho-specific Akt immunostaining compared with adjacent nonneoplastic kidney tissue, while 30 (62.5%) demonstrated low immunostaining. Elevated immunostaining was significantly associated with tumor grade (p = 0.0354) and metastatic disease (p = 0.0044), while it was not associated with tumor stage or histological subtype. In addition, high antiphospho-specific Akt immunostaining was significantly associated with a poor cancer specific survival rate on univariate analysis (p = 0.0109) but not on multivariate analysis. CONCLUSIONS: Elevated Akt activation could be a common finding, especially in high grade tumor and metastatic disease. It could have an important role in the pathogenesis and progression of renal cell carcinoma.

Adult↗