Association of Daily Physical Activity with Disability in Community-Dwelling Older Adults With/Without Chronic Kidney Disease.

OBJECTIVES: Physical activity is recommended for disability prevention in the older adult population; however, the level of physical activity required for older adults with chronic kidney disease (CKD) remains unknown. This study aimed to examine the associations between daily physical activity and disability incidence in older adults with and without CKD to determine relevant daily physical activity levels. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: 3,786 community-dwelling older adults aged ≥65 years. MEASUREMENTS: Mean daily times spent in light- (LPA) and moderate-to-vigorous physical activity (MVPA) were measured using triaxial accelerometers. CKD was defined by a creatinine estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Disability incidence was identified as long-term care insurance certification during a 60-month follow-up period. Associations between physical activity and disability incidence were examined using Cox proportional hazard models stratified by the CKD status. Non-linear and linear associations were tested using the restricted cubic spline. RESULTS: A total of 1,054 individuals were identified to have CKD. Disability incidence was higher in the CKD group than in the non-CKD group. The adjusted cox proportional hazard models indicated that a 10-minute increase in MVPA time was associated with lower disability incidence in the non-CKD group (hazard ratio [HR], 0.838; 95% confidence interval [CI]: 0.764-0.918) and the CKD group (HR, 0.859; 95% CI: 0.766-0.960). Linear associations were observed in MVPA for the non-CKD and CKD groups. CONCLUSION: Increasing MVPA was associated with lower disability incidence in older adults with and without CKD. These findings can help devise disability prevention strategies for older CKD patients.

Amide proton transfer and chemical exchange saturation transfer MRI differentiates between growing and non-growing intracranial meningiomas: a pilot study.

AIM: To differentiate between growing and non-growing intracranial meningiomas using magnetisation transfer ratio (MTR) values with amide proton transfer (APT) and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventeen patients with suspected intracranial meningiomas who underwent APT-CEST MRI from November 2020 to April 2021 were evaluated retrospectively. MTR values on APT-CEST imaging as well as conventional MRI features were evaluated. These parameters were compared in growing meningiomas versus non-growing meningiomas and the findings compared with previous MRI examinations. ROC curve analysis was also performed to determine the diagnostic cut-offs for MTR. RESULTS: The cohort comprised 10 patients with growing meningiomas (two men [20%], eight women [80%]; mean age [standard deviation (SD)]: 59.9 years [16]) and seven patients with non-growing meningiomas (seven women [100%]; mean age [SD]: 63.9 years [18.6]). Significant differences were found in MTR values (0.0198 ± 0.0003 versus 0.0131 ± 0.0002; p<0.0001) between the growing meningiomas and non-growing meningiomas groups, respectively. The receiver operating characteristic (ROC) curve analysis showed that MTR values clearly differentiated between growing and non-growing meningiomas. At an area under the ROC curve (AUC) threshold of 0.0151, diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTR were 100%, 85.7%, 90.9%, and 100%, respectively. CONCLUSION: Patients with growing meningiomas could be discriminated from patients with non-growing meningiomas, using the MTR values on post-growth tumour APT-CEST imaging.

RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma.

This corrects the article DOI: 10.1038/onc.2016.35.

Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells.

Bone morphogenetic protein (BMP) signaling exerts antitumor activities in glioblastoma; however, its precise mechanisms remain to be elucidated. Here, we demonstrated that the BMP type I receptor ALK-2 (encoded by the ACVR1 gene) has crucial roles in apoptosis induction of patient-derived glioma-initiating cells (GICs), TGS-01 and TGS-04. We also characterized a BMP target gene, Distal-less homeobox 2 (DLX2), and found that DLX2 promoted apoptosis and neural differentiation of GICs. The tumor-suppressive effects of ALK-2 and DLX2 were further confirmed in a mouse orthotopic transplantation model. Interestingly, valproic acid (VPA), an anti-epileptic compound, induced BMP2, BMP4, ACVR1 and DLX2 mRNA expression with a concomitant increase in phosphorylation of Smad1/5. Consistently, we showed that treatment with VPA induced apoptosis of GICs, whereas silencing of ALK-2 or DLX2 expression partially suppressed it. Our study thus reveals BMP-mediated inhibitory mechanisms for glioblastoma, which explains, at least in part, the therapeutic effects of VPA.

RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma.

RNA-binding proteins provide a new layer of posttranscriptional regulation of RNA during cancer progression. We identified RNA-binding motif protein 47 (RBM47) as a target gene of transforming growth factor (TGF)-ß in mammary gland epithelial cells (NMuMG cells) that have undergone the epithelial-to-mesenchymal transition. TGF-ß repressed RBM47 expression in NMuMG cells and lung cancer cell lines. Expression of RBM47 correlated with good prognosis in patients with lung, breast and gastric cancer. RBM47 suppressed the expression of cell metabolism-related genes, which were the direct targets of nuclear factor erythroid 2-related factor 2 (Nrf2; also known as NFE2L2). RBM47 bound to KEAP1 and Cullin 3 mRNAs, and knockdown of RBM47 inhibited their protein expression, which led to enhanced binding of Nrf2 to target genomic regions. Knockdown of RBM47 also enhanced the expression of some Nrf2 activators, p21/CDKN1A and MafK induced by TGF-ß. Both mitochondrial respiration rates and the side population cells in lung cancer cells increased in the absence of RBM47. Our findings, together with the enhanced tumor formation and metastasis of xenografted mice by knockdown of the RBM47 expression, suggested tumor-suppressive roles for RBM47 through the inhibition of Nrf2 activity.

Occult fetomaternal hemorrhage in women with pathological placenta with respect to permeability.

AIM: Women with pre-eclampsia (PE), placenta previa (PP), placental abruption (PA), and placental mesenchymal dysplasia (PMD) have been described as having placental permeability dysfunction. This study was performed to determine whether occult fetomaternal hemorrhage (FMH) is common in women with such complications and in women with non-reassuring fetal status. METHODS: Forty-one antenatal and 39 postnatal blood samples were obtained from 46 women, including 11 with placental permeability dysfunction (5, 3, 2, and 1 with PE, PP, PA, and PMD, respectively) and 35 controls without such complications. To estimate the amount of fetal red blood cells, flow cytometry was performed using the fetal cell count system with two antibodies against fetal hemoglobin and carbonic anhydrase and the ß-γ system with two monoclonal antibodies against hemoglobin ß-chain and hemoglobin γ-chain. A diagnosis of FMH was made when the fraction size of the isolated cell population on scatter plots expressing fetal hemoglobin alone or hemoglobin γ-chain alone accounted for ≥0.02% of the total cell population on scatter plots. RESULTS: FMH was identified in five women, including one each with PE, PA, PP, PMD, and no complications. Thus, the prevalence rate of FMH was significantly higher in women with complications than in controls (36% [4/11] vs 2.9% [1/35], respectively, P =  0.009). The FMH occurrence rate did not differ between women with and without non-reassuring fetal status (7.7% [1/13] vs 12% [4/33], respectively, P =  1.000). CONCLUSION: The risk of fetal red blood cells trafficking into the maternal circulation may be increased in women complicated with PE, PA, PP, and PMD.

Draft Genome Sequence of the Biofilm-Producing Bacillus subtilis Strain B-1, Isolated from an Oil Field.

We report here the draft genome sequence of the Bacillus subtilis strain B-1, a strain known to form biofilms. The biofilm matrix mainly consists of the biopolymer γ-polyglutamate (γ-PGA). The sequence of the genome of this strain allows the study of specific genes involved in biofilm formation.

Setting up equine embryo gender determination by preimplantation genetic diagnosis in a commercial embryo transfer program.

Preimplantation genetic diagnosis (PGD) allows identifying genetic traits in early embryos. Because in some equine breeds, like Polo Argentino, females are preferred to males for competition, PGD can be used to determine the gender of the embryo before transfer and thus allow the production of only female pregnancies. This procedure could have a great impact on commercial embryo production programs. The present study was conducted to adapt gender selection by PGD to a large-scale equine embryo transfer program. To achieve this, we studied (i) the effect on pregnancy rates of holding biopsied embryos for 7 to 10 hours in holding medium at 32 °C before transfer, (ii) the effect on pregnancy rates of using embryos of different sizes for biopsy, and (iii) the efficiency of amplification by heating biopsies before polymerase chain reaction. Equine embryos were classified by size (≤300, 300-1000, and >1000 µm), biopsied, and transferred 1 to 2 or 7 to 10 hours after flushing. Some of the biopsy samples obtained were incubated for 10 minutes at 95 °C and the rest remained untreated. Pregnancy rates were recorded at 25 days of gestation; fetal gender was determined using ultrasonography and compared with PGD results. Holding biopsied embryos for 7 to 10 hours before transfer produced pregnancy rates similar to those for biopsied embryos transferred within 2 hours (63% and 57%, respectively). These results did not differ from pregnancy rates of nonbiopsied embryos undergoing the same holding times (50% for 7-10 hours and 63% for 1-2 hours). Pregnancy rates for biopsied and nonbiopsied embryos did not differ between size groups or between biopsied and nonbiopsied embryos within the same size group (P > 0.05). Incubating biopsy samples for 10 minutes at 95 °C before polymerase chain reaction significantly increased the diagnosis rate (78.5% vs. 45.5% for treated and nontreated biopsy samples respectively). Gender determination using incubated biopsy samples matched the results obtained using ultrasonography in all pregnancies assessed (11/11, 100%); untreated biopsy samples were correctly diagnosed in 36 of 41 assessed pregnancies (87.8%), although the difference between treated and untreated biopsy samples was not significant. Our results demonstrated that biopsied embryos can remain in holding medium before being transferred, until gender diagnosis by PGD is complete (7-10 hours), without affecting pregnancy rates. This simplifies the management of an embryo transfer program willing to incorporate PGD for gender selection, by transferring only embryos of the desired sex. Embryo biopsy can be performed in a clinical setting on embryos of different sizes, without affecting their viability. Additionally, we showed that pretreating biopsy samples with a short incubation at 95 °C improved the overall efficiency of embryo sex determination.

Genome-wide mechanisms of Smad binding.

A dual role of transforming growth factor ß (TGF-ß), to both suppress and promote tumor progression and metastasis, has been well established, but its molecular basis has remained elusive. In this review, we focus on Smad proteins, which are central mediators of the signal transduction of TGF-ß family members. We describe current knowledge of cell-type-specific binding patterns of Smad proteins and mechanisms of transcriptional regulation, obtained from recent studies on genome-wide binding sites of Smad molecules. We also discuss potential application of the genome-wide analyses for cancer research, which will allow clarification of the complex mechanisms occurring during cancer progression, and the identification of potential biomarkers for future cancer diagnosis, prognosis and therapy.

Effect of nutrient intake on intramuscular glucose metabolism during the early growth stage in cross-bred steers (Japanese Black male × Holstein female).

The objective was to investigate the impact of nutrient intake during the early growth period on the expression of glucose metabolism-related genes in skeletal muscle of cross-bred cattle. From 1.5 to 5 months of age, group H (n=7) animals were intensively fed a high-protein and low-fat milk replacer [crude protein (CP) 28%; ether extracts (EE) 18%; max: 2.0 kg, 12 l/day], and group R (n=7) animals were fed a restricted amount of normal milk replacer (CP 25%; EE 23%; max 0.5 kg, 4 l/day). From 6 to 10 months of age, group H cattle were fed a high-nutrition total mixed ration mainly prepared from grain feed, and group R cattle were fed only roughage. Blood samples were taken from each animal at three biopsy times (1.5, 5 and 10 months of age), and the blood plasma concentration of glucose and insulin was analysed. In glucose concentration, there were no significant differences; however, the concentrations of insulin were higher in group H than in group R at 5 and 10 months of age. Muscle samples were taken by biopsy from longissimus thoracis muscle (LT) at 1.5, 5 and 10 months of age. We analysed mRNA expression levels using the quantitative real-time polymerase chain reaction (PCR) assay for glucose transporters (GLUT1 and GLUT4), insulin receptor, phosphatidylinositol 3-kinase (PI-3K), protein kinase B (PKB, also known as Akt), hexokinase 1 (HK1) and tumour necrosis factor alpha (TNFα). Although no differences were detected at 1.5 and 5 months of age, at 10 months of age, GLUT1, HK1 and TNFα mRNA expression levels were significantly higher in group H than in group R. These results suggested Glut1 that affects insulin-independently mediated glucose uptake was more responsive to improved nutrition during early growth stage than GLUT4 that insulin-dependently mediated glucose uptake in LT of cattle.

Successful endovascular occlusion of an aneurysm of the cervical vertebral artery associated with neurofibromatosis-1.

A 30 year old female with a fusiform aneurysm of the cervical vertebral artery causing nerve root compression and associated with neurofibromatosis-1 was successfully treated with endovascular methods which resolved the mass effect. This is the first report demonstrating the reduction of the mass effect of an aneurysm on a cervical nerve root with endovascular treatment by using MR neurography.

Propofol sedation during endoscopic procedures: safe and effective administration by registered nurses supervised by endoscopists.

BACKGROUND AND STUDY AIMS: Propofol has several attractive properties, including a rapid onset of action and rapid recovery. However, the administration of propofol sedation in the absence of anesthesiologists remains controversial. This report describes the safety profile of propofol sedation for endoscopy when administered by registered nurses under the supervision of endoscopists. PATIENTS AND METHODS: The study was conducted in the endoscopic center of a Japanese private hospital. With assistance from an anesthesiologist, a protocol for administration of propofol by registered nurses was developed. Over the past 6 years, 27,500 patients received nurse-administered propofol sedation. The safety and patient satisfaction with this sedation procedure were evaluated. RESULTS: Among the participating patients, 6.7% developed hypoxemia (Sp(O2) < 90%); 6.2% required oxygen administration via a nasal cannula. Severe hypoxemia (Sp(O2) < 85%) occurred in 121 patients (0.62%) during upper gastrointestinal endoscopy and 20 patients (0.25%) during colonoscopy, but neither mask ventilation nor endotracheal intubation was necessary. A decline in blood pressure (systolic blood pressure < 90 mm Hg) was seen in 3.5% of the colonoscopy patients and 1.2% of the upper endoscopy patients. However, hypotension was corrected immediately using an intravenous saline solution. Patients who received propofol sedation expressed overall satisfaction on a 10-point visual analogue scale (with an average of 9.4 points). Among patients who had previously received a combination of midazolam and pethidine for colonoscopy, 85% preferred propofol sedation. The mean time from the end of the procedure to full recovery was 14.6 min. CONCLUSIONS: Administration of propofol by registered nurses under the supervision of endoscopists was safe, and resulted in high rates of patient satisfaction.

2D Thick-section MR digital subtraction angiography for the assessment of dural arteriovenous fistulas.

BACKGROUND AND PURPOSE: Although dynamic contrast-enhanced MR angiography studies for arteriovenous malformations (AVFs) and brain tumors have shown promising results, no formal attempt has yet been made to similarly evaluate dural AVFs. To assess the practical applicability of 2D thick-section contrast enhanced MR digital subtraction angiography (MRDSA) for the diagnosis and management of dural AVFs, MRDSA and intra-arterial digital subtraction angiography (IADSA) were comparatively evaluated. METHODS: We performed 80 consecutive MRDSA studies for 25 dural AVFs, including 11 cavenous sinuses, 9 sigmoid sinuses, 2 tentorial sinuses, one anterior condylar vein, one craniocervical junction, and one spine. MR images were continuously obtained following the initiation of a bolus injection of gadrinium chelates and subtraction images were constructed. We thereafter evaluated the imaging quality and hemodynamic information from all 46 MRDSA images performed in parallel with IADSA in either perioperative or follow-up studies. RESULTS: Most MRDSA images detected early venous filling, sinus occlusion, leptomeningeal venous drainage, and varices. It was difficult, however, to identify the feeding arteries because of both the partial volume effect and a low spatial resolution. Most important, MRDSA accurately detected aggressive lesions with leptomeningeal venous drainage and varices. CONCLUSION: Our MRDSA technique was found to have limited value for depicting all the anatomic details of dural AVFs, though it was able to identify important hemodynamic abnormalities related to the risk of hemorrhaging. MRDSA is therefore useful as a less invasive, dynamic angiographic tool, not only for perioperative studies but also for follow-up studies.

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss.

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.

Activation of WNT family expression and signaling in squamous cell carcinomas of the oral cavity.

The WNT family activates an oncogenic signaling mediated through beta-catenin and is up-regulated in a variety of malignant neoplasms. The signaling translocates beta-catenin into the nucleus and stimulates carcinoma cells in the epithelial-mesenchymal transition (EMT). However, WNT expression and signaling in oral carcinomas have not been examined. The present study focused on unveiling the involvement of WNTs in oral carcinomas, and showed that carcinoma cells express 11 of 19 WNT family members by reverse-transcription/PCR. WNT-expressing carcinoma cells exhibited increased beta-catenin levels in the cytoplasmic pool and translocation to the nucleus. The activation state of signaling correlated with the expression of membrane-type 1 matrix metalloproteinase, which degrades territorial matrices in carcinoma invasion. Immunohistochemistry disclosed that WNT3 expression and nuclear localization of beta-catenin were predominant in carcinoma cells at the invasive front. These results suggest that enhanced WNT expression and signaling accelerate the progression of carcinomas via activating EMTs and local invasiveness.

[Reoperation for double-outlet right ventricle (SDL type) following the Rastelli procedure: report of a case].

The relationship of the conduit to the sternum is crucial in the Rastelli operation. Right-sided conduits are more greatly affected by sternal compression than left, since the position of the right ventricular infundibulum is more anterior. A 37-year-old woman developed right ventricular outflow tract obstruction, left ventricular outflow tract obstruction, and aortic valve regurgitation secondary to infective endocarditis 15 years after Rastelli repair for double-outlet right ventricle (SDL). We enlarged the ventricular septal defect, performed intraventricular rerouting and aortic valve replacement, and reconstructed the valved conduit using a Carpentier-Edwards conduit. The old conduit was densely adherent to the sternum. Subaortic stenosis was caused by a narrow fibromuscular ridge associated with a bulge of the underlying septal muscle. The patient's recovery was uneventful. She is alive and well without any complaints 1 year after surgery.

[Congenital tracheal stenosis due to complete cartilage rings with right pulmonary agenesis].

A 2-month-old male infant with severe dyspnea was diagnosed as having right pulmonary agenesis at birth and was admitted to our hospital after tracheal intubation with an endotracheal tube of 3 mm in diameter. However, the trachea was too stenotic to place the tube in the proper position. Chest X-ray on admission showed pneumonia of the left lung. Preoperative chest computed tomography (CT) scan and bronchoscopy showed that from the level of 12 mm beneath the coricoid cartilage, the trachea tapered and continuing to the tracheal carina and that the smallest tracheal level was located 18 mm distal from the coricoid cartilage, the area of which was 4 mm2. His respiratory condition rapidly deteriorated in spite of intravenous administration of antibiotics and mechanical ventilation. Percutaneous cardiopulmonary support (PCPS) was used to maintain his pulmonary function, and pericardial tracheoplasty was performed. Chest X-ray immediately after the operation did not show left lung reexpansion due to severe pulmonary edema. High-dose steroid pulse therapy was performed, but it was not effective. He died from acute respiratory failure due to infantile respiratory distress syndrome (IRDS) on postoperative day 3. The outcome in this case shows that it is very risky to repair tracheal stenosis in a patient with pneumonia using PCPS.

[Long-term results of atriopulmonary fontan connection for complex cardiac anomalies].

To evaluate the long-term results of atriopulmonary Fontan connection, we reviewed the outcome of 20 consecutive patients (single ventricle 8, double outlet right ventricle 8, tricuspid atresia 3, mitral atresia 1; mean age, 13 +/- 11) who underwent this operation between 1981 and 1997 at our institution. Glenn shunt preceded Fontan operation in 1 patient. Four patients had a concomitant bidirectional Glenn anastomosis at the time of the Fontan operation. Follow-up was 100% complete, and total cumulative follow-up of all patients was 241 patient-years (maximum, 20 years). Three hospital deaths and 5 late deaths were observed, resulting in 58 +/- 11% of cumulative survival at 20 years after the operation. Sudden death probably due to arrhythmias was the major cause of the late death, and occurred in 3 patients. Reoperation was required in 5 patients (2%/patient-year) at 1 to 17 years postoperatively. Re-closure of an atrioventricular valve was performed for failure of the valve closure in 3 patients at 1 to 6 years postoperatively. Reconstruction of the stenotic atriopulmonary connection (APC) was concomitantly required in 2 of the 3 patients. Pacemaker implantation was required for bradycardia with atrial fibrillation in 1 patient at 17 years. One patient with atrial flutter developed intraright atrial thrombosis at 12 years after the initial Fontan operation, and this patient underwent conversion to extracardiac conduit cavopulmonary connection with right atrial maze procedure. Atrial tachyarrhythmias are most common complications, and occurred in 12 patients (5.0%/patient-year), resulting in 40 +/- 13% of the cumulative free rate at 15 years after the operation. Thus, failure of the atrioventricular valve closure and stenosis of APC were important early to intermediate complications after the atriopulmonary Fontan connection. On the other hand, atrial tachyarrhythmias were inevitable, and were most common late complications leading to intra-right atrial thrombosis, which was successfully resolved by conversion of the conventional atriopulmonary Fontan anastomosis to extracardiac conduit cavopulmonary connection.

Three-dimensional fast recovery fast spin-echo imaging of the inner ear and the vestibulocochlear nerve.

The aim of this study was to assess the performance of three-dimensional fast recovery fast spin-echo (3DFRFSE) for imaging of the inner ear as well as the facial and vestibulocochlear nerves. We evaluated 3DFRFSE sequences, comparing it with 3D fast spin-echo (3DFSE) in a water phantom and in 12 normal volunteers. We also examined 66 patients using 3DFRFSE sequence and assessed the visualization of their pathologies. In a water phantom study, signal intensity (SI) on 3DFRFSE was higher than that on 3DFSE at the same TR ranging from 1,500 to 6,000 ms. In normal volunteers, 3DFRFSE with TR of 2,800 ms showed comparable SI, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) superior to those on 3DFSE with TR of 5,000 ms. In clinical setting, 3DFRFSE was useful in demonstrating anatomic details in the labyrinth and pathologic findings of inner ear. The 3DFRFSE can provide high-resolution heavily T2-weighted images (T2WI) with shorter scan time than 3DFSE without significant disadvantage. The 3DFRFSE is a beneficial technique for evaluation of lesions in the inner ear as well as the facial and vestibulocochlear nerves.

Distribution and partial characterisation of IgG Fc binding protein in various mucin producing cells and body fluids.

BACKGROUND AND AIMS: Mucus released from goblet cells is important in intestinal mucosal defence, and mucin glycoproteins are thought to be major components of mucus. Recently, we identified and cloned another component of human colonic mucus, IgG Fc binding protein (Fc gamma BP). Fc gamma BP is immunologically distinct from known Fc gamma receptors and its structure contains repeated cysteine rich unit sequences resembling those present in mucins. In this work, we assessed the tissue distribution of Fc gamma BP, its binding activity in various body fluids, and its ability to inhibit complement mediated haemolysis. METHODS: Immunohistochemical localisation of Fc gamma BP, using monoclonal antibodies against Fc gamma BP (K9 or K17) and labelled IgG, was conducted in various mucin producing tissues: colon, small intestine, stomach, gall bladder, cystic duct, choledochus, bronchus, submandibular gland, conjunctiva, and cervix uteri. The binding activity of Fc gamma BP in mucus extracted from colon, gastric juice, bile, nasal discharges, saliva, sputum, and tears was also examined by immunodotblot and immunoprecipitation using these monoclonal antibodies. Inhibition of complement mediated haemolysis by Fc gamma BP was investigated using sheep red blood cells (SRBC) and anti-SRBC IgG. RESULTS: The immunohistochemical study revealed that mucin secreting cells in the colon, small intestine, gall bladder, cystic duct, choledochus, bronchus, submandibular gland, and cervix uteri contained Fc gamma BP, and immunodotblot and immunoprecipitation analysis using IgG and monoclonal antibodies demonstrated that the fluids secreted by these cells were capable of binding IgG. Mucin producing cells of the conjunctiva did not express Fc gamma BP molecules or bind to IgG. The surface mucus cells in the stomach were variably positive for Fc gamma BP. Perhaps because of proteolytic degradation, Fc gamma BP in gut lavage fluid did not have IgG binding activity, although this activity was present in the mucus covering the colon. Fc gamma BP suppressed complement mediated haemolysis of SRBC. CONCLUSIONS: Fc gamma BP is widely expressed on mucosal surfaces and in external secretions. It is functionally intact in several fluids. These findings lend support to the concept that Fc gamma BP is an important component of mucosal immunological defences.