A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12)     

Obstructive sleep apnea

Purpose

Attempts to understand the causes of cognitive impairment in obstructive sleep apnea (OSA) are complicated by the overlap among clinical and demographic factors that may impact cognition. The goal of the current study was to isolate the contribution of hypoxemia to cognitive impairment in OSA.

Methods

Two groups of 20 patients with newly diagnosed OSA were compared. The groups differed on severity of hypoxemia but not other demographic (e.g., age, gender, education, estimated premorbid IQ) or clinical (e.g., sleep related respiratory disturbances, daytime sleepiness, depressive symptoms) variables. Participants completed polysonmography and cognitive assessment.

Results

We compared patients with high and low hypoxemia on measures of memory, attention, executive functioning, and motor coordination using independent sample t-tests. The high hypoxemia group performed significantly better on immediate recall (Hopkins Verbal Learning Test — Revised; t?=??2.50, p?<?0.02) than the low hypoxemia group. No group differences were observed on other neuropsychological measures.

Conclusions

This study is one of the first to compare the cognitive performance of patients with high and low hypoxemia after controlling for demographic factors and aspects of OSA severity that could confound the relationship. In our carefully matched sample, we observed an unexpected advantage of higher hypoxemia on memory. These preliminary findings are discussed in the context of basic science literature on the protective effects of adaptation to intermittent hypoxemia. Our data suggest that the association between hypoxemia and cognition may not straightforward. Future research targeting the effects of hypoxemia on cognition controlling for other clinical factors in large groups of patients with OSA will be important.     

Biliary stricture dilatation: multicenter review of clinical management in 73 patients

Eighty-nine biliary strictures in 73 patients who had undergone percutaneous balloon dilatation were reviewed to determine long-term patency rates and clinical management problems. The majority of dilatations were performed in patients with anastomotic strictures (n = 44), iatrogenic strictures (n = 28), and strictures associated with sclerosing cholangitis (n = 17). Patency rates after 36 months or more were 67%, 76%, and 42%, respectively. Complications, mostly minor, occurred in less than 7% of patients. Of patients with significant biliary obstruction, 15% had little or no intrahepatic biliary duct dilatation demonstrated by cross-sectional imaging and/or direct cholangiography. No definite conclusions could be drawn about the utility of long-term internal/external stenting.     

Superparamagnetic iron oxide: enhanced detection of focal splenic tumors with MR imaging

Superparamagnetic iron oxide (AMI-25), a reticuloendothelial cell-specific contrast agent for magnetic resonance (MR) imaging, was evaluated for its ability to permit detection of splenic metastases in 18 patients. Superparamagnetic iron oxide, at a dose of 30 mumol of iron per kilogram, decreased the signal intensity of spleen from 19.5 +/- 4.8 to 3.1 +/- 2.2 (spin-echo sequence, repetition time msec/echo time msec = 1,500/42; P less than .05), without changing the signal intensity of tumor. As a result, the tumor-spleen contrast-to-noise ratio increased from 0.2 (tumor isointense relative to spleen) to 18.0 (tumor hyperintense relative to spleen). As a consequence of increased contrast, splenic tumors were detected in four of 18 patients (45 individual lesions; P less than .05), whereas nonenhanced MR imaging permitted detection of splenic lesions in only two of 18 patients (four individual lesions). Maximum tumor-spleen contrast was achieved within 60 minutes after intravenous administration. These initial clinical results indicate that MR imaging with superparamagnetic iron oxide may offer improved accuracy in the diagnosis of splenic tumors.     

Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.      

Rapid MR imaging with suspended respiration: clinical application in the liver

The authors demonstrate that it is possible to obtain highly T1-weighted images of the abdomen using a suspended respiration partial saturation (SRPS) method in a breath-holding interval. T2*-weighted images, which reflect tissue T2 as well as variations in the static magnetic field, can also be rapidly obtained. The authors studied five healthy subjects and 19 patients with a variety of liver abnormalities, including benign and malignant hepatic neoplasms, fatty liver infiltration, ascites, and hematoma. On T1-weighted multisection acquisitions, the entire liver can be screened for mass lesions in a single 20-second breath-holding interval. Phase-contrast SRPS images are sensitive to fatty infiltration of the liver. SRPS images are more sensitive to variations in magnetic susceptibility than spin-echo images are, which has been proved to be of value in the detection of hemorrhage. With continued pulse sequence development and clinical study, this method has the potential to become the method of choice for evaluation of the upper abdomen.     

Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies

Diverse materials with varying physical and magnetic properties have been evaluated as gastrointestinal contrast agents for magnetic resonance (MR) imaging. Uniform marking of the small bowel remains the greatest challenge. Ferrites are magnetically active iron oxide particles that are miscible with water and cause loss of signal on MR images. The decrease in MR signal intensity produced by ferrites occurs with a wide range of iron concentrations (0.1-10 mM) and with both T1- and T2-weighted pulse sequences. These effects of ferrites are explained by predominant T2 shortening with negligible T1 effects. The ferrite preparation used in this study was stable in vitro, with little iron solubilized by acid. Intragastric administration of ferrite (5 mg of iron per kg in 6 ml) routinely marked the small bowel of rats. The authors conclude that ferrites represent a promising new class of contrast agents for gastrointestinal MR imaging.     

Tetrahydrocannabinol vs. prochlorperazine. The effects of two antiemetics on patients undergoing radiotherapy

The authors tested the effectiveness of orally administered delta-9-tetrahydrocannabinol (THC) as compared to prochlorperazine for the alleviation of symptoms, such as vomiting and nausea, experienced by patients receiving radiotherapy. The test subjects rated the severity of their illness, as well as the extent of their subsequent moods, their level of concentration, their amount of physical activity, and their desire for social interaction. They chose the drug they preferred and recorded its side effects. The use of THC was slightly more beneficial than the use of prochlorperazine.