Is subtyping of intestinal metaplasia in the upper gastrointestinal tract a worthwhile exercise? An evaluation of current mucin histochemical stains

Intestinal metaplasia is a premalignant condition that occurs in the upper gastrointestinal tract and can be subdivided into three types (I, II and III). Previous studies suggest that type III carries the highest cancer risk. The high iron diamine/alcian blue (HID/AB) technique traditionally has been used to identify this subtype; however, the technique uses reagents that are toxic and potentially carcinogenic. Therefore, in this study we evaluate various alternative histochemical techniques. Our results indicated that the only suitable alternative is Gomori's aldehyde fuchsin/AB technique. The study also revealed that subtyping of intestinal metaplasia is a subjective procedure, open to varying interpretation. Consequently, we suggest that previous work linking cancer risk to metaplasia subtypes should be viewed with some circumspection.     

Gram-negative bacteria induce proinflammatory cytokine production by monocytes in the absence of lipopolysaccharide (LPS)

Tumour necrosis factor-alpha (TNF-alpha), IL-1alpha and IL-6 production by human monocytes in response to a clinical strain of the Gram-negative encapsulated bacteria Neisseria meningitidis and an isogenic lpxA- strain deficient in LPS was investigated. Wild-type N. meningitidis at concentrations between 105 and 108 organisms/ml and purified LPS induced proinflammatory cytokine production. High levels of these cytokines were also produced in response to the lpxA- strain at 107 and 108 organisms/ml. The specific LPS antagonist bactericidal/permeability-increasing protein (rBPI21) inhibited cytokine production induced by LPS and wild-type bacteria at 105 organisms/ml but not at higher concentrations, and not by LPS-deficient bacteria at any concentration. These data show that proinflammatory cytokine production by monocytes in response to N. meningitidis does not require the presence of LPS. Therapeutic strategies designed to block LPS alone may not therefore be sufficient for interrupting the inflammatory response in severe meningococcal disease.     

Morphological organization and contractile properties of the wrist flexor muscles in the cat

A comparison of the anatomy, fiber type profiles, and contractile properties of the wrist flexor muscles was undertaken in the cat. Isometric contractile characteristics were measured for each muscle. Three muscle fiber types, FG, FOG, and SO, were differentiated by staining cross sections of each muscle for ATPase, NADH diaphorase, SDH, and α-GPD activities. The wrist flexor muscles ranged from less than 1% to 49% SO fiber content; with two of the five heads of the flexor digitorium profundus (FDP) having 1% or less SO fibers (FDP₁—1.07%, FDP₅—0.81%) and the humeral head of the flexor carpi ulnaris muscle (FCU_h) having the greatest content of SO fibers. The mean contraction time (CT) plus one-half relaxation time for an isometric twitch was correlated with the percentage of SO fibers and ranged from 40.5 to 111.8 ms. Except for the FCU (37 ms), the CT was less than 25 ms for the wrist flexor muscles. The uniarticular wrist flexor muscles, the flexor carpi radialis (FCR), and the FCU had the highest percentage of SO fibers and were more fatigue-resistant that the multiarticular muscles. Considerable differences exist in muscle structure, fiber type proportions, and contractile properties between the FCR and FCU, which may be related to functional differences between the two sides of the wrist that may exist during the placement of the foot during locomotion.     

Abnormal intestinal permeability and jejunal morphometry.

The cellobiose and mannitol differential sugar test is a non-invasive investigation of small bowel permeability, in which urinary recoveries of cellobiose and mannitol after a hyperosmolar oral load are expressed as a ratio to give a permeability index. Changes in the cellobiose:mannitol ratio often occur in coeliac disease, but some patients with abnormal permeability have normal jejunums by routine microscopy. Using computed morphometry the perimeter:lamina propria area index of jejunal biopsy samples was measured and compared with the cellobiose:mannitol ratio in three groups of patients: (i) those with coeliac disease with villous atrophy; (ii) those with normal jejunums and sugar test results: and (iii) those with normal jejunums but abnormal sugar test results. In addition to the expected difference in perimeter:lamina propria area index between patients with coeliac disease and those with normal findings (p less than 0.001), the index was also abnormal in patients with normal jejunums but abnormal sugar test results: (p less than 0.001 compared with group 1) and (0.01 greater than p greater than 0.001 compared with group 2). There was a significant overall correlation between the perimeter:lamina propria area index and cellobiose:mannitol ratio (p = 0.001). This study shows that computed jejunal morphometry can identify patients with subtle morphological changes that are related to abnormal intestinal permeability.     

High rates of clustering of strains causing tuberculosis in Harare, Zimbabwe: a molecular epidemiological study

We examined the pattern of tuberculosis (TB) transmission (i.e., reactivation versus recent transmission) and the impact of human immunodeficiency virus (HIV) infection in Harare, Zimbabwe. Consecutive adult smear-positive pulmonary TB patients presenting to an urban hospital in Harare were enrolled. A detailed epidemiological questionnaire was completed, and tests for HIV type 1 and CD4 cell counts were performed for each patient. Molecular fingerprinting of the genomic DNA recovered from cultures of sputum was performed by two molecular typing methods: spacer oligonucleotide typing (spoligotyping) and analysis of variable number of tandem DNA repeats (VNTRs). A cluster was defined as isolates from two or more patients that shared the same spoligotype pattern or the same VNTR pattern, or both. DNA suitable for typing was recovered from 224 patients. The prevalence of HIV infection was 79%. Of 187 patient isolates (78.6%) typed by both spoligotyping and analysis of VNTRs, 147 were identified as part of a cluster by both methods. By spoligotyping alone, 84.1% of patient isolates were grouped into 20 clusters. The cluster size was generally <8 patient isolates, although three large clusters comprised 68, 25, and 23 patient isolates. A total of 89.4% of the patient isolates grouped into 12 clusters defined by analysis of VNTRs, with 2 large clusters consisting of 127 and 13 patient isolates, respectively. Thirty-six percent of patient isolates with a shared spoligotype and 17% with a shared VNTR pattern were geographically linked within Harare, but they were not linked on the basis of the patient's home district. In a multivariate analysis, there were no independent predictors of clustering, including HIV infection status. Comparison with the International Spoligotype database (Pasteur Institute, Pointe a Pitre, Guadeloupe) demonstrated that our three largest spoligotype clusters are well recognized and ubiquitous in Africa. In this epidemiologically well characterized urban population with a high prevalence of HIV infection, we identified a very high level of strain clustering, indicating substantial ongoing recent TB transmission. Geographic linkage could be detected in a proportion of these clusters. A small group of actively circulating strains accounted for most of the cases of TB transmission.     

Physiological response and childhood anxiety: association with symptoms of anxiety disorders and cognitive bias.

This study examined the physiological response (skin conductance and heart rate [HR]) of youth exposed to a mildly phobic stimulus (video of a large dog) and its relation to child- and parent-reported anxiety symptoms and cognitive bias in a community-recruited sample of youth (n = 49). The results of this study indicated that HR and skin-conductance response were associated with youth report but not parent report of their child's symptoms of anxiety disorders and that HR response was more strongly associated with anxiety symptoms than skin-conductance response. Physiological response was uniquely associated with youth-reported symptoms of anxiety rather than youth-reported depression. Finally, HR response interacted with cognitive bias in predicting childhood anxiety disorder symptoms in a manner consistent with theories of the etiology of anxiety disorders.     

Absorption of amino penicillins from everted rat intestine.

1. Using an in vitro everted gut sac method based on that of Wilson & Wiseman (1954), a number of amino penicillins were tested in order to identify the involvement of any specialized transport mechanisms in their absorption across rat intestine. 2. Only one of the amino penicillins, cyclacillin (1-amino-cyclohexyl penicillin) was shown to be actively transported. The other penicillins appeared to diffuse passively across the intestine. 3. Cyclacillin was found to concentrate against a gradient at 37 degrees C but not at 19 degrees C. 4. Transport of cyclacillin across the mucosal membrane was saturated at mucosal concentrations greater than 1000 microgram/ml. 5. The rate of the forward flux of cyclacillin was many times that of its back flux. 6. No relationship between the active transport of cyclacillin and that of amino acids could be demonstrated.     

Association of DLG5 R30Q variant with inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system known as the inflammatory bowel diseases (IBD). Recently, Stoll and colleagues reported a novel finding of genetic variation in the DLG5 gene that is associated with IBD (CD and UC combined). We present here a study of the genetic variation described in that report in two well-powered, independent case-control cohorts and one family-based collection, and confirm the proposed association between IBD and the R30Q variant of DLG5 in two of the three studies. We are, however, unable to replicate the other proposed association to the common haplotype described in Stoll et al and suggest that this other finding could conceivably have been partially a statistical fluctuation and partially a result of LD with the replicated R30Q association. This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect.