Secretory immunoglobulin A (sIgA) deficiency in serum of patients with GALTectomy (appendectomy and tonsillectomy)

INTRODUCTION: In adult human beings, 80-85% of the immune cells are located in the digestive tract mucosa; hence the importance of the Gut Associated Lymphoid Tissue (GALT) in host defence. We studied the influence of the surgical removal of two important parts of the gut associated with lymphoid tissue (tonsillectomy and appendectomy) on immune parameters. METHODS: One hundred and sixty patients were enrolled in this study. They were divided into four groups of forty patients each and matched for gender and age: group 1, appendectomized and tonsillectomized; group 2, only appendectomized; group 3, only tonsillectomized; and group 4, control group, neither tonsillectomized nor appendectomized. We analysed in blood: hemogram, protein electrophoresis, lymphocytic populations (T4 cells, T8 cells, NK cells), IgG, IgM, IgA immunoglobulin, and their fractions IgA1, IgA2, and secretory IgA. RESULTS: Levels of secretory IgA in serum of patients in group 1 were significantly lower than in the other three groups (1.89 mg/dl, group 1; 2.32 mg/dl, group 2; 2.19 mg/dl, group 3 and 4.97 mg/dl, group 4; p<0.0001). Also, the values found in the two groups that had undergone only one of the operations were clearly lower than in control patients (p<0.0001). In this study, the reduction was sustained for a period of between 3 months and 3 years in appendectomized patients, and more than 20 years in tonsillectomized patients. IN SUMMARY: GALTectomy (appendectomy and tonsillectomy) significantly decreases secretory IgA levels in serum. The decrease is more intense when both operations have been done.     

A study of indefinite for dysplasia in Barrett’s oesophagus: reproducibility of diagnosis,clinical outcomes and predicting progression with AMACR (α‐methylacyl‐CoA‐racemase)

Sonwalkar S A, Rotimi O, Scott N, Verghese E, Dixon M, Axon A T R A & Everett S M
(2010) Histopathology 56, 900–907
A study of indefinite for dysplasia in Barrett’s oesophagus: reproducibility of diagnosis, clinical outcomes and predicting progression with AMACR (α‐methylacyl‐CoA‐racemase) Aims: To assess interobserver variation in the diagnosis of dysplasia in Barrett’s oesophagus, especially indefinite dysplasia (IND) using the revised Vienna classification. A secondary aim was to study clinical outcome of IND cases and to evaluate expression of alpha‐methyl‐CoA racemase (AMACR) as a marker predictive of progression. Methods and results: Cases of Barrett’s oesophagus and dysplasia over a 20 year period were assessed. Three experienced histopathologists reviewed 101 cases on set criteria in a blinded fashion. Slides were immunostained for AMACR and evaluated for the presence, extent and location of AMACR expression. Clinical and progression data were collected. Overall agreement for the diagnosis of dysplasia was fair (k = 0.35) but that for IND was poor (k = 0.18). 6 IND cases progressed after a median follow‐up of 31.4 months to a higher grade. The sensitivity of AMACR for the detection of abnormality was 22% for IND and specificity 100%. The positive predictive value of AMACR for progression was 0.44 and the negative predictive value was 0.92. Conclusion: Fair agreement was achieved for the diagnosis of dysplasia but poor agreement for IND. A proportion of IND cases progress. Re‐diagnosis or consensus diagnosis did not predict progression. AMACR shows promise as a marker to indicate IND patients in need of more intensive surveillance.     

Early and presymptomatic detection of Wilson's disease at the mandatory 3-year-old medical health care examination in Hokkaido Prefecture with the use of a novel automated urinary ceruloplasmin assay

Wilson’s disease (WND) is an autosomal recessive disorder of copper (Cu) accumulation leading to liver and/or brain damage. Oral chelating agents and diet are effective in treating WND. However, once irreversible damage has occurred, the effect of treatment is diminished and the patient’s quality of life is compromised. For these reasons an effective method for screening has been needed for early detection of presymptomatic patients. We conducted an early and presymptomatic detection of WND using a novel automated assay of ceruloplasmin (Cp) concentration in urine and selected the mandatory medical health care examination for 3-year-old children in Hokkaido Prefecture (the largest administrative division in Japan) as a sampling point. We measured urinary Cp concentrations in 11,362 children using an immunological latex agglutination assay kit developed by us. Among these children we identified a positive case with markedly reduced urinary Cp concentration. Detailed medical examination provided no clinical manifestations to support the diagnosis of WND, although serum Cp and Cu levels were remarkably low in this case. Therefore, we analyzed the WND gene in order to confirm the diagnosis. Sequence analysis revealed that the case was compound heterozygous for the WND gene mutations 2871del.C and D1296N. According to the Ferenci scoring system for WND diagnosis, the case was established as a WND patient at the presymptomatic stage. Consequently, the patient has maintained a good quality of life under medical treatment with polaprezinc administration to date. Our investigation suggests that the screening system for WND using the automated urinary assay at the mandatory medical health care examination for 3-year-old children is a noninvasive and efficient method for the early and presymptomatic diagnosis of WND.     

Subregional analysis of GABA(A) receptor subunit mRNAs in the hippocampus of older persons with and without cognitive impairment

We employed in situ hybridization and quantitative densitometry techniques to examine hippocampal mRNA expression of GABA(A) receptor subunits alpha1 and alpha5 in human subjects with progressing cognitive impairment. Included in this study were 17 participants of the Religious Order Study (ROS), who were categorized into three groups based upon degree of cognitive impairment: no cognitive impairment (n = 6); moderate cognitive impairment (n = 5); and probable Alzheimer's disease (AD) (n = 6). While the levels of each specific subunit mRNA were relatively homogeneously distributed throughout the five hippocampal subregions analyzed (CA1-4, and the granule cell layer of the dentate gyrus), mRNA expression of the alpha1 receptor subunit was found to be 20% reduced in the moderate cognitive impairment group as compared to the no cognitive impairment group. In addition, alpha1 mRNA expression was 25% reduced in the probable Alzheimer's disease group compared to the group with no cognitive impairment. Similarly, alpha5 subunit mRNA was reduced 32% between no cognitive impairment and moderate cognitive impairment groups, and 35% between no cognitive impairment and probable Alzheimer's disease groups. No significant reductions were found between moderate cognitive impairment and probable Alzheimer's disease groups for either subunit. Collectively, our data provide evidence for modest reductions in GABA(A) receptor subunit mRNAs, and suggest these changes occur very early in the progression of Alzheimer's disease cognitive impairment.