Arachidonic acid-stimulated platelet tests: Identification of patients less sensitive to aspirin treatment

Serum thromboxane-B2 (TxB2), together with arachidonic acid (AA)-induced platelet aggregation, are, at the moment, the most used tests to identify patients displaying high on-aspirin treatment platelet reactivity (HAPR). Both tests are specific for aspirin action on cyclooxygenase-1. While the correlation between serum TxB2 assay and clinical outcome is established, data are conflicting with regard to aspirin treatment and a possible association with AA-stimulated platelet markers and clinical outcome. To understand such discrepancy, we performed a retrospective study to compare both assays. We collected data from 132 patients receiving a daily dose of aspirin (100?mg/day) and data from 48 patients receiving aspirin on alternate days. All Patients who received a daily dose of aspirin were studied for AA-induced platelet aggregation together with serum TxB2 levels and AA-induced TxB2 formation was also studied in 71 patients out of entire population. Consistent with recommendations in the literature, we defined HAPR by setting a cut-off point at 3.1?ng/ml for serum levels of thromboxane B2 and 20% for AA-induced platelet aggregation. According to this cut-off point, we divided our overall population into two groups: (1) TxB2?<?3.1?ng/ml and (2) TxB2?>?3.1?ng/ml. We found low agreement between such tests to identify patients displaying HAPR. Our results show that AA-induced platelet aggregation >20% identify a smaller number of HAPR patients in comparison with TxB2. A good correlation between serum TxB2 and arachidonic acid-induced TxB2 production was found (r?=?0.76619).     

A case of immediate allergy to anisakis following saury intake]

We report here a 76-year-old male that presented with an immediate allergy to Anisakis following saury intake. Three and a half hours after eating pressed saury sushi, whole-body pomphus appeared including itching, facial dropsical swelling, and dyspnea. Diagnostic tests revealed specific IgE antibodies against anisakis simplex and a skin prick test was positive using an extraction of anisakis simplex. The results of skin prick tests using the body and internal organs of a saury were negative. Based on these results, we diagnosed the case as immediate allergy to Anisakis. Anisakis is parasitic to a diverse array of fish, and it seems rare that eating saury will induce an allergic response because the reported parasitic rate of Anisakis on saury is only 5%. In addition, as tropomyosin is currently considered to be the primary cause of allergies to Anisakis, renewed attention should be paid to other foods for which tropomyosin is also assumed to be a common antigen.     

Childhood Malignant Thymoma: Clinical, Therapeutic, and Immunohistochemical Considerations

Malignant thymomas are among the least common mediastinal tumors in the pediatric age group. Thymomas are considered malignant on the basis of macroscopic and microscopic invasiveness. As only 20 well-documented cases involving children have been reported in the literature, the pattern of responsiveness to therapy and the value of prognostic signs is obscure. Two cases of malignant pediatric thymomas are reported with pathognomonic histoimmunological features of aggressive thymoma. One was cured, with a follow-up of 70 months, and one died while on therapy. Analysis of the histological features and the immunoperoxidase staining displays the complexity of pediatric thymomas and the inability to prognosticate the outcome, respectively.     

MRI demonstration and CT correlation of the brain in patients with idiopathic intracerebral calcification

Twenty-two patients aged 36–63 years were diagnosed as having Fahr's syndrome on the basis of the presence on CT of unexpected extensive calcification of the basal ganglia. Even when associated with calcification of other brain areas, the main diagnostic criterion remained basal ganglia calcification larger than 800 mm². Normal values of parathormone, serum calcium and phosphorus excluded hypercalcaemia and hypoparathyroidism. Mitochondrial CNS disease was excluded clinically. MRI and repeated CT and neurological examination were performed in all of the patients. The patients were divided into two groups: neurologically asymptomatic (group 1) and neurologically symptomatic (group 2). T2-weighted sequences demonstrated hyperintense areas in all of the patients involving the white and the grey matter of the brain. In group 1 the hyperintense lesions were significantly smaller than in group 2. The neurological symptoms correlated better with the hyperintensities on T2-weighted MR images than with the calcification demonstrated on CT. Hyperintensities in T2-weighted MRI and the areas shown by CT to have calcification had different locations. In 15 patients with dementia, the white matter of the entire centrum semiovale was bilaterally hyperintense. In another 3 patients with hemiparesis, hyperintense areas in the internal capsule, contralateral to the side of hemiparesis, were demonstrated in the T2-weighted sequence. The hyperintense T2 signals may reflect a slowly progressive, metabolic or inflammatory process in the brain which subsequently calcifies and are probably responsible for the neurological deficit observed.     

A "housekeeping" gene on the X chromosome encodes a protein similar to ubiquitin

An X chromosome gene located 40 kilobases downstream from the G6PD gene, at Xq28, was isolated and sequenced. This gene, which we named GdX, spans about 3.5 kilobases of genomic DNA. GdX is a single-copy gene, is conserved in evolution, and has the features of a "housekeeping" gene. At its 5' end, a cluster of CpG dinucleotides is methylated on the inactive X chromosome and unmethylated on the active X chromosome. The GdX gene can code for a 157 amino acid protein, GdX. Residues 1-74 of GdX show 43% identity to ubiquitin, a highly conserved 76 amino acid protein. The COOH-terminal moiety of GdX is characterized in its central part (residues 110-128) by a sequence homologous to the COOH-terminal hormonogenic site of thyroglobulin. The structural organization of the GdX protein suggests the existence of a family of genes, in addition to the ubiquitin gene, that could play specific roles in key cellular processes, possibly through protein-protein recognition.     

Entomophthoromycosis in South Bengal (Eastern India): a 9 years study

Subcutaneous mycoses caused by the family Entomophthoraceae is very rare type of disease and is being reported sporadically from various Tropical countries including India. Here we report 8 cases of rhinoentomophthoromycosis caused by Conidiobolous coronatus and 7 cases of chronic subcutaneous phycomycosis caused by Basidiobolus ranarum. Cases were detected during a span of 9 years between 1991 to 1999, from 9 districts in and around Kolkata (Eastern India). Former type of lesions were detected among 20 to 65 age group of healthy individuals, predominantly males (7:1). In the latter type, male-female ratio was 2:5, and except for one all cases belonged to below 20 years age group of healthy individuals. Several cases were detected only after examination of repeat biopsy samples. With high degree of clinical suspicion, right approach is needed for laboratory confirmation of diagnosis.     

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

Optimedin: a novel olfactomedin-related protein that interacts with myocilin

Mutations in the MYOC gene may lead to juvenile open-angle glaucoma with high intraocular pressure, and are detected in about 4% of people with adult onset glaucoma. Most of these mutations are found in the third exon of the gene encoding the olfactomedin-like domain located at the C terminus of the protein. Another olfactomedin-related protein, known as noelin or pancortin, is involved in the generation of neural crest cells. Here we describe the identification of a novel olfactomedin-related gene, named optimedin, located on chromosome 1p21 in humans. Optimedin and noelin are both expressed in brain and retina. However, unlike noelin, rat optimedin is also highly expressed in the epithelial cells of the iris and the ciliary body in close proximity to the sites of Myoc expression. In the human eye, optimedin is expressed in the retina and the trabecular meshwork. Both optimedin and myocilin are localized in Golgi and are secreted proteins. The presence of mutant myocilin interferes with secretion of optimedin in transfected cells. Optimedin and myocilin interact with each other in vitro as judged by the GST pulldown, co-immunoprecipitation and far-western binding assays. The C-terminal olfactomedin domains are essential for interaction between optimedin and myocilin, while the N-terminal domains of both proteins are involved in the formation of protein homodimers. We suggest that optimedin may be a candidate gene for disorders involving the anterior segment of the eye and the retina.     

Polymorphism of germ-line immunoglobulin VH genes correlates with allotype and idiotype markers

The polymorphic nature of the immunoglobulin V_H genes was investigated by Southern blot analysis of liver DNA of sixteen different mouse strains and hybridization with V_H probes. Differences in restriction enzyme pattern (REP) were observed and six different patterns of restriction fragments were found for the sixteen strains analyzed. No equivalent polymorphism was observed in another multigene family, the actins. The six patterns correlate with immunoglobin constant region allotypes (Igh-1). Experiments with Igh-1-congenic strains suggest that the V_H REP is linked to immunoglobulin constant region haplotype. Mouse strains which share inherited idiotypes also share identical V_H restriction pattern. This provides a structural basis for the genetic linkage between idiotypes and allotypes. It also indicates that different strains carry different VH gene repertoires, which may be the basis for the expression of different inherited idiotypes in various strains. We propose that a V_H group is a set of linked genes that are coinherited as a cluster with the constant region genes and that V_H and C_H can be regarded as an extended haplotype.