Recognition of a dominant epitope in bovine heat-shock protein 70 in inner ear disease

OBJECTIVE: To investigate the specificity of antibodies to heat-shock protein 70 (HSP70) in patients with idiopathic, progressive, bilateral sensorineural hearing loss (IPBSNHL) and Meniere disease. STUDY DESIGN: Test immunoreactivity of patients' sera using recombinant human (rh) and bovine (rb) HSP70, as well as segments representing different regions of bovine HSP70 as antigen. METHODS: Sera were tested by Western blotting. RESULTS: Of 52 patients with IPB-SNHL, 40 sera reacted only with rbHSP70; 12 reacted with both rbHSP70 and rhHSP70. Sera from 13 patients with IPBSNHL and from 8 with Meniere disease were tested on the panel of bovine HSP70 segments. Eleven and 7 samples, respectively, reacted with amino acid segment 427-461 from the carboxy (C)-terminal region of the molecule. CONCLUSION: In IPBSNHL and Meniere disease, antibodies are directed primarily against an epitope(s) within the C-terminal region of HSP70 where diversity in sequence among different species, including possible pathogens, is greatest. These findings may provide clues to the pathogenesis or specific serodiagnosis (or both) of diseases of the inner ear.     

Defective sexual development in an infant with 46, XY, der(9)t(8;9)(q23.1;p23)mat

We report on a male infant with ambiguous genitalia (scrotal hypospadias, sinus urogenitalis) trisomic for 8q23-ter and monosomic for 9p23-ter, who shared craniofacial and other abnormalities with either phenotype. Gonadal histology was nearly normal for age. Normal endocrinological findings and exclusion of mutations in SRY, androgen receptor and alpha-reductase genes point to supplementary gene(s) located in 9p2305-ter, haplo-insufficiency (by deletion) of which is expected to cause defective male morphogenesis. Conclusion This observation lends further support to the hypothesis that genetic factors are located at 9p23-ter which are involved in normal sex determination. Received: 26 February 1998 / Accepted: 28 May 1998     

Discrepant outcome of intrauterine listeria infection in dichorionic twins

BACKGROUND AND CASE REPORT: We report on a case of fetal Listeriosis in a dichorionic twin pregnancy where both placentae, but only one of the twins were infected. While the firstborn child showed no infection and remained healthy until today, the other newborn had all clinical signs of granulomatosis infantiseptica and died despite of immediate resuscitation immediately after delivery. CONCLUSIONS: This discrepant course with Listeriosis in twins underlines, that fetal factors influence the clinical outcome in placental Listeriosis. The reasons for the infection of only one twin and the avoidance of the other twin remain unclarified. We speculate that immunologic mechanisms or the presence of meconium-stained amniotic fluid may play an important role for intrauterine infection with Listeriosis.     

Ménière's disease

There now exists a vast literature on Ménìere's disease. In this review, we examine closely the foundations of some of the current concepts regarding various aspects of the disorder, including definitions, clinical features, natural history, pathology, pathogenesis, pathophysiology, diagnosis and treatment. We will highlight areas where the current state of knowledge is incomplete and also suggest some avenues for further research.     

Prophylaxis of thromboembolic complications after the Fontan operation (total cavopulmonary anastomosis)

OBJECTIVES: Thrombotic events have been reported as a major cause of morbidity after the Fontan procedure. There is no consensus concerning the postoperative mode and duration of anticoagulation prophylaxis. In a retrospective study, we evaluated the results of a prophylactic regimen on the basis of the surgical technique, potentially predisposing risk factors, and specific sequelae. METHODS: We evaluated 142 surviving patients after total cavopulmonary anastomosis (mean follow-up was 91.1 +/- 43.9 months). Prophylactic antithrombotic treatment was initiated in 86 patients with partial prosthetic venous pathway with acetylsalicylic acid; 45 patients with complete autologous tissue venous pathway or partial prosthetic venous pathway received no anticoagulation, and 11 patients received warfarin sodium (Coumadin). During long-term follow-up, 22 patients (12 after acetylsalicylic acid medication) crossed over to warfarin. RESULTS: Thrombotic events occurred in 10 patients (7%), with systemic venous thrombus formation in 8 (5.6%), stroke in 2 (1.4%), and a peak incidence during the first postoperative year. Eight of 10 patients were receiving heparin therapy mainly for prolonged postoperative immobilization. During follow-up, none of the 74 patients receiving acetylsalicylic acid and 1 of 40 patients without medication presented with thrombus formation. Under warfarin medication, 1 of 28 patients had an asymptomatic thrombus. Expected freedom from a thromboembolic event was 92% at 5 years and 79% at 10 years. There was no association with coagulation factor abnormalities. Protein-losing enteropathy was present in 4 of 10 patients. CONCLUSION: A prophylactic anticoagulation strategy that considers the surgical technique and potential predisposing circumstances proved effective in the prevention of late thrombotic complications after total cavopulmonary anastomosis. There is no need for routine anticoagulation during long-term follow-up after Fontan-type surgery in pediatric patients.     

Neuroendocrine (Merkel cell) carcinoma of the skin

A case of neuroendocrine Merkel cell carcinoma of the skin in a 65-year-old female patient is reported. The definite diagnosis can be established only by ultrastructural and immunohistochemical investigations. Characteristic features are cytoplasmic neurosecretory granules and the identification of neuron-specific enolase.     

Methylated-CpG island recovery assay: a new technique for the rapid detection of methylated-CpG islands in cancer

Hypermethylation of CpG islands is a phenomenon commonly observed during the development and progression of human tumors. Detection of methylated-CpG islands in easily accessible biological materials such as serum has the potential to be useful for the early diagnosis of cancer. Most currently used methods for detecting methylated-CpG islands are based on sodium bisulfite conversion of genomic DNA, followed by PCR reactions. Here we describe a method, methylated-CpG island recovery assay (MIRA) that does not depend on the use of sodium bisulfite but has similar sensitivity and specificity as bisulfite-based approaches. Methyl-CpG-binding domain proteins, such as methyl-CpG-binding domain protein-2 (MBD2), have the capacity to bind specifically to methylated DNA sequences. In the MIRA procedure, sonicated genomic DNA isolated from cells or tissue is incubated with a matrix containing glutathione-S-transferase-MBD2b in the presence of methyl-CpG-binding domain protein 3-like-1, a binding partner of MBD2 that increases the affinity of MBD2 for methylated DNA. Specifically bound DNA is eluted from the matrix and gene-specific PCR reactions are performed to detect CpG island methylation. Methylation can be detected using 1 ng of DNA or 3000 cells. MIRA is a specific and sensitive, but not laborious, technique that can be clinically useful in the detection and diagnosis of any DNA methylation-associated disease, including cancer.     

Obsessive-compulsive disorder phenotypes: implications for genetic studies

Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes.