The first case report of medulloblastoma associated with Tatton‐Brown–Rahman syndrome

DNMT3A codes for a DNA methyl transferase enzyme that plays a central role embryogenesis. Somatic mutations in this gene have been associated with tumorigenesis and are associated with a number of cancers. The recently described Tatton‐Brown–Rahman syndrome (TBRS) is due to heterozygous germline mutations in the DNMT3A gene. So far, only one case of hematological malignancy associated with TBRS have been reported. Here, we describe the first case presenting with TBRS and medulloblastoma. We also discuss the associations between mutations in DNMT3A found in TBRS, AML, and medulloblastoma.     

Rapid species identification of group C streptococci isolated from horses.

Two commercial systems, the API 20S (Analytab Products, Plainview, N.Y.) and the Rapid Strep (API System S.A., Montalieu-Vercieu, France), were evaluated for ease of use and accuracy in the rapid identification of group C streptococci isolated from horses. A total of 85 Streptococcus isolates were tested, including S. equi (67 isolates), S. zooepidemicus (13 isolates), and S. equisimilis (5 isolates). All S. equi and S. zooepidemicus isolates were correctly identified within 24 h by the Rapid Strep system. Specific grouping sera was necessary to distinguish between S. equisimilis and group G or L strains. The API 20S system did not provide species identification of any of these isolates. An identification of randomly selected isolates to species level was performed by conventional methods and confirmed the identification derived through the Rapid Strep system. Our results indicate that the Rapid Strep system is a valuable aid for species identification of equine isolates of group C streptococci.     

Minitek urea disk test, a sensitive and cost-effective method to screen for Campylobacter pylori in gastric biopsies.

One hundred fifty-five biopsy specimens from the gastric mucosa of 81 patients undergoing routine endoscopy procedures were tested for the presence of Campylobacter pylori by three methods: Gram stain, culture, and modified Minitek, a rapid urea disk test (BBL Microbiology Systems, Cockeysville, Md.). Twenty-nine patients were infected with C. pylori. Sensitivities and specificities of detection were 100 and 94% with the Minitek test and 93 and 100% with Gram stain, respectively. Rapid testing by the urea disk is a simple, cost-effective, and accurate method for detecting the presence of C. pylori in gastric biopsy specimens.     

Ristocetin-induced platelet aggregate formation and adherence to the probe of an impedance aggregometer

The examination of the interaction between ristocetin and platelets generally is performed in an optical aggregometer where aggregate formation is detected by a change in turbidity. Ristocetin also will induce conductivity changes in an impedance aggregometer with either fresh whole blood or fresh platelet-rich plasma due to aggregate attachment to the electrical probe. Formaldehyde-fixed platelets, however, do not attach, and although fresh platelets agglutinate at extremes of pH, probe adhesion does not occur unless the pH is within a certain range. Incubation of platelet preparations with neuraminidase, colchicine, or cytochalasin-b affects neither aggregate formation nor probe adherence. Incubation of platelet preparations with a fibronectin tetrapeptide inhibitor eliminates aggregate formation in response to collagen but is without effect on ristocetin-induced attachment of aggregates to the impedance probe. It is suggested that the ability of platelet aggregates to attach to an impedance probe in response to ristocetin is dependent on additional aspects of the functional integrity of platelet preparations and that these changes required for probe adherence may have in vivo significance.     

Identification and characterization of the allergenic proteins of Bahia grass (Paspalum notatum) pollen

BACKGROUND: Pollen of Bahia grass (Paspalum notatum) represents a major cause of type I allergy in diverse geographical areas, particularly in the southeastern coastal plain area of the United States. The aqueous protein extract of Bahia grass pollen contains the allergenically active components that produce skin-test-positive reactions in sensitive patients. OBJECTIVE: The emphasis of this study included the identification and characterization of the allergenic proteins present in the crude protein aqueous extract of Bahia grass pollen. METHODS: The crude extract of Bahia grass pollen, partially purified by isoelectric focusing and fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was electroblotted onto nitrocellulose membranes, probed with sera from patients skin test positive to Bahia grass and detected using anti-human IgE conjugated peroxidase. RESULTS: Four allergenic proteins of Bahia grass pollen with estimated molecular weights of 45, 33, 31 and 28 kD were identified and characterized. Following treatments with deglycosylation enzymes, the 4 allergens retained their antigenic reactivity with Bahia-grass-allergic patient sera containing polyclonal IgE antibodies. CONCLUSION: The crude extract of Bahia grass pollen contains many proteins but only 4 have allergenic reactivity. Following deglycosylation treatment, Bahia grass allergenic proteins have retained their antigenic reactivity with Bahia-grass-allergic patient sera containing polyclonal IgE antibodies. Four proteins reactive with IgE were detected, but the 33-kD protein (pI of 6.59) was the most reactive.     

Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene

Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In >80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (approximately 70%) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counseling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.      

Quantitative immunoconfocal analysis of human myometrial gap junction connexin43 in relation to steroid hormone concentrations at term labour

The aim of this study was to quantify gap junction expression in the human myometrium in relation to progesterone and oestradiol concentrations, and to establish whether oxytocin-resistant dystocia is due to an abnormality in gap junction expression. Three groups of patients were investigated: (i) before labour (at term), (ii) normal labour and (iii) oxytocin-resistant dystocia (eight patients per group). For each patient, the concentrations of oestradiol and progesterone in maternal blood and in myometrial tissue were measured, and the number and area of immunostained connexin43 gap junctions per unit volume of tissue determined by quantitative analysis of digital images obtained by confocal microscopy. No significant difference in connexin43 gap junction content was observed between the three patient groups. When all groups were pooled, there was a significant positive correlation (P < 0.05) between the quantity of immunolabelled gap junctions and the oestradiol:progesterone ratio, but there was no significant difference in this correlation between the groups. Gap junction immunolabelling was not correlated with the progesterone or oestradiol concentration in the maternal blood or the myometrium. These data suggest that in human myometrium: (i) dystocia is not due to a reduced level of immunodetectable connexin43 gap junctions, (ii) onset of labour is not associated with a sudden increase in immunodetectable gap junction protein and (iii) gap junctions can be expressed in the presence of high progesterone concentrations.      

Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor

Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor. BACKGROUND: We have previously demonstrated an essential role for increased epidermal growth factor receptor (EGFR) activity in mediating renal cyst formation and biliary epithelial hyperplasia in murine models of autosomal recessive polycystic kidney disease (ARPKD). This study was designed to determine whether or not treatment with a newly developed inhibitor of EGFR tyrosine kinase activity (EKI-785) would reduce renal and biliary abnormalities in murine ARPKD. METHODS: Balb/c-bpk/bpk (BPK) litters were treated with EKI-785, an EGFR-specific tyrosine kinase inhibitor. Animals were treated by intraperitoneal injection beginning at postnatal day 7 and were treated until postnatal day 24 or 48. EKI-785's effectiveness was measured by a reduction in the renal cystic index, an increased life span, and maintenance of normal renal function. RESULTS: Treatment of BPK mice with EKI-785 resulted in a marked reduction of collecting tubule (CT) cystic lesions, improved renal function, decreased biliary epithelial abnormalities, and an increased life span. Untreated cystic animals died of renal failure at postnatal day 24 (P-24) with a CT cystic index of 4.8, a maximal urine osmolarity of 361 mOsm, and moderate to severe biliary abnormalities. Cystic animals treated with EKI-785 to postnatal day 48 (P-48) were alive and well with normal renal function, a reduced CT cystic index of 2.0 (P < 0.02), a threefold increased in maximum urinary concentrating ability (P < 0.01), and a significant decrease in biliary epithelial proliferation/fibrosis (P < 0.01). CONCLUSION: This study demonstrates that EKI-785 has therapeutic effectiveness in improving histopathologic abnormalities and decreasing mortality in murine ARPKD.     

Computer-assisted neurosurgery by using a noninvasive vacuum-affixed dental cast that acts as a reference base: another step toward a unified approach in the treatment of brain tumors

OBJECT: The purpose of the study was to evaluate the use of the Vogele-Bale-Hohner (VBH) mouthpiece, which is attached to the patient's upper jaw by negative pressure, for patient-image registration and for tracking the patient's head during image-guided neurosurgery. METHODS: A dynamic reference frame (DRF) is reproducibly mounted on the mouthpiece. Reference points, optimally distributed and attached to the mouthpiece, are used for registration in the patient's absence on the day before surgery. In the operating room, the mouthpiece and DRF are precisely repositioned using a vacuum, and the patient's anatomical structures are automatically registered to corresponding ones on the image. Experimental studies and clinical experiences in 10 patients confirmed repeated (rigid body) localization accuracy in the range of 0 to 2 mm, throughout the entire surgery despite movements by the patient. CONCLUSIONS: Because of its noninvasive, rigid, reliable, and reproducible connection to the patient's head, the VBH vacuum-affixed mouthpiece grants the registration device an accuracy comparable to invasive fiducial markers.     

Ethyl acrylate risk assessment with a hybrid computational fluid dynamics and physiologically based nasal dosimetry model.

Cytotoxicity in the nasal epithelium is frequently observed in rodents exposed to volatile organic acids and esters by inhalation. An interspecies, hybrid computational fluid dynamics and physiologically based pharmacokinetic (CFD-PBPK) dosimetry model for inhaled ethyl acrylate (EA) is available for estimating internal dose measures for EA, its metabolite acrylic acid (AA), and EA-mediated reductions in tissue glutathione (GSH). Nasal tissue concentrations of AA were previously used as the dose metric for a chronic Reference Concentration (RfC) calculation with this compound. However, EA was more toxic than expected, based on calculated tissue AA concentrations. Unlike AA, EA causes depletion of tissue GSH. We have developed an RfC for EA using tissue GSH depletion in the olfactory epithelium as the primary measure of nasal tissue dose. The hybrid CFD-PBPK model was refined to improve the accuracy of simulations for GSH in rat olfactory tissues. This refined model was used to determine the concentration for continuous human exposures to EA predicted to reduce nasal GSH levels to the same extent as seen in rats exposed to EA at the no-observed-effect level (NOEL). Importantly, AA concentrations in the human nasal olfactory epithelium at the proposed chronic RfC were predicted to be lower than the AA concentrations estimated in the rat at the NOEL. Thus, a chronic RfC based on maintaining GSH in the human nasal olfactory epithelium at levels equivalent to the rat NOEL would also provide an adequate margin of safety with respect to AA concentrations in nasal tissues.