C3 Glomerulopathy: Ten Years' Experience at Mayo Clinic

Objective

To describe the clinicopathological features, complement abnormalities, triggers, treatment, and outcomes of C3 glomerulopathy.

Effects of Ethanol, MK-801, and Chlordiazepoxide on Locomotor Activity in Different Rat Lines: Dissociation of Locomotor Stimulation from Ethanol Preference

Several lines of research have suggested a link between the reward value of a drug and its ability to stimulate locomotion. One goal of the present study was to determine whether ethanol preferentially stimulates locomotor activity in lines of rat that show a preference for ethanol. A secondary goal was to determine the extent to which the benzodiazepine-like and NMDA antagonistic action of ethanol accounted for its effect on locomotor activity. To meet these goals, the effects of varying doses of ethanol (0.125-1.0 g/kg), MK-801 (0.1-0.3 mg/kg), and chlordiazepoxide (0.3-3 mg/kg) on locomotor activity were studied in several lines of rats that had been habituated to the testing procedure. The effect of low doses of ethanol on motor activity in the Alcohol-Preferring (P) and Fawn-Hooded rats, which show a strong ethanol preference, were similar to those of the alcohol-nonpreferring (NP), Flinders Sensitive Line, and Flinders Resistant Line rats. Only the Flinder Resistant Line rats showed a small, but significant increase in locomotor activity after the administration of ethanol. The highest dose of ethanol (1.0 g/kg) produced locomotor depression in all lines except the P and NP lines, which were not tested at this dose. These findings do not support a link between locomotor stimulation by ethanol and ethanol preference. In contrast, all lines exhibited locomotor stimulation after moderate (0.1-0.3 mg/kg) doses of MK-801, but did not exhibit increases in activity following any dose of chlordiazepoxide. These data indicate that the profiles of activity after MK-801 and chlordiazepoxide were distinct from that of ethanol in the various rat lines. Therefore, the effects of ethanol on locomotor activity cannot be accounted for by reference solely to its antagonist-like action at NMDA receptors and/or its agonist-like action at GABA/benzodiazepine receptors.     

Autoimmune comorbidity in chronic spontaneous urticaria: A systematic review

Background and objective

Numerous autoimmune diseases (AIDs) have been linked to chronic spontaneous urticaria (CSU). Here, we provide the first extensive and comprehensive evaluation of the prevalence of AIDs in patients with CSU and vice versa.

Comparative study of cephalometric measurements using 3 imaging modalities

Background

The authors conducted a study to compare 2-dimensional (2D) lateral cephalometric radiography (LCR), 2D cone-beam computer tomographic (CBCT)–generated cephalogram and 3-dimensional (3D) CBCT for assessing cephalometric measurements.

Intrarater and Interrater Reliability of Angular Measures Using TEMPLO Two-dimensional Motion Analysis Software

ObjectiveThe purpose of this study was to assess the intrarater and interrater reliability of marking 2 angles with the TEMPLO software and to provide relevant information for clinical practice.MethodsA prospective test–retest study has been conducted. Four raters took measures on 2 days, with 2 weeks in between. Craniovertebral angle and trunk forward lean were drawn on 22 video frames using TEMPLO. Reliability was examined using intraclass correlation coefficients including standard errors of measurement and minimal detectable change values as measures of precision expressed in the unit of the test (°).ResultsIntraclass correlation coefficients for intrarater and interrater reliability ranged from 0.98 to 1.00. Standard errors of measurement and minimal detectable change values ranged from 0.4° to 0.8° and 0.8° to 2.3°, respectively.ConclusionThese results indicate excellent reliability for craniovertebral angle and trunk forward lean assessed with TEMPLO software. Changes exceeding 2.3° may be expected to fall outside the test’s variability.     

The role of heparan sulfate as determining pathogenic factor in complement factor H-associated diseases

Complement factor H (FH) systemically inhibits excessive complement activation in the microenvironment of host cells, but for instance not on microbes. This self-recognition is mediated by two binding sites that recognize distinctly sulfated heparan sulfate (HS) domains. The interaction with HS not only concentrates FH on host cells, but directly affects its activity, evoking novel models of conformational activation. Genetic aberrations in the HS-binding domains systemically disturb the protective function of FH, yet the resulting loss of complement control affects mainly ocular and renal tissues. Recent results suggest that the specific expression of HS domains in these tissues restricts the interaction of HS to a single binding site within FH. This lack of redundancy could predispose eyes and kidneys to complement-mediated damage, making HS a central determinant for FH-associated diseases.     

Semiquantitative multiplex PCR: a useful tool for large rearrangement screening and characterization

Methods presently employed for detection of large rearrangements have several drawbacks, such as the amount of sample and time required, technical difficulty, or the probability of false-negative carriers. Using the low-density-lipoprotein receptor (LDLR) gene, whose mutations are responsible for familial hypercholesterolemia (FH), we have developed a procedure to detect large rearrangements in this gene based on semiquantitative PCR, with important improvements as compared to previous methods. Our method covers the complete LDLR gene and introduces an internal control in the reaction. The procedure discriminates the four different large rearrangements (two deletions and two insertions) that we have used as positive mutation controls (Valencia-1 to -5). All altered exons from each rearrangement are identified. Furthermore, when families from probands carrying these large rearrangements (34 members) were analyzed, our results agreed with those obtained previously with Southern blot. We have also analyzed a sample of 110 unrelated FH probands and the method has correctly identified the two different large rearrangements present and insertions or deletions as small as 1 bp. In conclusion, the method we present allows the identification of large rearrangements affecting exons of the gene, including small insertions or deletions or complete gene deletion. In addition, it constitutes a first characterization step of rearrangements, and is easy to carry out fast, and can be applied to the analysis of any gene.