EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the literature.

Ectodermal dysplasia (ED) represents a collection of rare disorders that result from a failure of development of the tissues derived from the embryonic ectoderm. ED is often associated with hair, teeth, and skin abnormalities, which are serious conditions affecting the quality of life of the patient. To date, a large number of genes have been found to be associated with this syndrome. Here, we report a patient with hypohidrotic ED (HED) without family history. We identified that this patient's disorder arises from an X-linked HED with a mutation in the EDA gene (G299D) found by whole-exome sequencing. In addition, in this paper we summarize the disease-causing mutations based on current literature. Overall, recent clinical and genetic research involving patients with HED have uncovered a large number of pathogenic mutations in EDA, which might contribute to a full understanding of the function of EDA and the underlying mechanisms of HED caused by EDA mutations.

[Clinical follow-up and genetic analysis of six cases with hypophosphatasia].

Objective: To analyze the clinical, genetic characteristics and follow-up data of Chinese patients with hypophosphatasia (HPP). Methods: A retrospective analysis was conducted on six children with HPP admitted to the Department of Endocrinology, Genetics and Metabolism in Beijing Children's Hospital from October 2010 to January 2019. Summarized the clinical and follow-up data of all six patients, as well as the pathogenic variants of five children. Results: The serum alkaline phosphatase levels of all six children (five males and one female) were significantly reduced (2-49 U/L). The 6 patients aged from 2 months to 6 years and 4 months, 4 infantile HPP, 1 childhood HIP and 1 odonto HPP. The four patients with infantile HPP presented with anorexia, slow weight gain and hypercalcemia, whereas the one patient with childhood HPP and the other patient with odonto HPP had tooth loss. The patient with childhood HPP also manifested with motor dysfunction. Genetic testing was conducted for five patients and 4 unrelated Chinese families and revealed 10 variations in ALPL gene, including 7 missense variation, 1 insertion variation, 1 frameshift variation, 1 deletion variation.Of which 3 were novel (p.Y28C, p.268, F>L, p.A176V).One of the infantile patients lost follow-up and the other three deceased. The clinical conditions were much improved with medical intervention for patients with childhood, orodonto HPP. Conclusions: While HPP patients with different ages of onset present with common features, the prognosis differ significantly. The prognosis is good for patients with childhood, orodonto HPP and poor for patients with infantile HPP. Genetic testing is the main method for definitive diagnosis.

[A multicenter randomized controlled study on the treatment of acute and chronic pharyngitis with Binglianqingye Spray].

Objective:To further evaluate the clinical efficacy and safety of Binglianqingye Spray on acute and chronic pharyngitis by clinical observation. Method:A randomized, double-blind and multicenter clinical trial which served Jinsangzi Tablet and Jinhoujian Spray as the control groups was conducted to observe the effect of Binglianqingye Spray on 360 patients with acute and chronic pharyngitis. Result:Binglianqingye Spray could significantly improve the symptoms with the exact clinical efficacy of the acute pharyngitis or chronic pharyngitis, such as sore throat, pharyngeal mucosa and uvula, dry throat burning, headache, cough, pharynx posterior wall lymphoid follicles hyperemia swelling and mandibular angle lymph node swelling and so on, but it occasionally occurred urine abnormalities and urine sugar adverse reactions. At the same time, the taste satisfaction was 82.1%. Conclusion:The combined effects of Binglianqingye Spray on the treatment of acute pharyngitis or chronic pharyngitis are well, the adverse reaction is rare and the patient's compliance is high.

Altered expression of bone sialoproteins in vitamin D-deficient rBSP2.7Luc transgenic mice.

Bone sialoprotein (BSP) and osteopontin (OPN) are two major noncollagenous matrix proteins in mineralized connective tissue that have discrete roles in bone matrix formation, mineralization, and remodeling. The osteotropic secosteroid, 1,25-dihydroxyvitamin D3, a potent regulator of bone remodeling required for normal bone development, has been shown to exert differential effects on OPN and BSP expression by bone cells in vitro. To investigate these effects in vivo, we induced vitamin D3 deficiency in a transgenic mouse line (rBSP2.7Luc) that has a 2.7 kb rat BSP promoter linked to a luciferase reporter gene in its genome. Pregnant rBSP2.7Luc mice were fed vitamin D3-deficient food and demineralized water for 6 weeks. Their offspring were weaned at 3 weeks of age and then fed vitamin D-deficient food for an additional week. The control group were fed normal rodent pellets and water during the entire experimental procedure. Bone tissues from 40, 4-week-old offspring in each group were analyzed for BSP, OPN and luciferase expression. Vitamin D3-deficient mice displayed a rachitic phenotype that included reduced size and malformation of bones. Assays of the BSP promoter transgene in calvariae, mandibles, and tibiae of the rachitic mice showed increases in luciferase activity of 3.1-, 1.9-, and 4.6-fold, respectively, when compared with control littermates. Semiquantitative reverse transcriptase polymerase chain reaction assays of BSP mRNA revealed increases of 7-, 74-, and 66-fold, respectively, in the same rachitic bones, while OPN mRNA was reduced 12.5-fold in calvariae and 2-fold in tibiae and mandibles. In situ hybridization using mouse cRNA probes revealed that the increased BSP expression and decreased OPN expression in the vitamin D3-deficient mice was primarily in osteoblastic cells on the surface of calvariae and endosteal spaces of alveolar bone, on newly formed epiphyseal bone, and in cementoblasts and in hypertrophic chondrocytes. These studies are the first to show that BSP and OPN are differentially regulated by vitamin D3 in vivo, reflecting the diverse roles of these protein in bone remodeling. Moreover, the increased expression of the BSP transgene in the rachitic mice demonstrates that vitamin D3 regulation of BSP expression is mediated, in part, by element(s) within the 2.7 kb promoter region.

Inhibition of adenine nucleotide translocator by lipid peroxidation products.

Our previous data showed that aldehydic lipid peroxidation products, interacting with mitochondrial membrane lipids, could alter the physicochemical status of the membrane. This study was initiated to examine the interaction of these aldehydes with a major mitochondrial protein, the adenine nucleotide translocator (ANT). Our findings showed that the transporting activity of ANT in intact mitochondria was inhibited by two unsaturated aldehydes, 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE). To probe further into the underlying mechanism of this inhibition, a reconstituted ANT model was developed by incorporating isolated ANT into liposomes. Pretreatment of ANT with HNE prior to reconstitution resulted in decreased activity in the reconstituted ANT. Further investigation revealed that this decreased activity was probably due to loss of sulfhydryl groups, which are essential for ANT activity. Interestingly, pretreatment of the liposomes with HNE also caused a decrease in the reconstituted ANT activity by indirectly altering the physiochemical status of the lipid environment in which ANT was embedded. These results demonstrate that the reactive aldehydes derived from mitochondrial lipid peroxidation can impair the membrane function by interacting with both the protein and the lipid moieties in the membrane. Thus, the varied damaging effects associated with lipid peroxidation may be mediated by their secondary aldehydic byproducts.

RNA and protein synthesis in cultured human fibroblasts derived from donors of various ages.

RNA synthesis in human fibroblasts from donors of various ages was studied in fibroblasts made permeable to nucleoside triphosphates with the nonionic detergent Nonidet P40. Cells from donors of 11 years and older showed a 30-40% decline in total RNA synthesis. The decrease in RNA synthesis was primarily due to a lowering of RNA polymerase II activity (alpha-amanitin sensitive). Studies on the incorporation of leucine into protein also showed a 30-40% decrease in cells from older donors.

Localization of EMSP1 expression during tooth formation and cloning of mouse cDNA.

Enamel matrix serine proteinase 1 (EMSP1) is a proteolytic enzyme that has been isolated from the developing enamel of pig teeth. Its apparent function is to degrade the organic matrix in preparation for enamel maturation. The expression of EMSP1 has never been investigated in another organism besides the pig, and EMSP1 expression in the enamel organ has never been specifically demonstrated in ameloblasts. Here we report the expression of recombinant pig EMSP 1 (rpEMSP 1), the generation of rabbit polyclonal antibodies against rpEMSP1, the characterization of the antibodies and EMSP1 expression by Western blot and immunohistochemical analyses, the cloning and characterization of a full-length cDNA encoding mouse EMSP1, and the localization of EMSP1 expression in ameloblasts in mouse day 14 first and second molars by in situ hybridization. The full-length mouse EMSP1 cDNA clone has 1,237 nucleotides, excluding the poly(A+) tail, and encodes a preproprotein of 255 amino acids. Mouse EMSP1 shares 75% amino acid identity with pig EMSP1 and has three potential N-linked glycosylation sites, two of which are conserved in the pig homologue. Western blot analysis shows that the polyclonal antibodies are specific for EMSP1 and do not cross-react with trypsin. Immunohistochemistry of pig incisors shows discrete staining in the surface enamel at the earliest part of the maturation stage. In mouse molars, in situ hybridization gives a distinct and specific signal in maturation-stage ameloblasts, and in the junctional epithelium following tooth eruption. We conclude that EMSP1 is expressed by pig and mouse ameloblasts during the early maturation stage of amelogenesis.

Cloning human enamelin cDNA, chromosomal localization, and analysis of expression during tooth development.

Enamelin is the largest protein in the enamel matrix of developing teeth. In the pig, enamelin is secreted as 186-kDa phosphorylated glycoprotein, which is rapidly processed by enamel proteinases into smaller cleavage products. During the secretory stage of enamel formation, enamelin is found among the crystallites in the rod and interrod enamel and comprises roughly 5% of total matrix protein. Although the function of enamelin is unknown, it is thought to participate in enamel crystal nucleation and extension, and the regulation of crystal habit. Here we report the results of enamelin in situ hybridization in a day 1 mouse developing incisor that shows that enamelin is expressed by ameloblasts, but not by odontoblasts or other cells in the dental pulp. The restricted pattern of enamelin expression makes the human enamelin gene a prime candidate in the etiology of amelogenesis imperfecta (AI), a genetic disease in which defects of enamel formation occur in the absence of non-dental symptoms. We have cloned and characterized a full-length human enamelin cDNA and determined by radiation hybrid mapping and fluorescent in situ hybridization (FISH) that the gene is located on chromosome 4q near the ameloblastin gene in a region previously linked to local hypoplastic AI in six families. These findings will facilitate the search for specific mutations in the enamelin gene in kindreds suffering from amelogenesis imperfecta.

[Scanning electron microscopy of adult Trichuris trichiura].

The paper reports the result of the observation on the ultrastructure of the body surface of adult T. trichiura by scanning electron microscopy. Unique features of T. trichiura are described including the presence of labial-shape structures at the periphery of mouth, eight cephalic pores and a pair of amphids around the mouth pore and vesicle-shaped cuticular protuberances on the abdomen of T. trichiura. Cuticular pores were found scattering on the surface of T. trichiura. Detailed descriptions of male copulatory sheath and spicule were presented.

Retrospective evaluation of general anesthesia for oral and maxillofacial surgery during a 10-year period (1976-1985).

Anesthetic cases of oral and maxillofacial surgery during the period 1976-1985 were reviewed. There was a total of 653 cases, and the most frequently performed operation in this series was open reduction of maxillofacial bone fracture (22.8%). Special clinical problems were encountered in the 72 cases (11.02%) who underwent surgery for osteoradionecrosis, because most of them suffered from trismus and stiff neck. Nasotracheal intubation was more commonly used (84.69%). Sixty six cases received tracheostomy since they suffered from serious trismus and/or severe maxillofacial fracture. The recently introduced method of induction using etomidate and fentanyl seemed effective in maintaining hemodynamic stability. In 147 cases (22.51%), the anesthesia lasted more than 4 hours. In 366 cases (56.04%), a local infiltration of the operation field was performed with 1:100,000 epinephrine. Of these, 76 cases developed cardiac arrhythmia, mainly VPC (ventricular premature contraction) 12 of whom had a history of preoperative cardiac arrhythmias. The incidence of preoperative medical disease was 10.27%, the most common being cardiovascular (32.84%) and respiratory (26.87%) disease. Complications occurred during anesthesia in 122 cases (18.69%) with a high incidence of cardiac arrhythmia (67.21%).

Oral complications associated with endotracheal general anesthesia.

A series of 745 consecutive cases of endotracheal anesthesia were collected at the National Taiwan University Hospital. Evaluation of the oral conditions was performed before, during and after the anesthesia. Injuries to oral structures were recorded. An 18% incidence of oral injuries was noted and the frequency for dental damage was 12.1%. Maxillary incisors, especially the left ones, were accident-prone. Risk factors identified in this study included large decay or restoration, advanced periodontitis, presence of dental prosthesis, shedding deciduous tooth, class II jaw relationship and anterior crowding. More than one third of the complications occurred during the maintenance or emergence stage of the anesthesia. Recommendations for prevention and management of this problem were given.

Intrafamilial transmission of hepatitis C virus in hemodialysis patients.

The prevalence of hepatitis C virus (HCV) infection in chronic hemodialysis patients ranges from 20 to 50% and these patients may serve as a reservoir of infection for their household contacts. The aim of this study was to investigate the prevalence of anti-HCV in hemodialysis patients and their families, and to evaluate possible routes of infection. One hundred eighty-six family members of 84 hemodialysis patients and 529 healthy adults were enrolled. The family members consisted of 50 spouses, 96 children, 11 parents, 29 siblings, and other relatives living together with the patients. Serum samples were collected for testing anti-HCV. Exposure to risk factors was obtained by a questionnaire and an interview. The results showed that prevalence of anti-HCV in hemodialysis patients was 44%, whereas in family members it was 5.4%, not significantly different from that of age-matched healthy adults (standardized morbidity rate = 1.51, P = 0.390). The anti-HCV rate in family members tended to increase with age, and a spouse of an infected hemodialysis patient had a higher risk of HCV infection than other family members (15% vs. 2.6%, odds ratio 6.6, P = 0.058). Except for the age factor, no difference was found between seropositive and seronegative family members with respect to risk factors such as blood transfusion, surgery, frequent injections, dental procedures, or acupuncture. It was concluded that, although the anti-HCV positivity of hemodialysis patients is high, the risk of HCV infection for their family members is not higher than that of the general population. Among family members, spouses of seropositive hemodialysis patients have the highest risk of HCV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Profiling expression patterns and isolating differentially expressed genes by cDNA microarray system with colorimetry detection.

A high-density cDNA microarray with colorimetry detection system to simultaneously monitor the expression of many genes on nylon membrane is described and characterized. To quantify the expression of genes and to isolate differentially expressed genes, the southern hybridization process on filter membranes was employed. The levels of gene expression were represented by color intensities generated by colorimetric reactions in place of hazardous radioisotopes or costly laser-induced fluorescence detection. The gene expression patterns on nylon membranes were digitized by devices such as an economical flatbed scanner or a digital camera. The quantitative information of gene expression was retrieved by image analysis software. Quantitative comparison of the northern dot-blotting method with the microarray system is described. Applications employing single-color detection as well as dual-color detection to isolate differentially expressed genes among thousands of genes are demonstrated.