Clinical and radiographic features of Hutchinson-Gilford progeria syndrome: A case report

Hutchinson-Gilford progeria syndrome (HGPS) is a rare dysmorphic syndrome characterized by several features of premature aging with clinical involvement of the skin, bones, and cardiovascular system. HGPS has an estimated incidence of one in four million to one in eight million births. The main clinical features of HGPS include short stature, craniofacial dimorphism, alopecia, bone fragility, and cardiovascular disorders. The most frequent cause of death is myocardial infarction at a mean age of 13 years old. Dental manifestations include delayed development and eruption of teeth, discoloration, crowding and rotation of teeth, and displaced teeth. Cone beam computed tomography images revealed the absence of the sphenoid, frontal, and maxillary sinus, flattening of the condyles and glenoid fossa, and bilateral hypoplasia of the mandibular condyles. The disease is caused by mutations in lamin A/C (LMNA). Here, we present a case report of an 11-year-old boy with classical features of HGPS, which was caused by a de novo germ-line mutation (C1824T, G608G) in exon 11 of the LMNA gene. Some uncommon HGPS-associated features in our patient, such as alterations in the facial sinuses and hypoplasia of the condyles, contributed to the expansion of the phenotypic spectrum of this syndrome from a dentomaxillofacial perspective.     

Clinical and molecular genetic characterization of two female patients harboring the Xq27.3q28 deletion with different ratios of X chromosome inactivation

A heterozygous deletion at Xq27.3q28 including FMR1, AFF2, and IDS causing intellectual disability and characteristic facial features is very rare in females, with only 10 patients having been reported. Here, we examined two female patients with different clinical features harboring the Xq27.3q28 deletion and determined the chromosomal breakpoints. Moreover, we assessed the X chromosome inactivation (XCI) in peripheral blood from both patients. Both patients had an almost overlapping deletion at Xq27.3q28, however, the more severe patient (Patient 1) showed skewed XCI of the normal X chromosome (79:21) whereas the milder patient (Patient 2) showed random XCI. Therefore, deletion at Xq27.3q28 critically affected brain development, and the ratio of XCI of the normal X chromosome greatly affected the clinical characteristics of patients with deletion at Xq27.3q28. As the chromosomal breakpoints were determined, we analyzed a change in chromatin domains termed topologically associated domains (TADs) using published Hi‐C data on the Xq27.3q28 region, and found that only patient 1 had a possibility of a drastic change in TADs. The altered chromatin topologies on the Xq27.3q28 region might affect the clinical features of patient 1 by changing the expression of genes just outside the deletion and/or the XCI establishment during embryogenesis resulting in skewed XCI.     

Effect of p53 deficiency on external vascular cuff-induced neointima formation.

The p53 tumor suppressor gene may act as an inhibitor of vascular neointima formation in response to injury and in the present study the effects of p53 deficiency on external vascular cuff-induced neointima formation were evaluated. Vascular neointima formation was induced by an external vascular cuff; a polyethylene tube placed around a 2 mm segment of the left femoral artery ensheathed the adventitia, but avoided direct intraluminal injury. Two weeks after cuff placement, the cuff-sheathed and contralateral control arteries without cuff from wild-type (n=10) and p53 deficient (n=8) mice were harvested and analyzed by quantitative morphometry. The areas of the lumen, intima, and media were measured in 10 cross-sections from one edge to the other of the cuffed portion, and in the corresponding 2-mm segment of the contralateral control artery. The volume ratio of the intima to media (I/M) was calculated. The contralateral control arteries without a cuff did not have intima in either wild-type or p53 deficient mice. In the cuff-sheathed arteries, neointima formation of p53 deficient mice with an I/M of 93% was significantly greater than that of wild-type mice with an I/M of 50% (P=0.001). The absence of p53 is associated with increased neointima formation in response to cuff injury.     

Molecular biology as a tool for the treatment of cancer

Cancer is a genetic disease characterized by uncontrolled cell growth and metastasis. Cancer can have a number of causes, such the activation of oncogenes, the inactivation of tumor-suppressing genes, mutagenesis provoked by external factors, and epigenetic modifications. The development of diagnostic tools and treatments using a molecular biological approach permits the use of sensitive, low-cost, noninvasive tests for cancer patients. Biomarkers can be used to provide rapid, personalized oncology, in particular the molecular diagnosis of chronic myeloid leukemia, and gastric, colon, and breast cancers. Molecular tests based on DNA methylation can also be used to direct treatments or evaluate the toxic effects of chemotherapy. The adequate diagnosis, prognosis, and prediction of the response of cancer patients to treatment are essential to ensure the most effective therapy, reduce the damaging effects of treatment, and direct the therapy to specific targets, and in this context, molecular biology has become increasingly important in oncology. In this brief review, we will demonstrate the fundamental importance of molecular biology for the treatment of three types of cancer—chronic myeloid leukemia, hereditary diffuse gastric cancer, and astrocytomas (sporadic tumors of the central nervous system). In each of these three models, distinct biological mechanisms are involved in the transformation of the cells, but in all cases, molecular biology is fundamental to the development of personalized analyses for each patient and each type of neoplasia, and to guarantee the success of the treatment.     

6,7-dihydroxyflavone dramatically intensifies the susceptibility of methicillin-resistant or -sensitive Staphylococcus aureus to beta-lactams

We have demonstrated that 6,7-dihydroxyflavone by itself has only a weak antibacterial effect on methicillin-resistant Staphylococcus aureus (MRSA) but that at concentrations less than MIC it synergistically elevates the susceptibility of clinically isolated MRSA and methicillin-sensitive S. aureus strains to beta-lactam antibiotics from 8- to 32,800-fold.     

Pulmonary nocardiosis in a patient treated with corticosteroid therapy

We report a case of pulmonary nocardiosis in a 69-year-old man with rheumatoid arthritis who was receiving corticosteroid treatment. The patient received prednisolone for rheumatoid arthritis and antibiotics for his fever and pneumonia in another hospital, but the response to the therapy was poor. After admission to our hospital, he improved following treatment with imipenem/cilastatin for Nocardia asteroides. Pulmonary nocardiosis is difficult to diagnose and should be considered in the differential diagnosis, especially in an immunocompromised host.     

Mechanism of enhanced toxicity of 6-mercaptopurine with endotoxin

The enhanced toxicity of 6-mercaptopurine with endotoxin has been confirmed with BALB/c male mice. Striking increases in thioinosinic acid were seen in mice pretreated with endotoxin before injection of 6-mercaptopurine, and were in agreement with the time course of the inhibiting effect of endotoxin on sleeping time. However, there were no significant differences in hypoxanthineguanine phosphoribosyltransferase between control mice and endotoxin-treated mice. Furthermore, there were significant increases in xanthine oxidase after treatment with endotoxin. It is clear that metabolism of 6-mercaptopurine might be modified by activity of the drug-metabolizing enzyme in mouse liver. Based on the effect of endoxotin on 6-mercaptopurine metabolism and the enzymes responsible for 6-mercaptopurine, it is suggested that death caused by 6-mercaptopurine-endotoxin combinations is due to an enhancement of the lethal effect of 6-mercaptopurine. Simultaneous administration of 6-mercaptopurine and endotoxin resulted in a parallel potentiation of either 6-mercaptopurine toxicity or endotoxin toxicity. This interaction was abolished in mice made resistant to the effects of endotoxin. Based on time of death, it is suggested that death caused by 6-mercaptopurineendotoxin combinations is due to an enhancement of the lethal effect of endotoxin. These results indicate that the underlying mechanism of the interaction may involve a dualistic enhancement of each agent.