Lack of genetic association between cholesteryl ester transfer protein and Japanese sporadic Alzheimer's disease

Background: Cholesteryl ester transfer protein regulates the plasma high density lipoprotein cholesterol level, which is considered to play an antiatherogenic role in humans. The presence of apolipoprotein E epsilon4 allele is a strong risk factor for developing Alzheimer’s disease (AD). Since apolipoprotein E is a regulator of lipid metabolism, it is reasonable to assume that lipids play important roles in the pathogenesis of AD. Methods: We studied the relationship between polymorphisms of the cholesteryl ester transfer protein gene and risk for AD, analyzing two common polymorphisms of the gene and the relationship between them and plasma cholesterol level control samples. Results: These polymorphisms showed no association with risk for AD. In rs5882, there was no significant difference in the mean plasma cholesterol concentrations found between patients with the A/A, A/G and G/G genotype. For rs2303790, no significant difference in the mean baseline cholesterol concentrations was found between patients with the A/A genotype and carriers of the G allele. Conclusion: Our study indicates that these polymorphisms, rs5882 and rs2303790 were not associated with risk for AD. We also pointed out that these two polymorphisms do not affect plasma cholesterol levels in our Japanese AD samples.     

Endoscopic Sclerotherapy for Esophageal Varices after Renal Transplantation: Report of One Autopsy Case

Abstract: Endoscopic sclerotherapy has been used to manage esophageal varices. Severe complications resulting from this therapy including renal dysfunction have been reported. Therefore, particular caution must be taken with patients who have serious renal damage. Sclerotherapy was performed for esophagogastric varices in a patient that had received a kidney transplant following chronic renal dysfunction. Ethanolamine oleate was used as the sclerosant, and contained a contrast medium for varicealography in order that the flow of the sclerosant be monitored by fluoroscopy. Varicography during the injection allowed us to stop injection into the varices and into the irregular passageways of the feeders to the varices before the agent entered the systemic circulation. There were no complications during therapy. The patient died due to respiratory failure 41 months after the first treatment. Macroscopic findings of the autopsied specimens showed no esophagogastric varices and microscopic findings showed organized varices with recanalization into the submucosal layer of the esophagogastric lesions. Injection sclerotherapy using varicography with sclerosant-contrast medium mixture allowed treatment of this patient without incurring renal dysfunction.     

Langerhans-cell histiocytosis in an adult patient with multiple myeloma

A 44-year-old man who had suffered for 6 years from multiple myeloma developed multiple papules on the face and chest. Histological examination of these papules revealed the infiltration of predominantly histiocytic cells into the dermis and into parts of the epidermis. These cells were seen on electron-microscopic study to have Langerhans granules in the cytoplasm, which led to a diagnosis of Langerhans-cell histiocytosis concomitant with multiple myeloma. Possible explanations for this unusual association are discussed.     

A Case of Liposarcoma of the Cheek

A rare case of liposarcoma of the left cheek in a 51-year-oldwoman is reported. The first biopsy specimen was indicativeof lipoma. After one year, the patient consulted us again, becauseof rapid increase in size of the tumor, and then, since malignancywas suspected, another biopsy was performed and a diagnosisof a well-differentiated liposarcoma was made. The tumor wasexcised, and radiation and chemotherapy were given in the operativecourse. After one year, no evidence of recurrence or metastasiswas observed.     

A Novel Missense Mutation Causing a G487R Substitution in the S2–S3 Loop of Human ether‐à‐go‐go‐Related Gene Channel

hERG(G487R) Channel . Introduction: Mutations of human ether‐à‐go‐go‐related gene (hERG), which encodes a cardiac K⁺ channel responsible for the acceleration of the repolarizing phase of an action potential and the prevention of premature action potential regeneration, often cause severe arrhythmic disorders. We found a novel missense mutation of hERG that results in a G487R substitution in the S2–S3 loop of the channel subunit [hERG(G487R)] from a family and determined whether this mutant gene could induce an abnormality in channel function. Methods and Results: We made whole‐cell voltage‐clamp recordings from HEK‐293T cells transfected with wild‐type hERG [hERG(WT)], hERG(G487R), or both. We measured hERG channel‐mediated current as the “tail” of a depolarization‐elicited current. The current density of the tail current and its voltage‐ and time‐dependences were not different among all the cell groups. The time‐courses of deactivation, inactivation, and recovery from inactivation and their voltage‐dependences were not different among all the cell groups. Furthermore, we performed immunocytochemical analysis using an anti‐hERG subunit antibody. The ratio of the immunoreactivity of the plasma membrane to that of the cytoplasm was not different between cells transfected with hERG(WT), hERG(G487R), or both. Conclusion: hERG(G487R) can produce functional channels with normal gating kinetics and cell‐surface expression efficiency with or without the aid of hERG(WT). Therefore, neither the heterozygous nor homozygous inheritance of hERG(G487R) is thought to cause severe cardiac disorders. hERG(G487R) would be a candidate for a rare variant or polymorphism of hERG with an amino acid substitution in the unusual region of the channel subunit. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1246–1253, November 2012)