Trisomy 18/trisomy 13 mosaicism in an adult with profound mental retardation and multiple malformations

We report on an adult woman with profound mental retardation and multiple anomalies who consists of 3 cell lines: one with trisomy 18, one with trisomy 13, and a normal cell line. Her phenotype includes manifestations of both trisomy syndromes. The origin of these cell lines could have been a doubly aneuploid (48,XX+ 13, + 18) or singly aneuploid (47,XX + 18 or 47,XX, + 13) zygote with subsequent mitotic nondisjunctions, or a normal zygote with multiple mitotic nondisjunctions. There have been four previous reports of mosaicism involving both trisomy D and trisomy E; all died in the first six months of life. Two of these cases had a doubly aneuploid (48,XX, + D + E) cell line. Our patient illustrates the need for study of several tissues in patients with complex aneuploidy syndromes or atypical manifestations of a given syndrome (such as prolonged survival), as well as the need for caution in counseling families about prognosis for survival in autosomal trisomies which usually are lethal.     

Phagocytic efficiency of monocytes and macrophages obtained from Sydney blood bank cohort members infected with an attenuated strain of HIV-1

Defective function of monocyte-derived macrophages contributes to HIV-1 pathogenesis. We found that phagocytosis of the opportunistic pathogens Mycobacterium avium complex and Toxoplasma gondii was impaired in monocytes obtained from individuals infected with wild-type strains of HIV-1 but generally not in monocytes collected over a 6-year period from Sydney Blood Bank Cohort (SBBC) members infected with nef/long terminal repeats (LTR) region-defective strains of HIV-1. However, longitudinal analysis of phagocytosis in 1 SBBC member, C54, showed the development of defective engulfment of opportunistic pathogens at the most recent time points, coincident with the development of further molecular deletions in the nef/LTR region. Another SBBC member, C98, underwent bronchoscopy, which provided material to examine phagocytic signaling in alveolar macrophages. In contrast to normal phagocytic efficiency of C98's monocytes (over a 6-year period), defective signaling events during FcgammaR-mediated phagocytosis by C98's alveolar macrophages were observed. High basal phosphorylation within HIV-infected macrophages correlated with colocalization of tyrosine-phosphorylated proteins with HIV-1 p24 antigen rather than around the phagocytic targets as observed in uninfected cells. Thus, although phagocytic efficiency appears to be generally unimpaired in monocytes from SBBC members, evidence of impairment in recent samples from 1 SBBC member, coincident with further genetic changes within the virus, and abnormal phagocytic signaling in alveolar macrophages from another SBBC member may herald loss of attenuation of those strains.     

Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.

The plasma protein apolipoprotein (apo) E is an important determinant of lipid transport and metabolism in mammals. In the present study, immunocytochemistry has been used to identify apo E in specific cells of the central and peripheral nervous systems of the rat. Light microscopic examination revealed that all astrocytes, including specialized astrocytic cells (Bergmann glia of the cerebellum, tanycytes of the third ventricle, pituicytes of the neurohypophysis, and Müller cells of the retina), possessed significant concentrations of apo E. In all of the major subdivisions of the central nervous system, the perinuclear region of astrocytic cells, as well as their cell processes that end on basement membranes at either the pial surface or along blood vessels, were found to be rich in apo E. Extracellular apo E was present along many of these same surfaces. The impression that apo E is secreted by astrocytic cells was confirmed by electron microscopic immunocytochemical studies, which demonstrated the presence of apo E in the Golgi apparatus. Apo E was not present in neurons, oligodendroglia, microglia, ependymal cells, and choroidal cells. In the peripheral nervous system, apo E was present within the glia surrounding sensory and motor neurons; satellite cells of the dorsal root ganglia and superior cervical sympathetic ganglion as well as the enteric glia of the intestinal ganglia were reactive. Apo E was also present within the non-myelinating Schwann cells but not within the myelinating Schwann cells of peripheral nerves. These results suggest that apo E has an important, previously unsuspected role in the physiology of nervous tissue.     

HDL cholesterol and the acute phase reaction following myocardial infarction and acute pancreatitis

The response of HDL in the acute phase reaction following myocardial infarction (MI) (82 subjects) and acute pancreatitis (AP) (30 subjects) has been examined and compared with that in a control group (76 subjects) admitted to hospital with suspected MI but in whom the diagnosis was not subsequently confirmed. The temporal and quantitative characteristics of the changes in concentration of the positive acute phase reactants fibrinogen and alpha 1-antitrypsin and the negative acute phase reactants albumin and LDL were similar in the myocardial infarction and acute pancreatitis subjects. In contrast, the response of HDL was different to that of the other transport proteins both within each experimental group and between the two groups. This indicated that the response of HDL cannot be regarded as simply part of a secondary negative acute phase reaction. After adjustment for changes in plasma volume, the data indicated that hepatobiliary dysfunction was probably a major factor in the negative response of HDL following acute pancreatitis and may have contributed to its response following myocardial infarction.     

Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation

The recently identified histamine H4 receptor has revealed a potential new complexity for the role of histamine in the immune system. To begin to understand the role of this receptor in humans, one must first determine whether homologs exist and can be studied in lower species. To address this, we cloned the rat, mouse, and guinea pig cDNAs corresponding to the recently identified human histamine H4 receptor. The rat, mouse, and guinea pig H4 sequences are significantly different from the human H4 sequence at 69, 68, and 65% homology, respectively. The tissue distribution of the rat, mouse, and guinea pig H4 receptors is similar to human in that bone marrow and spleen are the most abundant sources of expression. The human and guinea pig H4 receptors display the highest binding affinity for [3H]histamine (KD = 5 nM each), whereas the affinities for rat and mouse receptors are substantially lower at 136 and 42 nM, respectively. With respect to the pharmacological profile of known H3/H4 ligands, even greater differences in binding affinities exist among the species homologs. There are also substantial differences in the signal transduction response to each of the four species of H4 receptor. This work demonstrates the existence of histamine H4 receptors in lower species and demonstrates that a clear knowledge of each species pharmacological profile will be essential to elucidate the role of this receptor subtype in vivo.     

No evidence for tumorigenesis of AAV vectors in a large-scale study in mice.

Six hundred ninety-five mice received adeno-associated virus (AAV) vectors, mostly via portal vein injection. At necropsy, the livers were inspected for tumors, and tissue sections were prepared for histology. We observed only one tumor, a lipoma, resulting in a tumor frequency of 0.14%. This tumor contained fewer vector genomes per total DNA than the surrounding liver tissue, as shown by quantitative PCR. In another mouse we found a macroscopically visible nodule containing lymphocytes. Immunohistochemistry revealed cells not of monoclonal origin, and they contained fewer AAV genomes than the surrounding hepatocytes. There were no macroscopic tumors in 226 control mice. Upon microscopic examination, lymphocytic infiltrates were found in 5% of livers of both control and vector-treated mice; no transgene expression was seen in those infiltrates in AAV-injected animals. Compared to an average frequency of spontaneous liver tumors in C57BL/6 mice (0-10%), and given the absence of high levels of vector DNA in the observed tumor, we conclude that AAV vectors do not predispose these target animals to the formation of liver tumors.     

牙列缺损的计算机三维建模

目的 建立牙列缺损的计算机三维模型。方法 采用表面绘制法,依据CT扫描头颅骨标本获得的二维断层图像数据在3D Studio Max中沿牙体长轴放样、微调并赋以材质,得到牙列缺损的计算机三维模型。结果 能在计算机中方便快速地模拟任意类型的牙列缺损,并可全方位地旋转、放大和缩小。结论 提供了一种牙列缺损三维建模的新方法,有利于三维义齿专家系统的开发和计算机辅助教学。