[11C]PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.

3D printed microfluidic circuitry via multijet-based additive manufacturing.

The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or "three-dimensional (3D) printing" technologies - predominantly stereolithography - as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) - a layer-by-layer, multi-material inkjetting process - for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community.

p53 protein expression and gene mutation in phyllodes tumors of the breast.

The malignant potential of mammary phyllodes tumors is difficult to assess on initial pathologic examination. Studies on the p53 tumor suppressor gene have shown that it has an important role in the development of a variety of malignancies, yet the specific contribution to the pathogenesis and development of the malignant potential of phyllodes tumor is largely unknown. We studied p53 protein expression in 25 cases of phyllodes tumors histologically classified as either malignant (12 cases) or benign (13 cases). Using microdissection approach, we also analyzed the p53 gene sequence in a case that demonstrated progression from benign to malignant phenotype. Nuclear p53 staining was detected in various proportions (1-90%) of neoplastic stromal cells of malignant tumors. No staining was found in benign tumors. Progression from benign to malignant phenotype was associated with a significant increase in the accumulation of p53 (more than 20 times). This was caused by an underlying missense mutation in exon 7, resulting in a change from Arg248 to Trp248 in the malignant component of the tumor. Stromal p53 over-expression was observed only in neoplasms histologically classified as malignant and was associated with an increased proliferation index (MIB-1 staining). These two markers may be used as useful adjuncts in the diagnosis of malignancy in difficult cases or when only a limited sample size is available. Somatic mutation in exon 7 of p53 gene in malignant phyllodes tumor points toward the importance of p53 in the malignant transformation of phyllodes tumors.

Use of combining in situ hybridization and immunohistochemistry in detecting human papillomavirus on routine sections in cases of diagnostic uncertainty.

OBJECTIVES: To determine the combined role of in situ hybridization (ISH) and immunohistochemistry (IHC) in the detection of human papilloma virus (HPV) infection in cases of diagnostic uncertainty. DESIGN: A retrospective study. SETTINGS: Department of Histopathology at the University of Zimbabwe and Department of Pathology at the University of Texas Medical Branch at Galveston in Texas, both teaching referral hospitals. SUBJECTS: 23 patients with a diagnosis suggestive but not diagnostic of HPV infection on routine histology sections of uterine cervical biopsies, in which 20 had enough material to complete the study. MAIN OUTCOME MEASURES: Surgical pathology records of cases with morphologic features suggestive but not diagnostic of HPV cases were identified. Representative sections of each case were investigated with ISH and IHC for HPV infection. RESULTS: HPV DNA was detected in 12 cases. The bovine papilloma virus (BPV) antibody immunoreacted with six of the cases and two of these had not been detected by ISH resulting in a combined ISH and IHC, HPV detection of 14 cases. CONCLUSION: This preliminary data seems to support the validity of combining IHC and ISH, even though IHC is less sensitive compared to ISH, it may detect certain HPV types not represented in the DNA probe.

Immunohistochemical diagnosis of typhus rickettsioses using an anti-lipopolysaccharide monoclonal antibody.

A monoclonal antibody directed against an epitope on the lipopolysaccharide of typhus-group rickettsiae was developed for the purpose of detecting this heat-stable, proteinase-resistant antigen in formalin-fixed, paraffin-embedded tissues. Rickettsia prowazekii organisms were identified in endothelium and macrophages in sections of the brains of three Egyptian men who died of epidemic louse-borne typhus in Cairo during World War II and in the brain from a recent case of typhus fever acquired in Burundi. R. typhi organisms were identified in endothelial cells from a fatal case of murine typhus and in experimentally infected mice. This approach is applicable not only to the study of archival tissues and experimental animal models but also could be used to establish a timely diagnosis of typhus-group rickettsiosis by immunohistochemical examination of cutaneous biopsies of rash lesions during the acute stage of illness.

Right heart pseudotumor simulated by ascitic pseudocyst. An unusual complication of peritoneovenous shunting.

Peritoneovenous shunting (PVS) for intractable ascites has an extensive clinical experience, with several well-described complications. We recently noted an unusual complication of PVS with a Denver shunt. A 37-year-old woman who had placement of a shunt for chylous ascites 18 months prior to presentation demonstrated on a large, mobile mass filling the right atrium which, during atrial systole, partially prolapsed into the right ventricle. At cardiac surgery, a 4 X 10 cm mass with attachment to the tip of the shunt was found. Intracardiac ascitic pseudocyst is a potentially lethal complication of PVS with the Denver shunt which should be considered with a high index of suspicion and evaluated with echocardiography.

Left main coronary artery disease in a 19-year-old woman. Treatment by saphenous vein grafting.

Syncope, palpitations, ventricular tachycardia, and electrocardiographic changes of acute myocardial ischemia in a 19-year-old woman resulted from significant narrowing of the left main coronary artery and its ostium, producing high-grade obstruction to flow as documented by selective coronary arteriography. Because of these findings and markedly positive results of cardiovascular stress testing, surgical treatment by aortocoronary artery saphenous vein bypass grafting to the left anterior descending artery was carried out. Four years postoperatively, the patient was asymptomatic, and there are no abnormal findings on cardiovascular stress testing.

HbE-beta-thalassemia associated with G6PD deficiency.

HbE, beta thalassemia, and G6PD deficiency were demonstrated in a 6-year-old Mexican-American child with anemia, jaundice, and delayed growth. The father was heterozygous for HbE, and the mother for beta-thalassemia and G6PD deficiency. The association of these three diseases should be included in the differential diagnosis of anemia in childhood, particularly after the recent influx of people form Southeast Asia into the United States.

Structure in relation to behavior of mutant hemoglobins in citrate agar electrophoresis.

The comparative mobilities, in citrate agar electrophoresis, of 91 mutant hemoglobins are presented in relation to their molecular structure and in some cases, to their mobilities in other types of electrophoresis. More than a third of the alpha chain mutants (11 of the 27 examined) and half of the beta chain mutants (29 of 55) differ to some extent from Hb A. The helical location of the substituted residue is an important determinant of hemoglobin mobility, which is also affected by a complex interplay of other factors. When the data are combined with those of several other types of electrophoresis, they often provide presumptive (or in some cases highly specific) identifications of mutant hemoglobins and hemoglobinopathies.

Abnormal hemoglobins in a quarter million people.

Hemolysates of erythrocytes from more than a quarter million people in Alabama were electrophoresed on cellulose acetate, pH 8.4, and those samples exhibiting an abnormality were also electrophoresed in citrate agar, pH 6.0. The globin chains of mutants other than Hb S and C were electrophoresed in urea-mercaptoethanol buffers at both pH 8.9 and pH 6.0, and 60 of them were also analyzed structurally. Of about 6000 samples from whites, only three contained abnormal hemoglobins--Hb D Los Angeles, Hb J Baltimore, and one unidentified. Of 249,000 samples from blacks, about 29,000 contained electrophoretically detectable abnormalities, most of them associated with Hb S or C, present in a frequency of about 9% and 3%, respectively. About 1000 samples resolved into patterns of potential clinical significance. Twenty other mutant hemoglobins were detected, in various genetic combinations in 164 kindreds; four of these-Hb Alabama, Montgomery, Titusville, and Mobile--were previously unknown. The methods used are rapid, economical, and well suited for large scale surveys. They provide highly specific characterizations of many mutant hemoglobins, and no discrepancies were found between the presumptive identifications based on these characterizations and the definitive identifications obtained from structural analyses.