Ancillary alpha-methylacyl-CoA racemase immunocytochemistry in the diagnosis of adenocarcinoma of the prostate in urinary cytology: a case report

BACKGROUND: Alpha-methylacyl-coA racemase (AMACR) was recently shown to be a sensitive immunohistochemical marker for substantiating a diagnosis of adenocarcinoma of the prostate. Its applicability to exfoliative urinary cytology has not been investigated before. CASE: The patient was a 77-year-old male with a history of persistent intermittent hematuria who was evaluated with urine cytology. Cytopathologic studies were interpreted to demonstrate "atypical urothelial cells." The patient was evaluated with computed tomography, which demonstrated new left hydroureter and hydronephrosis. He underwent cystoscopy, which showed an abnormal left hemitrigone with the left ureteral orifice obscured by an infiltrative mass. This area was biopsied, and histologic studies of the tissue chips demonstrated underlying prostatic adenocarcinoma directly invading the urothelium. We used AMACR immunoreactivity on a retrospectively studied, catheterized urine slide to confirm the diagnosis. CONCLUSION: This case suggests that combined cytomorphology and immunocytochemisty for AMACR may allow an accurate identification of cells of prostatic adenocarcinoma when cytomorphologic studies or the clinical history raises the differential diagnosis of prostate cancer presenting with exfoliation of malignant cells into the urine.     

Dynamics and diffusion in photosynthetic membranes from rhodospirillum photometricum

Photosynthetic organisms drive their metabolism by converting light energy into an electrochemical gradient with high efficiency. This conversion depends on the diffusion of quinones within the membrane. In purple photosynthetic bacteria, quinones reduced by the reaction center (RC) diffuse to the cytochrome bc(1) complex and then return once reoxidized to the RC. In Rhodospirillum photometricum the RC-containing core complexes are found in a disordered molecular environment, with fixed light-harvesting complex/core complex ratio but without a fixed architecture, whereas additional light-harvesting complexes synthesized under low-light conditions pack into large paracrystalline antenna domains. Here, we have analyzed, using time-lapse atomic force microscopy, the dynamics of the protein complexes in the different membrane domains and find that the disordered regions are dynamic whereas ordered antennae domains are static. Based on our observations we propose, and analyze using Monte Carlo simulations, a model for quinone diffusion in photosynthetic membranes. We show that the formation of large static antennae domains may represent a strategy for increasing electron transfer rates between distant complexes within the membrane and thus be important for photosynthetic efficiency.     

The photosynthetic apparatus of Rhodopseudomonas palustris: structures and organization

The structural analysis of the individual components of the photosynthetic apparatus of Rhodopseudomonas palustris, or those of related species, is almost complete. To shed light on the assembly and organization of this machinery, we have studied native membranes of Rps.palustris grown under different light conditions using atomic force microscopy (AFM). The organization of the complexes in the membranes is different from any previously observed: with areas of crystalline core-complexes, crystalline peripheral antennae, mixed domains, and apparently pure lipid membranes devoid of protein. Examination of antennae structure shows that chromatic adaptation is associated with modifications in absorption and size of the peripheral light harvesting complexes (LH2) as light intensity is reduced. The core-complex is observed to contain a reaction centre (RC) surrounded by an elliptical assembly of 15 LH1 subunits and a "gap" attributed to the W-subunit. The localization of the W-subunit is not restricted to the periapsis of the core-complex but randomly located with respect to the RC imposed axis.     

Incommensurable Worldviews? Is Public Use of Complementary and Alternative Medicines Incompatible with Support for Science and Conventional Medicine?

Proponents of controversial Complementary and Alternative Medicines, such as homeopathy, argue that these treatments can be used with great effect in addition to, and sometimes instead of, ‘conventional’ medicine. In doing so, they accept the idea that the scientific approach to the evaluation of treatment does not undermine use of and support for some of the more controversial CAM treatments. For those adhering to the scientific canon, however, such efficacy claims lack the requisite evidential basis from randomised controlled trials. It is not clear, however, whether such opposition characterises the views of the general public. In this paper we use data from the 2009 Wellcome Monitor survey to investigate public use of and beliefs about the efficacy of a prominent and controversial CAM within the United Kingdom, homeopathy. We proceed by using Latent Class Analysis to assess whether it is possible to identify a sub-group of the population who are at ease in combining support for science and conventional medicine with use of CAM treatments, and belief in the efficacy of homeopathy. Our results suggest that over 40% of the British public maintain positive evaluations of both homeopathy and conventional medicine simultaneously. Explanatory analyses reveal that simultaneous support for a controversial CAM treatment and conventional medicine is, in part, explained by a lack of scientific knowledge as well as concerns about the regulation of medical research.     

Common Single Nucleotide Polymorphisms in Genes Related to Immune Function and Risk of Papillary Thyroid Cancer

Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (P_SNP-trend) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region- and pathway-level associations (P_Region and P_Pathway) were assessed by combining individual P_SNP-trend values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (P_SNP-FDR/P_SNP-trend = 0.02/6×10⁻⁶ and P_SNP-FDR/P_SNP-trend = 0.04/2×10⁻⁵, respectively). These associations were independent of a history of autoimmune thyroiditis (OR = 6.4; 95% confidence interval: 3.0–13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (P_Region-FDR/P_Region =0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (P_Pathway = 0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC.     

Molecular population genetics of the alcohol dehydrogenase locus in the Hawaiian drosophilid D. mimica

Sequence variation among 10 alleles of the alcohol dehydrogenase (Adh) gene of the Hawaiian drosophilid D. mimica was analyzed with reference to the evolutionary history of the Hawaiian subgroup as well as to levels and patterns of polymorphism of the Adh gene in continental drosophilid species. The Adh gene of D. mimica is less polymorphic than that of other drosophilid species, and no replacement substitutions were found. Statistical analyses of the Adh alleles suggested the action of balancing selection and revealed significant linkage disequilibrium among three of the variable sites. The effective population size was estimated to be only slightly smaller than that of continental species and, surprisingly, on the same order of magnitude as the actual size.      

Supramolecular assembly of VDAC in native mitochondrial outer membranes

The voltage-dependent anion channel (VDAC) is the most abundant protein in the mitochondrial outer membrane (MOM). Due to its localization, VDAC is involved in a wide range of processes, such as passage of ATP out of mitochondria, and particularly plays a central role in apoptosis. Importantly, the assembly of VDAC provides interaction with a wide range of proteins, some implying oligomerization. However, many questions remain as to the VDAC structure, its supramolecular assembly, packing density, and oligomerization in the MOM is unknown. Here we report the so far highest resolution view of VDAC and its native supramolecular assembly. We have studied yeast MOM by high-resolution atomic force microscopy (AFM) in physiological buffer and found VDAC in two distinct types of membrane domains. We found regions where VDAC was packed at high density (approximately 80%), rendering the membrane a voltage-dependent molecular sieve. In other domains, VDAC has a low surface density (approximately 20%) and the pore assembly ranges from single molecules to groups of up to 20. We assume that these groups are mobile in the lipid bilayer and allow association and dissociation with the large assemblies. VDAC has no preferred oligomeric state and no long-range order was observed in densely packed domains. High-resolution topographs show an eye-shaped VDAC with 3.8 nm x 2.7 nm pore dimensions. Based on the observed VDAC structure and the pair correlation function (PCF) analysis of the domain architectures, we propose a simple model that could explain the phase behavior of VDAC, and illustrates the sensitivity of the molecular organization to conditions in the cell, and the possibility for modulation of its assembly. The implication of VDAC in cytochrome c release from the mitochondria during cell apoptosis has made it a target in cancer research.     

Diagnostic significance of 'benign pairs' and signet ring cells in fine needle aspirates (FNAs) of the breast

sturgis c. d., sethi s., cajulis r. s., hidvegi d. f. and yu g. h. (1998) Cytopathology 9, 308–319 Diagnostic significance of ‘benign pairs’ and signet ring cells in fine needle aspirates (FNAs) of the breast Most breast mass lesions are readily characterized by FNA with cytodiagnosis. Occasionally, benign but markedly proliferative lesions are diagnostically difficult to separate from well differentiated malignancies. We present information pertaining to the diagnostic significance of two cytologic findings observed in breast aspiration specimens, namely pairs of stripped bipolar nuclei and signet ring cells (SRC). We have evaluated aspirate smears from 219 cases of histologically proven benign (n= 114) and malignant (n= 105) breast lesions. Both singlets and pairs of bipolar nuclei and SRC were enumerated, and their numbers were correlated to histological diagnosis. Closely associated pairs of stripped bipolar nuclei were found in 68% of benign lesions compared with only 3.8% of carcinomas, establishing their presence as a highly specific indicator of a benign process. Large numbers of such ‘benign pairs’ also favoured the diagnosis of fibroadenoma. SRC were identified in 66% of histologically proven carcinomas (67% of ductal and 70% of lobular). SRC were also present in 10% of histologically benign cases. In the malignant cases, SRC were most frequently noted in a single cell distribution or within small, loosely cohesive tissue fragments. In the benign instances, SRC were most commonly noted within large fragments, and many of these cells were proved by immunohistochemical reactions to be vacuolated myoepithelial cells. We conclude that the presence of bipolar nuclei in closely associated pairs suggests benignity and aids in the subclassification of benign breast masses. In addition, the presence of SRC does not aid in the classification of tumour subtype (ductal vs lobular), and the occurrence of such cells in the proper context should prompt surgical biopsy.