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 To elucidate the pattern of lesions in the liver parenchyma after ethanol ingestion, the quantitative distribution profiles of both the cytosolic and the mitochondrial aldehyde dehydrogenase isoenzyme activities were determined by the use of ultrathin-layer electrophoresis. It was found that in human liver parenchyma, both isoforms of aldehyde dehydrogenase are almost homogeneously represented in the liver acinus. These quantitative data are supported by the results of an improved histochemical technique. Moreover, sex differences were not detected either in activity or in the distribution pattern. Consequently, it can be assumed that it is not the activity of total aldehyde dehydrogenase or its isoforms which is responsible for the higher susceptibility of the perivenous zone to alcohol-dependent damage.

Localization of sulfomucopolysaccharides in developing teeth of Swiss albino mice was detected by S35 autoradiography and histochemistry. A positive correlation was found to exist between autoradiographic and histochemical data with regard to the localization of sulfomucopolysaccharides. Autoradiography, however, revealed some sites of localization which were not detectable by histochemistry, namely, the odontoblasts and stratum intermedium. Fetuses which received the isotope via maternal injection at the cap stage of tooth development and were sacrificed after 2 hours of isotope action displayed rapid incorporation of the isotope in the components of the dental papilla. In the enamel organ, however, only moderate activity was recorded. When the time interval between injection and sacrifice of the experimental animals was increased to 20 hours, intense activity was observed in the enamel organ. With progressively longer intervals between injection and sacrifice, S35 was demonstrable first in odontoblasts and later in the predentin. This occurred as a band or active zone which migrated toward the dentino-enamel junction. With the increasing intervals between injection and sacrifice, first the odontoblasts were active, then predentin was active while the odontoblasts became reduced in activity, after which the dentin matrix gained activity while the predentin decreased somewhat in activity. This pattern is consistent with appositional growth. A linear band of activity was not observed in the enamel matrix; rather, the activity was present as a diffuse stippling over a relatively large area of the matrix. The sulfomucopolysaccharide which existed in dentin matrix was postulated to have originated from the cells of both the odontoblastic layer and the dental papilla.

Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxin which is specific for cholinergic nerve terminals. Besides its effects on elements of the acetylcholine system, we observed that, after 2 and 8 days, a single 20-nmol intracerebroventricular dose altered the Timm's staining of certain regions of the central nervous system and reduced the tissue levels of trace metals. In the hippocampal formation, there was a considerable decrease in the staining of the neuropil of the stratum radiatum and stratum oriens, which contain cholinergic nerve terminals. A reduction in staining was also demonstrated in the perikarya of cortical pyramidal cells. The diminished trace-metal level in both regions was confirmed by quantitative measurements of zinc and copper levels. A similar reduction was not observed at a lower dose (8 nmol) of the cholinotoxin. The results led to the conclusion that AF64A may cause the decrease of the trace-metal content of the postsynaptic neurons through an indirect mechanism.

Fluorescence microscopy is a highly effective tool for interrogating biological structure and function, particularly when imaging across multiple spatiotemporal scales. Here we survey recent innovations and applications in the relatively understudied area of multiscale fluorescence imaging of living samples. We discuss fundamental challenges in live multiscale imaging and describe successful examples that highlight the power of this approach. We attempt to synthesize general strategies from these test cases, aiming to help accelerate progress in this exciting area.

Genes have preferential non-random spatial positions within the cell nucleus. The nuclear position of a subset of genes differ between cell types and some genes undergo repositioning events in disease, including cancer. It is currently unclear whether the propensity of a gene to reposition reflects an intrinsic property of the locus or the tissue. Using quantitative FISH analysis of a set of genes which reposition in cancer, we test here the tissue specificity of gene repositioning in normal and malignant breast or prostate tissues. We find tissue-specific organization of the genome in normal breast and prostate with 40 % of genes occupying differential positions between the two tissue types. While we demonstrate limited overlap between gene sets that repositioned in breast and prostate cancer, we identify two genes that undergo disease-related gene repositioning in both cancer types. Our findings indicate that gene repositioning in cancer is tissue-of-origin specific.

Two methods to determine fructose-1,6-diphosphatase activity histochemically were tested on liver, intestine, skeletal muscle and heart of rats. Using lead ions to precipitate inorganic phosphate, according to Wachstein and Meisel, the addition of the specific inhibitor adenosine monophosphate caused an increase of phosphate precipitation. Therefore this method is often not suitable. A coupled assay, used to detect fructose-6-phosphate formed after conversion to glucose-6-phosphate (which in its turn may reduce tetrazolium dyes in the glucose-6-phosphate dehydrogenase reaction), was found to be satisfactory in liver to demonstrate specific fructose-1,6-diphosphatase activity, since adenosine monophosphate was strongly inhibitory. In intestine acid- and alkaline phosphatases, however, were found to interfere. In the latter organ, added adenosine monophosphate itself strongly stimulates formazan formation, which is probably due to high xanthine oxidase activity. In muscle, where a high aldolase activity is present, monoiodoacetate must be included in the incubation medium. Since fructose-1,6-diphosphatase activity in muscle is low compared with that of liver, the results obtained with muscle are often difficult to interpret.

The endocrine cells of the processus uncinatus in the dog pancreas were investigated with special reference to the formerly known F-cell. The F-cell was detected frequently in the periphery of pancreatic islets as well as among exocrine tissue. In both localizations the F-cell shows similar ultrastructural features. Membrane-bound irregularly shaped secretory granules of variable electron density were seen. The cell possesses all features of an endocrine polypeptide secreting cell. Using the immunofluorescence and immunoperoxidase technique in the uncinate processus of the dog, we could reveal that the anti-sera against bovine pancreatic polypeptide (BPP) reacts with the cell which is localized at the same sites as the F-cell. We therefore concludes that the pancreatic F-cell is identical to the pancreatic polypeptide-producing cell. The other endocrine cell types of the dog pancreas are glucagon-producing A-cells, insulin-producing B-cells, and somatostatin-producing D-cells, as well as serotonin-producing EC-cells which are regularly present in the dog pancreatics islets and also scattered among exocrine tissue and the duct epithelial cells.