Role of Glucose-6-phosphatase in Hepatic and Renal Gluconeogenesis

Comparison of the effects of a high fat and high protein diet on the capacity for glucose formation from pyruvate and glycerol was investigated in vivo and in vitro. Ratios of radioactivity incorporated from either pyruvate-3-¹⁴C or glycerol-l-¹⁴C into blood glucose to those into expired CO₂ were higher in both groups fed the high fat and the high protein diet than those in a group fed a high carbohydrate diet. Gluconeogenesis from pyruvate and glycerol by liver slices were both increased significantly in rats fed the high fat diet, while feeding the high protein diet caused increase of renal gluconeogenesis from pyruvate and glycerol. The activities of hepatic and renal glucose-6-phosphatase(s) were changed in a similar fashion to changes in hepatic and renal gluconeogenesis, respectively.

In addition, the response of the activity of hepatic glucose-6-phosphatase with high dietary fat was more rapid than that of the activity of renal glucose-6-phosphatase with high dietary protein. Furthermore, the intraperitoneal injection of actinomycin-D to rats resulted in decrease of the activities of renal glucose-6-phosphatase of both groups fed the high fat and the high protein diet, but no significant change of the activity of hepatic glucose-6-phosphatase was observed among dietary groups.

These findings suggested that the increases in the overall flow of metabolites towards glucose formation by feeding the high fat and the high protein diet might be based on the action of different mechanisms which regulate the activities of glucose-6-phosphatase(s) of the liver and kidney.     

Gradients of strain and strain rate in the hollow muscular organs of soft-bodied animals

The cylindrical shape of soft-bodied invertebrates is well suited to functions in skeletal support and locomotion, but may result in a previously unrecognized cost—large non-uniformities in muscle strain and strain rate among the circular muscle fibres of the body wall. We investigated such gradients of strain and strain rate in the mantle of eight long-finned squid Doryteuthis pealeii and two oval squid Sepioteuthis lessoniana. Transmural gradients of circumferential strain were present during all jets (n = 312); i.e. for a given change in the circumference of the outer surface of the mantle, the inner surface experienced a greater proportional change. The magnitude of the difference increased with the amplitude of the mantle movement, with circular muscle fibres at the inner surface of the mantle experiencing a total range of strains up to 1.45 times greater than fibres at the outer surface during vigorous jets. Differences in strain rate between the circular fibres near the inner versus the outer surface of the mantle were also present in all jets, with the greatest differences occurring during vigorous jetting. The transmural gradients of circumferential strain and strain rate we describe probably apply not only to squids and other coleoid cephalopods, but also to diverse soft-bodied invertebrates with hollow cylindrical or conical bodies and muscular organs.     

Proteomic analysis of B-cell malignancies

The identification of proteins aberrantly expressed in malignant B-cells can potentially be used to develop new diagnostic, prognostic or therapeutic targets. Proteomic studies of B-cell malignancies have made significant progress, but further studies are needed to increase our coverage of the B-cell malignant proteome. To achieve this goal we stress the advantages of using sub-cellular fractionation, protein separation, quantitation and affinity purification techniques to identify hitherto unidentified signalling and regulatory proteins. For example, proteomic analysis of B-cell plasma membranes isolated from patients with mantle cell lymphoma (MCL) identified the voltage-gated proton channel (HVCN1,[1]). This protein has now been characterised as a key modulator of B-cell receptor (BCR) signalling and abrogation of HVCN1 function could have a role in the treatment of B-cell malignancies dependent on maintained BCR signalling [2]. Similarly, proteomic studies on cell lysates from prognostic subtypes of CLL, distinguished by the absence (UM-CLL) or presence (M-CLL) of somatic hypermutation of the immunoglobulin heavy chain locus identified nucleophosmin 1 (NMP1) as a potential prognostic marker [3,4]. Thus, targeted proteomic analysis on selected organelles or sub-cellular compartments can identify novel proteins with unexpected localisation or function in malignant B-cells that could be developed for clinical purposes.     

FTY720-induced blockage of autophagy enhances anticancer efficacy of milatuzumab in mantle cell lymphoma: Is FTY720 the next autophagy-blocking agent in lymphoma treatment?

Inhibition of the autophagic pathway has recently revealed promising results in increasing pro-death activity of multiple cancer therapeutics. Here, we discuss our findings regarding the autophagy-blocking and anti-neoplastic effects of a synthetic sphingosine analog, FTY720, in mantle cell lymphoma (MCL). We also emphasize how FTY720 enhances the pro-death activity of the fully humanized monoclonal antibody milatuzumab by inhibiting the autophagy-lysosome dependent degradation of its therapeutic target, CD74. Our results provide justification for further evaluation of FTY720 and milatuzumab as a combination therapy for this aggressive B-cell malignancy.     

三倍体皱纹盘鲍活体倍性鉴定——用上足触手、外套膜活体组织制备染色体标本

以上足触手,外套膜活体组织为材料,采用PHA体外浸泡法,运用正交实验设计,探讨了暂养温度,PHA（植物血球凝集素）浓度及取材时间对细胞分裂频度的影响。根据直观分析,得出用上足触手,外套膜活体组织直接制备染色体标本进行三倍体皱纹盘鲍活体倍性鉴定的最优组合是：暂养温度20℃;PHA浓度为1．00％,取材时间17：00－18：00,3因素的主次顺序：暂养温度→PHA浓度→取材时间。并可获得大量图像清晰,长度适中,分散的中期分裂相。     

Functional morphology of the mantle of Nautilus pompilius (Mollusca, Cephalopoda)

This study presents histological and cytological findings on the structural differentiation of the mantle of Nautilus pompilius in order to characterize the cells that are responsible for shell formation. The lateral and front mantle edges split distally into three folds: an outer, middle, and inner fold. Within the upper part of the mantle the mantle edge is divided into two folds only; the inner fold disappears where the hood is attached to the mantle. At the base of the outer fold of the lateral and front mantle edge an endo-epithelial gland, the mantle edge gland, is localized. The gland cells are distinguished by a distinct rough endoplasmic reticulum and by numerous secretory vesicles. Furthermore, they show a strong accumulation of calcium compounds, indicating that the formation of the shell takes place in this region of the mantle. Numerous synaptic contacts between the gland cells and the axons of the nerve fibers reveal that the secretion in the area of the mantle edge gland is under nervous control. The whole mantle tissue is covered with a columnar epithelium having a microvillar border. The analyses of the outer epithelium show ultrastructural characteristics of a transport active epithelium, indicating that this region of the mantle is involved in the sclerotization of the shell. Ultrastructural findings concerning the epithelium between the outer and middle fold suggest that the periostracum is formed in this area of the mantle, as it is in other conchiferan molluscs.     

Shell formation and calcium transport in the barnacle Chthamalus fragilis

The mantle epithelium of the barnacle Chthamalus fragilis (Darwin) exhibits several ultrastructural features which may serve to regulate the calcification process. At the basis-mural plate and intermural plate junctions where rapid shell growth occurs, cells are characterized by long apical cytoplasmic projections and large intercellular spaces. These features may increase the functional surface area of the epithelium and enable more rapid deposition of calcium. The cells underlying the general shell surfaces contain numerous electron-dense inclusion bodies and show frequent cellular disintegration near the growing shell interface. Release of the granular contents of these inclusion bodies has been observed in both disintegrating and non-disintegrating cells. X-ray microanalysis revealed significantly higher calcium levels in the inclusion bodies than in the surrounding cytoplasm. This suggests a calcium transport role for these inclusion bodies. Cellular debris produced as a result of the disintegration of the mantle cells near the shell may play some role in the formation of the organic matrix of the shell. The presence of large numbers of mitochondria and well-developed apical microvilli in the cells of the inner mantle epithelium suggest that these cells serve to transport calcium into the mantle from the ambient sea water.     

Ribeiroia marini: Irradiated miracidia and induction of acquired resistance in Biomphalaria glabrata

Biomphalaria glabrata snails sensitized by exposure to X-irradiated miracidia of the trematode, Ribeiroia marini, acquired resistance to challenge with nonirradiated R. marini miracidia. Resistance was acquired within 1 day of sensitization; was strongest at 1 week, when infection rates of sensitized snails were 15% of the controls (i.e., $\text{S}\text{C}\text{= 0.15}$); and persisted for at least 3 weeks. By 30 days the difference between the infection rates of sensitized and control snails was no longer statistically significant. As in previous studies with echinostomes, acquired resistance to R. marini was characterized histologically by the destruction of irradiated sporocysts by host amoebocytes. Following destruction of all irradiated sporocysts, snails became resistant and encapsulated and destroyed nonirradiated challenge sporocysts within 1 day postchallenge. Associated with sporocyst destruction was an enlargement of the amoebocyte-producing organ, which showed intense mitotic activity. A proportion of the nonirradiated challenge sporocysts were also destroyed in most nonsensitized control snails, which consequently had a temporarily enlarged amoebocyte-producing organ. In contrast to acquired resistance reported to echinotomes, which is quite specific, acquired resistance to R. marini was associated with nonsusceptibility to both Echinostoma paraensei ($\text{S}\text{C}\text{= 0.19}$) and Schistosoma mansoni ($\text{S}\text{C}\text{= 0.81}$).     

The outer mantle epithelium of Haliotis tuberculata (Gastropoda Haliotidae): an ultrastructural and histochemical study using lectins

The mantle of molluscs has been the subject of many studies as it is the organ that forms the shell. Microscopic studies in particular focus on the outer mantle epithelium, but few studies address this epithelium in a histochemical way. In this study, the outer mantle epithelium in adult specimens of Haliotis tuberculata is studied, that is, in specimens involved in maintaining and repairing the shell rather than in generating it. The epithelial cells are studied by scanning (SEM) and transmission electron microscopy (TEM), and by histochemical techniques, including the use of lectins for their biochemical characterization. The epithelium is composed of pigmented epidermal cells with small microvilli and junctional complexes. It furthermore contains a few ciliated cells, as well as two types of secretory cells which differ in the ultrastructural appearance of their secretory granules and their glycoconjugate content. Histochemical study shows secretory cells containing sulphated glycoconjugates such as glycosaminoglycans or mucins rich in N‐acetylgalactosamine and N‐glycoproteins rich in fucose. Furthermore, the apical regions of the epidermal cells are positive for lectins that label fucose, mannose and N‐acetylglucosamine. The role of epithelial cells in the synthesis of structural components of the shell is discussed.