A glomerular permeability factor produced by human T cell hybridomas

A glomerular permeability factor produced by human T cell hybridomas. T cell hybridomas derived from the T cells of a patient with minimal change nephrotic syndrome (MCNS) made a glomerular permeability factor (GPF). Sufficient quantities of GPF were available for further analysis and characterization. We obtained four stable clones of human T cell hybridomas which produced a glomerular permeability factor. When this factor was injected intravenously into rats, significant proteinurias were induced, and in normal human lymphocyte culture, GPF enhanced Concanavalin-A (Con-A) induced lymphocyte histogenesis by greater than ten fold. GPF was cytotoxic to tumor cell lines of epithelial origin, but only cytostatic to tumor cells of hematopoietic origin. Electron microscopy studies, with polyethyleneimine (PEI) staining, indicated that GPF induced the changes in the arrangement of PEI particles and partial fusion of glomerular epithelial cells in the rats given this factor intravenously. The molecular weight of GPF were estimated to be between 60,000 and 160,000 daltons. The molecular weight of the factor and its TNF like activity, we speculated that the factor was a lymphokine, like lymphotoxins

The CRKL gene encoding an adaptor protein is amplified, overexpressed, and a possible therapeutic target in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Genomic DNA amplification is a genetic factor involved in cancer, and some oncogenes, such as <it>ERBB2</it>, are highly amplified in gastric cancer. We searched for the possible amplification of other genes in gastric cancer.</p> <p>Methods and Results</p> <p>A genome-wide single nucleotide polymorphism microarray analysis was performed using three cell lines of differentiated gastric cancers, and 22 genes (including <it>ERBB2</it>) in five highly amplified chromosome regions (with a copy number of more than 6) were identified. Particular attention was paid to the <it>CRKL</it> gene, the product of which is an adaptor protein containing Src homology 2 and 3 (SH2/SH3) domains. An extremely high <it>CRKL</it> copy number was confirmed in the MKN74 gastric cancer cell line using fluorescence <it>in situ</it> hybridization (FISH), and a high level of CRKL expression was also observed in the cells. The RNA-interference-mediated knockdown of CRKL in MKN74 disclosed the ability of CRKL to upregulate gastric cell proliferation. An immunohistochemical analysis revealed that CRKL protein was overexpressed in 24.4% (88/360) of the primary gastric cancers that were analyzed. The <it>CRKL</it> copy number was also examined in 360 primary gastric cancers using a FISH analysis, and <it>CRKL</it> amplification was found to be associated with CRKL overexpression. Finally, we showed that MKN74 cells with <it>CRKL</it> amplification were responsive to the dual Src/BCR-ABL kinase inhibitor BMS354825, likely via the inhibition of CRKL phosphorylation, and that the proliferation of MKN74 cells was suppressed by treatment with a CRKL-targeting peptide.</p> <p>Conclusion</p> <p>These results suggested that CRKL protein is overexpressed in a subset of gastric cancers and is associated with <it>CRKL</it> amplification in gastric cancer. Furthermore, our results suggested that CRKL protein has the ability to regulate gastric cell proliferation and has the potential to serve as a molecular therapy target for gastric cancer.</p

Small multimodal thermometry with detonation-created multi-color centers in detonation nanodiamond

微小ナノダイヤモンド量子センサで安定的に温度計測実現--細胞内などの微小領域での量子センシングに期待--.京都大学プレスリリース. 2024-05-16.Detonation nanodiamond (DND) is the smallest class of diamond nanocrystal capable of hosting various color centers with a size akin to molecular pores. Their negatively charged nitrogen-vacancy center (NV⁻) is a versatile tool for sensing a wide range of physical and even chemical parameters at the nanoscale. The NV⁻ is, therefore, attracting interest as the smallest quantum sensor in biological research. Nonetheless, recent NV⁻ enhancement in DND has yet to yield sufficient fluorescence per particle, leading to efforts to incorporate other group-IV color centers into DND. An example is adding a silicon dopant to the explosive mixture to create negatively charged silicon-vacancy centers (SiV⁻). In this paper, we report on efficient observation (∼50% of randomly selected spots) of the characteristic optically detected magnetic resonance (ODMR) NV⁻ signal in silicon-doped DND (Si-DND) subjected to boiling acid surface cleaning. The NV⁻ concentration is estimated by continuous-wave electron spin resonance spectroscopy to be 0.35 ppm without the NV⁻ enrichment process. A temperature sensitivity of 0.36 K/√HZ in an NV⁻ ensemble inside an aggregate of Si-DND is achieved via the ODMR-based technique. Transmission electron microscopy survey reveals that the Si-DNDs core sizes are ∼11.2 nm, the smallest among the nanodiamond’s temperature sensitivity studies. Furthermore, temperature sensing using both SiV⁻ (all-optical technique) and NV⁻ (ODMR-based technique) in the same confocal volume is demonstrated, showing Si-DND’s multimodal temperature sensing capability. The results of the study thereby pave a path for multi-color and multimodal biosensors and for decoupling the detected electrical field and temperature effects on the NV⁻ center

The Feature of Solitary Small Nodular Type of Hepatic Epithelioid Hemangioendothelioma

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor. Preoperative diagnosis of HEHE is difficult because it does not manifest specific symptoms or tumor markers. We report a resected case of small and solitary HEHE. The patient, a 74-year-old man, had undergone surgical resection for left renal cell carcinoma 20 years ago. During follow-up, a tumor approximately 1.3 cm in diameter was detected by computed tomography (CT) at liver segment VIII. It showed isodensity in the arterial phase, low density in the portal venous phase, and homogeneous enhancement in the late phase on CT and magnetic resonance imaging (MRI). We performed hepatic resection of the right hepatic vein drainage area. A pathological diagnosis of HEHE was made. Although small and solitary HEHE is rare, an enhancement pattern in each phase on CT and MRI, using contrast media, can yield clues for the diagnosis of HEHE

Distribution and expression of mRNAs for the proto-oncogenes c-fos and c-jun in bone cells in vivo

In this study we assessed the expression and localization of the proto-oncogenes c-fos and c-jun in normal bone so as to gain more insight into the role of these proto-oncogenes in bone tissue. Femurs of 4-weekold rats were examined by non-radioactive in situ hybridization. cDNA probes for c-fos- and c-jun-labeled digoxygenin were produced by Polymerase Chain Reaction (PCR). C-fos and c-jun exhibited similar distribution in growth plate and bone tissue. Expression of c-fos and cjun mRNAs in growth plate was observed in the proliferative zone and partly in the upper layer of the hypertrophic zone. In spongy bone, high expression of cfos and c-jun mRNAs was observed in the osteoblast cytoplasm. However, there was little expression in bone lining cells. In the bony trabeculae, slight expression of c-fos and c-jun was observed in the premature osteocytes situated close to the bone surface, but no expression was detected in osteocytes that possessed relatively large lacunae in the center of the trabeculae.C-fos and c-jun were also slightly expressed in osteoclasts. These data strongly suggest that c-fos and c-jun are involved in regulating chondrocyte proliferation as immediate early genes, and may also be involved in the gene expression of bone matrix proteins as transcription factor (M-1) in vivo. In addition, the fact that strong expression was observed in osteoblasts but hardly any expression at all in bone lining cells seems to suggest that these genes are also involved in osteoblast activation

Ulbactins F and G, Polycyclic Thiazoline Derivatives with Tumor Cell Migration Inhibitory Activity from Brevibacillus sp.

Two new structurally unique compounds bearing a nitrogen- and sulfur-containing tricyclic ring system, ulbactin F (<b>1</b>) and its diastereomeric isomer ulbactin G (<b>2</b>), were isolated from the culture extract of a sponge-derived Brevibacillus sp. The structures and absolute configurations of <b>1</b> and <b>2</b> were determined by NMR analysis and X-ray crystallographic analysis. These compounds inhibit the migration of tumor cells in the submicromolar to micromolar range