To clarify the effect of fibroblast mixture in in vitro sensitivity test using SDI method. I have investigated the influence of fibroblast on the anticancer sensitivity test in a colon cancer cell ...line. The anticancer drugs, such as MMC (mitomycin C), CDDP (cisplatin) and 5-FU (5-fluorouracil) were contacted with colon cancer cells at 8 different concentrations on the intervals from 24 to 168 hours. The drug sensitivity of cancer cells in mixture of fibroblast was influenced by the kind of anticancer drugs, sensitivity of fibroblast itself, and the difference of sensitivity of cancer cell and fibroblasts. With the increase of percentage of fibroblast, the sensitivity of cancer cells became almost equivalent to that of fibroblast in 5-FU. But the sensitivity was not influenced by MMC or CDDP. And the difference of sensitivity was within about 27% by using 5-FU when the cancer cell ratio is 50%. Drug sensitivity of cancer cells was greatly influenced by drug concentration and contact time. Although the optimal contact time of sensitivity test depended on the kinds of drugs, 72 hours was considered to be optimal.
Sudden death is common in patients with multiple system atrophy (MSA). In its early stages, the cerebellar presentation MSA‐C can be indistinguishable from idiopathic late‐onset cerebellar ataxia. We ...studied the hypoxic ventilatory response in MSA‐C and idiopathic late‐onset cerebellar ataxia patients. Six patients with idiopathic late‐onset cerebellar ataxia that later evolved to MSA had impaired hypoxic ventilatory response when minimal autonomic failure was still present, whereas for patients with unimpaired hypoxic ventilatory response their diagnosis remained idiopathic late‐onset cerebellar ataxia. The demonstration of impaired hypoxic ventilatory response appears to be a good marker enabling earlier diagnosis of MSA in patients presenting with idiopathic late‐onset cerebellar ataxia.
In the transposon copia-related retrovirus-like particles of Drosophila, a 39-nucleotide-long fragment from the 5'-region of Drosophila initiator methionine tRNA (tRNA(iMet)) is used as the primer ...for copia minus-strand reverse transcription. This primer tRNA(iMet) fragment is thought to be produced by cleavage within the mature tRNA(iMet) sequence. We call this cleavage hyperprocessing. We have previously reported that catalytic RNA of RNase P from Escherichia coli (M1RNA) cleaves the synthetic tRNA(iMet) precursor in vitro at several sites within the mature tRNA sequence. Based on this result, we proposed a model for formation of the primer tRNA fragment involving RNase P. Here we show that natural tRNA(iMet) prepared from Drosophila adult flies can be cleaved by M1RNA. Using mutant tRNA(iMet) substrates, we also show that these cleavages are dependent on the occurrence of an altered conformation of the tRNA substrate. This is evidence that a tRNA can exist in aqueous solution at least in part in an altered conformation.
To determine the sonographic features of uncomplicated acute diverticulitis of the cecum and ascending colon, the sonographic findings in 534 patients who presented with right lower quadrant pain ...were reviewed. Of these, 18 patients had uncomplicated acute diverticulitis of the cecum and ascending colon. The diagnosis was confirmed by surgery (one patient), clinical course (17 patients), CT (eight patients), or contrast enema (11 patients). On sonography, a round or oval focus of varying echogenicity, which protruded from a segmentally thickened colonic wall and was surrounded by a hyperechoic area, was seen in all 18 patients. These were hypoechoic foci (12 patients), hypoechoic foci with internal strong echoes (three patients), and echogenic shadowing foci with surrounding hypoechoic bands (three patients). Extraluminal gas (one patient) and thickening of lateroconal fascia (six patients) were seen also. Findings of enlarged appendix, frank abscess, and ascites were absent. All patients, including the one who had laparotomy, were successfully treated medically for diverticulitis. Of 515 patients without diverticulitis, in only one patient with acute appendicitis did sonography show a hypoechoic protruding focus. Our experience indicates that the major sonographic finding in patients with uncomplicated acute diverticulitis of the right colon is a hypoechoic round or oval focus protruding from a segmentally thickened colonic wall.
Multiple myeloma is currently considered incurable despite the use of high-dose chemotherapy with autologous hematopoietic stem cell transplantation support. Here, we show antitumor efficacy of a ...novel bivalent single-chain antibody fragment (scFv) against CD47 in an in vivo myeloma model. We generated two types of novel scFv molecules against CD47 having apoptosis-inducing activity for leukemic cell lines: a non-covalently linked scFv dimer (diabody) and a covalently linked bivalent scFv. Administration of these bivalent scFvs significantly prolonged the survival of mice transplanted with KPMM2 human myeloma cells. Because bivalent scFvs induced neither ADCC nor CDC, such antitumor activity by bivalent scFv is presumably attributable to cell death caused by the ligation of CD47. Thus, these apoptosis-inducing scFvs will be effective as a novel therapy for multiple myeloma which is considered incurable with conventional therapy.
Legionella pneumophila is an intracellular organism and the major aetiological agent of Legionnaires' disease. Although recent progress has identified Toll-like receptors (TLRs) as receptors for ...recognition of pathogen-associated molecular patterns in a variety of micro-organisms, understanding the contribution of TLRs to the host response in L. pneumophila infection is still limited. This study examined the roles of TLR2 and TLR4 in murine L. pneumophila pneumonia and an in vitro infection model using bone-marrow-derived macrophages. TLR2-deficient mice, but not TLR4-deficient mice, demonstrated higher lethal sensitivity to pulmonary challenge with L. pneumophila than wild-type mice (P<0.05). Although no differences in pulmonary bacterial burden were observed among the mouse strains examined, lower values of macrophage inflammatory protein-2 (MIP-2), keratinocyte-derived cytokine and interleukin (IL)-6 and higher IL-12 levels were noted in lung homogenates of TLR2-deficient mice compared with the wild-type control and TLR4-deficient mice. Recruitment of inflammatory cells, particularly neutrophils, was severely disturbed in the lungs of TLR2-deficient mice. Reduced MIP-2 production was demonstrated in bone-marrow-derived macrophages from TLR2-deficient mice in response to live L. pneumophila and purified LPS of this strain, but not Escherichia coli LPS. These data highlight the involvement and importance of TLR2 in the pathogenesis of L. pneumophila pneumonia in mice. The results showed that TLR2-mediated recognition of Legionella LPS and subsequent chemokine-dependent cellular recruitment may be a crucial host innate response in L. pneumophila pneumonia.
We report two cases of avulsion fractures at the fovea of the ulna. This injury is caused by a strong distraction force which avulses the insertion of the triangular ligament at the fovea of the ...ulna. This injury can be classed as an injury to the triangular fibrocartilage complex.
The retrovirus-like particles of Drosophila are intermediates of retrotransposition of the transposable element copia. In these particles, a 39-nucleotide-long fragment from the 5' region of ...Drosophila initiator methionine tRNA (tRNAMet
i) is used as the primer for copia minus-strand reverse transcription. To function as primer for this reverse transcription, the Drosophila tRNAMet
imust be cleaved in vivo at the site between nucleotides 39 and 40. When a synthetic Drosophila tRNAMet
iprecursor was incubated with M1RNA, the catalytic RNA of Escherichia coli RNase P, other cleavages within the mature tRNA sequence were detected in addition to the efficient removal of the 5' leader sequence of this tRNA precursor. One of these cleavage sites is between nucleotides 39 and 40 of Drosophila tRNAMet
i. Based on this result, we propose a model for formation of the primer tRNA fragment for reverse transcription in copia retrovirus-like particles.
Recently, von Hippel‐Lindau (VHL) gene mutations were detected in non‐inherited, sporadic human renal cell carcinomas (RCs) at a high frequency. In order to determine whether or not the VHL gene is ...also a critical gene in rat RCs, we cloned and sequenced the rat homologue of human VHL gene and searched for mutations of the VHL gene in rat RCs. Mutations in the VHL gene were not detected in spontaneous RCs of the Eker rat model or in ferric nitrilotriacetate‐induced rat RCs using the polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) method. These data indicate that mutation of the VHL tumor suppressor gene is not an event in rat renal carcinogenesis, at least in our present systems.
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