Photodynamic antisense regulation of human cervical carcinoma cell growth using psoralen-conjugated oligo(nucleoside phosphorothioate).

The antisense strategy has been applied to regulate gene expression in a sequence specific manner, which enables suppression of the proliferation of cancer cells and exploration of the functions of unknown genes. In order to generalize and to enhance the ability of the strategy, functionalization of antisense DNAs was done using a photo-crosslinking reagent, 4,5',8-trimethylpsoralen, and the possibility of photodynamic antisense regulation of gene expression was examined. Psoralen-conjugated oligo(nucleoside phosphorothioate)s (Ps-S-oligo) were prepared and used to inhibit the proliferation of human cervical carcinoma cells. Upon UVA irradiation of Ps-S-oligo treated cells, Ps-S-oligo complementary to the initiation codon region (Ps-P-As) of HPV18-E6*-mRNA of human cervical carcinoma cells inhibited drastically the cell growth (IC(50)=16 nM). In contrast, Ps-S-oligo with mismatched sequences and scrambled one showed lesser inhibitory effects than Ps-P-As. These results showed that the inhibition by Ps-S-oligo was dependent on (a) sequence, (b) UVA irradiation, (c) concentration and (d) cell line. The amount of intact HPV18-E6*-mRNA was decreased in a sequence dependent manner, indicating that the antiproliferative effect of Ps-P-As was an antisense manner. The psoralen-conjugated antisense DNA has significant potential to regulate gene expression, which may provide useful information to explore the novel gene regulating reagents.     

Topographical anatomy of Spiegel's lobe and its adjacent organs in mid‐term fetuses: Its implication on the development of the lesser sac and adult morphology of the upper abdomen

At 8–16 weeks of gestation, Spiegel's lobe of the caudate lobe appears as a sac‐like herniation of the liver parenchyma between the inferior vena cava and ductus venosus or Arantius' duct. In 5 of 11 fetuses at 20–30 weeks of gestation, we found that an external notch was formed into the posterior aspect of the caudate lobe by a peritoneal fold containing the left gastric artery. This notch appeared to correspond to that observed in adults, which is usually seen at the antero‐inferior margin of the lobe after rotation of the lobe along the horizontal or transverse axis. However, the notch did not accompany two of the three fetuses in which the left hepatic artery originated from the left gastric artery. Notably, until 9–10 weeks of gestation, the inferior and left part of Spiegel's lobe rode over the hepatoduodenal ligament and protruded medially into the lesser sac (bursa omentalis) behind the stomach. Thus, the fetal Winslow's foramen was located at the “superior” side of the ligament. However, as seen in adults, the protruding Spiegel's lobe was located at the posterior side of the lesser omentum. Therefore, a hypothetical rotation along the transverse axis in the later stages of development seems necessary to explain this repositioning. Considering that Spiegel's lobe develops faster than surrounding structures, it is likely that the lesser sac resulting from the rotation of the gastrointestinal tract, which actively contributes to facilitate the growth of the Spiegel lobe. Clin. Anat. 23:712–719, 2010. © 2010 Wiley‐Liss, Inc.     

Non-Hodgkin's lymphoma with Toxoplasma encephalitis]

A 62-year-old man was admitted to our hospital due to fever and systemic lymph-node swelling on June 9, 1998. He was given a diagnosis of non-Hodgkin's lymphoma (diffuse mixed T cell lymphoma) with involvement of mediastinum and para-aortic lymph nodes, pleura, peritoneum, and bone marrow. After diagnosis, combined chemotherapy (CHOP regimen) was started. On day 11, the patient's consciusness level suddenly deteriorated. A brain computed tomographic scan showed no abnormal findings. A cytospin smear of cerebrospinal fluid disclosed tachyzoides (Toxoplasmic bodies), thus yielding a diagnosis of Toxoplasma encephalitis. Oral sulfadoxine pyrimethamine rapidly alleviated the patient's consciousness disturbance. One month later, a cytospin smear and RT-PCR analysis of cerebrospinal fluid detected no tachyzoides. Complete remission of lymphoma was achieved after 2 courses of CHOP therapy. Toxoplasma encephalitis should be considered a potential cause of consciousness disturbance in immunocompromised hosts, such as patients with malignant lymphoma. Cytospin smears of cerebrospinal fluid are a useful tool for the early diagnosis of Toxoplasma encephalitis.