Expression of erythropoietin in human female reproductive organs.

Erythropoietin (Epo) is known to be a lineage specific cytokine which regulates the number of circulating erythrocytes. Most of it is produced in the kidney. Recently, Epo has been reported to be synthesized in the normal brain, placenta, and capillary endothelium. We also have found that uterine endometrium expresses Epo signals in an estrogen-dependent manner, and that Epo contributes to angiogenesis in the endometrium in mice. To clarify the functional activity of Epo in human reproductive organs, we examined Epo signaling in these organs by Southern analysis of RT-PCR products and studied the distribution of substances relevant to Epo signal transduction by immunohistochemistry and Western blotting. Epo mRNA is expressed in the normal human cervix, endometrium and ovary, but it is not always detected in the specimens. Immunohistochemical analysis revealed Epo-receptor (EpoR) protein in: a) the endothelium of vessels, in glandular and surface epithelial cells, in decidual cells of the endometrium, and b) in follicles at various stages including oocytes, granulosa, theca interna cells and lutein cells of the ovary. Moreover, co-expression of JAK2 and phosphotyrosine, which reflects tyrosine phosphorylation via JAK2, and co-expression of EpoR and STAT5, which is a transcriptional factor relevant to mitogenic activity, were seen at these Epo-responsive sites. Western blotting analysis of these organs confirmed the immunohistochemical results. These findings imply that female reproductive organs can produce Epo, and that signal transduction of Epo contributes to the cyclic changes in the female reproductive organs.

Persistent hypoglossal artery associated with arteriovenous malformation: a case report.

A rare case of persistent hypoglossal artery in conjunction with arteriovenous malformation was presented. MRA could delineate persistent hypoglossal artery and arteriovenous malformation very clearly. The patient suffered from intracranial hemorrhage from in the 37th week of pregnancy. MRI, MRA, angiography, and CT of this rare condition are reported.

Long-term results of fractionated strontium-90 radiation therapy for pterygia.

PURPOSE: The long-term safety and effectiveness of fractionated strontium-90 radiation therapy (RT) for pterygium were reviewed retrospectively. METHODS AND MATERIALS: Between 1984 and 1996, 399 patients with 490 pterygia were treated with a strontium-90 eye applicator following surgical removal of the pterygium. The median follow-up period was 61 months (range 2-178). Of the 490 pterygia, 452 were fresh, 17 were recurrences after surgical removal alone, and 21 were recurrences after surgical removal plus postoperative RT. Fractionated RT of 31-42 Gy/4-5 fractions/22-29 days was given for 95.1% of the pterygia. RESULTS: In total, 58 (11.8%) local recurrences of pterygia were noted. The median time of local recurrences was 10 months, ranging from 2 to 93 months, and 16 recurrences (28%) were noted later than 24 months after treatment. The interval between surgery and the start of RT (1-3 days vs. >3 days) and recurrent pterygia were significant variables for local control in the multivariate analysis, while total RT dose (7-29 Gy vs. 31-50 Gy) was a marginally significant variable. Late toxicities that may be associated with strontium-90 RT were scleromalacia (scleral thinning) in 4 eyes, adhesion of eyelids in 3 eyes, and scleral ulcer in 2 eyes. CONCLUSION: Fractionated strontium-90 RT of approximately 40 Gy/4-5 fractions was safe and effective for preventing recurrence of pterygia, when RT was started within 3 days of surgery.

Use of intra-operative ultrasonography to detect a small foreign body in the soft tissue of the upper lip.

Real-time ultrasonography was used to detect a small foreign body (a broken tip of a barbed broach) which had migrated into the upper lip of a 26-year-old female from the bone defect of the upper canine apex during root canal treatment 10 months previously. Intra-operative use of ultrasound was of great-help in clarifying the positional relationship between the foreign body and the surgical instruments used, and lead to a satisfactory result.

High invasiveness associated with augmentation of motility in a fos-transferred highly metastatic rat 3Y1 cell line.

We previously reported that v-fos transfer to a src-transformed rat 3Y1 cell line enhanced lung metastasis. To clarify the mechanism of this enhancement, we compared various biological factors related to metastatic potential between a fos-transferred highly metastatic cell line (fos-SR-3Y1-202) and the control cell line transferred with genetic marker (pSV2-neo) plus pBR322, neo-SR-3Y1-200. Lung arrest, the effect of lung extract on cell growth, or sensitivity to natural killer cells could not explain the higher metastasis of fos-SR-3Y1-202, compared to findings with neo-SR-3Y1-200. The invasiveness, assessed by penetration through a Matrigel-coated filter was about 5 times higher in fos-SR-3Y1-202 than in neo-SR-3Y1-200; high invasiveness in vitro was also observed in a fos-transferred mixed-population cell line (fos-SR-3Y1-200) and fos-transferred highly metastatic clones. Histopathological evidence of an in vivo tumor also showed the high invasiveness of fos-SR-3Y1-202 cells. To elucidate the causes of the increased invasiveness of fos-SR-3Y1-202, attachment of the cells to Matrigel and its components, such as laminin and type IV collagen, type IV collagenase activity, and motility were examined. Attachment of the cells to the substrate coated on Petri dishes or the activity of type IV collagenase did not differ significantly. On the other hand, cell motility, determined by a new method to directly quantitate alteration of cell shape continuously, using video image analysis and computer techniques, was higher in fos-SR-3Y1-202 than in neo-SR-3Y1-200. Thus, the fos-transferred cell line, fos-SR-3Y1-202 has a high invasiveness, in association with augmentation of motility, hence the enhancement of metastatic potential.

Enhancement of colony forming ability in the lung by transfer of the v-fos oncogene into a ras-transformed rat 3Y1 cell line.

Transfer of the v-fos oncogene into a rat 3Y1 cell line transformed by v-H-ras, which is tumorigenic but non-metastatic, enhanced lung metastasis, depending on the amount of fos-related transcripts. Enhancement of the metastatic potential was associated with increases in tumor growth rate i.m. of inoculated cells but not the rate of in vitro cell growth, irrespective of the addition of tissue (e.g. lung) extract to the regular medium. These results suggest that the v-fos oncogene increased the malignancy by altering biological factors of the recipient cells responsible for cell growth and/or survival rate in vivo.

Malignant progression of a transformed rat cell line by transfer of the v-fos oncogene.

Transfer of the v-fos oncogene into a rat cell line transformed by Rous sarcoma virus increased both the spontaneous and experimental lung-metastasis. Metastatic ability of each v-fos transferred cell line was dependent on both the manner of integration and transcriptional amount of the v-fos oncogene, but did not correlate with the growth rate in vivo. Expression of the src, myc or ras genes were not altered by transfer of the v-fos gene, except that the myc expression was enhanced in the cell line, which acquired augmentation of growth rate in vivo but not metastatic potential to the lung. Cells of the metastatic lung nodules of each cell line also possessed exogenous fos DNA and the transcripts. These results suggest that v-fos oncogene functions in the transfected cells and causes malignant progression.