MALIGNANT HEMANGIOENDOTHELIOMA

Background. The administration of interleukin-2 (il-2 ) has recently been reported to be favorable for treating malignant hemangioendothelioma (mhe ). Methods. Two patients with mhe responded well to intra-lesional injections of recombinant il-2 (ril-2 ) without major side effects. The purpose of this study was to characterize cells infiltrating the regressing tumor following ril-2 treatment. Immunohistochemical studies were performed on biopsy specimens taken from ril-2 -injected lesional skin. Results. It was shown that CD8⁺ lymphocytes and CD56⁺ natural killer (nk ) cells infiltrated at the ril-2 -injection sites, suggesting that these cells contributed to the tumor regression. In addition, MHE cells bore intercellular adhesion mole-cule-1 (icam -1) whose expression was augmented by rn-2 injections. Conclusions. These findings suggested, that ril-2 not only induces lymphokine-activated killer (lak ) cells and nk cells, but also facilitates these cytotoxic cells to adhere to MHE cells by enhancing icam -1 expression of tumor cells.     

EFFECT OF PORCINE CALCITONIN THERAPY ON VITAMIN D METABOLISM AND CLINICAL RESPONSE IN A PATIENT WITH OSTEOGENESIS IMPERFECTA

ABSTRACT. A 1 11/12-year-old girl with osteogenesis imperfecta was treated with porcine calcitonin. Eight bone fractures occurred in the previous 20 months before therapy, but none occurred during eight months of therapy. There was also a significant improvement in linear growth and radiographic bone density. This is the first study of the effect of calcitonin on vitamin D metabolism in a human. The high plasma levels of 1,25 dihydroxy-vitamin D (1,25-(OH)₂-D) and 24,25 dihydroxy-vitamin D (24,25-(OH)₂-D) before calcitonin therapy decreased after therapy. Plasma 25 hydroxy-vitamin D (25-OH-D) concentration, which normal in level before calcitonin therapy, was normal or slightly decreased during administration. It is concluded that calcitonin probably influences vitamin D metabolism in a patient with osteogenesis imperfecta.     

Suppressive Effects of Bay K 8644 on Toxicity of Calcium Channel Blockers in Cultured Rat Embryos

Previous study revealed that calcium channel blockers (CCBs)reduced embryonic heart rates (HRs) and produced morphologicalabnormalities when Gestational Day (GD) 11.5 rat embryos werecultured for 20 hr. The present study was to investigate whethera calcium channel agonist, Bay K 8644 (BAY), prevented CCB-inducedembryotoxicity in vitro. GD 11.5 embryos were exposed to nifedipine(NIF), diltiazem (DIL), and verapamil (VER) either alone orin combination with BAY at 0.1, 1.0, and 10 µg/ml. Thesedoses of BAY alone had no effect on gross morphology. EmbryonicHRs were increased at 10 µg/ml of BAY, but were withincontrol levels at 0.1 and 1.0 µg/ml. The doses of NIF,DIL, and VER were 40, 6.0, and 2.0 µg/ml, respectively,and were the minimum concentrations to produce a 100% effecton morphological abnormalities. Embryonic HRs were reduced to22, 31, and 34% below control levels in the NIF, DIL, and VERgroups, respectively. The negative chronotropic effects of CCBswere inhibited by coadministration with BAY, depending on itsconcentration. When embryos exposed to each CCB were supplementedwith BAY at 1.0 or 10 µg/ml, embryonic HRs were comparableto those of controls. Combined exposures of each CCB and 10µg/mlBAY did not cause any morphological abnormalities. These resultssuggested that mechanisms of CCB embryotoxicity were directlyrelated to pharmacological consequences of calcium channel blockagein developing rats.     

Involvement of growth factor receptor-bound protein-2 in rat hepatocyte growth

Growth factor receptor-bound protein-2 (GRB-2) is a protein linking receptor tyrosine kinase and Sos ( Son of Sevenless gene; Ras GDP/GTP exchange protein), leading to activation of the Ras-mitogen-activated protein kinase (MAPK) cascade. So far, it remains unclear how GRB-2 plays a role in signal transduction pathways evoked by hepatotrophic factors. This study was attempted to evaluate the involvement of GRB-2 in signalling in rat hepatocyte growth. Using rat cultured hepatocytes stimulated by hepatotrophic factors and regenerating livers after partial hepatectomy (PH) we examined GRB-2-mediated linkage of hepatotrophic factor receptors to signal transducing molecules such as Sos or dynamin-II by immunoprecipitation and western blot analysis. In primary cultured hepatocytes stimulated with hepatocyte growth factor (HGF) or epidermal growth factor (EGF), GRB-2 linked HGF receptor or EGF receptor, respectively, to Sos which activated the mitogen-activated protein kinase (MAPK) cascade. In contrast, in primary cultured hepatocytes stimulated with insulin, GRB-2 linked insulin receptor substrate-1 (IRS-1) to dynamin-II as well as Sos. In the early phase after PH, GRB-2 activated the Ras-MAPK cascade by linking HGF receptor, IRS-1, or EGF receptor to Sos. In the late phase after PH, a complex of IRS-1-GRB-2 associated with dynamin-II, indicating that GRB-2 may transduce signals from IRS-1 to dynamin-II. We conclude that GRB-2 may play a role in transmitting signals from hepatotrophic factors to not only MAPK but also to other signalling pathways in hepatocyte growth.     

Intraductal ultrasonography for the diagnosis of proximal invasion in extrahepatic bile duct cancer

Intraductal ultrasonograpy (IDUS) was performed on 22 patients with extrahepatic bile duct cancer, using the percutaneous transhepatic approach. Intraductal ultrasonograpy images of the proximal invasion of the bile duct cancer were defined. In addition, three patients were examined through the peroral approach, to try to diagnose whether or not the cancer invaded to the bifurcation of the hepatic duct. Intraductal ultrasonograpy images obtained through the percutaneous approach could be classified into three patterns, types 1, 2 and 3, according to the features of the interior surface of the bile duct and the thickness of the bile duct wall. Type 1 images, which did not show protrusions into the bile duct lumen and had a bile duct wall of even thickness, were not likely to show bile duct cancer. Type 2 images showed protrusions of the tumour into the bile duct lumen and the surfaces of the protrusions were irregular. Type 3 images showed single or multiple low echoic papillary masses in the bile duct. Using the peroral technique, we considered all three cases to be type 1 and could diagnose that cancer had not invaded to the bifurcation of the hepatic ducts. From the results of this study, we suggest that proximal invasion of extrahepatic bile duct cancer can be diagnosed using IDUS.     

Retroperitoneal lymph node dissection in patients with interaortocaval lymph node metastases of transitional cell carcinoma of the urinary tract

Three patients suffered from renal pelvic, ureteral and bladder cancers that were treated with both standard surgical treatments and two adjuvant cycles of cisplatin-based combination chemotherapy. Metastases of interaortocaval lymph nodes were detected in all patients between 9 and 33 months from the surgery for primary lesions. All patients received three cycles of cisplatin-based combination chemotherapy and retroperitoneal lymph node dissection (RPLND). The chemotherapy achieved partial response (62-98%). Two patients with viable cancer cells died with hepatic metastases; the first 15 months and the second 25 months from the date of diagnosis of distant lymph node metastasis. The third patient, who had no viable cancer cells, remains alive and disease-free 36 months later. Therefore, RPLND after chemotherapy provides prognostic information that helps to define patients who might benefit from additional systemic chemotherapy.     

An attempt of radar chart expression of a self-rating scale for sleep disturbance

Abstract We made an attempt to express a complaint of sleep disturbance by a self-rating scale of radar chart mode. The questionnaire for sleep disturbance is made up of eight items. Each item was scored from grade 1 to 4. The score of each item was projected to the MY radar chart, designed by us. It is noted that this method is useful in following the effect of hypnotics on sleep disturbance.     

Glomerular TGF-β1 expression in children with nephrotic syndrome

Summary: Transforming growth factor-β (TGF-β) has been suggested to contribute to the onset and/or progression of glomerulonephritis. However, data of TGF-β in connection with the pathogenesis of nephrotic syndrome are still insufficient. an immunohistochemical study on the glomerular TGF-β₁ in nephrotic syndrome was carried out in order to clarify the pathological role of this substance. Ten cases of nephrotic syndrome were subdivided histologically into two groups: (i) six cases of minor glomerular abnormality (group M); and (ii) four cases of focal glomerular sclerosis (group F). Two cases with normal glomeruli, one case of normal portion of adult renal cell carcinoma, one case of normal portion of Wilm's tumour were also studied as controls. Four cases of asymptomatic haematuria (group H) and four cases of chronic non-IgA glomerulonephritis syndrome (group C) were chosen compared to the nephrotic syndrome. Staining was evaluated semiquantitatively by light microscopy and by measuring the staining ratio compared to the glomerular area on an image analyzer. Both methods showed significantly larger staining in the glomeruli of group F, compared to group M. We concluded that TGF-β₁ plays an important role in the progression of nephrotic syndrome.     

Ureteral obstruction associated with pelvic inflammatory disease in a long-term intrauterine contraceptive device user

We report herein a case of ureteral obstruction associated with pelvic inflammatory disease in a long-term intrauterine contraceptive device (IUD) user. A 62-year-old woman presented with a 2-week history of left flank pain and high fever, but no abdominal pain. She had forgotten the use of an IUD. Retrograde pyelography showed a stricture in the lower third of the left ureter. Magnetic resonance showed swelling of the uterus wall and left parametria, but did not reveal the presence of an IUD. Subtotal hysterectomy, bilateral salpingo-oophorectomy and left nephronureterectomy was performed. The IUD was then found in the uterine cavity. The results of pathological and bacteriological findings for Actinomyces infection were negative. Therefore we diagnosed this case as ureteral obstruction associated with pelvic inflammatory disease. Ureteral obstruction associated with pelvic inflammatory disease in a long-term IUD user is extremely rare.     

Generation and Characterization of Monoclonal Antibodies Specific to Surface Antigens of Human Trophoblast Cells

PROBLEM : To generate and utilize specific monoclonal antibodies for routine fetal cell isolation from the maternal circulation. METHODS : Monoclonal antibodies specific to human trophoblast cell surface antigens were generated and characterized. After cell fusion, antibodies secreted by hybridomas were screened by enzyme-linked immunosorbent assay and immunohistochemical assays. RESULTS : By using cultured BeWo choriocarcinoma cells or the membrane fraction of human placenta as the immunogen, seven (BW-108, 110, 123, 124, HP-15, 16 and 17) antibodies specific to the surface antigens of trophoblast were produced. They were shown to have little cross-reactivity to other human tissues. Among the antibodies raised against human sperm, HSA-10 was also found to cross-react with human trophoblast, but not detected in other tissues. When immobilized to magnetic beads, these antibodies were shown to react only with BeWo cells in suspension, but not blood cells and ovarian carcinoma cell line, OC-3-VGH. CONCLUSION : Therefore, these antibodies may have potential application in fetal trophoblast cell isolation from the maternal circulation for prenatal genetic diagnosis.