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Leiomyosarcoma (LMS) of the fallopian tube is exceedingly uncommon. So far as we investigated, only eighteen cases of LMS of the fallopian tube have been reported. Here we report a nineteenth case which was International Federation of Gynecology and Obstetrics stage IIIc LMS of the fallopian tube successfully treated with intraperitoneal cisplatin followed by prolonged oral etoposide. A 70-year-old female was introduced to our institute due to intrapelvic tumor and ascites. Because of elevated serum lactate dehydrogenase and CA125 as well as the findings of pelvic magnetic resonance imaging and computerized tomography, the patient was suspected to have ovarian cancer. In laparotomy, the large pelvic tumor was seemed to originate from the right fallopian tube. Pathologically, the patient was diagnosed as stage IIIc fallopian tube LMS. At the end of the operation, cisplatin was given intraperitoneally followed by prolonged oral etoposide. Although a lot of dissemination was noted throughout the peritoneal cavity, the patient is alive without any evidence of recurrence for more than 6 years since the initial operation. In this uncommon entity, a cisplatin- and etoposide-based regimen could be considered.

So far, there is no recommended evidence-based chemotherapeutic regimen for recurrent or refractory ovarian carcinoma in the guideline. In our institute, combination chemotherapy of CPT-11 and CDDP (CPT-P) was administered for recurrent or refractory ovarian carcinoma patients previously treated with regimens including taxane. In fourteen cases treated with CPT-P, there were 2 cases of CR, 2 of PR, 3 of SD, and 7 of PD. Overall response rate was 28. 5%, and the median progression-free interval was 5.5 months. No severe side effect was observed except in one patient in whom chemotherapy was discontinued due to grade 4 neutropenia and grade 3 diarrhea. Thus CPT-P seemed to be effective and safe for the recurrent or refractory ovarian carcinoma previously treated with taxane-included regimen.

Although radical hysterectomy is the standard surgical treatment for patients with stage IB and II cervical cancer, it does not improve the prognosis of high-risk patients even if postoperative radiotherapy is added. There is therefore a need to establish some other therapeutic regimen. In the present retrospective study, the efficacy of concurrent nedaplatin after radical hysterectomy in high-risk stage IB to II cervical cancer was analyzed. From 1995 through 2005, patients with an International Federation of Gynecology and Obstetrics stage of IB2 and II cervical cancer who were given only radiotherapy (RT; n = 17) or postoperative concurrent chemoradiotherapy with biweekly nedaplatin at 70 mg/m(2) (p-CCRT; n = 13) were entered. All of the patients had at least one of the following risk factors: lymphovascular space infiltration, positive lymph nodes, or parametrial invasion. There was no significant difference between the RT and p-CCRT groups with regard to mean age and risk factors, except that more patients in the p-CCRT group had positive lymph nodes (P < 0.05). Five-year progression-free survival and overall survival after RT versus p-CCRT were 76.0% versus 83.3%, and 81.9% versus 83.3%, respectively. Although many patients in the p-CCRT group had positive lymph nodes, there was no significant difference in either PFS or OS. No grade 4 myelosuppression or other severe side effects were seen in the p-CCRT group. As CCRT with nedaplatin might have some benefit, a randomized control trial should be conducted in the future.

Aim: Taxanes are regarded as key chemotherapy agents for breast cancer and gynecologic malignancies; therefore the ovarian toxicity of paclitaxel (PTX) is a matter of importance to younger women with malignancies. We examined the ovarian toxicity of PTX and its influence on fertility in rats. Methods: Female Wistar rats aged 6–8 weeks received five doses of PTX at 3-day intervals. Ovarian toxicity was assessed by counting follicles, corpora lutea and atretic follicles, as well as by detecting apoptosis and measuring serum levels of estradiol (E2) and progesterone (P4). Fertility was assessed by mating females immediately or 24 days after PTX treatment. The number of fetuses, implantations and resorption sites was counted in each group. Results: Exposure to PTX caused a decrease of antral follicles, but not primordial or pre-antral follicles. The number of corpora lutea showed a significant decrease, while follicular atresia was increased significantly. Apoptosis was only detected in antral follicles. Serum E2 levels were lower than in control rats, but not significantly, while P4 levels did not differ from those in control rats. Rats mated immediately after PTX treatment showed a significant decrease of fetuses and implantations, but these effects were not detected in rats mated at 24 days after treatment. Conclusion: Our findings suggest that the ovarian toxicity of PTX is mild and transient. Use of PTX may help to maintain the fertility of younger women because the fertility of rats was not influenced at 24 days after exposure to this drug.

Aim: To determine the receptor subtypes of melatonin in estrogen receptor-positive endometrial cancer cell line, Ishikawa, and the influence of melatonin on chemosensitivity. Methods: To confirm the subtype of melatonin on Ishikawa cells, cells were treated with melatonin alone and with antagonists against melatonin receptor luzindole and 4-phenyl-2-propionamidotetralin (4-P-PDOT). Expression of MT1/MT2 mRNA was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Immunocytochemistry of MT1/MT2 was also performed. The effect of melatonin against expression of MT1, MT2, and ERα-receptors mRNA was compared with RT-PCR. To determine whether melatonin enhances the effect of anticancer agents, chemosensitivity test was performed with or without melatonin. Results: Our study revealed that Ishikawa cells express MT1 by both RT-PCR and immunocytochemistry. In contrast, expression of MT2 mRNA was not found. Furthermore, ERα mRNA expression was attenuated at melatonin level of 1 × 10−9 M. Chemosensitivity test revealed that melatonin enhanced anti-tumor effects of paclitaxel among anticancer drugs tested. Conclusion: Based on the above results, MT1 receptor, but not MT2, is expressed in Ishikawa cells. It was also revealed that the cytostatic effect of melatonin is partly an action mediated by MT1 receptor, and attenuation of ERα expression was predicted as the mechanism of action. Clinical application of melatonin to biochemotherapy might be also expected.

A novel serous surface papillary carcinoma of the ovary (SSPC) cell line, HYKSSPC, was established successfully. Carcinoma cells were obtained from ascitic fluid of a 60-year-old Japanese woman. The population doubling time was 51.4 h. A phase contrast micrograph showed a pavement stone-like arrangement without contact inhibition. The chromosome number showed a wide distribution of aneuploidy, and the mode was in 46–47. An immunocytochemical study showed that CA1 25, BerER4 and cytokeratin were positive and that CEA, calretinin and thrombomodulin were negative. This cell line preserved some characters of the adenocarcinoma while growing in vitro. A chemosensitivity test revealed that HYKSSPC cells were sensitive to CDDP (cis-platinum), 5-fluorouracil, mitomycin C, paclitaxel and irinotecan. To our knowledge, HYKSSPC is the first established cell line derived from SSPC, and it may offer some useful information for investigating this disease.

Our previous work showed that melatonin (N-acetyl-5-methoxytryptamine) inhibits proliferation of the human endometrial cancer cell line, Ishikawa, which is estrogen receptor-positive. The aim of the present study was to determine whether Ishikawa cells possess membrane melatonin receptors. Binding of the radioligand 2-[125I]-iodomelatonin to membrane preparations obtained from Ishikawa cells was detectable, saturable and stable. Scatchard analysis revealed that the dissociation constant (Kd) of the binding sites was 179.0 pm (similar to that of the MT2 [Mel1b] melatonin receptor subtype), and that the concentration (Bmax) of the binding sites was 12.9 fmol/mg protein. Luzindole, a selective MT2 melatonin receptor antagonist, significantly suppressed binding of 2-[125I]-iodomelatonin at all concentrations tested (10(-8) to 10(-4) m). These results suggest that the MT2 melatonin receptor subtype is present in the membranes of Ishikawa cells, and that the antiproliferative effect of melatonin on Ishikawa cells is mediated via the MT2 receptor. This may have implications for the use of melatonin in endometrial cancer therapy.

We recently established a cell line (designated 371M) derived from an ovarian mucinous cystadenocarcinoma. The tumor cells were obtained from the ascitic fluid of a 54-year-old Japanese woman while she was undergoing surgery. Adjuvant chemotherapy (combined paclitaxel and carboplatin) was administered, but was ineffective, and she died about 4 months after surgery. The 371M cells continuously propagated in vitro over a period of about 50 months and, to date, have undergone over 100 passages. They proliferated in a monolayered sheet with doubling times of 84 h and 37 h in the 10th and 34th passages, respectively. When transplanted into nude mice, the tumor histopathologically resembled the structure of the original tumor. The 371M cells secreted high levels of CA125 and CA19-9 into the culture medium. There were several abnormal chromosomes in all karyotypes selected at random. Sensitivity of 371M cells to a variety of anti-cancer drugs was examined by in vitro MTT assay, and the results suggested that CPT-11 and CDDP were more effective against 371M cells than other anti-cancer agents.

The possibility of oxatomide as the nasal dosage drug for the therapy of nasal allergy was studied. Oxatomide was well absorbed from the nasal cavity, indicating a high permeability to nasal epithelial layer after nasal administration. Acidic pH condition further enhanced the permeation of oxatomide across Caco-2 monolayers, due to the high solubility at the low pH range. Nasal dosage forms for oxatomide (dextrin form, hydroxypropyl-gamma-cyclodextrin form and the suspension of polyethylene glycol) was, therefore, adjusted to pH 5.0. This pH allowed a high solubility of oxatomide without the irritation to nasal epithelium. The effect of nasal administration of oxatomide was studied on experimental allergic rhinitis in sensitized guinea pig. All dosage forms of oxatomide significantly inhibited the dye leakage into the nasal cavity, and among three forms, dextrin form showed the highest effect. High viscosity of dextrin solution was considered to stabilize the dispersion of oxatomide and enhance the retention in the nasal cavity. These results suggest that oxatomide should be useful as nasal dosage drug for allergic rhinitis.

Study Objective To compare the intensity of stress responses caused by laparoscopy combined with CO 2 insufflation (CI) with those caused by mechanical elevation of the abdominal wall (MEA). Design Prospective study (Canadian Task Force classification I). Setting Tertiary care university hospital. Patients Thirty-one women. Intervention Laparoscopy, 16 with CI and 15 with MEA. Measurements and Main Results Circulating levels of norepinephrine, epinephrine, cortisol, and interleukin (IL)-6 were compared in the two groups. Arterial partial pressure of CO 2 (PaCO 2 ) did not increase during laparoscopy by either method. Plasma norepinephrine and epinephrine levels increased after extubation in the MEA group but not in the CI group. Circulating cortisol levels in both groups increased during laparoscopy; mean intraoperative levels were higher in the CI group. Serum IL-6 levels increased after extubation in the MEA but not the CI group. Mean heart rate increased during laparoscopy in both groups, whereas blood pressure increased only in the CI group. More patients in the MEA group required postoperative analgesia. Conclusion Laparoscopy with MEA caused more pronounced adrenosympathetic and cytokine responses than that with CI when PaCO 2 was maintained within the range of normocapnia.

Carrier multiplication (CM) was observed in CdTe quantum dots (QDs) capped with tetradecylphosphonic acid (TDPA) at hν⁄Eg>2.5 by picosecond single-photon timing spectroscopy, where hν and Eg are th...

The enhancing effects of various vehicles on the in vitro permeation of a hydrophilic model drug, 5-fluorouracil (5-FU), or a lipophilic model drug, tolnaftate (TN), through human nail plates were investigated using a modified side-by-side diffusion cell. Tip pieces from the 5th finger-nail, clipped from healthy volunteers, were used in this permeation study. The swelling and softening properties of the nail pieces were also measured in each vehicle. The weights and stresses of the nail pieces were dramatically changed after immersion in aqueous solvents containing N-acetyl-L-cysteine (AC) or 2-mercaptoethanol (ME). However, no significant change in the physicochemical properties of the nail pieces was found in the lipophilic vehicles. Thus, the water content in the nail plates absorbed from vehicles may relate to their physicochemical properties. Although keratin-softerning agents and new skin permeation enhancers did not significantly promote 5-FU permeation compared with water alone, the flux from solvent systems containing AC or ME was substantially higher. In addition, TN permeation from solvents containing AC or ME could be measured, whereas that from other solvents was undetectable. When the AC concentration was increased, the 5-FU permeation and the nail weight increased and the stress of each nail piece decreased. It is concluded from these experimental results that AC and ME may be useful as enhancers for increasing drug permeation through the human nail plate.

The study group led by Tokai University School of Medicine developed a medical network across the Asia Pacific regions using Mark 5 Engineering Test Satellite under the PARTNERS project conducted by the Communication Policy Bureau of the Posts and Telecommunications Ministry and the National Space Development Agency of Japan. The network was exclusively designed for medical use with communications satellite equipment installed at a total of 25 earth stations: five stations in Papua New Guinea, four in Cambodia, four in Fiji, one in China and six in Japan. Operating from 1992 through 1996, the medical network was commonly called 'Network 2' or 'AMINE' (Asia Pacific Medical Information Network via ETS -V) in the PARTNERS project. An analog FM wave with a transmission band of 16kHz, the administration of AMINE/PARTNERS was limited to color still image, sound and packet network. However, the network enabled 24 hour international communications and local communications among developing countries without the help of hub stations for more than 320 days a year, offering teleconferences, teleconsultations and personal computer communications. The result was that a large number of lives were saved during the period. 1. Purpose To develop a medical purpose network across the Asia Pacific regions and study the applications and merits of the system. 2. Method

A monoclonal antibody, MSN-1, was used for flow cytometric analysis of cells from normal endometrium, endometrial hyperplasia, and endometrial carcinoma. The 90th percentile of the specimen control was used as a threshold. Reactivity was defined by the percentage of stained cell about the thresholds, adjusted for the expected percentage. A sample was considered positive if the reactivity exceeded 10%. The positivity rate for normal endometrium, endometrial hyperplasia, and endometrial carcinoma specimens was 9.2%, 19.2%, and 84.6%, respectively. The mean (+/-SD) reactivity rate of MSN-1 for normal endometrium, endometrial hyperplasia, and endometrial carcinoma was 3.3 +/- 6.2%, 7.4 +/- 13.8%, and 34.4 +/- 24.2%, respectively. There was a significant difference of the reactivity rates between normal endometrium and endometrial hyperplasia, and between endometrial hyperplasia and endometrial carcinoma (P < 0.01). In the subgroup of endometrial carcinoma patients with confined muscular invasion, the reactivity and the positivity rates were also analyzed. There was no relationship between the depth of muscular invasion and the reactivity rate or the positivity rate. In endometrial carcinoma patients who simultaneously underwent endometrial cytology, the relationship of the results of cytology and the positivity rate was also analyzed. When the results of cytology and flow-cytometric analysis were combined, the positivity rate of endometrial carcinoma was 100% (30/30). In conclusion, flow-cytometric analysis of endometrial cells employing MSN-1 could be a useful supplementary diagnostic method for endometrial carcinoma.

A case of undifferentiated carcinoma of the broad ligament is reported. The patient was a 28-year-old Japanese woman who underwent laparotomy for a cystic and solid tumor of the left broad ligament. The tumor measured 9 cm in diameter and was unattached to the uterus, ipsilateral ovary, or salpinx. Histological examination revealed tumor tissue consisting of solid nests of irregular configuration and rather small to medium-sized undifferentiated epithelial cells. The tumor cells were positive for cytokeratin, but negative for CA125, epithelial membrane antigen, S-100 protein, amylase, carcinoembryonic antigen, chromogranin A, synaptophysin, HHF35, desmin, and vimentin. Electron-microscopic examination revealed gap junctions and primitive cellular junctions, but no intracytoplasmic mucous granules or microvilli on the surface of the tumor cells. This is the first report of undifferentiated carcinoma of the broad ligament as far as we have been able to determine from a search of the literature.

not Available.

Our previous work showed that melatonin (N-acetyl-5-methoxytryptamine) inhibits proliferation of the human endometrial cancer cell line, Ishikawa, which is estrogen receptor-positive. The aim of the present study was to determine whether Ishikawa cells possess membrane melatonin receptors. Binding of the radioligand 2-[125I]-iodomelatonin to membrane preparations obtained from Ishikawa cells was detectable, saturable and stable. Scatchard analysis revealed that the dissociation constant (Kd) of the binding sites was 179.0 pm (similar to that of the MT2 [Mel1b] melatonin receptor subtype), and that the concentration (Bmax) of the binding sites was 12.9 fmol/mg protein. Luzindole, a selective MT2 melatonin receptor antagonist, significantly suppressed binding of 2-[125I]-iodomelatonin at all concentrations tested (10(-8) to 10(-4) m). These results suggest that the MT2 melatonin receptor subtype is present in the membranes of Ishikawa cells, and that the antiproliferative effect of melatonin on Ishikawa cells is mediated via the MT2 receptor. This may have implications for the use of melatonin in endometrial cancer therapy.

The uses of spinning rotor pressure gages for tritium handling systems dicsussed. The calibration of these gages and their compatibility with tritium handling systems and fusion experiments is also discussed. (AIP)

Greffage de monomeres vinyliques sur les copolymeres du titre; applications comme emulsifiant polymere et electoresist negatif

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells and systemic administration of recombinant Interleukin-2 (RIL-2) was carried out in a case of malignant melanoma with lung metastases. Histological specimens from the lung showed a metastatic melanoma heavily invaded by atypical lymphoid cells with convoluted nuclei of varying size. Immunohistochemistry revealed that these cells had the characteristic exclusively of natural killer cell (Leu-7+). Nodules of these cells mimicked the appearance of non-Hodgkin's lymphoma of pleomorphic type. Molecular cytogenetic analysis, however, showed the absence of rearranged bands for the T-cell receptor beta-chain gene, indicating the absence of T-cell clones. At autopsy, 1 month after the LAK therapy, the heavy invasion of convoluted cells had disappeared. These findings clearly indicate that the LAK cell plus RIL-2 therapy induced Leu-7+ lymphoid cells, phenotypically suggestive of natural killer cell aggregation in the tumours.

Reactivity of scleroderma fibroblasts to lymphoid cell-derived fibroblast growth factor (FGF) was assessed in this study. The fibroblasts from the sclerotic lesion failed to respond to FGF, whereas those from scleroedematous lesions responded equally to normal fibroblast. Response of the fibroblast from sclerotic lesion was also lower than that of the fibroblast from mature scar. Fibroblasts obtained from three different layers of healthy skin, papillary dermis, reticular dermis, and reticular-subcutaneous layer, responded equally to FGF, whereas the fibroblast of reticular dermis from sclerotic lesion failed to respond to FGF. It is suggested that the fibroblast of reticular dermis in scleroderma is variously activated by some unknown factors, so that they do not have enough reserve to respond to further stimuli.

A 30-year-old man developed severe erosive lesions in his oral cavity and transient Raynaud's phenomenon followed by discoid lupus erythematosus (DLE)-like lesions and non-scarring erythema. He had a high titer of RNP antibody as well. Widespread DLE (w-DLE), subacute cutaneous lupus erythematosus (SCLE) and mixed connective tissue disease (MCTD) were suspected as his condition. Finally we diagnosed him as having SCLE accompanied with a high titer of RNP antibody.

The release of digoxin and its simultaneous conversion to digoxigenin bisdigitoxoside, digoxigenin monodigitoxoside, and digoxigenin in a USP dissolution test medium were followed by high-pressure liquid chromatography. Two products, Tablets A and B, were manufactured by solvent deposition and simple blending methods, respectively. Tablet A released digoxin faster than Tablet B in distilled water and in artificial intestinal juice, and no decomposition was observed. In the USP dissolution test medium, the rate of hydrolysis to digoxigenin bisdigitoxoside was almost equal to that of hydrolysis to digoxigenin monodigitoxoside, and a comparatively large formation rate of digoxigenin was observed. Concentrations of digoxin and its decomposition products were described by differential equations that included dissolution rates of digoxin (rapidly dissolving digoxin and digoxin crystals) and an apparent hydrolysis rate. In the earlier stage of dissolution, hydrolysis was rate determining; in the later stage, dissolution became the rate-determining step for overall digoxin degradation. To suppress digoxin hydrolysis in the USP dissolution test medium, a developmental formulation study was performed. The incorporation of magnesium oxide and magnesium hydroxide-aluminum hydroxide in the tablet formulations inhibited digoxin hydrolysis by 15.3 and 14.5%, respectively, after dissolution for 30 min without serious delay of drug release.

The effect of Lactobacillus species on urinary indican excretion in two types of gnotobiotic rats (GBH-9 and GB-5) and in man was studied. L. salivarius, L. plantarum and L. casei colonized in the cecum and colon of both types of rats at levels of 10(7) to 10(8) per gram of contents following one-dose oral administration and caused a significant reduction in urinary indican excretion, whereas two strains of L. acidophilus which colonized at low levels (10(4) to 10(5)/g) did not reduce indican excretion. Daily feeding of Lactobacillus concentrates caused a further significant reduction in indican excretion which was corrected by tryptophan intake, even in the case of L. acidophilus. There was a clear relationship between fecal lactobacillus counts and urinary indican. A significant reduction of indican secretion was obtained only when the fecal counts of lactobacilli exceeded 10(7).4/g in rats. L. casei also had an effect in man, reducing urinary excretion of indican and p-cresol. Reduction in indican excretion seems to be accompanied by decreasing fecal tryptophanase activity in rats and man. A negative correlation was also obtained between fecal resident lactobacilli and urinary indican in man (r = -0.532, n = 28, p less than 0.01). Subjects with lactobacilli at a level of 10(6)/g or more excreted less indican than those harboring the bacteria at levels below 10(5)/g.

Questiomycin A (3-aminophenoxazone-(2)) showed stable ESR spectra in both solid state and organic solvents. The structure of the free radical was discussed by analysis of the hyperfine structure of the radicals produced from questiomycin A and the isotope compounds and simulation using an electronic computor. It was concluded that the spin density of the compound mainly existed in the nitrogen atom of the amino group.

Immune response-associated (Ia) antigens are important as molecules in antigen recognition by T cells. Keratinocytes can express Ia antigens in many inflammatory dermatoses and by action of gamma interferon (IFN-gamma). A keratinocyte cell line, Pam 212 cells, expressed Ia antigens at maintaining culture. They also expressed Ia antigens under the influence of IFN-gamma. Liposomes carrying molecules from trinitrophenylated-Pam cells did not stimulate lymphnode cells (LCs) of contact sensitivity; however, liposomes carrying a large amount of those molecules stimulated LCs. This stimulation was attributable to contaminated Ia antigens in those molecules. Liposomes with a small amount of those molecules or trinitrophenylated-proteins from Pam cells were prepared. Into them were inserted Ia antigen-rich proteins from Pam cells, spleen cells, IFN-gamma-treated Pam cells, or epidermal cells containing Langerhans cells. Thus prepared liposomes stimulated the LCs significantly. The Ia antigens obtained from IFN-gamma-treated Pam cells worked as well as Ia antigens from epidermal cells that contained Langerhans cells as the molecule of antigen presentation in contact sensitivity.

Specimens from cutaneous amyloidoses (lichen amyloidosis and macular amyloidosis) were stained immunohistochemically with monoclonal anti-keratin antibodies. One monoclonal antibody raised against hair keratin (HKN-6) reacted with the amyloids of both primary amyloidoses. Another monoclonal antibody, HKN-2, did not decorate the amyloid deposit. HKN-6 did not stain the interfollicular epidermis, but HKN-2 did. The possible explanations of these findings are 1) amyloid deposits contain keratin protein modulated to react with HKN-6; 2) amyloid deposits contain a protein unrelated to keratin protein, but reactive to HKN-6.

A case of female with a large cystic tumor in her infrascapular region is reported. The tumor was 8 cm x 7 cm in size. Histologically, it was a pseudocyst with calcification. The patient showed no abnormal renal functions other than proteinuria. Because she had suffered from overlap syndromes of systemic lupus erythematosus, progressive systemic sclerosis, and suspected dermatomyositis, we diagnosed this a unique case of dystrophic calcinosis. There have been several reports of cases with connective tissue diseases showing subcutaneous calcification, but to our knowledge no such giant calcifying pseudocyst has ever been reported.

Pigmentary demarcation lines were observed in a 27-year-old Japanese woman during her ninth month of pregnancy. She stated that they were not present before pregnancy. The lines became marked during pregnancy and subsided after delivery. Pigmentary demarcation lines associated with pregnancy have never been reported before in Japanese.

A simulation system has been developed for making comprehensive predictions and assessments of the various and interrelated indices of vehicle performance. This system draws upon a database containing information on the characteristics of the different units making up a vehicle. The system includes fuel economy and emissions calculation programs incorporating a large number of evaluation items. It also features an acceleration calculation program by which the transient characteristics of a turbocharger can be studied and a vehicle exterior noise program that makes accurate predictions of the pass by noise level during acceleration. Equipped with a large number of calculation functions the system is an effective tool for improving total vehicle performance (a).