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The ESR spectrum of methyl methacrylate, which had been mixed with 0.1 wt.-% benzoyl peroxide as the initiator and irradiated by UV at 77°K., was observed. The observed spectrum was found to be the superposition of the singlet, triplet, quintet, and septet spectra. In addition to this superposed spectrum, the spectrum due to hydrogen atom was also observed. The four kinds of radical which give these four components of the superposed spectrum could be identified. On warming up the sample to 115°K., 195°K., both the pattern and the intensities of ESR spectra were found to be changed. Based on this change of spectra induced by the heat treatment and on the identification of the radical species, the initiation mechanism of this UV-induced polymerization is discussed.

A super radiation-resistant motor was developed for ITER, consisting of high radiation-durable organic insulation materials, such as poly(benzimidazole), poly-liquid-crystal (VECRUS/spl reg/, VECTRA/spl reg/), and poly(phenyl ether)/urea grease. The motor was subjected to irradiation tests carried out by /sup 60/Co /spl gamma/-ray at room temperature, and its radiation resistance was confirmed to be more than 100 MGy, which is 50 times of that of an ordinary radiation durable motor. The key factor for attaining high radiation resistance was the application of aluminum (Al) thin leaves (thickness: 0.2 /spl mu/m) mainly having faces. In a /sup 60/Co /spl gamma/-rays irradiation test conducted on VECRUS/spl reg/ paper containing Al leaves and overcoated by a silicon layer, an average absorption cross section for the Compton effect was found to decrease by 20% from the theoretical value calculated by the formula of Klein and Nishina. These results show that a secondary electron beam generated from a /spl gamma/-ray can easily pass through VECRUS/spl reg/ paper coated by a silicon layer including the dispersing Al leaf, by means of the channeling effect through the crystal lattice, thereby avoiding a close single collision and reducing serious damage.

In MnSi thin films the magnetic properties of the B20 compound are influenced by induced uniaxial anisotropy. In comparison to bulk MnSi the critical magnetic fields are enhanced and the Skyrmion phase is found to be enlarged within the magnetic phase diagram. Furthermore the ordering temperature depends on the film thickness reaching 43 K for films of around 10 nm and is considerably higher than in bulk crystals (${T}_{c,\mathrm{bulk}}=29$ K). In bulk MnSi the ordering temperature can be reduced by pressure, where at 1.46 GPa the magnetic order is completely suppressed and a non-Fermi-liquid behavior characterized by a ${T}^{3/2}$ law of the resistivity is observed. We present resistance measurements on MnSi thin films under applied pressure of up to 3.44 GPa. Qualitatively, the behavior is similar to bulk MnSi. However, the critical pressure is considerably enhanced to 3.1 GPa, which is assumed to be a consequence of strain. At high pressure non-Fermi-liquid behavior evidenced by a ${T}^{3/2}$ behavior of the resistance is observed up to ${T}_{\mathrm{lin}}=30$ K, i. e., in a larger temperature range than for bulk MnSi. Uniaxial anisotropy might play an important role in this breakdown of Fermi-liquid behavior, since it stabilizes nontrivial spin structures.

The effect of filler concentration on the dielectric properties in the ultralow-frequency region and on the electrical conductivity was studied for ethylene propylene rubber. First, we investigated the relation between the electrical conductivity and filler concentration: as the volume fraction of fillers q/sub a/ increased, the conductivity decreased in the low filler concentration region but increased abruptly in the high filler concentration region. The decrease and increase in conductivity can be explained with the action of carrier traps at the interface between EPR and fillers and with the formation of highly conductive paths of filler across the sample, respectively. Secondly, we studied the dielectric properties in the ultralow-frequency region which was obtained from the discharge current. As q/sub a/ increased, the relaxation time decreased in the low filler concentration region and then rose in the high filler concentration region. The polarization in the high filler concentration region can be explained by two-layer interfacial polarization between filler and rubber. >

Radiation effects on mechanical properties of the glass fiber-reinforced bisphenol-A type epoxy resin were studied. The threshold dose, where 3-point bending strength started to change, was 30 MGy. Radiation-induced latent degradation within the threshold dose was observed by the analysis of differential modulus from the curve of load against displacement. The differential modulus curves could be divided into two displacement regions. It was concluded through the data of water absorption and observations with scanning acoustic microscopes, that the two regions were due to the debonding of matrix-fiber interface and the micro-cracking in the matrix resin, respectively.

Transforming growth factor-beta (TGF-beta) is secreted in a latent form and activated during co-culture of endothelial cells and smooth muscle cells. Plasmin located on the surface of endothelial cells is required for the activation of latent TGF-beta (LTGF-beta) during co-culture, and the targeting of LTGF-beta to the cellular surface is requisite for its activation. In the present study, the cellular targeting of LTGF-beta was examined. We detected the specific binding of 125I-large LTGF-beta 1 isolated from human platelets to smooth muscle cells but not to endothelial cells. A mAb against the latency-associated peptide (LAP) of large LTGF-beta 1 complex, which blocked the binding of 125I-large LTGF-beta 1 to smooth muscle cells, inhibited the activation of LTGF-beta during co-culture. The binding of 125I-large LTGF-beta 1 could not be competed either by mannose-6-phosphate (300 microM) or by the synthetic peptide Arg-Gly-Asp-Ser (300 micrograms/ml). These results indicate that the targeting of LTGF-beta to smooth muscle cells is required for the activation of LTGF-beta during co-culture of endothelial cells and smooth muscle cells. The targeting of LTGF-beta to smooth muscle cells is mediated by LAP, and the domain of LAP responsible for the targeting to smooth muscle cells may not be related to mannose-6-phosphate or an Arg-Gly-Asp sequence, both of which have been previously proposed as candidates for the cellular binding domains within LAP.

We have isolated brefeldin A (BFA)-resistant cell lines, KB/BF-1 and KB/BF-2, from the human epidermoid carcinoma KB cell line. The BFA-resistant phenotypes have been stably maintained for more than 3 months in the absence of BFA. KB/BF-1 and KB/BF-2 showed 10-30-fold higher resistance to cytotoxicity of BFA but were 2-3-fold more sensitive to monensin and nigericin, than KB cells. KB/BF-1 showed aberrant structures of the Golgi complex with poorly developed cisternae surrounded by many small vesicles. Immunocytochemical studies were done with antibodies against a Golgi-specific antigen (chronic rheumatoid arthritis antigen) and a coatomer subunit (beta-subunit for coat proteins of non-clathrin-coated vesicles). Golgi-specific markers were distributed into the small vesicles which were localized diffusedly in cytoplasm of KB/BF-1 cells. Such Golgi markers were observed in a strictly confined perinuclear region of the parental KB cells, whereas in the mutant cells the markers were distributed more diffusedly in dot-like structures at perinuclear regions. In addition, when exposed to BFA, the mutant and parental cells showed a different distribution of these markers. Synthesis and maturation of low density lipoprotein receptor showed apparently slower rates in processing of low density lipoprotein receptor in KB/BF-1 and KB/BF-2 cells than those observed in their parental KB cells. Protein secretion in KB/BF-1 and KB/BF-2 cells was about 30% less than that in KB cells. Much less inhibition by BFA on the secretion was observed in KB/BF-1 and KB/BF-2 cells. A BFA-resistant mutation in BFA-resistant KB cell lines appears to affect assembly of the Golgi apparatus as well as some Golgi-specific functions.

E-glass fabric-reinforced epoxy and polyimide composites were irradiated with 60Co γ-rays or 2 MeV electrons at room temperature. Three-point bend tests were then carried out at 77 K and at room temperature for rectangular specimens having their length axis in a 0° or 45° orientation with respect to the warp and fill of the reinforcing fabrics. Irrespective of the composite type and the test temperature, the 0° specimens fail in a flexural mode, while the 45° specimens fail in a shear or shear/flexural mixed mode. For the 0° specimens, the dose dependence of the ultimate flexural strength depends not only on the test temperature but also on the matrix resin in the composite. The complicated dose dependence can be explained systematically by the mechanism that the degradation of the composite flexural strength is virtually determined by a change in the matrix ultimate strain due to irradiation. For the 45 ° specimens, on the other hand, the dose dependence of the ultimate interlaminar shear strength is dependent only on the test temperature, and is independent of the matrix resin in the composite. This result suggests that the degradation of the composite shear strength is dominated by the radiation damage at the fiber/matrix interface rather than that in the matrix.

The low-density lipoprotein (LDL) receptor is a surface glycoprotein that mediates the cellular uptake of LDL, a cholesterol-carrying plasma protein (Goldstein etal. 1985). After receptor-mediated endocytosis of LDL, LDL receptor recycles to the cell surface from the acid compartment, the endosome, and LDL is then transported and degraded in lysosomes where the cholesterol ester core is hydrolysed and from which the unesterified cholesterol is released. The cholesterol molecules from LDL regulate de novo cholesterol biosynthesis and LDL receptor expression. Mutations in the receptor gene for the LDL receptor impair LDL uptake into cells and cause familial hypercholesterolemia (FH) because of the lack of normal regulation of cholesterol metabolism (Goldstein et al. 1985). The mature LDL receptor consists of 839 amino acids and five domains (Yamamoto et al. 1984; Russell et al. 1984). The first domain (Fig. 1 (1)) of the LDL receptor consists of the NH2-terminal 292 amino acids with a seven cysteine-rich repeat sequence; the second domain (2) of 400 amino acids is 35% homologous to a portion of the extracellular domain for EGF; the third domain (3) of 58 amino acids contains 18 serine/threonine residues where O-linked oligosaccharide chains are clustered; the fourth domain (4) of 22 hydrophobic amino acids spans the plasma membrane; the fifth domain (5) of a 50 amino acid cytoplasmic tail is a COOH-terminal segment (Fig. 1). The mature LDL receptor contains both N-linked and O-linked oligosaccharides (Fig. 2). Among the five major domains of LDL receptor the third domain contains many serine/ threonine (Ser/Thr) residues that are the clustered sites for the O-glycosylation. In addition to the clustered Ser/Thr-linked oligosaccharides, the O-glycosylation site is supposed to be located within the first or/and second domains of the receptor (Cummings et al. 1983; Davis et al. 1986). The LDL receptor also contains two asparaginelinked oligosaccharides (Cummings et al. 1983) (Fig. 1). The LDL receptor is synthesized in rough endoplasmic reticulum (ER) as a precursor form of 120 000 Mr and processed into a mature from of 160 000 Mr. During processing in the ER-Golgi complex, high-mannose relinked sugar chains of the precursor are converted into the complex N-linked sugar chains in the mature form (see Fig. 2). The human LDL receptor precursor carries Ser/Thr-linked core oligosaccharides with only one monosaccharide, 7V-acetylgalactosamine (GalNAc) (Cummings

Gas evolution, oxygen consumption, and change of mechanical property induced by the γ-irradiation of ultra-high molecular weight polyethylene (UHMW-PE) fiber were studied, and compared with those of high density PE (HDPE). Samples were irradiated in oxygen under pressure from 0 to 60 kPa by 60Co γ-ray up to 1.0 MGy at room temperature. For irradiation under vacuum, G(H2) is 2.4 and G(CH4) is 2.0 × 10-3. In the presence of oxygen, G(H2) was about the same, and the G-values for other hydrocarbons were more than 20 times those under vacuum. The tensile strength of the fiber was decreased greatly by irradiation in oxygen.

This paper examines the adaptability of fuzzy systems to gradual and sudden changes in the environment of a market selection game. Agents use fuzzy systems for iterative game playing. Training data are successively generated from each round of our game as a result of the market selection by fuzzy systems.

The /spl gamma/-irradiation effect on electrical conductivity is described for EPR (ethylene-propylene rubber) formulated for a cable insulator. The irradiation produces both permanent and temporary changes in the conductivity. Annealing reduces the temporarily increased conductivity toward that of unirradiated samples. The permanent change in conductivity is probably caused by a chemical change and the temporary change is likely due to such physical processes such as the trapping of carriers excited by /spl gamma/-irradiation. >

We are investigating the polarization phenomena of ethylene propylene rubber (EPR) with hard clay. In this paper we have investigated the effect of electrode materials on thermally stimulated current (TSC) of EPR, and found that the TSC of EPR with evaporated gold electrodes has three peaks, P/sub 1/, P/sub 2/ and P/sub 3/ which appear around 60, 35 and 20/spl deg/C, respectively. The P/sub 1/ and P/sub 2/ peaks are reduced rapidly with decreasing the polarizing temperature Tp from 35 to 9/spl deg/C, and disappear if Tp

We are studying the dielectric properties of EPR with and without filler. In this paper, we investigate the electrical conductivity and the discharge current of EPR without filler at high temperatures from 60 to 90/spl deg/C. We obtain three parameters /spl alpha/, /spl tau//sub 0/ and /spl epsiv//sub r0/-/spl epsiv//sub r/spl infin//, from the curve fitting of the experimental results for the discharge currents to the theoretical equation. The parameters, /spl alpha/ and /spl epsiv//sub r0/-/spl epsiv//sub r/spl infin//, are almost independent of temperature. In contrast, the characteristic relaxation time, /spl tau//sub 0/, decreases with increasing temperature. The activation energies for the electrical conductivity and relaxation time are 0.74 and 0.89 eV, respectively, being close each to each. Therefore, it is suggested that the dielectric relaxation is associated with the conduction process.

In this paper, we have calculated the TSC curve and the discharge current due to two interfacial polarizations in order to interpret experimental results on EPR quantitatively. The simulation results showed that the interfacial polarization due to a small portion of filler, with a long relaxation time, presents a peak around 30/spl deg/C, and the discharge current at room temperature is caused by this polarization. On the other hand, we have affirmed that the polarization caused by the remaining large portion of filler, which has a short relaxation time, presents a small TSC peak at a lower temperature. The discharge current due to this polarization appears in the short time region compared with the measurement time of the discharge current. The simulations are compatible with experimental results.

We are studying the effect of filler on the electrical properties of Ethylene-Propylene Rubber (EPR). In this paper we have measured the Thermally Stimulated Currents (TSC) of EPR with hard clay to investigate the distribution of the relaxation time, and obtained the variation of TSC curve with the temperature T/sub b/ at which the sample is polarized. When the temperature T/sub b/ is lower than room temperature, the TSC curve has only one peak. But for higher values of T/sub b/, the TSC curve exhibits three peaks (P/sub H/, P/sub M/, and P/sub L/ peaks in the order of descending temperature). Assuming two layer interfacial polarization between rubber and filler having a distributed thickness of rubber layer, we have calculated the relation between the TSC curve and the polarizing temperature T/sub b/. From these calculation we think that the P/sub M/ peak is caused by two layer interfacial polarization having a distributed thickness of rubber layer.

10 cases of contact dermatitis which began during the application of povidone-iodine preparations were examined with patch tests using 2 kinds of povidone-iodine preparations and their ingredients, i.e., povidone-iodine, polyoxyethylene nonylphenyl ether and glycerin, and also the components of povidone-iodine, i.e., iodine and polyvinylpyrrolidone. All 10 cases reacted positively to the povidone-iodine preparations and povidone-iodine, 3 out of the 10 to polyoxyethylene nonylphenyl ether, 1 out of the 9 tested to iodine, while no positive response was found to glycerin or polyvinyl-pyrrolidone. It was difficult to distinguish between allergic responses from irritation, as responses to patches of povidone-iodine and its preparations usually include irritation at high frequencies. Based on comparison of results with a control group, however, those showing + or stronger reactions to 2% povidone-iodine at days 3 to 5 were considered to be allergic. Thus, 4 out of the 10 cases were considered as sensitization to povidone-iodine. Another 3 cases were found to be polyoxyethylene nonylphenyl ether sensitized, and another 1 iodine sensitized, while the patch test reactions of the other 2 were considered to have been elicited by irritation.

A 55-year-old male visited our hospital with a complaint of gross hematuria and right lower abdominal pain. Cytological findings of voided urine suggested the presence of malignant cells. Cystoscopic examination revealed bloody urine discharge from the right ureteral orifice and no abnormality in the bladder wall. The retrograde pyelogram showed no tumor masses. However, malignant cells were detected cytologically in the right ureteral catheteral urine twice. Under the preoperative diagnosis of primary urothelial tumor of the right upper urinary tract, right total nephroureterectomy was performed. A histological study revealed transitional cell carcinoma in situ in the lower portion of the ureter. We reviewed 46 cases of primary carcinoma in situ of the upper urinary tract previously reported in Japan.

A 63-year-old male visited our hospital with a complaint of painless swelling of the left scrotum. Left high orchiectomy was performed since ultrasonography suggested a testicular tumor. Histologically, this testicular mass was a Leydig cell tumor. We reviewed 47 cases of this tumor previously reported in Japan.

A 26-year-old man presented with a painless mass in the right scrotum. Physical examination revealed another smaller mass in the left testis. The patient underwent right radical orchiectomy and enucleation of the tumor in the left testis, followed by radiotherapy for right iliac and para-aortic lymph nodes up to a total dose of 30 Gy. Histology proved typical seminoma of the right testis and mature teratoma in the left testis. Imaging study including abdominal CT and chest X-ray and prompt lowering of beta-HCG level within the normal limit after surgery confirmed the diagnosis of stage I disease. Human leukocyte antigen (HLA)-A24 was identified in this case, suggesting its potential association with bilateral testicular tumor. He is now leading an uneventful life without recurrence of the disease at 30 months after surgery.

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors is a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of acute monocytic leukemia occurring in a 44-year-old man who received etoposide-based chemotherapy and radiotherapy for a recurrent, metastatic testicular germ cell tumor. The patient received 14 cycles of systemic chemotherapy for pulmonary and para-aortic lymph node metastases following his initial orchiectomy. The total amount of etoposide this patient received was 6,400 mg/m2. Leukemia occurred 11 years after orchiectomy. A literature review revealed 25 other reported cases of secondary leukemias after treatment for testicular carcinoma. It is not clear whether chemotherapy, radiotherapy or both are responsible for the secondary leukemias seen in these patients.

We studied the level of analgesia obtained with epidural injection of 2% mepivacaine using combined spinal and epidural analgesia (CSE) and compared with the level obtained by epidural analgesia (EA). We inserted a catheter into the epidural space through the L2/3 interspace, and hyperbaric tetracaine was injected through the L3/4 interspace with 26G spinal needle in thirty patients for CSE. We checked the the level of analgesia 90 min after spinal anesthesia. After this, 23 out of 30 patients showed the extension of analgesia 15 min after injection of mepivacaine into the epidural catheter. In these patients, the level of analgesia and the dose of mepivacaine showed the regression line Y = 10.2-0.4X (Y: the level of analgesia, X: the dose of 2% mepivacaine, P0.05). We also showed the regression line Y = 16.1-0.7X (P0.05) for EA 15 min after epidural injection of mepivacaine in other 23 patients. To achieve the same level of analgesia of Th8 or Th6 with CSE and EA, the doses for epidural injection were calculated as 5.5 ml, 10.5 ml with CSE and 11.5 ml, 14.4 ml with EA, respectively. These results show that the epidural dose of local anesthetic for CSE is 1/2 to 2/3 of that necessary for EA.

A case of metachronous presentation of renal cell carcinoma and testicular seminoma is reported. A 48-year-old man underwent left radical nephrectomy for a renal tumor on September 4, 1991. Pathological examination revealed clear cell carcinoma with no capsular penetration. There was no evidence of distant metastases. During postoperative follow-up, he noticed a painless left testicular induration in July, 1994. Serum human chorionic gonadotropin beta subunit as a tumor marker was elevated. Left radical orchiectomy was performed on October 17, 1994. Pathological examination revealed an anaplastic seminoma localized within the testis. Chest X-ray was normal and CT of the abdomen demonstrated no evidence of retroperitoneal lymphadenopathy. The patient was diagnosed as clinical stage I left testicular seminoma. He was free of disease 8 months postoperatively. Including our case, 15 cases of clinically detected double cancers of renal cell carcinoma and testicular germ cell tumor have been reported worldwide. This is the first case of a metachronous presentation of these two cancer types preceded by renal cell carcinoma.

A case of solitary metastasis to residual ureter from renal cell carcinoma is reported. In November, 1987, a 56-year-old male had undergone left radical nephrectomy with renal cell carcinoma (clear cell subtype, G2, Inf alpha). He was doing well until June in 1989 when macroscopic hematuria occurred. A tumor from residual ureter with a large blood clot was detected on cystoscopy. A malignant tumor from the residual ureter was suspected and it was extirpated. Histological diagnosis revealed the same findings as the primary renal tumor. No other metastasis was detected. Only 8 cases of ureteral metastasis from renal cell carcinoma after radical nephrectomy have been previously reported in the Japanese literature.

We monitored serum BFP, a broad-spectrum tumor marker, in 36 patients with kidney transplantation. Serum BFP was elevated in close association with acute rejection and dropped to a normal level after reversal of rejection. As Western blot analysis has revealed that BFP is present in the normal kidney, it is believed that serum BFP may be useful for the detection of various types of renal damage such as acute rejection.

Combination chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC regimen) or with methotrexate, etoposide and cisplatin (MEP regimen) was administered to 32 patients with advanced measurable uroepithelial cancers. Fifteen patients among them were adequately treated with M-VAC regimen, and 11 with MEP regimen. Complete remission was not achieved clinically in any patients. Partial remission occurred in 73.3% (11/15) of M-VAC patients and 72.7% (8/11) of MEP patients. Of eleven MEP patients, six were treated with MEP therapy as second line chemotherapy for the recurrence after other chemotherapy (5 cases after M-VAC, 1 case after intraarterial cisplatin). They showed a considerable response (4 patients, PR; 2 patients, MR) and an appreciable remission period, not inferior to those of first line chemotherapy with M-VAC regimen. The present study shows that MEP may be a promising regimen for advanced uroepithelial cancers, especially as a second line chemotherapy for relapsed cases after M-VAC therapy.

The production of neopterin is closely correlated with activation of cell-mediated immunity. Neopterin appears to be produced by human macrophages specifically stimulated with interferon-gamma (IFN-gamma). Interleukin-4 (IL-4), a B and T stimulatory factor, has recently been shown to inhibit monocyte/macrophage functions, including the ability to suppress monocyte-generated cytokines. In this report we confirmed previous studies that identified the monocyte/macrophage as the main producing cell among human blood cells and that secretion is stimulated by IFN-gamma and lipopolysaccharides (LPS). IL-4 inhibits the generation of neopterin from unstimulated monocytes. This inhibitory effect was dose dependent and occurred at concentrations lower than 0.01 ng/ml. However, IL-4 had only a minimal inhibitory effect on LPS-induced generation of neopterin and could not reverse IFN-gamma-induced neopterin secretion from adherent monocytes. Furthermore, we report that LPS induced IFN-gamma production in monocyte culture. This production is strongly inhibited by IL-4 treatment. These findings indicate that IL-4 can regulate the synthesis of neopterin by adherent blood mononuclear cells and provide further evidence that LPS-induced neopterin in macrophages may act by IFN-gamma-independent mechanisms.

We have previously reported that tumor necrosis factor-alpha (TNF-alpha) enhances expression of interleukin-6, collagenase, plasminogen activator inhibitor-1, and basic fibroblast growth factor genes in human omental microvascular endothelial (HOME) cells in culture. In this study, we found that treatment of HOME cells with TNF-alpha or interleukin-1 (IL-1) caused enhanced expression of low density lipoprotein (LDL) receptor. A few-fold increase in both LDL binding activity and the receptor mRNA levels was observed when HOME cells were treated with either TNF-alpha or IL-1. Northern blot analysis showed that cellular expression of LDL receptor gene was significantly increased 12-24 h after exposure to TNF-alpha. No significant changes in the life-span of LDL receptor mRNA were observed in untreated and TNF-alpha-treated cells. Scatchard analysis showed an increased receptor number for LDL in TNF-alpha-treated cells. Parallel to increased LDL binding activity, internalization and degradation of LDL were also increased in HOME cells treated with TNF-alpha or IL-1. TNF-alpha-induced enhancement of LDL receptor gene expression was not observed when cycloheximide was present. Cellular mRNA level of SP-1 gene was increased about 3-4-fold at 12 h after treatment with TNF-alpha. Nuclear run-on assays showed increased transcription of LDL receptor gene as well as SP-1 gene by TNF-alpha. Gel retardation assay with the SP-1 consensus fragment showed that SP-1 binding activity was increased about 4-5-fold 12-24 h after treatment with TNF-alpha. NF-kB binding activity was also dramatically increased, but there is no NF-kB motif on the promoter for LDL receptor gene. The induction of LDL receptor by TNF might be mediated through a transcription factor, SP-1.

The serum basic fetoprotein (BFP) in patients with urogenital diseases was measured by enzyme immunoassay (EIA). The positive range of serum BFP was defined to be 75 ng/ml or more. In benign cases except for renal transplantation, the positive rate of serum BFP was 11.1% (5/45), and relatively high (21.4%, 3/14) in benign prostatic hypertrophy. In cases of urogenital cancers before treatment, the positive rate of serum BFP was 29.1% (16/55), and increased with the progression of clinical stage. Eleven of the patients with positive serum BFP before treatment were re-examined after treatment, and all of them exhibited a marked decrease of the titer of serum BFP. In seventeen renal transplant patients, the positive rate of serum BFP was 100% (8/8) in acute rejection, 66.7% (2/3) in chronic rejection and 0% (0/6) in rejection-free condition. We conclude that serum BFP is a clinically beneficial marker for renal transplant rejections and urogenital malignancies.

We have characterized seven human renal cell carcinoma cell lines established from primary sites of five patients between 1987 and 1989. Two lines, OUR-20P and OUR-20S, were derived from the OUR-20 cells by cloning with a dilution method 3 months after the primary culture. These three cell lines were tumorigenic in athymic nude mice when inoculated subcutaneously. Examined by a dye uptake method, OUR-20 was highly sensitive to interferon-alpha (IFN-alpha); OUR-20P, OUR-20S and OUR-30 showed slight sensitivities, while the other three cell lines were insensitive. All seven cell lines have been maintained for more than 2 years and over 50 passages in vitro. Cytogenetic analyses performed 1.5 to 3 years after the starts of primary cultures indicated that all seven cell lines, which exhibited different morphologies in phase-contrast micrographs, were aneuploid with modal chromosome numbers 41 to 89.

The combination of carumonam (CRMN) and cefotiam (CTM), expected to have a broader spectrum of coverage in connection with urinary tract infections, was evaluated for its effectiveness and safety at the Department of Urology, Osaka University Hospital and 17 affiliated hospitals. CRMN and CTM were given together to 109 patients with complicated urinary tract infections (UTI), of whom 65 cases satisfied the "Criteria of UTI Committee for the Evaluation of Drug Efficacy in the UTI (3rd Ed.)", which was modified by adopting the midstream urine data for women. CRMN and CTM were administered by drip or one-shot infusion at a total daily dose of 4 g (equally mixed 1 g plus 1 g each, twice a day) for 5 consecutive days or longer. The overall clinical efficacy rate in the 65 cases of complicated UTI was 72%, estimated by the criteria cited above. The efficacy rate according to the infection type groupings was 72% for the 29 patients in the 1st group, 100% for the 1 patient in the 2nd group, 100% for the 7 patients in the 3rd group, 83% for the 6 patients in the 4th group, 50% for the 14 patients in the 5th group and 75% for the 8 patients in the 6th group. The disappearance rate of both urinary Gram positive cocci and Gram negative bacilli was 83.3%. Fifteen strains appeared after the treatment, only 4 of which were Gram positive cocci. Among the 109 patients treated with CRMN+CTM, no subjective side effects were recorded and the abnormalized laboratory findings observed were: eosinophilia in one patient, increases in both GPT and GOT in one patient, and lowered creatinine clearance in one patient. With a broader spectrum and safe regimen, the combination of CRMN/CTM is recommended as the first choice against complicated UTI.

The Chinese hamster ovary (CHO) cell line Monr31, which is resistant to the cytotoxic ionophore monensin, produces a receptor for the low density lipoprotein (LDL) that has a lowered binding affinity for LDL and is approximately 5 kDa smaller in size than the receptor from parental CHO cells. It has been proposed that the reduced size and affinity for LDL are associated with a reduced level of O-glycosylation of Ser/Thr residues in the receptor. To examine this possibility in more detail, both parental CHO and Monr31 cells were metabolically radiolabeled with [3H]glucosamine, and the labeled LDL receptors were purified by immunoprecipitation and identified by SDS-PAGE-fluorography. The Ser/Thrlinked oligosaccharides in the receptors from both parental CHO and Monr31 cells are mono- and disialylated species having the common core structure Galβ1-3GalNAc. The receptor from Monr31 cells, however, contains about one-third fewer Ser/Thr-linked oligosaccharides than the receptor from parental CHO cells. Analysis of the glycopeptides derived from the Monr31 cell LDL receptors indicates that they contain Ser/Thrlinked oligosaccharides only in the clustered domain and are missing Ser/Thr-linked oligosaccharides in the unclustered regions of the protein. Additionally, analysis of a human LDL receptor lacking the domain for attachment of the clustered Ser/Thr-linked oligosaccharides and expressed in both parental CHO and Monr31 cells indicated that the truncated human receptor from Monr31 cells is devoid of Ser/Thr-linked oligosaccharides. In contrast, the truncated human receptor produced by parental CHO cells contains Ser/Thr-linked oligosaccharides contributing approximately 5 kDa to its apparent size. Collectively, these results demonstrate that the LDL receptor produced by the Monr31 cells contains Ser/Thr-linked oligosaccharides in the clustered domain but is missing Ser/Thr-linked oligosaccharides in the unclustered, NH2-terminal domains of the receptor.

Low density lipoprotein receptor (LDL-R) is a membrane glycoprotein carrying both N- and O-linked oligosaccharides, processing of which is reflected in conversion from a precursor to mature form during its synthesis and intracellular transport. Treatment with brefeldin A (BFA) of mouse macrophage-like J774 cells, Chinese hamster ovary cells, and two human cancer cell lines (A431 and IMC-2) resulted in production of LDL-R with a molecular size 5-10 kDa smaller than that of the mature form in the control cells. Treatment with sialidase caused apparent reduction in the molecular size of LDL-R synthesized in all BFA-treated J774, Chinese hamster ovary, A431, and IMC-2 cell lines as observed for the mature form of the control cells. Thus, O-linked sugar chains of LDL-R were apparently sialylated in the BFA-treated cells. We also examined the effect of BFA on the processing of another membranous glycoprotein, epidermal growth factor receptor (EGF-R) carrying only N-linked oligosaccharides. EGF-R synthesized in the presence of BFA was found to have no response to sialidase treatment, suggesting that the drug blocks the sialylation of EGF-R. The results indicate that BFA causes different effects on the sialylation of LDL-R and EGF-R depending upon linkage types of their oligosaccharides.

The low-density lipoprotein (LDL) receptor of molecular mass 155 kDa was expressed on the cell surface of cultured mouse macrophage J774 cells. The conversion rate of precursor to mature form of LDL receptor in J774 cells was comparable to that in mouse fibroblast L cells. The half-life of the LDL receptor of J774 cells was about 2 h, that of L cells was about 11 h. The rapid degradation of LDL receptor was not significantly inhibited by the lysosomotropic agents, chloroquine and NH4Cl, nor by the thiol-protease inhibitors leupeptin and E-64. By contrast, incubation at 18 degrees C retarded the degradation of LDL receptor. Treatment of J774 cells with brefeldin A, an inhibitor of membrane transport between the endoplasmic reticulum and the Golgi apparatus, inhibited the rapid turnover of the LDL receptor. Even after a 9-h chase in the presence of brefeldin A, LDL receptor 5-10 kDa smaller than the normal mature form was found to be stable. Rapid turnover of the LDL receptor in the macrophages appeared to occur after exit from the Golgi apparatus, possibly during transport of the LDL receptor to the plasma membrane.

A case of leiomyoma of the urinary bladder in a 46-year-old woman is reported. The patient was referred to us because of incidental finding of a mass in the bladder. Cystoscopy revealed a protruding tumor covered with normal-appearing urothelium on the right posterior wall of the bladder. The tumor was well-demarcated from adjacent organs on echography and computed tomographic scan. Transurethral biopsy revealed a bladder leiomyoma. Partial cystectomy was performed. The patient is now apparently free of disease 7 months after the operation.

Biosynthesis, processing, and degradation of low density lipoprotein (LDL) receptors were studied in a mouse macrophage-like cell line, J774.1, by immunoprecipitation and immunoblotting with an antibody directed against the COOH-terminal 14 amino acids of the LDL receptor. The molecular weight of the mature LDL receptor of J774.1 cells maintained in RPMI medium was 140,000 under nonreducing condition and 160,000 under reducing condition in sodium dodecyl sulfate-polyacrylamide gels. These sizes are 10,000-15,000 daltons larger than those of the receptor in other mouse fibroblastic cells or P388 leucocyte. However, when J774.1 cells were cultured in Dulbecco's modified Eagle's medium, the molecular weight of the mouse cell lines, 123,000 under nonreducing condition and 153,000 under reducing condition. The larger LDL receptor molecules produced by J774.1 cells cultured in RPMI were insensitive to the treatment with end-alpha-N-acetylgalactosaminidase (O-glycanase), suggesting that aberrant serine/threonine-linked (O-linked) glycosylation might account for the apparent large size. Pulse-chase experiments revealed that the rate of processing of the LDL receptor from precursor to mature form in J774.1 was similar to that in other mouse cell lines, but the rate of degradation was much faster: half-life of the LDL receptor of J774.1 was about 2 h. No significant difference in biological function or lifetime was observed between the normal and the larger LDL receptor. This novel character of molecular size and lifetime of the LDL receptor in J774.1 is discussed in relation to altered maturation and/or modification during receptor biosynthesis.

We have studied function and structure of the low density lipoprotein (LDL) receptors in a monensin-resistant (Monr-31) mutant isolated from Chinese hamster ovary (CHO) cells. To assay the ability of the receptor to bind LDL, we employed three methods, 125I-LDL binding to the cells at 4 degrees C, 125I-LDL binding to the receptor-phospholipid complex (Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1980) J. Biol. Chem. 255, 11442-11447), and ligand blotting (Daniel, T.O., Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1983) J. Biol. Chem. 258, 4606-4611). The LDL receptor number was similar in both CHO and Monr-31, but the binding affinity was reduced in the mutant. The semi-quantitative immunoblotting assay with an antibody directed against the COOH-terminal 14 amino acids and the ligand-blotting assay with LDL also showed that the relative steady-state level of the receptor in Monr-31 was comparable to that in CHO, whereas the binding capacity of the receptor in Monr-31 was lower than that in CHO. The precursor and degradation forms of the LDL receptors produced in the mutant cells were similar in size to those in the parental cells, but the apparent molecular mass of the mature receptor protein in sodium dodecyl sulfate-polyacrylamide gels was reduced about 5000 daltons in the mutant. These results suggest a structural change at the NH2-terminal LDL binding domain. Tests of the effects of tunicamycin, endo-alpha-N-acetylgalactosaminidase (O-glycanase), and sialidase (neuraminidase) on the molecular size of the mature receptors indicated that the reduced size of the receptor in the mutant cells resulted from altered oligosaccharide chain(s) linked to serine/threonine residues in the binding domain. We compared the molecular sizes and binding activity of human LDL receptors in several clones derived from CHO and Monr-31 cells which were transfected with human LDL receptor cDNA. The human LDL receptors produced in the transfected clones of Monr-31 were also smaller in molecular size and lower in binding capacity than those produced in the transfected clones of CHO. These results suggest that both structural and functional alteration of the LDL receptor of Monr-31 is not caused by a mutation in the structural gene of the LDL receptor but by altered processing or maturation of the receptor. The correlation of the decrease in molecular size and reduced binding capacity of the LDL receptor is discussed.