[Intratubular beta-glucuronidase concentration in various states of diuresis].
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Biomedical subjects
Publications and source records attributed to F Suzuki.
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To investigate characteristics of pancreatic carcinoma growth behavior, the cloned cell lines, HPD1NR, HPD2NR, and HPD3NR, were established from a transplantable hamster ductal adenocarcinoma induced by N-nitrosobis(2-hydroxypropyl)amine (BHP). All three clones showed similar epithelial cell morphology and grew as sheets in culture with no differences in doubling times, ranging from 23-28 h. Mutation in the c-Ki-ras exon 1 was detected in common. The modal chromosome numbers were also found to be similar at 60, 62, and 60-62 in the less than tetraploid cells in the three clones. In contrast, a clear difference in frequencies of tetraploid or polyploid cells at 24.7, 22.5, and 75.5% in HPD1NR, HPD2NR, and HPD3NR, respectively, was evident. Tumorigenic potency evaluated by transplanting individual clones revealed HPD3NR to display pronouncedly less growth in syngeneic hamsters. The results suggest that increase in frequency of tetraploid or polyploid cells might be associated with a decreased in vivo growth potential of hamster pancreatic ductal adenocarcinomas, and suggest that these clones might become a valuable tool for understanding in vivo growth mechanisms of cancer cells.
The role of CD8+ suppressor T cells in acute herpes simplex virus type 1 (HSV) infection was investigated in mice. CD8+ CD11b+ TCR-gamma/delta + suppressor T cells (HSV-STC) were demonstrated in spleens of mice infected intraperitoneally (i.p.) with HSV. When HSV-STC from mice infected with a 10 LD50 of HSV (donors) were adoptively transferred to mice 3 days after being infected with a 1 LD50 dose of HSV (recipients), the morbidity and mortality of recipients were greatly increased (mean survival time in days (MSD): 9.4 days; mortality, 100%) as compared with controls that received CD4+ T cells or a whole T-cell lysate from donors (MSD, > 19.6 days or > 19.1 days; mortality, 38% or 50%). The morbidity and mortality of mice exposed to a 1 LD50 of HSV were also increased when they were continuously treated with recombinant murine IL-4. However, the survival rate of mice exposed to a 10 LD50 of HSV increased after multiple treatments of these mice with anti-IL-4 monoclonal antibody. IL-4-producing cells were detected in a population of HSV-STC, and IL-4 was produced when these cells were cultured in the presence of UV-inactivated HSV in vitro. These results indicate that IL-4 plays an important role in the progression of acute HSV infection and, through the production of IL-4, HSV-STC may increase the severity of the acute-phase infection of HSV in mice.
Chinese hamster spermatozoa during epididymal maturation were examined by thin sectioning, freeze-fracture, and surface replica. Membrane-limited vesicles and tubules (MVTs) attach to the plasma membrane over the acrosome of the spermatozoa in the distal caput through proximal cauda epididymidis. The origin of these MVTs is likely to be spermatozoa degenerating in the epididymal lumen. The attachment of MVTs to the plasma membrane seems to be mediated by a paste-like substance covering the plasma membrane. A parallel striation pattern of intramembranous particles (IMPs) is seen in the plasma membrane of almost the entire postacrosomal region of the epididymal spermatozoa. The patterned domain begins to appear in the proximal caput epididymidis. The number and density of IMPs in the plasma membrane of the postacrosomal region increases with the development of striated pattern of IMPs in this region. In the cauda epididymidis, the redundant nuclear envelope elongates to form a shirt-like membrane covering the mitochondrial sheath. The elongated portion of the nuclear envelope is devoid of nuclear pores and has few IMPs.
An 11C-labeled selective adenosine A2A antagonist, (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-[11C]-methylxanthine ([11C]KF17837), was prepared by reaction of (E)-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine and [11C]methyl iodide with decay-corrected radiochemical yield of 19-50%, radiochemical purity of > 99%, sp. act. of 17-100 GBq/mumol and preparation time of 20-25 min. In mice, the myocardium showed the highest (13.4% ID/g) at 5 min after i.v. injection, which decreased gradually with time. The specific myocardial uptake was visualized by gamma-camera. In the brain region the radioactivity level was higher in the A2A receptors-rich striatum than in the cortex and cerebellum. The specific striatal uptake in rats was clearly demonstrated by PET. These results have shown that [11C]KF17837 is a potential PET radioligand for mapping the adenosine A2A receptors in the heart and brain.
PURPOSE: To study the changes in the distribution of postsynaptic benzodiazepine (BDZ) and presynaptic adenosine A(1) (AA(1)) receptors in the superior colliculus (SC) and visual cortex (VC) of rats following monocular enucleation. METHODS: The right eyes of 6-week-old Long-Evans rats were enucleated and ex vivo autoradiography was performed on the SC and VC obtained at different times up to 8 weeks after the enucleation. [14C]deoxyglucose was used to detect glucose metabolism, and [11C]flumazenil and [1-methyl-(11)C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine ([11C]MPDX) were used to map BDZ and AA(1) receptors, respectively. The receptor-specific binding for 11C was determined, and 11C and 14C activities were evaluated separately in the same tissue by a double tracing method. RESULTS: The uptake of [14C]deoxyglucose in the SC was depressed immediately after enucleation and gradually recovered. The binding of [11C]flumazenil to BDZ receptors in the contralateral SC was increased at week 2, and then returned to the pre-enucleation levels. The uptake of [11C]MPDX by the AA(1) receptors in the contralateral SC decreased by about 67% on day 5 after enucleation and remained low thereafter. In the contralateral VC, the uptake of [14C]deoxyglucose decreased immediately after the enucleation followed by a gradual recovery, whereas the uptake of [11C]flumazenil and [11C]MPDX was not altered. CONCLUSIONS: The axon degeneration related decrease of the AA(1) receptor density resulted in a transient up-regulation of postsynaptic BDZ receptor density in monocularly enucleated adult rats. These results suggest that these radioligands can be used to study the distribution of the postsynaptic BDZ and presynaptic AA(1) receptors in the visual system and can probably be applied to the human visual system for positron emission tomography.
We have constructed three different plasmids containing parts of the human growth hormone gene using chemically synthesized oligomers and cloned them for the purpose of expressing them in Escherichia coli. AB, B and BC gene segments corresponding to ABhGH (residue 1-138), BhGH (residue 44-138) and BChGH (residue 44-192) were placed under the control of a tryptophan promoter in the expression vector. Upon induction with 3-indolylacrylic acid, ABhGH accumulated in cells but the BhGH and BChGH segments were not detected appreciably. Northern blotting analysis showed that the amount of mRNA transcribed from the AB gene segment was about ten-fold higher than that from the B or BC gene segment. ABhGH was found to have insulin-like growth factor I (IGF-I) activity, which could be explained by the hydrophilicity curves of these proteins.
OBJECTIVE: To examine estrogen receptor (ER) detection using cytologic specimens and to compare the results with those obtained by the dextran-coated charcoal (DCC) method and enzyme immunoassay (EIA). STUDY DESIGN: Immunocytochemical staining was conducted on 60 cases of breast cancer resected at our hospital between April 1993 and November 1997 in which ER had been measured by DCC or EIA. Specimens for immunocytochemical staining were prepared by a cell transfer method using archival Papanicolaou-stained imprint smears, and ER staining was performed by the labeled streptavidin method using an anti-ER monoclonal antibody. These results were compared with those obtained by DCC or EIA. RESULTS: In immunocytochemical staining for ER, positive staining was observed in the nuclei of tumor cells. A good correlation was obtained between the immunocytochemical staining results and biochemical results. Five cases were positive in anti-ER staining but negative in biochemical tests, and two cases were negative in anti-ER staining and positive in biochemical tests. CONCLUSION: Unlike biochemical assays, the immunocytochemical method does not necessitate use of fresh frozen materials and can be performed even using archival Papanicolaou-stained smears. Immunocytochemical study is a highly useful method for routine ER determination.
BACKGROUND: Endodermal sinus tumor (EST) of vaginal origin is extremely rare, and few previously published reports have described the cytology of this tumor. CASE: A high serum alpha-fetoprotein (AFP) level and magnetic resonance imaging findings in a 10-year-old female suggested EST of the lower genital tract. Laparotomy revealed EST occupying the pelvic cavity. The patient died on the 17th postoperative day due to complications from disseminated intravascular coagulation. Autopsy was performed immediately after death. The tumor originated in the posterior vaginal wall directly below the ectocervical area. Both ovaries were involved, and the tumor proliferated to occupy the cavity of the pelvis minor. A vaginal smear, obtained on two occasions, revealed severe necrosis with few cells, and a diagnosis could not be made. An imprint smear of the tumor obtained during surgery showed relatively characteristic cytologic findings of EST. Immunocytochemical and immunohistochemical studies revealed staining positive for AFP. CONCLUSION: Vaginal EST usually occurs in patients under 3 years of age. This 10-year-old patient was the oldest among the reported cases. Vaginal EST is clinically similar to sarcoma botryoides and clear cell carcinoma, and a differential diagnosis is necessary. Immunocytostaining for AFP is essential for a definitive cytologic diagnosis of EST.
BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of trophoblastic neoplasm. Approximately 100 cases of PSTT have been reported, but we found no report on its cytodiagnosis. CASES: Case 1, a 39-year-old female, came to the hospital because of abnormal genital bleeding. Case 2, a 36-year-old female came because of amenorrhea for a year. In both cases, endometrial smear and intrauterine curettage suggested trophoblastic disease, and hysterectomy was performed. Laboratory data revealed a mild increase in human chorionic gonadotropin (hCG) and beta-hCG but normal human placental lactogen (hPL). In the cytologic examination, the background contained some hemorrhagic and fibrinous areas but no necrosis. Most tumor cells stained light green, were round or polygonal, and contained abundant cytoplasm. Some were palely stained and had vacuoles. Some cells showed hyperchromatism, an irregular nucleus, fine-to-coarse chromatin granules and markedly different sizes. Most of the cells were hPL positive, and a few were hCG positive. CONCLUSION: Both cases were considered benign because of rare mitoses despite cellular pleomorphism. However, careful follow-up is required. The differential diagnosis of PSTT is difficult from cytologic and biopsy specimens alone but may be achieved with additional magnetic resonance imaging findings and positive staining of hPL and hCG.
BACKGROUND: Malignant melanoma of soft tissue (MMST) is a rare tumor and consists of < 1% of all soft tissue neoplasms. There are few reports on its cytodiagnosis. CASE: A 14-year-old male attended the Department of Orthopedics, Juntendo University Urayasu Hospital, in August 1994 because of a painless tumor in the distal portion of the left thigh. Intraoperative imprint smear examination led to a diagnosis of malignant melanoma, and wide resection of the tumor, including the surrounding normal tissue, was performed. On cytologic examination, the background was relatively clean, with tumor cells distributing individually or in clusters. Under high magnification, the tumor cells were seen to contain a slightly enlarged, conspicuous nucleolus and large cell body. The cells varied in shape from polygonal to spindle shaped, with a few multinuclear giant cells. Melanin and glycogen were observed in varying degrees in the tumor cells. CONCLUSION: MMST can be diagnosed easily if melanin is observed in the cytoplasm. Even in the absence of melanin, the tumor has relatively characteristic cytomorphology. Intraoperative cytology is useful for an accurate diagnosis of the tumor.
BACKGROUND/AIMS: Conflicting results have been reported concerning the effect of endoscopic injection sclerotherapy upon the long-term survival of cirrhotic patients with esophageal varix. The recurrence and rebleeding of esophageal varices seems to be an important factor influencing long-term survival. We investigated the long-term survival of patients after complete eradication of esophageal varices. METHODOLOGY: Forty patients treated by endoscopic injection sclerotherapy for acute esophageal variceal bleeding were studied. The recurrence rate of varices and the long-term survival of patients in whom complete eradication of esophageal varices was obtained were compared with those of patients in whom the eradication of varices was incomplete. RESULTS: The frequency of the recurrence/deterioration rate of varices and rebleeding in the complete eradication group was significantly lower than that in the incomplete eradication group (10.7% vs. 100%, 0% vs. 58.3%, respectively, p < 0.01). Accumulated 5-year survival rate of the complete eradication group was significantly higher than that of the incomplete eradication group (68.2% vs. 43.2%, p < 0.05). CONCLUSIONS: Complete eradication of esophageal varices by endoscopic injection sclerotherapy is effective both in preventing variceal re-bleeding and in improving the survival of cirrhotic patients with esophageal varices.
The antitumor activity of an oily formulation of SMANCS (oily SMANCS), which is a product of conjugation between a proteinaceous antitumor antibiotic neocarzinostatin and poly (styrene-co-maleic acid), after oral administration to mice inoculated with various murine tumors was investigated. BALB/c mice, inoculated either s.c. or i.p. with allogeneic (sarcoma-180) or syngeneic (RL male 1 leukemia and Meth A fibrosarcoma) tumors, were treated with oily SMANCS orally or with an aqueous formulation of SMANCS (aqueous SMANCS) i.v. or i.p. Oral administrations of oily SMANCS or i.v. administrations of aqueous SMANCS to mice bearing three types of tumors in the ascites form resulted in a weak inhibition of tumor growth as compared to the complete inhibition of these tumors by aqueous SMANCS administered i.p. In mice bearing solid tumors, tumor growth was inhibited by 63-82% when a 10 mg/kg dose of oily SMANCS was administered orally to these mice. The antitumor potential of oily SMANCS administered orally was comparable to that obtained from solid tumor-bearing mice receiving i.v. doses of aqueous SMANCS. These results suggest that the oral administration of oily SMANCS to mice bearing various solid tumors inhibits the tumor growth as effectively as aqueous SMANCS administered i.v.
The effect of glycyrrhizin (GR), a Chinese herbal drug extracted from licorice roots, on the host resistance to tumors was investigated in a murine system. Administration of GR to BALB/c mice, which were inoculated s.c. with 1 x 10(6) cells/mouse of Meth A tumors, resulted in either no antitumor effect (8/20, 40%), a delay in tumor growth (9/20, 45%), or elimination of tumor growth (3/20, 15%) in these mice. In addition, the incidence of Meth A solid tumors was inhibited by GR when mice were inoculated with 1.5 x 10(4) cells/mouse or less of Meth A tumor cells, but not 7.5 x 10(4) cells/mouse or more. These results indicate that in this murine tumor system GR has a very weak antitumor effect. When GR at a dose of 20 mg/kg was administered to mice immunized with allogeneic lymphocytes 1 to 9 days after the immunization, the generation of suppressor macrophages (S-M phi) was clearly reduced as compared with that of S-M phi generated in immunized controls. In addition, when allospecific CTL (allo-CTL), which were generated in alloimmunized mice treated with GR followed by in vitro stimulation with allogeneic lymphocytes in a mixed lymphocyte reaction, were adoptively transferred to tumor-bearing mice treated with GR, the antitumor activity of allo-CTL derived from immunized mice treated with GR was markedly enhanced as compared with that of allo-CTL from immunized mice. Furthermore, established solid tumors were completely eliminated when interleukin-2 immunotherapy was performed in these mice in combination with GR treatments, but not interleukin-2 or GR alone.(ABSTRACT TRUNCATED AT 250 WORDS)
The antitumor activity of three interleukin-3 (IL-3) preparations administered intralesionally into mice bearing syngeneic solid tumors was investigated. IL-3 preparations used in this study included S-IL-3, which was isolated from the culture fluid of murine inguinal lymph node cells stimulated with an arabinomannan extracted from Mycobacterium tuberculosis (SSM), the culture fluid of WEHI-3 cells (W-IL-3) and recombinant IL-3 (rIL-3). When a 1,500 U/kg dose of S-IL-3 or W-IL-3 was injected intralesionally into BALB/c mice bearing Meth-A solid tumors three time per week beginning 3 days after tumor inoculation, tumor growth was inhibited by 60% or 74% at 24 days after tumor inoculation, respectively. In these experiments, 1 unit of IL-3 activity was determined to be the concentration that induced 50% of maximal proliferation of an IL-3 dependent cell line (FCD-P2 cells). The administration of this dose of rIL-3 inhibited tumor growth by 34%. When these three preparations of IL-3 were pretreated with anti-IL-3 monoclonal antibody in vitro, the antitumor activity, as well as their growth promoting activity on FDC-P2 cells, was eliminated. Since direct cytotoxic activities of these IL-3 preparations against cultured Meth-A tumor cells in vitro have not been demonstrated, these results suggest that their antitumor activities might be expressed through interactions between tumor cells and antitumor effector cells which were stimulated by the intralesional administration of the IL-3 preparations.
Two cases of progressive interstitial lung disease associated with polymyositis/dermatomyositis are presented. Both patients were refractory to conventional therapy with high-dose corticosteroids, cyclosporine, and intermittent pulse cyclophosphamide, and thus a therapeutic trial of tacrolimus was instituted. Tacrolimus was markedly effective in achieving subjective, laboratory and radiographic improvement in both patients.
Previously we reported that rabbit costal chondrocytes in primary culture produced an anti-angiogenic anti-tumor factor. We also established a clonal human chondrosarcoma cell line, HCS-2/8, which had typical cartilage phenotypes. In the present study, we investigated whether HCS-2/8 cells produce an anti-angiogenic anti-tumor factor. Serum-free medium conditioned by exposure to HCS-2/8 cells in culture inhibited the proliferation of bovine pulmonary artery endothelial cells in culture. The inhibition was not due to general cytotoxicity because the endothelial cells started to proliferate after the conditioned medium was removed from the cultures. The factor in conditioned medium also inhibited DNA synthesis in bovine pulmonary artery endothelial cells, but not in B16 melanoma cells, normal rat kidney cells or chick embryo fibroblasts. Production of the factor by HCS-2/8 cells did not change during serial passages. It also inhibited angiogenesis in the chorioallantoic membrane of chick embryos induced by B16 melanoma and growth of the tumor transplanted onto the membrane. Treatment with protease destroyed the inhibitory activities of conditioned medium on angiogenesis and tumor growth. These findings suggest that HCS-2/8 cells produce a peptide factor with anti-angiogenic, antitumor activity and that the cell line should be a useful source of the factor.