Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 397 records · Page 22Linked to original sources

PubMed1997

Human Taenia eggs develop into cysticerci in scid mice.

The intermediate hosts for Taenia saginata and T. solium are cattle and pigs (and humans for the latter), respectively. In vitro-hatched (but not activated) oncospheres of both Asian Taenia (T. saginata asiatica, a new subspecies of T. saginata or T. asiatica, a new species) and T. solium injected subcutaneously into the backs of mice with severe combined immunodeficiency (scid) developed into fully matured cysticerci. Five-month-old metacestodes of Asian Taenia had no hooklets and were bigger in size than those previously reported and similar to those of T. saginata. Their morphology suggested that the cysticerci were more advanced than those in the intermediate host animals. It is suggested that scid mice are valuable experimental animal models for studying human taeniid cestode infections.

Animals↗

PubMed1997

Geographical genetic structure within the human lung fluke, Paragonimus westermani, detected from DNA sequences.

Nucleotide sequences were obtained for the second internal transcribed spacer of the ribosomal gene repeat and for part of the mitochondrial-cytochrome c oxidase subunit I gene from geographical isolates of Paragonimus westermani from Japan, China, Korea, Taiwan, the Philippines, peninsular Malaysia and Thailand. Sequences were obtained from several other species of Paragonimus for comparative purposes. Two groups were recognized within P. westermani: an NE group (China, Japan, Korea, Taiwan) which was relatively uniform and included both diploid and triploid forms, and a southern group (Malaysia, Thailand, Philippines), members of which were genetically distant from one another. According to both ITS2 and COI data, genetic distances among P. westermani isolates equalled or exceeded those between some distinct species of Paragonimus. The ITS2 sequences were conserved relative to COI sequences. Substitutions among the latter may be approaching saturation within the genus Paragonimus.

Animals↗

PubMed1997

Phylogenetic relationships of three hymenolepidid species inferred from nuclear ribosomal and mitochondrial DNA sequences.

Three hymenolepidid tapeworms, Hymenolepis diminuta, H. nana and H. microstoma, are commonly maintained in laboratory rodents and used in many experimental model systems of tapeworm infections. We examined partial sequences from the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene and nuclear ribosomal internal transcribed spacer 2 (ITS2) sequences to infer phylogenetic relationships of the 3 hymenolepidid species. Parts of the CO1 gene and ITS2 were amplified by PCR and sequenced directly. The CO1 gene sequence obtained was the same in length (391 bp) among all specimens. In the case of ITS2, however, several insertions and deletions were detected (671-741 bp) not only among species but also between an American isolate and a Japanese isolate of H. diminuta. Percentage nucleotide differences between H. diminuta and H. microstoma, or H. diminuta and H. nana were 16.6-18.2% for the CO1 gene and 21.3-22.9% for ITS2. The differences in both sequences between H. microstoma and H. nana were about 14%. Phylogenetic trees inferred from both of the nucleotide sequences showed similar topology, and suggest that H. diminuta may have diverged from the common ancestral line the earliest, and that H. nana is closer to H. microstoma than to H. diminuta.

Amino Acid Sequence↗

PubMed1997

Inhibitory effects of fluorinated pyrimidines, 5'-DFUR, UFT and T-506, in a model of hepatic metastasis of mouse colon 26 adenocarcinoma-assessment of inhibitory activity and adverse reactions at the maximum tolerated dose.

The effects of fluorinated pyrimidines, 5'-DFUR, UFT and T-506, on a mouse model of hepatic metastasis were assessed in regard to inhibitory activity and adverse reactions at the maximum tolerated dose. The model was prepared by injecting the mouse colonic cancer cell line, colon 26, into the portal vein of CDF1 mice. At the treatment regimens employed for 5'-DFUR (1.0 mmol/kg/day, p.o., daily from days 1 to 7), UFT (0.1 mmol/kg/day, p.o., daily from days 1 to 7), and T-506 (0.074 mmol/kg/day, i.v., days 1, 4, 7, and 10), complete inhibition of hepatic metastasis was obtained in six out of seven mice (85.7%) with 5'-DFUR, and in five out of six mice (83.3%) with T-506. Significant inhibition of hepatic metastasis was not achieved with UFT (3/7, 42.9%). 5'-DFUR and T-506 showed the highest rate of inhibition of hepatic metastasis, suggesting that these drugs would be effective for the prophylactic treatment of metastatic disease. 5'-DFUR and UFT exhibited mild adverse reactions such as loss of body weight.

Adenocarcinoma↗

PubMed1997

Proliferative effects of several hematopoietic growth factors on acute myelogenous leukemia cells and correlation with treatment outcome.

The response of human acute myelogenous leukemia (AML) cells to four different hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 beta (IL-1beta), interleukin-3 (IL-3), and stem cell factor (SCF)) and the relationship of the proliferative response of the AML cells to treatment outcome were studied. Proliferative responses were analyzed in 79 patients with de novo AML and 19 patients with AML arising from myelodysplastic syndrome (MDS). In de novo AML, a positive proliferative response (stimulation index >2) was seen in 65 to 75% of cases. AML cells arising from MDS had a much higher incidence of proliferative response to each growth factor (79 to 90%) and a much higher level of 3H-TdR incorporation. The relationship to treatment outcome was evaluated in 79 patients with de novo AML. The patients whose leukemic cells had a positive proliferative response to any growth factor, especially IL-3 and SCF, had a poorer outcome, ie a lower complete remission (CR) rate, shorter CR duration, and shorter survival. The outcome was particularly poor in patients whose leukemic cells had proliferative responses to all four or any of the growth factors, compared to patients whose leukemic cells had no response. This increased response may be a marker of poor prognosis in patients with AML.

Adolescent↗

PubMed1997

Simultaneous demonstration of lens regeneration from dorsal iris and tumour production from ventral iris in the same newt eye after carcinogen administration.

It is well known that urodeles have the most powerful regenerative capacities among vertebrates, but there is little realisation that they are extremely resistant to spontaneous or chemically induced tumours. Regeneration and carcinogenesis have been considered to be two sides of the same mechanism. Since antagonism between regeneration and carcinogenesis was expected in previous studies, the present study was intended to clarify this relationship in greater detail by changing the amounts of carcinogen stepwise. When 1 microliter nickel subsulfide solution was administered in various amounts (1 microgram/microliter approximately 40 micrograms/microliter) into lentectomized newt eyes, the delay of initiation in lens regeneration for 6 months and an increased inhibition rate of lens regeneration at 6 months were observed in proportion to the increase in carcinogen dosage. The tumour production rate increased in accordance with the increase in the amounts of carcinogen. The conspicuous result obtained in the present study was that lens regeneration from dorsal iris and tumour induction from ventral iris occurred simultaneously in the same eye after administration of moderate amounts (10 micrograms/microliter) of carcinogen. These data clearly indicated that the regenerating dorsal iris is persistently resistant to carcinogen, whereas the ventral iris, which cannot regenerate lens, is susceptible to tumour induction. This strongly suggests that the lens regeneration system in the newt has special advantages for research on the relationship between regeneration and carcinogenesis.

Animals↗

PubMed1997

An assessment of the usefulness of serum prostate-specific antigen level and cancer volume in biopsy specimens to predict the extent of prostate cancer.

OBJECTIVE: To evaluate the usefulness of the combination of serum prostate-specific antigen (PSA) and cancer volume in biopsy specimens as markers to predict the extent of prostate cancer. PATIENTS AND METHODS: Of patients presenting at our hospital with urinary symptoms suggesting prostatic disease, 311 (median age 70 years, range 42-88) with either nodules in the prostate detected by digital rectal examination or with elevated serum PSA levels (> 2.0 ng/mL) underwent systematic biopsy; 69 had prostate cancer. The cancer volume in the biopsy specimens was examined pathologically by measuring the percentage of the biopsy core involved with cancer, the length of cancer tissue per biopsy core and the percentage of cancer in the biopsy specimen. The relationship of serum PSA level, cancer volume in the biopsy specimen and the extent of disease was examined. RESULTS: The volume of cancer in the biopsy specimens increased with increasing serum PSA concentration and the incidence of skeletal metastasis. The number of patients with extraprostatic disease or bony metastasis was significantly higher for these Japanese patients with a serum PSA of < 10 ng/mL. All six patients with a positive bone scan and who had a serum PSA level of < 10 ng/mL had a larger volume of cancer in their biopsy specimens. Among patients who underwent radical prostatectomy and pelvic lymphadenectomy, the incidence of extraprostatic disease increased with the value of each biopsy variable. Among patients with similar serum PSA levels, those showing higher values for the biopsy variables also showed extraprostatic disease. Among those with extraprostatic disease, seminal vesicles were involved by cancer in four of six patients with > 40% positivity in the biopsy cores, > 1.5 mm of cancer per biopsy core or > 20% cancer in the biopsy specimens. Lymph node metastasis was found in four of five patients with serum PSA levels of > 20 ng/mL and a large cancer volume in the biopsy specimen. CONCLUSIONS: These results indicate that a combination of serum PSA level and cancer volume in the biopsy specimen could be useful markers for predicting the extent of prostate cancer.

Adult↗

PubMed1997

Heat-induced apoptosis and p53 in cultured mammalian cells.

Heat-induced apoptosis was studied in M10 and MOLT-4 cells by determining nuclear morphological changes, decrease in cell size, DNA degradation into fragments of about 30 kbp, and the appearance of internucleosomal DNA fragments (DNA ladders). Morphological changes in the nucleus were detected within 30 min after heat-treatment at 44 degrees C in M10 cells, but much later (> 5 h) in MOLT-4 cells. In M10 cells, 30 kbp-DNA fragments were observed even at the end of the heat-treatment and decreased 10 min later, while the DNA ladder increased at 10-30 min after heat treatment. DNA fragments of 30 kbp appeared in MOLT-4 cells at 1 h after the heat-treatment and apparently accumulated for up to 24 h. Heat-treatment increased p53 protein in MOLT-4 cells but not in M10 cells. Analysis of the DNA sequence of the p53 gene revealed that M10 cells have a heterozygous mutation in codon 173 of exon 5. These results suggest that apoptosis is induced by hyperthermia in a cell-line dependent manner, that the formation of 30 kbp-DNA fragments is a very early event in apoptosis, that DNA fragmentation into a DNA ladder occurs via the 30 kbp fragments, and that apoptosis in heat-treated M10 cells may be independent of p53.

Apoptosis↗

PubMed1997

Inhibition of interleukin-6-induced human immunodeficiency virus type 1 expression by anti-gp130 monoclonal antibody.

Interleukin 6 (IL-6) has been reported to upregulate the expression of human immunodeficiency virus type 1 (HIV-1) in infected monocyte/macrophages. Since IL-6 signal is transduced through the membrane glycoprotein gp130, we investigated the inhibitory effect of anti-gp130 monoclonal antibody (mAb) on IL-6-induced viral expression in monocytic cell lines latently infected with HIV-1. IL-6 significantly induced the expression of HIV-1 in U1 cells, whereas it had no effect in OM-10.1 cells. Flow cytometric analysis revealed that U1 but not OM-10.1 cells expressed gp130 on their surface. The anti-gp130 mAb could inhibit IL-6-induced HIV-1 expression in U1 cells in a dose dependent fashion. These results suggest that blocking the gp130 signal transduction may have therapeutic potential for the treatment of HIV-1 infection.

Antibodies, Monoclonal↗

PubMed1997

Transforming growth factor beta type I receptor acts as a potent tumor suppressor in rat bladder carcinoma.

Transforming growth factor beta1 (TGFbeta1) is a potent growth inhibitor for most cells, including neoplastic cells. However, there are several types of malignant cells that are resistant to its growth-inhibitory effect. LMC19, a highly malignant rat urothelial cell line, lacks TGFbeta1 receptor (TbetaRI) and is insensitive to the growth-suppresive effect of TGFbeta1. We transfected an expression vector containing human TbetaRI into this cell line. In control cells transfected with the neo gene alone, no inhibitory effect on growth was observed in vitro by the addition of anti-TGFbeta1 antibody or recombinant TGFbeta1 into serum-free medium. In contrast, the growth of all transfectants tested was inhibited significantly under serum-free conditions because of their endogenous TGFbeta synthesis. The growth was reduced further by the addition of recombinant TGFbeta1. This response pattern is consistent with TGFbeta1 mediating its effects by an autocrine and paracrine mechanism. The tumorigenicity of the cells was tested in a heterotopically transplanted urinary bladder system, which was generated as an orthotopic test site in athymic nude mice. All nine mice tested receiving control cells formed deeply invasive, undifferentiated-cell carcinomas and multiple metastatic foci in the lungs. In contrast, none of the mice receiving transfectants of TbetaRI formed bladder tumors or metastases. Taken together, these observations indicate that TbetaRI exhibits a potent tumor suppressor effect in bladder carcinoma.

Animals↗

PubMed1997

Prediction of the biologically active sites in eclosion hormone from the silkworm, Bombyx mori.

The structure-activity relationship of eclosion hormone from the silkworm, Bombyx mori, was analyzed. First, the probable active residues in silkworm eclosion hormone and also tobacco hornworm eclosion hormone were predicted by the average distance map method. To examine the contributions of those residues to the activity of silkworm eclosion hormone, Gly-substituted mutants for those predicted residues were produced by site-directed mutagenesis and their activities were evaluated by a bioassay. Finally, Glu12, Met24 and Phe25 were estimated to be the crucial residues for the eclosion hormone activity. The possibility of the development of a blocker of an eclosion hormone receptor on the basis of the present work is also discussed.

Amino Acid Sequence↗

PubMed1997

Positive effect of partial zona-pellucida dissection on the in vitro fertilizing capacity of cryopreserved C57BL/6J transgenic mouse spermatozoa of low motility.

Although cryopreservation of mouse spermatozoa has recently become available for use, as yet there are considerable differences in fertilization efficiency of cryopreserved spermatozoa among various mouse strains. In this study, oocytes subjected to partial dissection of the zona pellucida (PZD) were inseminated with frozen-thawed C57BL/6J mouse spermatozoa. At 30, 60, 120, and 240 min after insemination, the oocytes were washed in human tubal fluid medium and cultured for 3-6 h. The fertilization rates of the PZD oocytes in each group at 6-7 h after insemination were significantly higher than that of the zona-intact control (73-88% vs 12%, respectively) (p < 0.01); but the incidence of polyspermy was nevertheless quite low (1.3-2.4%). The development rates of the monospermic oocytes to the morula and early blastocyst stages were in the 87-92% range, with 31-40% of those developing into offspring after embryo transfer. When the cryopreserved spermatozoa of C57BL/6J transgenic mice were used to fertilize PZD oocytes, the fertilization rates were as high as (73-76%) those of the PZD oocytes inseminated with the cryopreserved C57BL/6J spermatozoa, with 30-31% of the morulae and early blastocysts derived from the monospermatic oocytes developing into offspring. These results indicate that PZD of oocytes may provide an alternative when the fertilizing capacity of mouse spermatozoa has been compromised by cryopreservation.

Animals↗

PubMed1997

Anaplastic large cell lymphoma: a distinct molecular pathologic entity: a reappraisal with special reference to p80(NPM/ALK) expression.

The p80(NPM/ALK) expression activated by the t(2;5) (p23;q35) translocation recently has been shown to play an important role in the pathogenesis of anaplastic large cell lymphoma (ALCL). However, the clinicopathologic significance of identification of p80 among ALCL cases has not been completely resolved. Difficulties also exist in the histologic and immunophenotypic identification of ALCL and Hodgkin's disease (HD) as separate processes, often complicating the clinicopathologic evaluation of and therapeutic approach to these entities. In order to clarify these issues, 67 specimens of ALCL and 63 specimens of HD (31 of the nodular-sclerosing type [NS-HD] and 32 of the mixed-cellularity type [MC-HD]) were immunostained using anti-p80 antibody and other relevant markers on paraffin sections. The clinicopathologic and immunophenotypic features were reviewed on the basis of p80 reactivity. The expression of p80 was detected in 43 of 67 cases of ALCL (64%), but none of HD. The p80+ ALCL cases constituted a very homogeneous group of tumors, characterized by the occurrence in a much younger group and relatively more favorable clinical course than the p80- ALCL, which were in keeping with the data previously reported. They showed virtually the identical immunophenotypic findings of p80+, CD30+, EMA+, CD15-, bcl-2-, and Epstein-Barr virus (EBV) with T- and null-cell phenotype, and showed the distinct morphologic features, including three cases of lymphohistiocytic/small-cell variant, as follows: the indented nuclei, often termed as reniform, embryolike, and horseshoelike; multiple, irregular, but indistinct nucleoli; and few reactive cells of eosinophils and epithelioid cells. Conversely, the 24 p80- ALCL cases, in which epithelial membrane antigen (EMA) and bcl-2 positivities were 33% and 55%, respectively, were heterogeneous and could be subdivided into five different categories, namely (a) 11 cases of HD-like ALCLs, (b) six cases of p80 common ALCL, (c) three cases of secondary ALCL, (d) two cases of primary cutaneous ALCL, and (e) two cases of primary classical ALCL that lacked p80 expression. This study clearly demonstrated that the immunohistochemical detection of p80 is of a crucial importance in delineating the biologically distinct entity of "primary classical ALCL" from various diseases that show morphologic and immunohistologic overlap, including HD and HD-like ALCL.

Adolescent↗

PubMed1997

Effects of chronic isoproterenol treatment or submandibular and sublingual ablation on microflora of mouse tooth surfaces.

BALB/cA mice were examined for the effects of chronic isoproterenol treatment or submandibular-sublingual gland ablation on the natural patterns of oral bacterial colonization on tooth surfaces. Indigenous microflora on the tooth surfaces of BALB/cA mice was relatively simple. The predominant bacterial groups were Enterobacteriaceae (45.9%), enterococci (29.4%) and staphylococci (15.7%). Isoproterenol, which resulted in the induced synthesis of proline-rich proteins, caused a decrease in the total cultivable bacteria on the tooth surfaces. The proportion of Enterobacteriaceae in the isoproterenol-treated mice decreased, although the proportion of other bacterial groups increased. Salivary gland ablation, which caused the loss of mucins in saliva, showed essentially the same number of total bacteria as the control. Salivary gland ablation resulted in a decrease in the proportion of Enterobacteriaceae, while the proportion of Gram-positive rods and staphylococci increased.

Adrenergic beta-Agonists↗

PubMed1997

Potent and selective inhibition of human immunodeficiency virus type 1 transcription by piperazinyloxoquinoline derivatives.

We have found novel piperazinyloxoquinoline derivatives to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in both acutely and chronically infected cells. 8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-didehydro-7-[4-(2-met hoxyphenyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12), the most potent congener of the series, completely inhibited HIV-1 replication in acutely infected MOLT-4 cells at a concentration of 0.16 to 0.8 microM without showing any cytotoxicity. The compound completely suppressed tumor necrosis factor alpha (TNF-alpha)-induced HIV-1 expression in latently infected cells (OM-10.1) and constitutive viral production in chronically infected cells (MOLT-4/III(B)) at a concentration of 0.8 microM. K-12 could also inhibit HIV-1 antigen expression in OM-10.1 and MOLT-4/III(B) cells at this concentration. Northern blot analysis revealed that K-12 selectively prevented the accumulation of HIV-1 mRNA in MOLT-4/III(B) and TNF-alpha-treated OM-10.1 cells in a dose-dependent fashion. It was not inhibitory to HIV-1 Tat or the cellular transcription factors NF-kappaB and Sp1, suggesting that the piperazinyloxoquinoline derivatives are a group of HIV-1 transcription inhibitors with a unique mechanism of action.

Anti-HIV Agents↗

PubMed1997

Immunodiagnosis of alveolar echinococcosis by enzyme-linked immunosorbent assay using a partially purified Em18/16 enriched fraction.

An improved enzyme-linked immunosorbent assay (ELISA) system using partially purified Eml8/16 enriched fraction (PP-Em18/16) prepared by isoelectric focusing was evaluated for serodiagnosis of alveolar echinococcosis (AE). The PP-Em18/16-ELISA was compared with Em2plus-ELISA by using sera from AE and cystic echinococcosis (CE) patients in China, where both AE and CE are endemic; sera from CE patients in Australia, where only CE exists; and sera from patients with cysticercosis, paragonimiasis, or sparganosis in Korea, where no indigenous AE or CE exists. We used Em2plus-ELISA as a standard ELISA and found 24.6% (17 of 69 specimens) cross-reactivity with sera from CE. Furthermore, some of the sera from paragonimiasis, sparganosis, and cysticercosis patients were also cross-reactive in the Em2plus-ELISA. When we tested for similar cross-reactivity in the same sera from CE patients by PP-Em18/16-ELISA (23.2%, 16 of 69), it became evident that the specificity of the PP-Em18/16-ELISA was better than that of the Em2plus-ELISA, since no sera from patients with the examined parasitic diseases except CE showed cross-reactivity. Some CE patients from China showed exceptionally high levels of antibody in comparison with those of CE patients from Australia, where no AE occurs. It is speculated that these patients with strongly positive cases of CE from China may have been exposed to both species of Echinococcus.

Animals↗

PubMed1997

Autocrine effect of androgen on proliferation of an androgen responsive prostatic carcinoma cell line, LNCAP: role of interleukin-6.

LNCaP is an androgen-responsive prostatic carcinoma cell line that exhibits a bell-shaped growth response curve to increasing doses of dihydrotestosterone (DHT) in culture. Although the precise mechanism responsible for this unique growth response to androgen stimulation remains unclear, many studies have suggested that androgen modulates the level of various growth factors. In an early study, we demonstrated that LNCaP proliferation was stimulated by interleukin (IL)-6 in a paracrine manner, because these cells did not express a significant amount of IL-6. In the present study, the role of IL-6 in mediating androgen regulated proliferation in LNCaP cells was investigated. DHT, at increasing doses up to 10(-8) M, resulted in a release of IL-6 from LNCaP cells. This dose-dependent effect of DHT on LNCaP proliferation could be partially inhibited by the addition of antibody against IL-6 into the culture medium. These results indicate that the DHT-induced expression of IL-6 stimulates proliferation of LNCaP cells in culture in an autocrine manner.

Androgens↗

PubMed1997

Effects of volume loading on pulmonary venous flow and its relation to left atrial functions.

Although pulmonary venous (PV) flow is closely related to left atrial (LA) pressure dynamics, few investigators have discussed it in relation to LA functions, i.e., reservoir, conduit, and booster pump functions. We examined changes in PV flow rate, LA dimension, and left ventricular filling volume in 11 dogs, and assessed the effects of multistaged volume loading on PV flow and LA functions. Systolic PV flow rate (S) increased significantly and reached a plateau, reflecting a limited LA reservoir function. Diastolic PV flow rate (D) increased significantly with an increase in LA pressure. S/D ratio increased non-significantly from 0.87 +/- 0.07 before volume loading to 0.96 +/- 0.08 until S reached a plateau and then decreased to 0.76 +/- 0.08 (p < 0.05) because of a significant increase in D without an increase in S at the higher stages of volume loading. During atrial contraction, increases in LA active shortening and left ventricular filling volume were limited, indicating a limited LA forward ejection. The difference between PV flow rate just before and at the end of atrial contraction increased and correlated positively with left ventricular end-diastolic pressure (r = 0.57, p < 0.01). PV flow varies according to the degree of volume loading and reflects LA functions, which exhibit limited increases in response to volume loading.

Animals↗