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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 577 records · Page 32Linked to original sources
PubMed1994

High-level expression of human lipocortin I in the fission yeast Schizosaccharomyces pombe using a novel expression vector.

We have developed a novel expression system that allows the fission yeast, Schizosaccharomyces pombe, to be used for the efficient overproduction of heterologous proteins. As an example of the utility of this system, human lipocortin I was expressed to 50 percent of soluble protein, and 150 mg of highly purified material was obtained from 10 grams of wet cell paste. Expression of lipocortin I was driven by the human cytomegalovirus (hCMV) promoter in a vector that also contains a neomycin resistance gene (neo) under the control of the SV40 early promoter, permitting selection for increasing copy-number with increasing concentrations of the antibiotic G418. The purified protein was equivalent to its native counterpart with respect to antigenicity and biochemical properties such as phospholipase A2 inhibition, actin binding and N-terminal acetylation. We have also used this system to produce comparable amounts of other proteins including rat arginase, rat NDP-kinase and human interleukin-6.

Animals↗
PubMed1994

Effects of vasopressin V1 and V2 receptor antagonists on progressive renal failure in rats.

1. The relationship between vasopressin and the progression of renal failure has been proposed, but not intensively investigated because of a lack of orally available, selective vasopressin antagonists. 2. The effects of novel, orally available vasopressin V1 and V2 receptor antagonists on several indices of the progression of chronic renal failure, i.e. blood pressure, urinary protein excretion, sodium balance and renal histopathology, were investigated by using Wistar rats with adriamycin-induced nephropathy accelerated by deoxycorticosterone acetate-salt hypertension. Groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as the control. To block the effects of vasopressin efficaciously, V1 and V2 antagonists were simultaneously administered (group 4). 3. At week 6, 2 weeks after the beginning of administration of deoxycorticosterone acetate-salt and vasopressin antagonists after the second injection of adriamycin, V1 and V2 antagonists given either alone or in combination significantly reduced the systolic blood pressure as compared with the control, and urine volume was increased in groups 3 and 4. The proteinuria was also decreased at week 10 in groups 2, 3 and 4. Differences in sodium excretion between all groups were not significant. Histopathological alterations in the kidneys of group 4 were significantly ameliorated. 4. These results suggest that a combination of V1 and V2 antagonists can have therapeutic effects in certain types of chronic renal failure.

Animals↗
PubMed1994

Inhibition of topoisomerase II by a novel antitumor cyclic depsipeptide, BE-22179.

BE-22179, a novel cyclic depsipeptide antibiotic having two 3-hydroxyquinoline moieties, inhibited the DNA-relaxing activity of L1210 topoisomerase II completely at 0.08 microM. This effect was far stronger than that of VP-16. However, it did not show any marked effect on topoisomerase II-mediated DNA cleavage. BE-22179 was ineffective in inhibiting the DNA relaxation by topoisomerase I at concentrations up to 10 microM, but showed DNA-intercalating ability (DNA unwinding) at 30 microM. The structure of BE-22179 is quite novel for a topoisomerase II inhibitor. Echinomycin, a quinoxaline antibiotic structurally related to BE-22179, interfered with DNA relaxation by topoisomerase II, though the effect was not due to inhibition of the catalytic activity of topoisomerase II but to conformational change of DNA based on its intercalation into DNA. Therefore, the potent inhibitory activity on topoisomerase II might not be a common activity of quinoxaline antibiotics, but might rather be specific to BE-22179. BE-22179 prevented DNA synthesis as well as RNA synthesis in L1210 cells and inhibited the growth of the cells. However, it remains unclear to what extent the topoisomerase II inhibition was responsible for the cytotoxicity of BE-22179.

Animals↗
PubMed1994

Membrane-bound complement regulatory activity is decreased on vaccinia virus-infected cells.

Decay accelerating factor (DAF), membrane cofactor protein (MCP), complement receptor 1 and mouse Crry are cell surface-bound complement regulatory proteins capable of inhibiting C3 convertase activity on cell membranes, and therefore provide a substantial protection from attack by homologous complement activated either by the classical or by the alternative pathway. Decrease in complement regulatory activity might lead to spontaneous complement deposition and subsequent cell injury. MoAb 5I2 can inhibit the complement regulatory activity of molecules on rat cells, resulting in deposition of homologous complement. The antigen recognized by 5I2 MoAb in rats is homologous to mouse Crry. Fifteen to 20 h after infection with vaccinia virus, in vitro cultured KDH-8 rat hepatoma cells show a strong decrease in expression of Crry-like antigen, and proved to be sensitive to complement deposition when 1:5 diluted normal rat serum was added to the culture medium as a source of complement. Addition of complement to the cultured KDH-8 cells infected with a very low dose of vaccinia virus (1 plaque-forming unit (PFU)/1000 cells) substantially reduced spreading of virus infection in the cell culture, while inactivation of complement by heat or zymosan treatment abrogated the protective effect.

Animals↗
PubMed1994

Müllerian duct cyst with 46, XYq-.

We report a case of a müllerian duct cyst associated with a 46, XYq- chromosome anomaly. Müllerian duct cyst is a consequence of the abnormal regression of paramesonephric derivative. In the past many different manifestations have been associated with the 46, XYq-, anomaly. We discuss the possibility that a müllerian duct cyst may be one clinical manifestation of 46, XYq-.

Adult↗
PubMed1994

Clinical usefulness of low-dose oral contraceptives for the treatment of adolescent hyperandrogenemia.

In the early stage of adolescence, irregular menstruation and an anovulation often occurs. During this period, some adolescent women suffer from hyperandrogenemia, which results in acne, adiposity, and hirsutism. If adequate treatment is not given to these hyperandrogenic young women, severe hirsutism and polycystic ovary (PCO), which could be a proximate cause of juvenile endometrial carcinoma, might occur. Young women with hyperandrogenemia show increased levels of luteinizing hormone (LH) levels and free testosterone (T)/total T ratio, and a decreased level of steroid hormone binding globulin (SHBG) in serum. Low-dose oral contraceptives might reduce the hormone unbalance and hyperandrogenemia without leading to negative effects in the ovarian function of adolescent women.

Adolescent↗
PubMed1994

[Bacteremia of in-patients of the department of urology].

Thirty cases of bacteremia out of 1512 patients who had been admitted to our Department between February 1988 and June 1991 were reviewed. They consisted of 22 males and 8 females and their age ranged from 32 to 88 years (mean 62.7). 25 of the patients (83.3%) had malignant diseases of which bladder cancer (15 cases) was predominant and 5 had benign diseases. Gram positive bacteria were isolated in 18 cases (56.2%) and fungi in 4 cases (12.5%) from blood culture. Of these MRSA was most prevalent: 6 cases (18.8%), followed by S. epidermidis: 4 cases (12.5%), P. aeruginosa: 3 cases: E. faecalis: 3 cases and Corynebacterium: 3 cases (9.4%). Analysing the onset of bacteremia for each case, in three cases urinary tract infections, in one case a surgical wound infection and in one case a skin infection were prominent before the diagnosis of bacteremia. From their background, 23 cases (76.7%) were so-called compromised hosts. A total of 7 cases had died, 6 cases of bladder cancer and one case of testicular cancer, five of them were on systemic anti-cancer chemotherapy. Of those cases who expired, P. aeruginosa was isolated in two cases, Candida in two cases, MRSA in one case and E. faecium in one case, Corynebacterium in one case. It was noteworthy that in two cases where blood cultures were positive for P. aeruginosa and one case where the blood culture proved positive for Candida, drastic decrease of the peripheral leukocyte number during anti-cancer chemotherapy was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Type C retrovirus inactivation by human complement is determined by both the viral genome and the producer cell.

The inactivation of type C retroviruses by human serum may be a considerable impediment to the use of retroviral vectors in vivo for gene therapy. Here we show that virus inactivation is dependent both on the virus and on the cell line used to produce the virus. All viruses produced from murine NIH 3T3 or dog Cf2ThS+L- cells are sensitive to human serum. In contrast, those produced from mink Mv-1-Lu and human HOS or TE671 cells are at least partially resistant, with the exception of murine leukemia viruses. In particular, the feline endogenous virus RD114 is completely resistant to a panel of eight human sera when produced from Mv-1-Lu or HOS cells. This differential resistance is controlled by the viral envelope proteins. Virus inactivation can be correlated with the ability of the producer cells to be lysed by human serum. Inactivation of sensitive viruses requires the classical pathway of complement but does not require virion lysis.

3T3 Cells↗
PubMed1994

An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans.

Several cytotoxic T-lymphocyte (CTL) epitopes have been defined in hepatitis C virus (HCV) proteins. CTL may play an important role in the control of infection by HCV. Here, we identify a highly conserved antigenic site in the HCV core recognized by both murine and human CTL. Spleen cells from mice immunized with a recombinant vaccinia virus expressing the HCV core gene were restimulated in vitro with 11 peptides from the core protein. CTL from H-2d mice responded to a single 16-residue synthetic peptide (HCV 129-144). This conserved epitope was presented by a murine class I major histocompatibility molecule (H-2Dd) to conventional CD4- CD8+ CTL mapped by using transfectants expressing Dd, Ld, or Kd, but was not seen by CTL restricted by H-2b. The murine epitope was mapped to the decapeptide LMGYIPLVGA. The same 16-residue peptide was recognized by CTL from two HCV-seropositive patients but not by CTL from any seronegative donors. CTL from two HLA-A2-positive patients with acute and chronic hepatitides C recognized a 9-residue fragment (DLMGYIPLV) of the peptide presented by HLA-A2 and containing an HLA-A2-binding motif, extending only 1 residue beyond the murine epitope. Therefore, this conserved peptide, seen with murine CTL and human CTL with a very prevalent HLA class I molecule, may be a valuable component of an HCV vaccine against a broad range of HCV isolates. This study demonstrates that the screening for CTL epitopes in mice prior to human study may be useful.

Amino Acid Sequence↗
PubMed1994

Canine salivary secretion from the submaxillary glands before and during retching.

To investigate the changes in salivary secretion associated with emesis, salivary secretion from the submaxillary gland and centrifugal discharge from the parasympathetic postganglionic nerve fibers from the submandibular ganglion were measured after emetic stimulation in chloralose-anesthetized and paralyzed dogs. In the basal condition, saliva flow and the basal frequencies of single unit discharges from the parasympathetic nerve were very low. Esophageal and gastric distension and lingual nerve afferent stimulation generally increased salivary secretion and nerve activity. Administration of apomorphine (0.2-0.3 mg/kg im) or intragastric infusion of copper sulfate (10%, 50 ml) elicited an excitation of parasympathetic nerve activity, and salivary secretion was facilitated in parallel to this nerve activity. The excitatory responses induced by emetic stimulation were suddenly depressed in correspondence with retching activities. This depression in nerve activity appeared 200-400 ms after the beginning of retching volleys of the phrenic nerve and continued during retching. These results indicate that the salivary center receives excitatory and inhibitory inputs from two different sources before and during retching activities, respectively.

Animals↗
PubMed1994

Chronic and selective vasopressin blockade in spontaneously hypertensive rats.

Chronic effects of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on conscious spontaneously hypertensive rats (SHR) were investigated. SHR and Wistar rats were divided into four groups, groups S-1 to S-4 and W-1 to W-4, respectively. Groups S-1 and W-1 were untreated as control. Groups S-2 and W-2 were treated with V1 antagonist, groups S-3 and W-3 received V2 antagonist, and groups S-4 and W-4 were treated with both of V1 and V2 antagonists. V1 and/or V2 antagonists did not affect degree of blood pressure of W-2, W-3, and W-4 rats, and V1 antagonist, alone or combined with V2 antagonist, slightly reduced increases in blood pressure of S-2 and S-4 rats without significance. However, V2 antagonist induced significantly massive and hyposmolar urine in W-3 rats compared with that in S-3 rats. In conclusion, in SHR, circulating vasopressin contributes to increases in blood pressure via either V1 or V2 receptors less than expected from previous studies with antibodies or peptide antagonists.

Animals↗
PubMed1994

Pro-carboxypeptidase R cleaves bradykinin following activation.

Arginine carboxypeptidase (CPR) is a labile enzyme present in human serum which is unrelated to carboxypeptidase N. In this study we demonstrate that CPR exists in a precursor form in plasma and can be converted to the active form by trypsin and presumable trypsin-like enzymes. The trypsin-generated active form can not only cleave a small synthetic substrate, hippuryl-L-arginine, but can remove terminal arginine from bradykinin.

Bradykinin↗
PubMed1994

Antiestrogenic effects of danazol on rabbit uterus.

To examine antiestrogenic effects of danazol through the receptor system and to clarify its direct effects on the endometrium in vivo, we applied danazol jelly directly into the rabbit uterine cavity and measured uterine estrogen, progesterone and androgen receptors (ER, PR and AR, respectively). Danazol significantly reduced ER, PR and AR (p < 0.05). Treatment with receptor-blocking agents (RU 486 and oxendolone) showed that the decrease in the ER level showed a closer association with that in PR than with AR. These results indicate that danazol directly administered into the uterine cavity is absorbed by the endometrial tissue and exerts its antiestrogenic effects possibly through PR in the cells.

Animals↗
PubMed1994

Effects of humoral hypercalcemia of malignancy and gallium nitrate on thyroid C cells in nude mice: immunohistochemical and ultrastructural investigations.

Immunohistochemical and ultrastructural investigations of thyroid C cells were conducted in male nude (athymic) mice bearing a serially transplantable canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy following subcutaneous administration of gallium nitrate. The following four groups were investigated: 1) vehicle-treated non-tumor-bearing control mice; 2) non-tumor-bearing mice treated with gallium nitrate; 3) vehicle-treated hypercalcemic mice bearing CAC-8; and 4) CAC-8 tumor-bearing mice treated with gallium nitrate. Gallium nitrate-treated tumor-bearing mice had a significant decrease in serum calcium as compared with tumor-bearing controls. C cells of non-tumor-bearing mice stained intensely for calcitonin and calcitonin gene-related peptide and weakly for chromogranin A and neuron-specific enolase. In C cells of both vehicle- and gallium-treated tumor-bearing mice, immunoreactive staining was decreased for calcitonin, calcitonin gene-related peptide, and chromogranin A, whereas there was a moderate increase in staining for neuron-specific enolase. Ultrastructurally, thyroid C cells in hypercalcemic tumor-bearing control and gallium-treated mice were hypertrophic and markedly degranulated as compared with those of non-tumor-bearing controls. Hypertrophic C cells contained few mature secretory granules, a well-developed Golgi apparatus, and lamellar arrays of rough endoplasmic reticulum. There was no evidence of C-cell hyperplasia. Immunohistochemical and ultrastructural findings revealed that C cells in mice with cancer-associated hypercalcemia were primarily in the actively synthesizing phase of the secretory cycle and had diminished immunoreactivity for calcitonin, calcitonin gene-related peptide, and chromogranin A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Marine natural products. XXXIII. Theonellapeptolide IId, a new tridecapeptide lactone from the Okinawan marine sponge Theonella swinhoei.

Following the characterization of theonellapeptolides Ia-Ie (2-6), another new tridecapeptide lactone named theonellapeptolide IId (1) was isolated from the Okinawan marine sponge Theonella swinhoei. The structure of 1 has been determined on the bases of chemical and physicochemical examinations which included an HPLC-CD combined analysis of the amino acid composition. Theonellapeptolide IId (1) prevented fertilization of the sea urchin Hemicentrotus pulcherrimus at the concentration of 25 micrograms/ml or greater but did not affect early embryonic development of fertilized eggs up to the gastrula stage.

Amino Acid Sequence↗