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Biomedical subjects

K Hirota

Publications and source records attributed to K Hirota.

At least 433 records · Page 24Linked to original sources
PubMed1987

[Clinical significance of sialic acid determinations in patients with gynecologic cancer].

Sialic acid (SA) levels were measured in human sera by the enzymatic procedure using neuraminidase. Sera were obtained from healthy controls (70 females), patients with uterine myoma (27 cases), cervical cancer (53 cases), benign ovarian tumor (36 cases) and ovarian cancer (70 cases). The upper normal limit of 72mg/dl was obtained from the mean +2SD for healthy controls. The mean value for serum SA in patients with primary ovarian cancer (71.2 +/- 20.6mg/dl) was statistically higher than those for both uterine myomas (59.0 +/- 12.4mg/dl) and controls. The mean level for SA in patients with ovarian cancer was further elevated and it was statistically higher than that for benign ovarian tumors (58.8 +/- 14.3mg/dl), uterine myomas and cervical cancers. SA levels were not well correlated with tumor histologic types or clinical stages of cancer patients. As to the relationship between SA and the clinical course of cancer patients, changes in SA values were well correlated with the curability of tumor resection. The lack of specificity, however, will require careful interpretation of the SA value to assure that inflammation is not causing changes in the test values, because SA shows a transient increase due to the inflammatory reaction during the postoperative period even in patients with benign tumor. These results indicate that SA determination is highly recommended as an addition to the conventional diagnostic methods.

Adult↗
PubMed1986

Prolongation of the action potential and reduction of the delayed outward K+ current by halothane in single frog atrial cells.

Halothane has been shown to produce significant changes in heart rate and strength of contraction. We have studied the mechanism(s) of these effects by recording action potentials and transmembrane ionic currents in single cardiac cells from bullfrog atrium. Our results show that the action potential was prolonged and its plateau was depressed; and that there was a significant inhibition of a potassium current, Ik, and a Ca2+ current, Isi, following halothane (2%) application.

Action Potentials↗
PubMed1986

Gonadotropin release and redistribution of calcium-activated, phospholipid-dependent protein kinase in phorbol-stimulated rat pituitary cells.

The effect of phorbol esters on calcium-activated, phospholipid-dependent kinase (protein kinase C) and luteinizing hormone (LH) secretion was examined in cultured rat anterior pituitary cells. The potent tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) stimulated LH secretion and activated pituitary protein kinase C in the presence of calcium and phosphatidylserine. The enzyme activity present in cytosol and particulate fractions was eluted at about 0.05 M NaCl during DE52-cellulose chromatography. Preincubation of pituitary cells with TPA markedly decreased cytosolic protein kinase C activity and increased enzyme activity in the particulate fraction. The maximal TPA-induced change in enzyme activity, with a 76% decrease in cytosol and a 4.3-fold increase in the particulate fraction, occurred within 10 min. The dose-dependent changes in protein kinase C redistribution in TPA-treated cells were correlated with the stimulation of LH release by the phorbol ester. These results suggest that activation of protein kinase C by TPA is associated with intracellular redistribution of the enzyme and is related to the process of secretory granule release from gonadotrophs.

Animals↗
PubMed1986

Foscarnet decreases serum and liver duck hepatitis B virus DNA in chronically infected ducks.

Foscarnet (trisodium phosphonoformate) is a new antiviral compound with in vitro inhibitory effects against the DNA polymerases of hepadna viruses. To study the effects of the drug in chronic hepadna virus infection, we treated ducks chronically infected with duck hepatitis B virus for 10 days with either low-dose foscarnet (50 mg/kg i.p. b.i.d.), high-dose foscarnet (250 mg/kg i.p. b.i.d.), or sterile water injections. Serum duck hepatitis B virus DNA and intrahepatic replicative forms of the virus were measured using molecular biological techniques with both a double-stranded radiolabeled DNA probe and a plus-strand (noncoding) specific RNA probe. We found a dose-related decrease in serum and intrahepatic duck hepatitis B virus DNA during treatment, with a rapid return toward baseline values after the cessation of treatment. There was a disproportionate decrease in the plus strand of viral DNA with treatment. We conclude that foscarnet exerts its effect in hepadna virus infection through inhibition of viral DNA polymerase. Further study is necessary to determine whether foscarnet, by itself or in combination with other treatment modalities, has a role to play in the treatment of chronic hepatitis B infections in humans.

Animals↗
PubMed1986

In vivo study of the mechanism of action of antiviral agents against hepadna virus replication in the liver. Resistance of supercoiled viral DNA.

The mode of action of antiviral agents (interferon and adenine arabinoside) was studied in human and in animals chronically infected with hepadna virus. Interferon (36-100 megaunits) was given to 20 carrier patients, and hepatitis B virus (HBV)-DNA replicative forms were studied in pre- and post-treatment biopsies. ARA-A was given intravenously to duck hepatitis B virus (DHBV)-infected ducks. Changes in intrahepatic viral replicative forms were studied by Southern blotting using 32P-labelled HBV or DHBV probe. Our study indicates that both interferon and ARA-A seem to effectively decrease 'mature' forms of viral DNA by an effect on either mRNA or DNA polymerase. However, the supercoiled viral DNA tends to resist the treatment, and may become the transcribing template for a new cycle of viral replication after cessation of the drugs.

Animals↗
PubMed1986

[Significance of CA 125 antigen levels in patients with ovarian cancer].

CA 125 antigen levels were measured in patients with ovarian cancer (54 cases) by the RIA method using a monoclonal antibody OC 125 and were examined as a marker for ovarian cancer. The upper normal limit of CA 125 of 35 U/ml was derived from the mean value (15.7 U/ml) + 2 SD (9.3 U/ml) of CA 125 in healthy controls. The mean value of CA 125 in patients with ovarian cancer (1160 +/- 1850 U/ml) was statistically (p less than 0.001) higher than those of healthy controls, benign ovarian tumors (28 +/- 20 U/ml) and cervical cancers (226 +/- 526 U/ml). Elevated CA 125 levels were also found in the early stages pregnancy and endometriosis, but these cases did not show such high CA 125 values as those of ovarian cancers. In addition, CA 125 levels were not affected by the menstrual cycle. Among ovarian malignancies, elevated CA 125 values were specifically demonstrated in serous cystadenocarcinoma (positivity 89%) and markedly low in mucinous cystadenocarcinoma (positivity 16%). No positive correlation of CA 125 values with clinical stage (FIGO) were found in any ovarian cancer patients. The rise or fall of CA 125 level was well correlated with the progression or regression observed in cancer patients with positive CA 125 levels. In conclusion, serum CA 125 determinations may be useful in patients with ovarian cancer (except for mucinous type) for diagnosis and for monitoring the results of treatment.

Antigens, Neoplasm↗
PubMed1986

[Left ventricular wall motion abnormalities evaluated by factor analysis as compared with Fourier analysis].

Factor analysis was applied to multigated cardiac pool scintigraphy to evaluate its ability to detect left ventricular wall motion abnormalities in 35 patients with old myocardial infarction (MI), and in 12 control cases with normal left ventriculography. All cases were also evaluated by conventional Fourier analysis. In most cases with normal left ventriculography, the ventricular and atrial factors were extracted by factor analysis. In cases with MI, the third factor was obtained in the left ventricle corresponding to wall motion abnormality. Each case was scored according to the coincidence of findings of ventriculography and those of factor analysis or Fourier analysis. Scores were recorded for three items; the existence, location, and degree of asynergy. In cases of MI, the detection rate of asynergy was 94% by factor analysis, 83% by Fourier analysis, and the agreement in respect to location was 71% and 66%, respectively. Factor analysis had higher scores than Fourier analysis, but this was not significant. The interobserver error of factor analysis was less than that of Fourier analysis. Factor analysis can display locations and dynamic motion curves of asynergy, and it is regarded as a useful method for detecting and evaluating left ventricular wall motion abnormalities.

Adult↗
PubMed1986

[The effect of vigorous exercise training on cholesterol metabolism in rats].

Twenty-eight male Wistar rats, aged 7 weeks, were subjected to a vigorous exercise regimen of running for 5 weeks and 35 rats were selected as their controls. After 5 weeks both exercised and control rats were injected 2 microCi of 14C-mevalonate per 100 g body weight into peritoneal cavities and sequentially sacrificed at 20, 40, 60, 80, 100, 120, and 180 min after the injections in each subgroup. The exercised rats showed a significantly lower level of serum total cholesterol than the control rats. The activity of HMG-CoA reductase in liver microsome was significantly higher in the exercised rats than in the control rats. No differences existed in intestinal HMG-CoA reductase activity between exercise and control groups. The incorporation of mevalonate into liver cholesterol and serum cholesterol (especially HDL fraction) in the exercised rats were significantly higher compared with these of the control. Furthermore, the exercised rats showed a higher rate of cholesterol synthesis activity in liver. From these results it was concluded that the hepatic lipoprotein cholesterol production was elevated by exercise compared with that of control.

Animals↗
PubMed1986

Novel reactions of 5-bromouracil derivatives with active methylene compounds.

5-Bromouracil derivatives (1) reacted with carbanions at room temperature to give 6-substituted uracils (6), 2,4-diazabicyclo[4,1,0] heptanes (8) and 2,4-diazabicyclo[4,3,0]nonane derivative (9), which depend largely upon the structure of the active methylene compounds employed for the generation of carbanions.

Alkanes↗
PubMed1986

[Significance of immunosuppressive acidic protein in the diagnosis and follow-up of patients with ovarian cancer, in particular as a marker for chemotherapeutic effects].

Serum immunosuppressive acidic protein (IAP) was determined in patients with ovarian cancer and was examined as a marker for ovarian cancer when, chemotherapy in particular, was applied. Samples were sera obtained from 68 ovarian cancers, 74 benign ovarian tumors, 54 cervical cancers, 57 uterine myomas and 88 healthy controls. Elevated levels of IAP were found in 89.5% of patients with ovarian cancer and this high positive ratio was not affected by tumor histologic features. The measurement of the serum IAP level is useful for the initial diagnosis of ovarian cancer because of low false positive rates (8.1%) in benign ovarian tumors and high positive rates even in the early stage of ovarian cancer. Serial determinations of serum IAP levels were well correlated with the response to the treatment (chemotherapy in particular) and the prognosis of cancer patients, even in the case of patients with leucocytopenia induced by the intensive chemotherapy. In case of recurrent patients (whose lesions were observed in the intraperitoneal space), IAP values tended to increase earlier than other conventional tumor-derived markers. Therefore, IAP may also be a useful follow-up marker for patients with ovarian cancer (particularly, for the early detection of recurrence).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

[Consecutive intra-arterial infusion of cis-diamminedichloroplatinum with continuous intra-arterial infusion of 5-fluorouracil in locally advanced ovarian cancer].

Consecutive intraarterial infusion of cis-diamminedichloroplatinum (CDDP) with continuous intraarterial infusion of 5-fluorouracil (5-FU) (250 mg/day) was administered to 10 patients with locally advanced (peritonitis carcinomatosa) ovarian cancer. The dose of CDDP was 10 mg/5 min/body/day and it was administered for about 10-20 consecutive days per one course. Each course was repeated at about 3-week intervals. The main dose-limiting factor was the number of peripheral leucocytes. The results were 6 PR, 1 MR and 2 NC out of 9 evaluable cases, all of whom had had previous therapy. The antitumor effect needed over 200 mg of intraarterial CDDP and the response lasted from 2 to more than 9 months. Among 6 patients who obtained PR, 4 had failed to respond to intravenous or intraperitoneal infusion of CDDP, which suggested that a high concentration and a critical drug gradient across the tumor cell membrane were more essential for a significant tumor cell kill, with CDDP, than the time of exposure. The toxic effects of intraarterial infusion of CDDP were almost absent as compared with those of intravenous infusion, which consisted of nausea and vomiting. Renal dysfunction was also mild. Other toxic effects were not different from those observed in intravenous infusion. Our results with intraarterial infusion of CDDP clearly indicate that this approach can deliver a high therapeutic efficacy in patients with advanced ovarian cancer with markedly less toxic effects.

Adolescent↗
PubMed1986

Effects of adenine arabinoside and corticosteroid on replication of duck hepatitis B virus DNA in the liver.

Adenine arabinoside (Ara-A) therapy and abrupt withdrawal of corticosteroids have both been used in the treatment of chronic infections due to hepatitis B virus (HBV). In order to better understand the effects and mechanism of action of these treatments, we treated ducks chronically infected with duck hepatitis B virus (DHBV) with different dosage regimens of the two therapies. We measured endogenous DNA polymerase activity and used sensitive molecular biological techniques to monitor serum and intrahepatic viral replicative forms during and after drug treatment. Ara-A had a transient, dose related inhibitory effect on DHBV replication. Viral plus strand synthesis was disproportionately affected. Following the cessation of Ara-A treatment markers of viral replication returned to their baseline values. We conclude that Ara-A exerts its effect through inhibition of viral DNA polymerase. Corticosteroid treatment results in an increase in DHBV replication, but steroid withdrawal results in a short-lived transient decrease in markers of viral replication to below pretreatment values. Our results suggest that steroid withdrawal decreases hepadna virus replication through a mechanisms of immune modulation. On the basis of these results and previous trials in HBV infected patients, we predict that neither agent will efficiently eliminate viral replication in chronic hepadna virus infection when used as the sole therapeutic modality. We suggest that the differences in the mechanisms of action of Ara-A treatment and corticosteroid withdrawal be exploited, and the use of combination therapy be explored.

Adrenal Cortex Hormones↗
PubMed1985

Physicochemical characterization of a new glucocorticoid receptor.

A new glucocorticoid-binding protein (Peak C) eluted with 0.14 M NaCl on DEAE-cellulose chromatography was identified previously in the rats subjected to stress or treated with glucocorticoid (100 micrograms/100 g body wt.), while the 'classic' glucocorticoid receptor (Peak B) eluted with 0.07 M NaCl was found predominantly in untreated rats. The new glucocorticoid-binding protein, Peak C, was characterized by Scatchard analysis and competition with other steroids as a glucocorticoid receptor. The saturation curve of Peak C for dexamethasone was sigmoidal, whereas that of Peak B was hyperbolic. The Hill coefficient was 1.0 for Peak B and 3.1 for Peak C. These results show that Peak C has multiple binding sites. Peak C bound specifically to only natural or synthetic glucocorticoids, whereas Peak B bound not only to glucocorticoids but also to progesterone and aldosterone. Peak C was far more labile than Peak B, its binding activity decreasing 80% when it was incubated for 30 min at 25 degrees C. The molecular sizes of these two peaks (B and C) were similar, being about 90 000-100 000 as determined by Sepharose 6B column chromatography at high ionic strength (0.34 M KCl). The hormone-receptor complex of Peak C bound to rat liver chromatin specifically, but did not bind to calf thymus DNA. The complex of Peak B bound to not only the chromatin but also calf thymus DNA. Peak B reacted well with antiserum to the 'classic' glucocorticoid receptor, but Peak C did not react with this antiserum. These results indicate that Peak C is a different glucocorticoid receptor protein from Peak B, or classic glucocorticoid receptor, and plays physiologically important roles as a glucocorticoid receptor mediating the action of the hormone at a high level.

Animals↗