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Biomedical subjects

H Ohmori

Publications and source records attributed to H Ohmori.

At least 217 records · Page 12Linked to original sources

[Phase II study of 5'-DFUR treatment of the bladder and prostatic cancer].

Phase 2 study of 5'-DFUR in bladder and prostatic cancer was conducted at 15 collaborative institutions including Okayama University. 5'-DFUR was orally administered to patients at a daily dose of 800-1200 mg for more than 4 weeks. Forty-one patients with bladder cancer and 12 patients with prostatic cancer were evaluated. The response rate for bladder cancer was 31.7% (CR, 1 case: PR, 12 cases), against no response with prostatic cancer. Moreover, the concentration of 5-FU in bladder tumors was confirmed to be high. Adverse reactions such as diarrhea, anorexia, and nausea were observed. Thus, 5'-DFUR seems to be useful for the treatment of bladder cancer.

Administration, Oral↗

[Clinical phase III study on TAP-144-SR, an LH-RH agonist depot formulation, in patients with prostatic cancer].

A randomized controlled phase III clinical trial comparing TAP-144-SR (TAP) and diethylstilbestrol diphosphate was conducted for patients with prostatic cancer. Patients with Stage B, C, or D disease, who were previously untreated, were enrolled. TAP-144-SR 3.75 mg was administered subcutaneously at 4-week intervals for 12 weeks (a total of 3 injections) in the TAP-144-SR group, while 100 mg of diethylstilbestrol diphosphate was administered orally three times a day (before meals) for 12 weeks in the control group. A total of 141 patients were enrolled using a centralized telephone registration system. Four of these patients were ineligible, and there were 3 drop-outs who never received drugs because they withdrew their consents to participate in the trial. These 7 were excluded from the evaluation, and as a result, 134 patients (66 in the TAP group and 68 in the control group) were evaluable in safety and efficacy. Between the two groups, there were no significant differences in patient characteristics, except the age distribution. Clinical response rates (CR+PR) in evaluable patients according to the criteria of Japanese Prostatic Cancer Study Group were 54.5% in the TAP group and 47.1% in the control group. In addition, the rates according to the criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria were 7.6% in the TAP group and 8.8% in the control group and 18.2% in the TAP group and 20.6% in the control group, respectively. Using any of the three criteria, there were no significant differences in response rate between the two groups. The incidence of side effects was 64.1% in the TAP group and 95.4% in the control group; the incidence being significantly higher in the control group (p less than 0.001; chi 2-test). Therefore, the overall safety was significantly greater in the TAP group than in the control group (p less than 0.001; chi 2-test). On the basis of the efficacy and safety the clinical usefulness rate of TAP-144-SR was significantly higher than that of diethylstilbestrol diphosphate (p = 0.038; U-test). In conclusion, TAP-144-SR was confirmed to be more useful than diethylstilbestrol diphosphate as a standard drug for hormonal therapy of prostatic cancer.

Aged↗

Mobilization of intracellular Ca2+ and suppression of inward currents in a neuronal hybrid cell line triggered by bradykinin.

Bradykinin triggered intracellular Ca mobilizations and ionic conductance changes were studied in the neuroblastoma x glioma hybrid cell line NG108-15 using Ca-sensitive fluorescent indicator fura-2 under patch pipette whole cell voltage clamp condition. The time course of outward current induced by bradykinin was closely related to the time-course of [Ca2+]i change. Following application of bradykinin, [Ca2+]i increased transiently and then decreased below the basal level before bradykinin application. The inward currents activated by step-depolarization were suppressed after bradykinin application, but the time-course of the suppression did not go in parallel with the [Ca2+]i changes: the suppression started before the [Ca2+]i change emerged and outlasted the phase of [Ca2+]i increase. Both transient type and long-lasting type Ca current were suppressed by bradykinin. [Ca2+]i increase induced by high potassium depolarization was suppressed by bradykinin. Pertussis toxin did not affect the Ca transient nor the suppression of Ca channel induced by bradykinin. Our results suggest that the modifications of ionic channels by bradykinin could be through the other mechanisms than the well established activation of the G-protein leading to the IP3 mechanisms and that the bradykinin receptor might couple with the pertussis toxin-insensitive G protein which regulates the calcium channels.

Animals↗

DNA transfection of mouse lymphoid cells by the combination of DEAE-dextran-mediated DNA uptake and osmotic shock procedure.

Several mouse lymphoid cell lines were efficiently transfected with plasmid DNA by a novel method combining DEAE-dextran-mediated DNA uptake and osmotic shock procedure. The cells were first incubated with DNA-DEAE-dextran complex, treated with hypertonic Tris-HCl buffer containing 0.5 M sucrose and 10% poly(ethylene glycol), and then exposed to hypotonic RPMI 1640 medium. This transfection protocol exhibited maximal frequencies of 0.3% and 3.10(-5) for transient gene expression and stable transformation in P3-NSI/1-Ag4-1 cells, respectively.

Animals↗

Prostaglandin E2 as a selective stimulator of antigen-specific IgE response in murine lymphocytes.

Anti-2,4,6-trinitrophenyl (TNP) IgE antibody response was elicited by stimulating TNP-keyhole limpet hemocyanin-primed murine spleen cells with the same antigen in vitro. The released anti-TNP IgE was assayed by antigen- and isotype-specific enzyme immunoassay developed in our laboratory. When prostaglandin E2 (PGE2) was added to the lymphocyte culture at 10(-7) M, anti-TNP IgE response was augmented two- to fourfold. Interestingly, PGE2 did not affect the production of anti-TNP antibodies belonging to other isotypes including IgM, IgG1, IgG2a, IgG2b, IgG3 and IgA. Moreover, PGE2 showed neither enhancing nor interleukin 4-replacing activities in the polyclonal IgE response by B cells stimulated with lipopolysaccharide and interleukin 4. When endogenous prostaglandin synthesis was inhibited by 10(-6) M indomethacin, the anti-TNP IgE response, but not the corresponding IgG response, was suppressed by 30%-60%. These results suggest a potential role of PGE2 in the up-regulation of the antigen-specific IgE response.

Animals↗

Synaptic responses to mechanical stimulation in calyceal and bouton type vestibular afferents studied in an isolated preparation of semicircular canal ampullae of chicken.

Relationships between the response patterns of semicircular canal afferents to mechanical stimulation and the morphologies of their peripheral endings were investigated in an isolated preparation of the anterior semicircular canal ampulla of chicken, using a combination of electrical recording with intracellular injections of Lucifer Yellow CH. The hair bundle mechanical stimulus was applied in a diffuse manner by a glass rod vibrating in the nearby bathing medium. Two types of spike discharge patterns and postsynaptic potentials were recorded. One type was found exclusively in the bouton type afferent and demonstrated a phasic increase of firing frequency and transient depolarizing postsynaptic potentials at the beginning of mechanical stimulation. These synaptic potentials were also observed spontaneously and their amplitudes were increased by membrane hyperpolarization. The other type was found exclusively in afferents with calyceal endings and showed a tonic increase of spiking frequency and depolarizing DC postsynaptic potentials with superimposing AC responses at the frequency of the mechanical stimulation. Amplitudes of postsynaptic potentials were increased by hyperpolarization. Hair cells generated depolarizing DC transduction potentials superimposed with AC potentials at frequency of the mechanical stimulation. The spontaneous spike discharging patterns of afferent nerve fibres were classified either as a regular type (CV less than 0.10) or as an irregular type (CV greater than 0.25) on the basis of coefficient of variation (CV) of interspike intervals. The spontaneous firing rate of regular units was higher than that of irregular units. Several membrane characteristics are different between these two types of afferent fibers; irregular units had short membrane time constants and fast spikes associated with clear spike-afterhyperpolarization. These features fit with the fact that irregular units tend to have phasic responses to mechanical stimulation while regular units typically have tonic responses. Irregular units had bouton endings with an average axonal diameter thicker than the regular units which had calix endings.

Action Potentials↗

Simultaneous activation of heat shock protein (hsp 70) and nucleolin genes during in vivo and in vitro prereplicative stages of rat hepatocytes.

Rapidly growing cells usually have high levels of ribosome biogenesis. The sequential expression of protooncogenes during the transition of quiescent hepatocytes to the replicative stage was assumed to be followed by activation of cellular genes related to cell growth such as ribosome biosynthesis. First, the expression of major nucleolar protein (nucleolin or C23) and major heat-shock protein (hsp 70) genes was examined during rat liver regeneration. hsp 70 may function in cell growth and has a characteristic nucleolar location after heat shock. Both nucleolin and hsp 70 mRNA began to increase simultaneously after peaks of c-fos and c-myc, showed a peak 6 h after partial hepatectomy, and declined to the control levels around 20 h. That is, the peaks of nucleolin and hsp 70 mRNA precede the peak of ribosome formation (12-20 h) and DNA replication (24 h). Second, the behavior of nucleolin and hsp 70 mRNA was examined in primary cultured hepatocytes during their G0-G1 transition. Although the amounts of c-myc mRNA reached a plateau around 20 h after the initiation of culture and remained at these levels, DNA synthesis has never been found to start without the addition of EGF and insulin to this system. Both nucleolin and hsp 70 mRNA began to increase at around 20 h (prereplicative stage) and simultaneously decreased in inverse proportion to DNA synthesis induced by these growth factors. Thus, it is possible that the simultaneous enhancement of nucleolin and hsp 70 genes as described above is not merely coincidental, but is important biologically during the transition of quiescent hepatocytes to proliferative cells.

Animals↗

Effects of interleukin 4 on an antigen-specific IgE response in vitro in murine lymphocytes.

The present study shows that interleukin 4 (IL4) can exert either stimulatory or inhibitory effects on an antigen-specific IgE response in vitro. Spleen cells from BALB/c mice that had been primed with trinitrophenyl keyhole limpet hemocyanin (TNP-KLH) were cultured with the same antigen for 2 days, washed, transferred to an antigen-free culture medium, and then cultured for 4 days. Anti-TNP IgE antibodies secreted into the medium were determined by an enzyme immunoassay developed in our laboratory. Anti-TNP IgE response was elicited by TNP-KLH in cultures of the spleen cells from mice that had been primed twice with the antigen at an interval of 3 weeks, but not in cells from animals that had received only a single injection of the antigen. When the latter cells were cultured with the antigen in the presence of mouse recombinant IL4, a considerable level of the antigen-specific IgE response was induced. In contrast, the IgE response elicited in the cells of mice that had been primed twice with the antigen was markedly down-regulated by added IL4. These observations suggest a novel function of IL4 in the regulation of IgE antibody responses.

Animals↗

Naphthalene derivatives that selectively inhibit an antigen-specific IgE response in murine lymphocytes.

When the spleen cells from BALB/c mice that had been immunized twice with TNP-KLH were cultured with the same antigen, the synthesis of anti-TNP IgE as well as anti-TNP IgG was induced. We found that the addition of a naphthalene derivative, (E)-N-(2-methoxy-carbonylphenyl)-8-(2-naphthyl)-5,6-trans-5,6-meth ano-7- octenamide (TEI-1338) or methyl-6,7-dihydroxy-2-naphthylthioacetate (TEI-3332) to this lymphocyte culture system resulted in a marked suppression of anti-TNP IgE response without affecting the corresponding IgG production. These compounds are expected to be a prototype for the drug that can be used for the treatment of IgE-mediated allergic diseases.

Animals↗

Endoscopic diagnosis and treatment of chronic unilateral hematuria of uncertain etiology.

We evaluated 12 patients with unilateral unexplained gross hematuria by flexible ureteropyeloscopy and percutaneous pyeloscopy. All patients had localized bleeding except for 1 with diffuse bleeding caused by the nutcracker phenomenon, and 2 in whom no hematuria appeared upon examination and no gross lesions were observed. Among the 9 patients with localized bleeding transitional cell carcinoma was found in 1, hemangioma in 4 and minute venous rupture in 4. These 9 patients were treated endoscopically and no recurrences were observed during a follow-up of 6 to 21 months (average 10.3 months). Our results underscore the importance and efficacy of flexible ureteropyeloscopy in the evaluation and management of chronic unilateral hematuria.

Adolescent↗

Muscarinic agonists and ATP increase the intracellular Ca2+ concentration in chick cochlear hair cells.

1. Cholinergic muscarinic agonists applied by the pressure puff method increased intracellular Ca2+ concentration in Fura-2-loaded hair cells. The Ca2+ response outlasted the agonist application. 2. The Ca2+ response induced by acetylcholine (ACh) was ACh dose dependent with a KD of 200 microM. Desensitization was negligible, and almost identical Ca2+ responses were observed when two ACh puffs were separated by 150 s. The response was blocked by d-tubocurarine (dTC). The KD of dTC blocking was 500 microM when 100 microM-ACh induced the Ca2+ response. 3. The amplitude of the ACh-induced Ca2+ responses were potentiated to 3 times the control by incubation with calcitonin gene-related peptide (CGRP; 0.1-1 microM). CGRP did not affect the resting Ca2+ concentration. Glycine (100 microM) potentiated the ACh response to 1.4 times the control, and also increased the resting Ca2+ concentration slightly. 4. The ACh-induced Ca2+ response was suppressed by atropine. It was induced in Ca2(+)-free extracellular medium, and in Ca2(+)-free medium desensitization to a second ACh stimulation was significant. The amplitude of the second Ca2+ response was 44% of the first when two ACh puffs were separated by 117 s in Ca2+ free medium. 5. Muscarine and carbamylcholine induced similar Ca2+ responses, with KD values of 130 microM for muscarine and 340 microM for carbamylcholine. Desensitization of Ca2+ responses was negligible in both agonists. 6. ATP co-exists with ACh in some presynaptic nerve terminals (Burnstock, 1981). Puff-applied ATP (100 microM) generated a Ca2+ response with a rapid rising phase and a following slow phase. In Ca2(+)-free medium the rapid phase disappeared and only the slow phase was observed. The rapid phase is due to the influx of Ca2+ ions and the slow phase is due to a release of Ca2+ ions from an intracellular reservoir. Under voltage clamp ATP induced a fast inward current and a following slow outward current. 7. Nicotine, adenosine, glycine, GABA, glutamate and bradykinin did not induce Ca2+ responses in the hair cell. 8. ACh induced hyperpolarization of the hair cell membrane under current clamp, most probably by the activation of Ca2+ activated K+ conductance. Therefore, a cholinergic muscarinic receptor may mediate the inhibitory effects of efferent innervation observed in hair cells.

Acetylcholine↗

Voltage-gated and chemically gated ionic channels in the cultured cochlear ganglion neurone of the chick.

1. Electrophysiological properties of ionic channels of isolated or cultured cochlear ganglion (CG) neurones from chick embryo were studied under voltage-clamp conditions using a patch electrode. 2. Tetrodotoxin-sensitive Na+ current was activated by a step depolarization more positive than -40 mV, and was inactivated rapidly. 3. Outward-going K+ current was activated by step depolarization to membrane potentials more positive than -62 mV. 4. Two types of Ca2+ currents were demonstrated, an inactivating and a non-inactivating type. The inactivating type was activated by step depolarizations more positive than -69 mV and was inactivated rapidly. The non-inactivating type was activated by step depolarizations more positive than -52 or -41 mV depending on the external divalent cation species. 5. The I-V relationship and the activation kinetics of the non-inactivating type Ca2+ channel was shifted in a positive direction along the voltage axis by 12 mV when extracellular 2.5 mM-Sr2+ or Ba2+ were replaced by Ca2+. This shift was not observed in the inactivating type Ca2+ channel. 6. The amplitude of peak current through the inactivating type Ca2+ channel was in the order of Ca2+ greater than Sr2+ greater than Ba2+. The order of relative permeability through the non-inactivating type estimated from the tail current amplitude was Ba2+ greater than Sr2+ greater than Ca2+. 7. After 5 days in culture, glutamate (30 microM), aspartate (100 microM), kainate (100 microM) and N-methyl-D-aspartic acid (NMDA; 100 microM) elicited ionic currents. The glutamate response was depressed by 1 mM-Mg2+ in a voltage-dependent manner at negative membrane potentials and was almost extinguished by amino-phosphonovalerate (APV) (0.1 mM). The major subtype of glutamate receptor could be of the NMDA type. 8. The permeability of the NMDA receptor channel to Na+ and Li+ was estimated from the reversal potential and was 1.0 and 0.7 compared with that of Cs+, respectively. 9. Divalent cations were more permeable than the monovalent cations through the NMDA receptor channel: PCa greater than or equal to PBa greater than PSr greater than PCs.

2-Amino-5-phosphonovalerate↗

Control of intracellular calcium by ATP in isolated outer hair cells of the guinea-pig cochlea.

1. Intracellular calcium levels were monitored in isolated outer hair cells of the guinea-pig cochlea using the calcium-sensitive dye Fura-2. 2. The calcium in the cells was studied during application of ATP externally applied from a pipette. ATP induced a rise of intracellular calcium which could be separated into two components: a rapid rise, peaking in 20 s, localized around the apical end of the cell, and a slower rise, peaking in 50-150 s but spread throughout the cell. The effects were observed with 5, 25 and 100 microM-ATP concentrations. 3. In the absence of external Ca2+, ATP was still able to trigger a rise in Ca2+, but with a longer delay. Under these conditions, the cells did not show the initial rapid Ca2+ rise. The result suggests that ATP can mobilize intracellular stores. 4. A rise in intracellular Ca2+ was also observed when 5 mM-caffeine was applied to the bath. 5. Simultaneous measurements were made of whole-cell currents and intracellular calcium. ATP activated an inward current at resting potentials of -60 mV. Internal Ca2+ levels increased during the inward current. In current-clamped cells Ca2+ levels also increased during the associated depolarization produced by ATP. 6. Adenosine (150 microM) did not produce any measurable inward current. Acetylcholine (ACh, 100 microM-1 mM) produced only a small rise in Ca2+. However, applied simultaneously with ATP, ACh suppressed the rise in intracellular Ca2+ produced by ATP, with the kinetics of a competitive antagonist. 7. Intracellular Ca2+ increased with step depolarizations of the cell above -20 mV during whole-cell clamp. Large rises in Ca2+ were also observed on depolarizing the cell with isotonic KCl. 8. Calcium levels in supporting cells of the organ of Corti were sensitive to ATP. In these cells, rises in intracellular Ca2+ did not require the presence of extracellular Ca2+. 9. It is concluded that the organ of Corti contains receptors for ATP on a variety of the cells. ATP controls a direct entry of Ca2+ through the membrane and also may mobilize intracellular stores.

Acetylcholine↗

Enhanced ketone body uptake by perfused skeletal muscle in trained rats.

Training effect on exercise-induced hyperketonemia was investigated in normal post-absorptive rats subjected to running exercise on a treadmill. Furthermore, rat hindlimb-muscle perfusion was performed to elucidate the mechanism of the training effect. A medium intensity prolonged exercise (running at 15 m/min for 90 min) caused a greater increase in plasma 3-hydroxybutyrate than in acetoacetate both during and after the exercise. Training with medium-intensity exercise (15 m/min) for 90 min 3 times per week for 14 wks or 28 wks caused 1) a reduction of the increase in plasma ketone body (mainly 3-hydroxybutyrate), free fatty acids and glucagon induced by the exercise, and 2) an increase in ketone body (mainly acetoacetate) uptake by perfused skeletal muscle. The present study demonstrates that the reduction of exercise-induced hyperketonemia by prolonged training is caused by increased ketone body utilization in skeletal muscle, and suggested that inhibition of hepatic ketogenesis might also participate in this reduction.

Animals↗

[Isoantigens ABH in bladder tumors as an indicator of malignant potential. The staining pattern by PAP method and its correlation with prognosis].

Blood group antigens (BGA) were stained by PAP methods and the relation between staining pattern (classified into five types: I, II, IIIa, IIIb and IV) and tumor prognosis was examined in 54 patients with primary superficial bladder tumor. The recurrence rate was significantly higher in BGA negative (Type IIIb or IV) or Type IIIa cases than in antigen positive (Type I or II) cases. Stage-up was observed only in BGA negative cases. Although staining pattern of recurrent tumor differed from that of primary tumor in some cases, it is believed that prediction of malignant potential should be performed at the primary development, when tumor has not been influenced by treatments. With regard to the relation between staining pattern and tumor prognosis, no significant difference was found between the cases of A, B and AB blood groups and those of O group.

ABO Blood-Group System↗

[A clinical study of complements as a marker of a hepatocellular carcinoma].

Serum complement C3, C4, and C3 proactivator (C3PA) have been evaluated for their diagnostic power in detecting a hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). It was found that serum complement levels were lower in LC patients than in HCC patients and that difference of the serum C4 and C3PA levels between LC patients and HCC patients were statistically significant. In addition, serum C3 PA levels were found to correlate significantly with the serum gamma-GTP levels in HCC patients. Thus, using the cutoff values of C4 and C3PA as the mean values for HCC patients, examination of serum complement levels enabled the detection of 38% of the HCC patients with low AFP levels. These findings suggest that the examination of the serum complements may be a useful a tool for the detection of HCCs in LC patients.

Biomarkers, Tumor↗