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Biomedical subjects

A Fujii

Publications and source records attributed to A Fujii.

At least 91 records · Page 5Linked to original sources

Immunohistochemical localization of inositol 1,4,5-trisphosphate receptors in non-neural tissues, with special reference to epithelia, the reproductive system, and muscular tissues.

Although the pharmacological properties and distribution of inositol 1,4,5-trisphosphate (IP3)-sensitive calcium stores vary considerably among tissues, studies of its localization have been devoted mostly to the central nervous system. In this report we have analyzed the localization of IP3 receptors in diverse non-neural tissues of the mouse, using polyclonal antibodies raised against purified IP3 receptors through immunoblotting and immunohistochemistry. These antibodies mainly recognized type 1 IP3 receptors, although they also reacted with other types of IP3 receptors. The receptors were localized in the apical surface areas of highly polarized epithelia, such as the choroid plexus, retinal pigment epithelium, and columnar epithelium lining the interlobular ducts in the sublingual and submaxillary salivary glands. Immunoelectron microscopy of choroidal cells revealed that IP3 receptors are localized on the surfaces of several structures, including clear vesicles, tubules and vesicular profiles of smooth endoplasmic reticulum, rough endoplasmic reticulum and a part of the nuclear envelope, as well as clusters of ribosomes in the cytoplasmic matrix. The surface areas of ciliated epithelia, such as those of the trachea and oviduct, also stained positive. The cytoplasmic distribution was homogeneous in mesangial cells, myoepithelial cells, and endothelial cells accompanying muscle, as well as in a population of endocrine cells. Intense immunostaining was found in the surface areas as well as in the cytoplasm of diverse smooth muscle cells. Staining intensity of smooth muscle varied among cells in the same tissue. Staining was intense in the cytoplasm of premature oocytes in the primary follicle, but then attenuated as these cells matured. The Sertoli cells with clusters of elongating maturing sperm were stained, but mature sperm were unstained. These results indicate a heterogeneous cellular distribution, and possibly a heterogeneous subcellular distribution, of a population of IP3 receptors in a variety of non-neural tissues.

Animals↗

Re-examination for pharmacological properties of serotonin-induced tachycardia in isolated guinea-pig atrium.

In the presence of 10(-6) M atropine, 5-HT induced a positive chronotropic and inotropic effect in isolated guinea-pig atrium preparation. Both propranolol, a beta-adrenoceptor blocker, and imipramine, a 5-HT uptake inhibitor, did not affect the response induced by 5-HT, indicating that a tyramine-like mechanism is not involved. The positive chronotropic effect of 5-HT was mimicked by several 5-HT3 receptor agonists. N omega-Methyl-5-HT, reported to have a high affinity for 5-HT1B recognition sites, was found to act as a 5-HT3 receptor agonist with higher efficacy. The other 5-HT receptor agonists tested did not produced any responses. The positive chronotropic effect of 5-HT was inhibited by various 5-HT3 receptor antagonists, such as tropisetron, granisetron, ondansetron, cisapride and zacopride, but it was unaffected by various 5-HT receptor antagonists which are not selective for 5-HT3 receptor. Thus, the positive chronotropic response to 5-HT is a direct effect, and it was suggested to be mediated by 5-HT3 receptor subtype with rather an atypical profile.

Adrenergic Uptake Inhibitors↗

Cefaclor concentration in pus from abscess caused by odontogenic infection after a single oral administration.

1. Cefaclor concentrations in serum and pus from abscess of odontogenic infection after a single oral administration of 500-mg cefaclor were assayed and pus concentrations were compared with minimum inhibitory concentration (MIC) of oral streptococci isolated from odontogenic infection. 2. The mean peak concentrations in serum and pus were found at identical times, 1.5 hr after administration, which were 7.22 and 0.72 micrograms/ml, respectively. 3. The mean ratio of pus:serum concentration at the peak time was 0.10. 4. Most cefaclor concentrations in pus at the peak time (seven of nine cases) exceeded the MIC for 90% of oral streptococci (0.5 micrograms/ml).

Administration, Oral↗

Effect of vitamin B complex on neurotransmission and neurite outgrowth.

1. The effect of vitamin B complex (vitamin B1, B6 and B12) was studied on nerve conduction velocity in acrylamide-neuropathy rats maintained on refined semisynthetic complete vitamin and vitamin B-deficient diets in vivo and on neurite outgrowth in vitro using cells obtained from dorsal root ganglions of mice. 2. Acrylamide neuropathy was clearer in the group maintained on a refined semisynthetic vitamin B-deficient diet than in those on a refined semisynthetic complete vitamin diet. The neurotoxicity was lowest in the group given vitamin B complex prophylactic-therapeutically, next higher following therapeutic administration and last with no vitamin B complex administration in both groups maintained on a refined semisynthetic vitamin B-deficient diet and a refined semisynthetic complete vitamin diet. 3. The nerve conduction velocity tended to decrease by treatment with acrylamide. The decrement of nerve conduction velocity was partially inhibited by vitamin B complex. No significant difference was found in the groups treated with acrylamide and given vitamin B complex prophylactic-therapeutically and the control (no acrylamide treatment) in the group maintained on a refined semisynthetic vitamin B-deficient diet. 4. The greatest neurite outgrowth was found in the group treated with vitamins B1, B6 and B12-enriched medium, followed by the group of vitamin B12-enriched and vitamin B1-enriched media. All groups treated with a vitamin B-enriched medium had significantly greater (P < 0.01) outgrowth than the controls.

Acrylamide↗

5-HT3 receptor blocking properties of the antiparkinsonian agent, talipexole.

1. Talipexole showed moderate displacement activity of 3H-GR 65630 binding to 5-HT3 receptors in both rat cortical and intestinal membrane fractions with Ki values of 0.35 microM and 0.22 microM, respectively. 2. Bromocriptine failed to displace the binding activity in either experimental system even at a concentration of 10 microM. 3. Both talipexole and tropisetron were found to significantly inhibit 5-HT3 receptor-mediated effects of 5-HT in isolated guinea-pig ileum or atrium; however, the effect of talipexole was weaker than that of tropisetron. 4. Bromocriptine, in contrast, had no antagonistic effects on 5-HT3 receptor-mediated activity in guinea-pig ileum or atrium. 5. It was concluded that talipexole might act as an antagonist on 5-HT3 receptors in both brain and intestinal tissues.

Animals↗

Comparative effects of type 1 angiotensin II-receptor blockade with angiotensin-converting-enzyme inhibitor on left ventricular distensibility and collagen metabolism in spontaneously hypertensive rats.

We compared the cardiac effects of the selective angiotensin II type 1 (AT1)-receptor blockade, FK-739, with an angiotensin-converting-enzyme (ACE) inhibitor, enalapril, on left ventricular (LV) distensibility and collagen metabolism in spontaneously hypertensive rats (SHRs). We treated 14-week-old SHRs with FK-739 (30 mg/kg/day) or enalapril (10 mg/kg/day) for 6 weeks. Both FK-739 and enalapril induced a significant decrease in blood pressure (p < 0.001) and regression of LV hypertrophy (p < 0.001) compared with vehicle, with no differences between the treated groups. Furthermore, FK-739 caused a greater decrease in LV collagen content than did enalapril (FK-739-treated group, 3.06 +/- 0.11 mg/g; enalapril-treated group, 3.47 +/- 0.05 mg/g; p = 0.015) with no change in collagen phenotypes. Hearts taken from rats treated with FK-739 also showed greater LV distensibility than those taken from enalapril-treated rats (FK-739-treated group vs. enalapril-treated group at > or = 15 mm Hg, p < 0.001). These results suggest that, compared with ACE inhibition, AT1-receptor blockade may have additional effects on LV distensibility and collagen metabolism in the regression of LV hypertrophy induced by pressure overload.

Angiotensin Receptor Antagonists↗

Inferior vena cava filter used for unresectable renal cell carcinoma with tumor thrombi.

A titanium Greenfield inferior vena cava filter was used for the treatment of 2 patients with unresectable renal cell carcinomas with tumor thrombi to prevent a fatal pulmonary embolism induced by tumor clots released during systemic interferon therapy and embolization of the primary tumor. After treatment, the size of the renal cell carcinomas at the primary site and the tumor thrombi decreased by 50%. There were no fatal pulmonary embolisms or complications related to the filter during the observation period (24 and 25 months) after therapy. This method may be useful in the prevention of a fatal pulmonary embolism induced by embolization and systemic interferon therapy in these patients.

Aged↗

Cyclo (LL-dimethionine) is not utilized by rats as a methionine source.

A low casein diet supplemented with 0.2-0.3% L-methionine promotes growth in rats, although it causes liver fat accumulation. Oligo-L-methionine on the other hand, prepared by papain-catalyzed oligomerization of L-methionine ethylester, stimulates growth in rats without causing liver fat accumulation, when added to a 8% casein diet. Oligo-L-methionine is a mixture of oligomers, with a oligomerization degree of 5 to 12, and is hydrolyzed very slowly by pancreatic juice and everted gut rings of rats. A methionine derivative, cyclo (LL-dimethionine), was examined in this study as it is hydrolyzed and/or absorbed very slowly from the intestinal tract and it was expected to be utilized as a methionine source without causing liver fat accumulation, when added to a low casein diet. It consists of two methionine residues linked together by two cis-peptide bonds and, therefore, is expected to be hydrolyzed and/or absorbed very slowly from intestinal tract. However, although cyclo (LL-dimethionine) was absorbed slowly from the intestinal tract, it was not utilized by rats as a methionine source, when added to 8% casein.

Animals↗

[Clinical studies of newly diagnosed prostate cancer].

BACKGROUND: The objective of this study is to report the outcome of various treatments in patients who were newly diagnosed prostate cancer from May 1984 to December 1994, at a single institution. METHODS: A retrospective study was carried out in the 142 patients. RESULTS: Total retropubic prostatectomy were performed in 52 patients (37%). The 5-year survival rates (Kaplan-Meier) in the patients with total prostatectomy were 89% in stage B (24), 86% in stage C (7), and 87% in stage D1 (17), respectively. Endocrine therapies (33) or endocrine therapies in combination with chemotherapies (37) as a initial therapy for stage D2 were performed. Among these therapies, endocrine therapy in combination with cyclophosphamide (700 mg/m2/4 weeks, i.v.) was superior to any of the other treatments in stage D2. The response rate, median response duration and median survival time in this combination therapy were 83%, 29 months and 49 months. The overall 3, 5, and 10-year survival rate in the 142 patients were 67%, 51% and 26%, respectively. The 5-year survival rates according to grade were 73% in grade 1, 45% in grade 2, 42% in grade 3, respectively. CONCLUSION: The 5-year survival rates in pathological stage C and D1 patients who received adjuvant hormone and radiation therapy after radical prostatectomy were 86% and 87%. The most effective therapy for stage D2 was hormone in combination with cyclophosphamide. The response rate and median response duration were 83% and 29 months.

Aged↗

Spatial distribution of omega-agatoxin IVA binding sites in mouse brain slices.

A peptide toxin derived from funnel-web spider venom, omega-agatoxin IVA, blocks voltage-sensitive calcium channels. Many pharmacological and electrophysiological studies have shown that these channels are widely distributed in both the central nervous system (CNS) and neuromuscular junctions. However, a direct morphological demonstration of the binding sites of this toxin is still lacking. To identify which cells have the binding sites, a biologically active, biotin-conjugated omega-agatoxin IVA was applied to mouse cerebellar and hippocampal slices. Confocal microscopy revealed that omega-agatoxin IVA binding sites were distributed on the somata of Purkinje cells, cerebellar granule cells and interneurons, as well as on the dendrites of Purkinje cells. In the hippocampus, the binding sites were localized on the somata of pyramidal cells of the CA1-CA4 region and on the somata of granule cells in the dentate gyrus. A sequential competitive reaction confirmed the specificity of the binding in the cerebellum and CA1 pyramidal cells, and also suggested a difference in the binding affinity between CA1 and CA3 pyramidal cells. Since a high concentration of omega-agatoxin IVA (2 microM) was needed for the present study, the omega-agatoxin IVA binding sites presented in this study may represent "P-type" and "Q-type" calcium channels.

Animals↗

Detection of K-ras mutations in DNAs isolated from feces of patients with colorectal tumors by mutant-allele-specific amplification (MASA).

K-ras mutations are found in approximately half of all colorectal tumors examined. To explore the possibility of detecting mutated K-ras rapidly and efficiently in DNAs isolated from fecal material, we applied the mutant allele specific amplification (MASA)-PCR method to DNA from feces of patients with colorectal tumors. Among 55 colorectal adenocarcinomas or adenomas examined, 19 were found to carry K-ras mutations in codons 12 or 13. We were able to PCR-amplify DNAs isolated from feces of 15 of these 19 patients, but in only three of the fecal samples, we were able to detect the K-ras mutations corresponding to tumor DNA by MASA and ethidiumbromide staining of the gel. The carcinomas in these three cases were more than 40 mm x 40 mm in size and located in the sigmoid colon or rectum. However, we identified the K-ras mutations in fecal DNAs of additional seven patients by MASA when the gels were blotted and probed with a radio-labeled oligonucleotide; the tumors in those patients had arisen in the distal half of the colon and the smallest of these tumors was only 7 mm x 5 mm. No K-ras mutations were detectable in feces of the remaining five cases, whose tumors were relatively small and/or located in the proximal region. The results suggested that the MASA-PCR system has potential for development as a simple, rapid and noninvasive method for diagnosing the presence of colorectal tumors that carry mutant K-ras alleles, particularly tumors located in the distal colon.

Adenocarcinoma↗

Two-dimensional domain shape transitions in photosensitive monolayer assemblies.

Bubble-stripe shape transitions of gaseous domains are observed in Langmuir monolayers of porphyrin/arachidic acid and porphyrin/spiropyran mixtures using fluorescence microscopy. Characteristics of the transition such as critical bubble size are found to be controllable by subphase pH or UV/visible irradiation. These features are discussed in terms of a balance between dipolar repulsions and line tension in the monolayer.

Benzopyrans↗

Optical neural device based on memory-type organic photoconductors.

A variable-sensitivity organic-photoconductive device has been developed by using a memory-type organic photoconductor. The device is composed of an input layer and a memory layer acting as a charge generation and a charge transport layer, respectively. A persistent high-sensitivity state, which corresponds to a modulation of synaptic weights in a neuron model, was obtained by blue light illumination. A photochemical reaction of thiomichler's ketone (TMK) in the memory layer was found to be responsible for the memory formation. As a potential application of this memory-type organic photoconductor to an optical neural device, 2-D pattern storage and calculations were performed successfully.

Animals↗

Usefulness of digital rectal examination, serum prostate-specific antigen, transrectal ultrasonography and systematic prostate biopsy for the detection of organ-confined prostate cancer.

The detection rate of organ-confined prostate cancer by digital rectal examination (DRE), serum prostate-specific antigen (PSA), and transrectal ultrasound (TRUS) of the prostate, as well as the value of a directed, guided transrectal core biopsy for the prostate (TRUS-guided biopsy) combined with systematic biopsy, were evaluated. The subjects were 171 patients with urinary symptoms suggestive of prostatic disease excluding those with clinical stage C and D prostate cancer. Twenty-five patients (14.6%) had prostate cancer, 127 (74.2%) had benign prostate hypertrophy, four (2.3%) had prostatic intraepithelial neoplasia, eleven (6.4%) had inflammation, and four (2.3%) had normal prostate tissue. The incidence of detection of hypoechoic findings by TRUS in the patients in whom nodules were detected by DRE or who had elevated serum PSA was higher than that in patients with negative diagnostic findings. In 22 of the 25 patients with prostate cancer, the cancer was detected by recognition of a hypoechoic area on TRUS. In 10 of these 22 patients, prostate cancer was also detected by systematic biopsy in isoechoic areas. Prostate cancer was detected by systematic biopsy in three patients without hypoechoic findings. The positive predictive value for patients with abnormal findings on all three tests was 64.3%, which is significantly higher than that for patients with any other combination of findings (p < 0.05). Our results indicate that the combination of DRE, serum PSA and TRUS is useful for the detection of organ-confined prostate cancer, and that TRUS and TRUS-guided prostate biopsy combined with systematic biopsy should be performed in patients with abnormal findings for both DRE and PSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Correlation of transrectal ultrasound imaging and the results of systematic biopsy with pathological examination of radical prostatectomy specimens.

OBJECTIVE: To determine the usefulness of transrectal ultrasound (TRUS) and systematic biopsy by correlating these results with pathological findings after radical prostatectomy. PATIENTS AND METHODS: Pre-operative TRUS examination combined with the findings on systematic biopsy in 15 patients (mean age 70.6 years, range 57-87) who underwent radical prostatectomy between October 1992 and February 1994 were compared retrospectively to the histological features of whole mount sections of the surgical specimens. RESULTS: In all cases, the tumour was visualized as a hypoechoic area on the sonogram. In addition, in six of 15 cases the tumour was localized in an isoechoic area which was examined before the operation by systematic biopsy. In this series, a systematic biopsy before operating detected tumour grade and localization of the tumour in 14 and 15 patients, respectively. The positive predictive value of capsular penetration and seminal vesicle invasion on the sonogram was 0.71 and 1.00, respectively, while sensitivity was 1.00 and 0.33, respectively. Five of seven patients with findings of capsular penetration on the sonogram revealed capsular penetration in the resected prostate, whereas, of three patients with pathologically detected seminal vesical invasion, only one had findings of seminal vesicle invasion by ultrasonography. The serum prostate specific antigen level of all three patients was more than 30 ng/mL. Moreover, in this series of 15 patients TRUS detected the precise stage in 11 patients. In the remaining four patients, two were overstaged and two were understaged. Tumours with hypoechogenicity were of higher grade and larger than tumours with isoechogenicity. All tumours with hypoechogenicity were palpable and all with isoechogenicity were not. CONCLUSIONS: TRUS combined with a systematic biopsy was useful in predicting tumour grade, exact location and capsular penetration. However, it was not useful for determining tumour stage or predicting seminal vesicle invasion of prostate cancer. TRUS-guided seminal vesicle biopsy must be performed in patients with a serum prostate specific antigen of more than 30 ng/mL.

Adenocarcinoma↗

Three distinct quinoprotein alcohol dehydrogenases are expressed when Pseudomonas putida is grown on different alcohols.

A bacterial strain that can utilize several kinds of alcohols as its sole carbon and energy sources was isolated from soil and tentatively identified as Pseudomonas putida HK5. Three distinct dye-linked alcohol dehydrogenases (ADHs), each of which contained the prosthetic group pyrroloquinoline quinone (PQQ), were formed in the soluble fractions of this strain grown on different alcohols. ADH I was formed most abundantly in the cells grown on ethanol and was similar to the quinoprotein ADH reported for P. putida (H. Görisch and M. Rupp, Antonie Leeuwenhoek 56:35-45, 1989) except for its isoelectric point. The other two ADHs, ADH IIB and ADH IIG, were formed separately in the cells grown on 1-butanol and 1,2-propanediol, respectively. Both of these enzymes contained heme c in addition to PQQ and functioned as quinohemoprotein dehydrogenases. Potassium ferricyanide was an available electron acceptor for ADHs IIB and IIG but not for ADH I. The molecular weights were estimated to be 69,000 for ADH IIB and 72,000 for ADH IIG, and both enzymes were shown to be monomers. Antibodies raised against each of the purified ADHs could distinguish the ADHs from one another. Immunoblot analysis showed that ADH I was detected in cells grown on each alcohol tested, but ethanol was the most effective inducer. ADH IIB was formed in the cells grown on alcohols of medium chain length and also on 1,3-butanediol. Induction of ADH IIG was restricted to 1,2-propanediol or glycerol, of which the former alcohol was more effective. These results from immunoblot analysis correlated well with the substrate specificities of the respective enzymes. Thus, three distinct quinoprotein ADHs were shown to be synthesized by a single bacterium under different growth conditions.

1-Butanol↗

A novel hexahydrodibenzofuran derivative with potent inhibitory activity on melanin biosynthesis of cultured B-16 melanoma cells from Lindera umbellata bark.

A novel cinnamoyl-hexahydrodibenzofuran derivative (1) was isolated from the bark of Lindera umbellata. The structure was determined by extensive spectroscopic analysis to be (5aR*,6R*,9R*,9aS*)-4-cinnamoyl-3,6-dihydroxy-1-methoxy-6-me thyl- 9-(1-methylethyl)-5a,6,7,8,9,9a-hexahydrodibenzofuran. Compound 1 showed potent inhibitory activity on melanin biosynthesis of cultured B-16 melanoma cells without causing any cytotoxicity in the cultured cells or skin irritation in guinea pig.

Animals↗