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Biomedical subjects

H Fujioka

Publications and source records attributed to H Fujioka.

At least 217 records · Page 12Linked to original sources

[Growth fractions of bladder cancer determined by proliferating cell nuclear antigen immunostaining].

Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) can be performed on conventionally fixed and processed tissue. We applied anti-PCNA monoclonal antibodies to transurethrally resected bladder cancer specimens. The labelling index (LI) of PCNA increased with tumor grade and that of the invasive tumor group was higher than that of the non-invasive tumor group. Especially in large tumors, there was intratumoral variation of labelled cell distribution, which may represent tumor heterogeneity. These findings suggest that PCNA might be a useful marker for bladder cancer proliferation.

Adult↗

[Effect of low calcium diet on blood pressure and pressure natriuresis response in rats: role of the renin-angiotensin system].

Dietary Ca is an important modulator of arterial blood pressure in humans and rats. Since the kidney plays a key role in the pathogenesis of hypertension, the effect of a low Ca diet (0.01%Ca) on blood pressure and pressure natriuresis response was studied in Sprague-Dawley rats. In addition, a possible role of the renin-angiotensin system in the development of hypertension and an altered pressure natriuresis response resulting from low dietary Ca intake was investigated. In the low Ca diet group, systolic blood pressure determined by the tail-cuff method was significantly higher than in the normal Ca diet group (1.1%Ca) 1 week after the diet (113.0 +/- 7.1 vs. 105.0 +/- 9.5 mmHg, p < 0.05). Furthermore, low dietary Ca treatment significantly inhibited the water and sodium excretory responses to acute elevation of renal perfusion pressure. Treatment with an inhibitor of angiotensin converting enzyme, captopril (30 mg/kg/day), attenuated both the development of hypertension and the reduced pressure natriuresis response observed in Ca-deficient rats. Although plasma renin activity was not different between the low and normal Ca diet groups after the 2-week dietary regimen, the pressor response to angiotensin II injection was significantly greater in the low Ca diet group. These results indicate a possible involvement of the renin-angiotensin system in the development of hypertension and the inhibitory effects of the pressure natriuresis response caused by low dietary Ca intake, via enhanced sensitivity to angiotensin II.

Animals↗

[Leiomyosarcoma of the prostate accompanied by multiple hepatocellular carcinoma: report of a case].

A case of leiomyosarcoma of the prostate accompanied by multiple hepatocellular carcinoma in a 51-year-old man is presented. He visited our hospital with the complaints of feeling of residual urine and pain of the coccygeal bone in November, 1990. A histopathological study of the transrectal needle biopsy specimens revealed leiomyosarcoma of the prostate. Since multiple liver tumors were pointed out, the patient was given combined chemotherapy (CYVADIC: cyclophosphamide, vincristine, adriamycin and DTIC). He died 1 year and 2 months after the initial diagnosis due to hepatic failure. The autopsy findings revealed that the histology of the liver tumors was hepatocellular carcinoma, and that the leiomyosarcoma of the prostate had directly invaded the wall of the urinary bladder and the rectum, but there was no obvious distant metastasis.

Carcinoma, Hepatocellular↗

[Role of endothelium-derived nitric oxide in mediating the natriuretic response to acute extracellular volume expansion].

To determine the role of endothelium-derived nitric oxide (EDNO) in mediating the natriuretic response to acute extracellular volume expansion (ECVE) with isotonic saline (3% of body weight per hour), the diuretic and natriuretic responses to ECVE were studied in anesthetized Sprague-Dawley rats during the intravenous infusion of an EDNO synthesis inhibitor, NW-nitro-L-arginine methyl ester (L-NAME). Intravenous infusion of L-NAME at the dose of 5 micrograms/kg/min significantly inhibited the diuresis and natriuresis in response to ECVE by 58% and 67%, without altering arterial pressure, effective renal plasma flow, glomerular filtration rate and basal excretory function. This inhibitory effect of L-NAME on the diuretic and natriuretic responses to ECVE was attenuated by the infusion of the EDNO synthesis precursor, L-arginine (1mg/kg/min), but not by D-arginine. In addition, pretreatment with 0.3 mg/kg of the angiotensin II receptor antagonist, L-158,809, normalized the diuretic and natriuretic responses to ECVE in L-NAME-treated rats, suggesting an angiotensin-II-dependency of the reduced renal excretory response to ECVE during EDNO synthesis inhibition. Neither L-arginine nor L-158,809 alone significantly altered the renal excretory response to ECVE compared with vehicle-treated control rats. These results suggest that EDNO might play an important role in the regulation of sodium and water excretion during ECVE, and indicate a possible interaction between EDNO and angiotensin II on the renal excretory function.

Angiotensin II↗

[Assessment of the distribution of renal cortical blood flow by contrast ultrasonography].

The importance of the distribution of intrarenal blood flow in the regulation of various renal functions, such as urine concentration and sodium excretion, has been well recognized. However, there have been no reliable methods to measure local flow in the kidney in vivo. The present study demonstrated the usefulness of contrast ultrasonography combined with injection of sonicated 5% albumin for assessment of the distribution of renal cortical blood flow in eleven mongrel dogs. The left kidney was displayed by tomographic echography, and microbubbles of sonicated albumin were injected into the abdominal aorta above the left renal artery. Video density time curves were generated and fitted to a time-intensity curve. Intrarenal infusion of acetylcholine (4.0 micrograms/kg/min) increased renal blood flow (RBF) from 2.5 +/- 0.3 to 4.6 +/- 1.0 ml/min/g kwt (p < 0.01), and norepinephrine (0.5 microgram/kg/min) decreased RBF from 2.5 +/- 0.3 to 1.2 +/- 0.5 ml/min/g kwt (p < 0.01). There were significant positive correlations between percent change in RBF and peak intensity and area under the curve, which were calculated with a time-intensity curve. Furthermore, the inner/outer renal cortex ratio of peak intensity significantly increased during acetylcholine infusion (0.72 +/- 0.11 vs 0.86 +/- 0.09; p < 0.01), whereas no significant change was observed during norepinephrine infusion. These results suggest that renal contrast ultrasonography may be useful for real-time assessment of the distribution of renal cortical blood flow in vivo.

Acetylcholine↗

Pfs2400 can mediate antibody-dependent malaria transmission inhibition and may be the Plasmodium falciparum 11.1 gene product.

Monoclonal antibodies (mAb) have been raised against Plasmodium falciparum gametocyte stage protein extracts, in an effort to identify novel parasite antigens that might mediate malaria transmission-blocking immunity. mAb 1A1 identified Pfs2400, a sexual stage-specific antigen of greater than 2 megadaltons, that is associated with the outer leaflet of the parasitophorous vacuole membrane in mature circulating gametocyte-infected red blood cells. Upon induction of gametogenesis, Pfs2400 partitions between the gamete plasmalemma and the degenerating erythrocyte membrane. The antigen is no longer detectable in the fully emerged gamete. mAb 1A1 dramatically reduces the number of oocysts formed in P. falciparum gametocyte-fed mosquitoes. The cognate antigen is probably the product of the Pf11.1 gene (Scherf et al. 1988. EMBO [Eur. Mol. Biol. Organ.]J. 7:1129) on the basis that a peptide composed of two copies of the degenerate nine amino acid repeat sequence in the Pf11.1 protein, can inhibit binding of mAb1A1 to the native antigen. The mechanism of transmission inhibition mediated by the Pfs2400 is discussed.

Amino Acid Sequence↗

Triphasic vascular effects of thiol compounds and their oxidized forms on dog coronary arteries.

The vascular effects of 2-mercaptoethanol, cysteamine, L-cysteine, glutathione (GSH), cystamine and oxidized GSH (GSSG) on the isometric tension of isolated dog coronary arterial strips were examined, and these effects were compared with the triphasic response induced by dithiothreitol (DTT); a rapid and weak contraction (phase A), an intervening slow relaxation (phase B) and a slowly-developing strong contraction (phase C) which we previously reported. The responses of the arteries induced by 2-mercaptoethanol, cysteamine and L-cysteine consisted of phases A, B and C. The order of contractile potency (ED50 of phase C) was DTT approximately L-cysteine > 2-mercaptoethanol approximately cysteamine, while the order of relaxant potency (ED50 of phase B) was DTT > cysteamine approximately 2-mercaptoethanol. GSSG and cystamine mainly produced relaxation, which corresponded to phase B. The phase C contraction was specific to the reduced forms of thiols, except for GSH, which produced only relaxation. The participation of endothelial cells was not essential for the contracting or relaxing effects of the thiol compounds. The phase C contraction was depressed by W-7, a calmodulin antagonist, while phase A was not. Therefore calmodulin-dependent protein kinases may participate in phase C, not in phase A.

Animals↗

Low-dose dobutamine stress test for the evaluation of cardiac function using ultrafast computed tomography.

High dose-dobutamine (DOB) has been previously used as a pharmacological stress test to evaluate wall motion abnormalities. As a result, recent stress echocardiography with low-dose DOB has been reported to be valuable for investigating stunned myocardium after thrombolysis. However, echocardiography requires an operator's skill and experience to evaluate wall motion abnormalities which are subjectively determined by the observer. In contrast, ultrafast computed tomography (UFCT) does not necessarily require extreme technical skill and experience. To evaluate the feasibility of stress UFCT with low-dose DOB, we scanned 10 normal subjects along the short-axis by 8-slice-multicine mode. After scanning at rest for baseline, we scanned during the administration of 4 and 8 micrograms/kg/min of DOB, respectively, for 5 min. Ejection fraction, contraction, and thickening were higher during 8 micrograms/kg/min of DOB than during 4 micrograms/kg/min of DOB and baseline, while the above values were higher during 4 micrograms/kg/min of DOB than during baseline (p < 0.01). It was possible to detect changes of cardiac function and wall motion due to low-dose DOB by UFCT. We therefore conclude that UFCT is a reliable modality for evaluating cardiac function and wall motion for low-dose DOB stress test because of its excellent spatial and contrast resolution.

Adolescent↗

Morphological changes of clefts in Plasmodium-infected erythrocytes under adverse conditions.

Blood infected with human or rodent malaria parasites, Plasmodium falciparum or Plasmodium berghei, was exposed to higher pH, higher PO2, and lower temperature than those used in standard cultivation conditions. Parasitized blood was incubated for 20, 25, and 30 min with RPMI 1640 medium, 10% (vol/vol) serum, pH 8.0, at 20 degrees C in the air, conditions which are ultimately lethal to the asexual stages of malarial parasites. Markedly dilated clefts were observed in the cytoplasm of the malaria-infected erythrocytes so treated. These clefts can take up colloidal gold particles and macromolecules such as Protein A, rhodamine-dextran, and lucifer yellow-dextran. Such dilated clefts were not seen in the cytoplasm of infected erythrocytes that were incubated under normal cultivation conditions before fixation. These had slender clefts of the usual sort that did not take up colloidal gold particles and macromolecules.

Animals↗

Cloning and characterization of a Plasmodium falciparum gene encoding a novel high-molecular weight host membrane-associated protein, PfEMP3.

The rat monoclonal antibody, mAb 12C11, reacts with numerous proteins from mature asexual stages of Plasmodium falciparum. The largest is 315 kDa and is designated PfEMP3. A lambda gt11 expression library, generated from genomic DNA of Malayan Camp strain parasites, was screened with mAb 12C11. One positive clone, lambda 12.1.3, contained a 1.4-kb fragment in frame with the beta-galactosidase gene of lambda gt11. The deduced 455-amino acid sequence is a novel, highly charged sequence encoding two 15-amino acid repeats at the N-terminus followed by 27 repeats of 13 amino acids. The last 59 C-terminal residues are non-repetitive. Two in-frame stop codons at the 3' end of the DNA suggests that this DNA fragment encodes the C-terminus of the protein. Southern blotting with the cloned fragment identified two copies of this fragment per haploid genome in knob-positive, parasitized erythrocytes (K+PE). Both DNA fragments are absent from K - PE. Northern blotting of trophozoite-stage PE total RNA revealed mRNAs of 10, 4.4 and 2 kb in K+PE, but no hybridization with K - PE. Immune sera were elicited against the lambda 12.1.3 beta-galactosidase fusion protein and peptides generated from the predicted lambda 12.1.3 amino acid sequence. These sera and mAb 12C11 reacted specifically with PfEMP3 in Western blots of mature K+PE but not with K - PE. Rat and mouse sera against the recombinant protein produced an immunofluorescence pattern in fixed mature K+PE almost identical to the pattern produced by a monoclonal antibody against the knob-associated protein, Histidine Rich Protein 1. The same antibodies were immunofluorescence negative with fixed K - PE. Mouse antibodies against the recombinant protein reacted on immunoelectron microscopy with the erythrocyte membrane of K+PE, labeling knobs as well as the membrane between knobs. In contrast, a mAb against Histidine Rich Protein 1 reacted only under the electron dense material of knobs. We conclude that the lambda 12.1.3 clone encodes the C-terminal portion of the 315 kD PfEMP3 antigen and that PfEMP3 may be involved in knob formation or other perturbations of the erythrocyte membrane.

Amino Acid Sequence↗

Dissociation of hemodynamic and coronary arterial tolerance to nitroglycerin in dogs.

To investigate the development of tolerance to nitroglycerin (NTG), therapeutic doses of NTG (1 microgram/kg/min in group 1G and 10 micrograms/kg/min in group 10G) or vehicle alone (group 0G) were infused intravenously (i.v.) for 24 h into anesthetized mongrel dogs. The reduction of pulmonary artery pressure (PAP) by NTG was attenuated after the first 3 and 6 h of NTG infusion in groups 1G and 10G, respectively. At the end of infusion, coronary artery strips were excised for study of isometric tension responses to cumulative doses of NTG. The ED50 value for group 10G (17.5 +/- 2.9 nM) was greater than that for group 0G (5.2 +/- 1.1 nM, p < 0.001), but the ED50 value of group 1G (5.5 +/- 0.7 nM) was not. Maximum relaxation did not alter in the three groups. The concentration of cyclic GMP in the isolated coronary artery strips was measured by radioimmunoassay (RIA). Administration of 10(-8.5) M NTG increased the cyclic GMP level in group 0G (42.7 +/- 1.5%, p < 0.05) and group 1G (38.8 +/- 10.5%, p < 0.05), but not in group 10G (3.5 +/- 5.6%). The degree of increment in cyclic GMP corresponded with the relaxation response to 10(-8.5) M NTG. These results demonstrated the hemodynamic tolerance to NTG is different from vascular tolerance at therapeutic doses.

Animals↗

A novel fine granule system for masking bitter taste.

In order to prepare fine granules of sparfloxacin (SPFX), a new quinolone anti-bacterial drug that shows masking of the bitter taste of SPFX and dissolutes at a rapid rate, various film-coated fine granules containing 20% SPFX and 0-52% low-substituted hydroxypropylcellulose(L-HPC) in the cores, were prepared by a spray method. Mixtures of ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC), titanium dioxide and sucrose stearate in weight ratios of X:Y:2:1 (X + Y = 6) were used as film materials. The degree of masking of the bitter taste by water-insoluble film, mainly consisting of EC and HPMC, increased by increasing the content ratio of EC to HPMC and the amount of films, but was also slightly affected by the amount of L-HPC in the cores, which were coated with either EC or EC/HPMC (4/2). On the other hand, the dissolution rate increased with an increased amount of L-HPC in the cores and with a decreasing ratio of EC to HPMC in the films. Increasing the amount of L-HPC in the cores, which induced a considerable expansion of the fine granules owing to their taking up of water from the dissolution medium, resulted in bursting of the film after a short lag time. The bioavailability of the film-coated fine granules containing 20% SPFX and 52% L-HPC in the cores and 10% EC/HPMC (4/2) in the coating film, which masked the bitter taste of SPFX and showed the optimal release characteristics, was equivalent to that of conventional tablets containing 100 mg SPFX in beagle dogs.

Animals↗

Cryoprotective effect of gelatin and albumin on recombinant human tumor necrosis factor liposome.

A search for a cryoprotective agent of a liposome containing recombinant human tumor necrosis factor (rHuTNF) was undertaken. Various additives were added and liposomes were freeze-thawed. As a result of these studies, albumin and gelatin were found to suppress the leakage of rHuTNF from liposome. This cryoprotective effect was only observed when the additives were added to the inside of the liposomal membrane; their addition to the outside of the membrane stimulated the leakage. This characteristic was clearly different from well-known cryoprotective agents, such as saccharides which have the cryoprotective effect on both sides of the liposomal membrane. Although this cryoprotective effect was also observed for recombinant human interleukin-1 alpha (rHuIL-1 alpha), it was not observed for fluorescein sodium. These effects of gelatin and albumin were restricted to macromolecular proteins such as rHuTNF and rHuIL-1 alpha, but both substances were very effective cryoprotectants for a liposome containing protein.

Albumins↗

Morphologic effects of artemisinin in Plasmodium falciparum.

Ultrastructural changes induced in Plasmodium falciparum by artemisinin were studied in vitro. Electron microscopic autoradiography was performed on infected erythrocytes that were exposed in vitro to 3H-dihydroartemisinin and 14C-artemisinin. These drugs consistently were located in food vacuoles and mitochondria. Two hours after administration, changes were observed in parasite mitochondria, rough endoplasmic reticulum, and nuclear envelope. At four hours, in addition to the earlier changes, nuclear membranes and, to a lesser extent, some plasma membranes formed myelin figures. In addition, there was a disappearance of ribosomes, and a destruction of food vacuole membranes. These changes may lead to the total disorganization of the parasites. Approximately 30% of the parasites manifested these alterations.

Animals↗

[Metachronous bilateral testicular seminomas. A case report].

A case of metachronous bilateral testicular seminomas on a 36-year-old male is reported. He had a history of right testicular typical seminoma treated with right high orchiectomy and adjuvant irradiation therapy 6 years previously. He returned to our clinic complaining of painless left testicular enlargement in August 1990, and under a diagnosis of testicular neoplasm left high orchiectomy was performed. Histopathological examination revealed anaplastic seminoma. DNA histograms of both testicles revealed almost the same aneuploid pattern. The patient was diagnosed as stage I seminoma, has been followed up closely. Recently genetic factors as human leukocyte antigens (HLA)-A24, B14, DR5 and DR7, have been shown to be important in the development of metachronous bilateral testicular tumors. HLA antigens were determined in our case, and HLA-A24 shown in our case was compatible with the review.

Adult↗

Doppler sonographic measurement of phasic renal artery blood flow velocity in patients with chronic glomerulonephritis.

The phasic arterial blood flow velocity at the renal hilus was measured by Doppler sonography in 25 healthy subjects and 78 patients with chronic glomerulonephritis. Doppler velocity waveform was analyzed to give peak systolic velocity (S), end-diastolic velocity (D), resistive index (RI), and pulsatility index (PI). Creatinine clearance correlated with S (r = 0.76), D (r = 0.80), RI (r = -0.74), and PI (r = -0.85). Color Doppler sonography facilitated the detection of blood flow and permitted the measurement of absolute blood flow velocity, which previously had been difficult to determine. These results suggest that renal arterial blood flow as detected by Doppler ultrasonography may be useful for noninvasive, direct, rapid, and simple evaluation of renal function, although various modifying factors also need to be considered.

Adult↗

[Primary squamous cell carcinoma of the ureter: report of a case].

A case of squamous cell carcinoma of the ureter in a 63-year-old female is reported. Right hydronephrosis was found by examination of duodenal ulcer. Ureteroscopy and biopsy revealed squamous cell carcinoma (SCC) of the lower ureter. Total nephroureterectomy with a bladder cuff was performed. Pathological diagnosis was SCC pT3 G2 INF beta pL1 pV0 pR0. Three cycles of chemotherapy were performed postoperatively with bleomycin, methotrexate and cisplatin. Fifty-three cases of primary ureteral squamous cell carcinoma from the Japanese literature are reviewed and characteristic clinical figures of the tumor are discussed.

Antineoplastic Combined Chemotherapy Protocols↗