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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 379 records · Page 21Linked to original sources

Effect of cyproterone acetate on active and inactive renin secretion in patients with precocious puberty and genetic short stature.

To evaluate the effect of cyproterone acetate (CA) on the renin-angiotensin-aldosterone axis, we measured the plasma active, inactive and total renin concentrations (PARC, PIRC and PTRC) during and after CA treatment in patients with precocious puberty and genetic short stature. CA was administered at a daily dose of 150-170 mg/m2 in all subjects. PARC and PTRC were measured by immunoradiometric assays. During CA treatment, PARC, PIRC, PTRC and the PARC/PTRC ratio were significantly decreased. The plasma renin activity, measured by enzymatic assay, and the plasma aldosterone concentration were also decreased. After CA discontinuation, all of these were increased immediately along normal ranges. PARC closely correlated with plasma renin activity. These results suggest that CA produces mineralocorticoid action and suppresses the production and activation of renin.

Androgen Antagonists↗

Molecular nature and possible presence of a membranous glycan-phosphatidylinositol anchor of CA125 antigen.

The molecular nature and possible presence of a glycan-phosphatidylinositol anchor (GPI-anchor) in CA125 molecules was investigated. Serial lectin affinity chromatography and N- or O-glycanase treatment to reduce antigenicity showed that CA125 contained certain N- and O-glycosylated sugar chains in the molecule, like a glycoprotein. CA125 released from ovarian cancer tissues increased time-dependently following phosphatidylinositol-specific phospholipase C (PI-PLC) treatment, concomitant with the release of tissue-unspecific alkaline phosphatase. Western blotting of CA125 treated by PI-PLC showed a single band of 90 kD instead of the 162- and 76-kD bands of the native antigen. Further, ovarian cancer tissues subjected to PI-PLC treatment lost the immunohistochemical localization of CA125 with OC125 antibody. Consequently, it is strongly suggested that CA125 is a glycoprotein that has both N- and O-linked sugar chains and a membranous GPI-anchoring moiety, and further, that its 90-kD form is the antigen without the GPI-anchor.

Adenocarcinoma↗

Effect of S-312, a new calcium channel blocker, on the 1,4-dihydropyridine binding sites in porcine basilar blood vessels and rat aortic smooth muscle cells.

We examined the interaction of two isomers of S-312, a new calcium channel blocker with a bicyclic dihydrothienopyridine structure, with 1,4-dihydropyridine binding sites. Specific bindings of [3H]nitrendipine and (+)-[3H] PN200-110 in membranes prepared from porcine basilar blood vessels were saturable, reversible, and stereoselective, and had high affinities. The binding properties were very similar to those in membranes from other tissues such as the aorta, myocardium, and cerebral cortex. 1,4-Dihydropyridine calcium channel blockers competed for each radioligand binding in the order of: nisoldipine = nicardipine = S-(+)-S-312 greater than nifedipine greater than R-(-)-S-312. S-(+)-S-312 caused a decrease in the Kd values for both radioligands without changing the maximal binding capacity. 1,4-Dihydropyridines inhibited the high K(+)-induced increase in cytosolic free Ca2+ concentration in rat aortic smooth muscle A7r5 cells. S-(+)-S-312 was 3.3-4.9 times more potent than nicardipine or nisoldipine in inhibiting the Ca2+ increase, although S-(+)-S-312 bound to A7r5 cells with almost the same affinity. These and earlier findings show that S-(+)-S-312 exerts effects more potent than expected from the affinity for [3H]nitrendipine or (+)-[3H]PN200-110 binding sites. This was the case with R-(-)-S-312. These dihydrothienopyridine derivatives appear to interact with the Ca2+ channel in a manner slightly different from the conventional 1,4-dihydropyridines.

Animals↗

[Computer-aided three-dimensional reconstruction of the human vestibular aqueduct and the parvestibular canaliculus].

The vestibular aqueduct (VA) and paravestibular canaliculus (PVC) were reconstructed using a computer-aided three-dimensional reconstruction system (SERSERS) from five series of the serial, histopathological sections of the human temporal bones without alignment markers. In order to align the serial sections, more than ten sectional tissue structure images on a section such as the cochlea, VA, PVC, semicircular canals, ossicles and facial canal were compared with those on the consecutive section and the position was determined where the deviation of each sectional image pair would be the minimum in every direction. Repeating this procedure throughout the series of the sections, we could perform the overall alignment of the sections. As the standard viewing axis of reconstruction, we used the modiolus and constructed a triplet of images; posteromedial view image viewing from posterior surface side of the pyramis parallel to the modiolus, superior view image viewing from anterior surface side of the pyramis perpendicularly to the modiolus, anteromedial view image viewing from the internal carotid artery side perpendicularly to the modiolus. The triplet images of the cochlea, VA and PVC presented us their three-dimensional configuration and the spatial relationship among them. Superior view showed that the angle between the plane of the proximal portion of the VA and that of the basal turn of cochlea varied in a wide range from 53 degrees to 68 degrees. Anteromedial view showed that the angle between the plane of the distal portion of the VA and that of the posterior semicircular canal also varied in a wide range from 22 degrees to 49 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Ion-selective microelectrodes to study proton and bicarbonate transport in the renal epithelium.

We have developed several kinds of ISM, and obtained valuable information. The method presented provides (1) the data in situ, and (2) simultaneous data of the membrane potential and the selected ionic activities. Both of these give the driving forces for ion fluxes across the individual membrane border. They provide not only the knowledge of ionic status in minute spaces but also the relationship between different ionic species which are measured simultaneously in the living cell. Further information could also be available by employing this ISM method in combination with the relevant techniques, such as patch-clamp and fluorescent dye techniques.

Animals↗

[Primary myelofibrosis transforming into multiple subcutaneous monoblastoma--a case report].

A 83-year-old man was diagnosed with primary myelofibrosis based on the presence of leukoerythroblastosis, splenomegaly, chromosome 46 XY, a dry tap bone marrow aspiration and fibrosis on bone marrow biopsy, when he was admitted for herpes zoster in June 1987. He was admitted for a second time with multiple subcutaneous tumors over his entire body in July, 1989. He had mild splenomegaly, but no hepatomegaly nor lymphadenopathy. Laboratory tests were as follows: RBC 214 x 10(4)/microliters, Hb 5.1 g/dl, Ht 17.7%, WBC 3,200/microliters with leukoerythroblastosis, platelets 11.6 x 10(4)/microliters, s-lysozyme 251 micrograms/ml, u-lysozyme 770 micrograms/ml, NAP ratio 98%, score 278. Bone marrow aspiration resulted in a dry tap. Bone marrow biopsy showed marked fibrosis. Histologic examination of subcutaneous tumor biopsy specimens revealed a diffuse infiltration of monocytes with flexuous nuclei. These cells were positive for alpha-naphtyl butyrate esterase stain, and negative for peroxidase, alpha-naphtol ASD chloroacetate esterase stain and platelet glycoprotein IIb/IIIa stain (APAAP). Ultrastructurally, these cells were mostly monocytes and promonocytes, while phenotypically, CD11b, CD13, CD14, CD33 and HLA-DR were positive. These date indicated that the subcutaneous tumors originated from monocytes.

Aged↗

[Bone metastases in breast cancer and its risk factor--follow up study by bone scintigraphy].

Breast cancer is considered to often involve bone metastasis. Early detection and treatment of bone metastasis are essential in improving the prognosis of this disease. In 47 patients with bone metastasis confirmed with bone scintigraphy, we examined the appearance time of bone metastasis; bone metastasis was frequently observed with the progress of stage, but no association with the appearance time was found. Age was not associated with the incidence of bone metastasis but was found to be closely related to its appearance time. That is to say, patients with breast cancer below 40 years of age showed relatively early bone metastasis. Bone scintigraphy is required every 6 months at least for 3 years after the operation. In patients over 40 years of age, on the other hand, bone scintigraphy is required only once a year but has to be continued for 5 years or more, because they often show relatively late bone metastasis.

Adult↗

[Cefepime in the treatment of patients with surgical infections].

Between March 1988 and June 1990, we gave cefepime to 5 subjects after surgery and studied the pharmacokinetics of the drug. In the same period, we treated 23 patients with surgical infections with the same drug and evaluated its clinical efficacy. In the pharmacokinetic study, 1 g was given intravenously to each individual over a 30 minutes period. The peak levels in the plasma, 59.9-118 micrograms/ml, were obtained at around the end of this time. The peak levels in the bile, 7.1-28.2 micrograms/ml, were reached at 1-5 hours after administration, depending on the patient. At hours 5 and 6, the range of plasma concentration was 3.7-12.3 micrograms/ml. In the 22 patients with surgical infections, clinical efficacy of the drug was excellent in 12, good in 5, fair in 1, and poor in 4, with an overall efficacy rate of 77%. The bacteriological response was evaluated in the 16 patients for whom the species of the probable causative organisms were identified. Those bacteria were eradicated in 10 patients, decreased in 3, and were persisted in 3, with an eradication rate of 63%. Against 5 strains of Escherichia coli isolated, the highest MIC was 0.05 micrograms/ml, and against 2 strains of Pseudomonas aeruginosa isolated, the MIC was 1.56 micrograms/ml, so this drug should be highly effective toward these species. Three strains of Staphylococcus aureus were isolated, one of which was resistant to methicillin. It was not eradicated.

Adolescent↗

Enhancement of bradykinin-induced prostacyclin synthesis in porcine aortic endothelial cells by pertussis toxin. Possible implication of lipocortin I.

Bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells was enhanced by pretreatment of the cells with pertussis toxin or islet-activating protein (IAP) for 5 hr or longer. Although ADP-ribosylation of a protein with a molecular weight of 41-42 kD in the cell membranes was completed by 3 hr after the addition of IAP into the incubation medium, there was good correlation between enhancement of bradykinin-induced prostacyclin synthesis and ADP-ribosylation of the IAP substrate over a wide range of IAP concentrations. Furthermore, even if IAP was removed from the incubation medium at 3 hr, bradykinin-induced prostaglandin synthesis at 24 hr was still potentiated. Cycloheximide and actinomycin D enhanced bradykinin-induced prostacyclin synthesis and apparently blocked the effect of IAP. Since this result suggested the involvement of an inhibitor protein(s) of prostacyclin synthesis in the IAP effect, we studied the effect of IAP on the level of lipocortin I which is known to inhibit phospholipase A2. Western and Northern blot analyses revealed that IAP decreased the amounts of protein and mRNA of lipocortin I. These results suggest that the enhancement of bradykinin-induced prostacyclin synthesis by IAP is associated with a decrease in the level of lipocortin I.

Adenosine Diphosphate Ribose↗

Interaction of lipocortin I with peripheral-type benzodiazepine binding sites.

Recombinant rat lipocortin I increased [3H]PK 11195 binding to porcine aortic smooth muscle membranes, whereas a polyclonal anti-rat lipocortin I antiserum decreased both basal and lipocortin I-enhanced [3H]PK 11195 binding. The results suggest the possibility of lipocortin I being involved in the function of peripheral-type benzodiazepine binding sites.

Animals↗

Neurenteric cysts with meningomyelocele or meningocele. Split notochord syndrome.

Two rare cases of neurenteric cysts with meningomyelocele and meningocele were treated. The mechanism of the development of these anomalies is discussed. It is considered that the terminal, dorsal part of the enteric fistula, which is produced between the endoderm and the ectoderm through a partially duplicated notochord in the development of the embryo, remains after obliteration of the fistula and, consequently, that the mucosa of the enteric remnant is inverted and projects through the skin of the back.

Abnormalities, Multiple↗

Regulation of inwardly rectifying K+ channels by intracellular pH in opossum kidney cells.

The effects of intracellular pH on an inwardly rectifying K+ channel ("Kin channel") in opossum kidney (OK) cells were examined using the patch-clamp technique. Experiments with inside-out patches were first carried out in Mg2(+)- and adenosine triphosphate (ATP)-free conditions, where Mg2(+)-induced inactivation and ATP-induced reactivation of Kin channels were suppressed. When the bath (cytoplasmic side) pH was decreased from 7.3 to either 6.8 or 6.3, Kin channels were markedly inhibited. The effect of acid pH was not fully reversible. When the bath pH was increased from 7.3 to 7.8, 8.3 or 8.8, the channels were activated reversibly. The channel activity exhibited a sigmoidal pH dependence with a maximum sensitivity at pH 7.5. Inside-out experiments were also carried out with a solution containing 3 mM Mg-ATP and a similar pH sensitivity was observed. However, in contrast with the results obtained in the absence of Mg2+ and ATP, the effect of acid pH was fully reversible. Experiments with cell-attached patches demonstrated that changes in intracellular pH, which were induced by changing extracellular pH in the presence of an H+ ionophore, could influence the channel activity reversibly. It is concluded that the activity of Kin channels can be controlled by the intracellular pH under physiological conditions.

Adenosine Triphosphate↗

Quantitative detection of blood-brain barrier-associated enzymes in cultured endothelial cells of porcine brain microvessels.

The present study deals with a rapid and convenient assay for blood-brain barrier (BBB)-associated enzymes, gamma-glutamyl transpeptidase (gamma-GTP) and alkaline phosphatase (ALP), in cultured endothelial cells and other cells. These enzyme activities in cultured cells could be efficiently measured by direct incubation of each substrate in the culture plates without pretreatment of the cells. This new direct in situ-in plate assay was more rapid and convenient than conventional ex-plate assays, and these assays gave similar values for specific enzyme activities. gamma-GTP and ALP activities could be detected by this in situ method in primary-cultured endothelial cells of porcine brain microvessels, but their levels were lower than those before culture. The degree of loss due to culture differed between gamma-GTP and ALP; a relatively large amount of ALP remained but the gamma-GTP level decreased greatly. In this direct in situ-in plate assay, cultured porcine aortic endothelial cells exhibited negligibly small activities for both enzymes, whereas cultured astroglial cells of neonatal porcine brain showed moderate gamma-GTP activity and a trace of ALP activity. This direct in situ-in plate assay can be used for microculture and automatic measurement and offers a convenient means for studying the possible regulatory mechanisms of the expression of the BBB-associated enzymes.

Alkaline Phosphatase↗

An enzyme-linked immunosorbent assay (ELISA) for adenosine 3',5'-cyclic monophosphate (cAMP) in human plasma and urine using monoclonal antibody.

A reliable and sensitive ELISA for cAMP in human plasma and urine is described, using a monoclonal antibody and a 96 well microtiter plate. Succinyl cAMP is conjugated to human serum albumin and adsorbed to the ELISA plate, giving an immobilized antigen approach which simplifies subsequent assay procedures. As low as 1.56 fmol/well of both plasma and urinary cAMP is measurable. Recoveries of added cAMP in plasma and urine were from 99% to 109%. Intra-assay coefficients of variation were less than 6.1% for plasma and 7.0% for urine samples. Inter-assay coefficients of variation for plasma and urine samples were less than 8.9% and 9.5%, respectively. There was a good correlation between the values obtained by ELISA and radioimmunoassay (RIA) (plasma: r = 0.94, n = 66; urine: r = 0.98, n = 64; nephrogenous cAMP: r = 0.96, n = 51).

Antibodies, Monoclonal↗