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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 541 records · Page 30Linked to original sources

Fasting prevents acute pancreatitis induced by cerulein in rats.

We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitum throughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivo and in vitro. Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.

Acute Disease↗

New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats.

We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr. The contents of pancreatic protein, DNA, and digestive enzymes were markedly reduced after the arginine injection and reached their nadirs at 72 hr. After 14 days these levels were almost normal. Histologic examination revealed a number of small vesicles within acinar cells at 6 hr, which were identified as markedly swollen mitochondria by the electron microscope. Other intracellular organelles and nuclei also showed degenerative changes. At 12 hr interstitial edema appeared, and acinar cell necrosis was seen after 24 hr. The extent and severity of necrotic changes of pancreatic exocrine tissue with inflammatory cell infiltration were maximal at 72 hr. At seven days, pancreatic acinar cells began to regenerate, and pancreatic architecture appeared almost normal after 14 days. The present study has demonstrated that the administration of excessive doses of arginine induces a new, noninvasive experimental model of acute necrotizing pancreatitis.

Acute Disease↗

Enzyme immunoassay for human pancreatic amylase.

An enzyme immunoassay (EIA) for human pancreatic amylase has been developed for the detection of human serum amylase content. Our monoclonal antibody is highly specific for human pancreatic amylase; it cross reacted negligibly with the salivary isoenzyme. We developed a solid phase enzyme immunoassay for determination of pancreatic amylase in human serum with this antibody. The assay required 20 microL of serum and the standard curve was linear to at least 1000 ng/mL of pancreatic amylase. Inter- and intra-assay CVs were less than 10%. The results obtained by the EIA correlated well with those determined by the conventional electrophoretic method. In normal subjects, the mean concentration of serum pancreatic amylase determined by the EIA was found to be 92.3 +/- 26.1 ng/mL (mean +/- SD). The EIA we describe is useful for directly determining pancreatic amylase in human serum. Specifically distinguishing pancreatic from salivary amylase may have considerable clinical value.

Amylases↗

Acid triacyglycerol lipase inhibitor in chicken plasma: purification and properties.

1. Acid triacylglycerol lipase inhibitor was highly purified from chicken plasma by ammonium sulfate fractionation (0.6-1 saturation) followed by successive chromatographies on Hydroxyapatite, Blue-Cellulofine, Phenyl-Sepharose and Cellulofine GCL-2000 columns, and isoelectric focusing. 2. The lipase inhibitor showed its inhibitory action on triacylglycerol lipases in chicken erythrocytes ghosts and in chicken liver lysosome, but did not on pancreatic lipase, Rhizopus arrhizus lipase, or wheat germ lipase. 3. The inhibitor showed its molecular weight of 32,000 by Cellulofine GCL-2000 gel filtration. The inhibitor showed some heterogeneity on isoelectric focusing, and the main band had a pI of 5.10. 4. The lipase inhibitor did not show any inhibitory action on trypsin or chymotrypsin.

Ammonium Sulfate↗

Induction of human TCR gamma delta + and TCR gamma delta-CD2+CD3- double negative lymphocytes by bacterial stimulation.

When human blood mononuclear cells (MNC) were incubated with heat-killed bacteria, proliferation of MNC was observed 5 days after stimulation, showing a peak on day 7. Interestingly, the bioassay of the culture supernatant and Northern blot analysis of mRNA demonstrated that no IL-2 production was associated with these proliferative responses. The induced lymphoblasts consisted predominantly of TCR gamma delta + (22.4 +/- 9.3%) and TCR gamma delta-CD2+CD3-(33.2 +/- 11.8%) double negative lymphocytes (n = 10), which were initially minor populations (less than 10%) in freshly isolated MNC. The prominent induction of TCR gamma delta + cells was confirmed by Northern blot analysis. TCR gamma delta + cells induced by bacterial stimulation seemed to generate from lymphocytes lacking the apparent expression of gamma delta TCR. The inducing capability for double negative cells is present in a large number of species of bacteria, especially Gram-positive bacteria. Gel filtration analysis of ultrasonicated filtrates of Staphylococcus aureus and Streptococcus pyogenes revealed that a substance with an Mr of 25-26 kd could be substituted for whole bacterial particles in the cell proliferative responses. In contrast to the purified protein derivative (PPD)-induced response, the response described here was inducible in the cord blood of neonates who had not yet been exposed to the corresponding bacterial infection. The physicochemical properties of the sonicated filtrates were different from those of PPD. These results suggested that the present phenomenon may be nonspecific, polyclonal (or oligoclonal) activation of TCR gamma delta + and TCR gamma delta -CD2+CD3- cells by bacterial stimulation.

Adult↗

Effects of L-364,718 on pancreatic exocrine and endocrine secretion in the rat.

We examined the inhibitory effect of L-364,718, a nonpeptide cholecystokinin (CCK) antagonist, on CCK stimulation of pancreatic exocrine and endocrine secretion in both the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, L-364,718 inhibited CCK octapeptide (CCK-8)-stimulated amylase release and binding of 125I-CCK-8 in a dose-dependent manner without appreciable effects on the basal amylase secretion. L-364,718 also inhibited amylase release in response to caerulein and gastrin I, but had no effect on amylase release stimulated by other secretagogues or by agents bypassing receptors. Similarly, binding of N-methylscopolamine to pancreatic acini was not inhibited by L-364,718. In the isolated perfused pancreata, L-364,718 inhibited CCK-8-stimulated pancreatic exocrine secretion and insulin release. The inhibitory effects of L-364,718 were more potent for insulin release than for exocrine secretion and persisted even after the removal of L-364,718 infusion. These results clearly demonstrate that L-364,718 is a specific, potent, and prolonged antagonist of CCK's stimulatory actions on pancreatic acinar and B cells.

Amylases↗

Effect of a new cholecystokinin receptor antagonist loxiglumide on acute pancreatitis in two experimental animal models.

We evaluated the effects of a new cholecystokinin (CCK) receptor antagonist, loxiglumide, in a model of mild pancreatitis induced by repeated injections of cerulein and in a severe necrotizing form of pancreatitis induced by retrograde ductal injection of sodium taurocholate (NaTc) in rats. A single subcutaneous injection or oral administration of 50 mg/kg of body weight of loxiglumide almost completely reduced the increases of serum amylase activity and pancreatic wet weight, and caused histologic improvements of the cerulein-induced acute pancreatitis when given 30 min before the first cerulein injection. Loxiglumide was also effective in reducing the elevated serum amylase activity, pancreatic wet weight, and histologic alterations even when administered after the induction of acute pancreatitis. However, loxiglumide offered no apparent beneficial effects when given 30 min before and 3 h after the induction of acute pancreatitis by NaTc as determined by changes in serum amylase activity, pancreatic wet weight, and histology. These results do not necessarily suggest that CCK is not important in the pathogenesis of pancreatitis, but do suggest that the sole blockade of peripheral CCK receptors is ineffective against NaTc-induced severe necrotizing pancreatitis.

Acute Disease↗

Proglumide analogues CR 1409 and CR 1392 inhibit cholecystokinin-stimulated insulin release more potently than exocrine secretion from the isolated perfused rat pancreas.

The effects of proglumide-related cholecystokinin (CCK) receptor antagonists CR 1409 and CR 1392 on CCK-octapeptide (CCK-8)-stimulated immunoreactive insulin (IRI) release and exocrine secretion were examined simultaneously in the isolated perfused rat pancreas. The CR 1409, at concentrations of 10-100 nM, significantly inhibited CCK-8 (100 pM) stimulation on IRI release but failed to inhibit the stimulatory effect of CCK-8 on both pancreatic juice flow and protein secretion. Increasing concentrations of CR 1409 inhibited both CCK-8-stimulated IRI release and exocrine secretion. Half-maximal inhibition was observed with approximately 2 nM for IRI release and 1 microM for protein secretion. When a higher dose (1 nM) of CCK-8 was used, the inhibitory effect of 10 nM CR 1409 on CCK-8-stimulated IRI release was abolished, whereas 10 microM CR 1409 retained significant inhibitory effect. Furthermore, 1 microM carbachol-induced IRI release was not altered by the addition of 10 microM CR 1409. The CR 1392 also had an inhibitory effect on both CCK-8-stimulated IRI release and exocrine secretion. The concentration of CR 1392 that caused half-maximal inhibition of CCK-8-stimulated IRI release was 300 times lower than that of exocrine secretion. In addition, 1 microM carbachol-stimulated IRI release was not altered by 100 microM CR 1392. Thus, the inhibitory effects of CR 1409 and CR 1392 on IRI release were mediated through the interaction at the CCK receptor and were more potent than those on juice and protein secretion. This study suggests, therefore, that CCK receptors on B cells might be different from those on acinar cells in terms of their relative affinities for antagonists.

Animals↗

Action of a new cholinergic agonist, aclatonium napadisilate, on isolated rat pancreatic acini.

The effect of aclatonium napadisilate, a newly synthesized choline ester, on pancreatic exocrine function was compared with that of the muscarinic agonist carbamylcholine in isolated rat pancreatic acini. Both compounds increased amylase release and 45Ca2+ efflux in a dose-dependent fashion, and similarly decreased the binding of [N-methyl-3H]scopolamine to isolated rat pancreatic acini. While aclatonium napadisilate was 20-30 times less potent than carbamylcholine in stimulations of amylase release and 45Ca2+ efflux, the potency of aclatonium napadisilate in inhibiting [N-methyl-3H]scopolamine binding was nearly the same as that of carbamylcholine. These results indicate that aclatonium napadisilate stimulates pancreatic exocrine secretion via muscarinic receptors and Ca2+ mobilization, and its intrinsic activity is less than carbamylcholine in the isolated rat pancreatic acini. Since aclatonium napadisilate is known to increase motility and peristalsis of the gastrointestinal tract, stimulatory effects of aclatonium napadisilate, shown in the present study, on digestive enzyme secretion from the pancreas may provide additional benefit of aclatonium napadisilate in the treatment of various gastrointestinal disorders.

Acetylcholine↗

Nerve fiber analysis and the aging process of the vestibulocochlear nerve.

Nerve fiber analyses were performed on the human vestibulocochlear nerve stained with Luxol fast blue-periodic acid-Schiff-hematoxylin with use of a combination of an image-analyzer and a computer. The axons were counted and their transverse (cross-sectional) areas were measured in 12 individuals. The average numbers of axons in each vestibular and cochlear nerve were 17,727 and 25,098, and the average transverse areas of their axons were 4.02 and 1.79 microns 2, respectively. Amyloid bodies and intervening Schwann cells in the vestibulocochlear nerve were also counted. The average number of amyloid bodies was 246 per transverse section of the nerve and their average size was 114 microns 2. The average number of intervening Schwann cells was 1,513. Our results indicated that the transverse axonal areas of the cochlear nerve became reduced with age, while the transverse areas of the amyloid bodies in the vestibulocochlear nerve increased with age. The number of vestibular nerve fibers did not seem to change with age.

Adult↗

Physiochemical properties of phenobarbital solid dispersion with phosphatidylcholine.

We prepared a phenobarbital (PB) solid dispersion (SD) with phosphatidylcholine (PC). PB was present in an amorphous state in SD if its mole fraction was under 0.75. An infrared (IR) spectra study suggested a hydrogen bond between NH in PB and phosphate in PC, with a ratio of about 1:1. When the mole fraction of PB was less than 0.50, differential scanning calorimetry (DSC) curves showed endothermic peaks at 57, 90 and 145 degrees C, and an exothermic peak at 60 degrees C. The IR spectrum and X-ray diffraction pattern changed after holding at 70 degrees C, so at this point it is considered that the metastable state of SD changed into a stable state, and extra energy was released. When the mole fraction of PB was high, PB also arranged near hydrophobic group because an endothermic peak was observed at 46-52 degrees C, which was lower than fully hydrated PC. PB is similar to indomethacin (IM) in molecular shape and to phenytoin (PHT) in chemical structure. Its DSC curve and IR spectra are similar to PHT, and the limit ratio of its amorphous state is the same as IM. It is considered that the chemical structure is an important factor in its interaction to PC, and also, the molecular shape is important to arrange into PC lattice.

Calorimetry, Differential Scanning↗

Study on digestibility and energy availability of daily food intake in Japanese (Part 3. Cereals).

Four male Japanese were fed a semisynthetic diet including egg and soy powder as protein source for seven days (Basal-diet period), and in the following seven days 200 g of polished rice, wheat flour and buckwheat flour added at the expense of part of the corn starch and sugar in the basal diets (Test-diet period). Urine and feces were collected throughout both periods and the contents of nitrogen, fat and energy in these excreta were determined. Digestibility of protein (N), fat and carbohydrate (by difference) was calculated. The protein digestibilities of the polished rice (in the form of cooked grains), wheat flour (in the form of cooked powder) and buckwheat flour were 89.6 +/- 5.0%, 93.4 +/- 2.9% and 85.1 +/- 2.5%, respectively. The fat digestibilities of the polished rice, wheat flour and buckwheat flour were 93.6 +/- 1.8%, 70.8 +/- 13.5% and 103.1 +/- 8.4%, respectively showing relatively large variation (This results may be caused by an errors in measurement). The carbohydrate digestibility was close to 100%. The net energy availabilities of the polished rice, wheat flour and buckwheat flour were 100.6 +/- 1.4%, 96.5 +/- 1.1% and 96.0 +/- 1.1%, respectively.

Adult↗

[Quantitative analysis of glia in the facial and vestibulocochlear nerves].

Human normal vestibulocochlear and facial nerve trunks were cut off near the brain stem of the individuals who ages ranged from 24 to 93 years old. For this study, the discriminative staining method (Luxol fast blue--periodic acid-Shiff--hematoxylin triple stain) was adopted. It is admitted that the vestibulocochlear nerve medial to the internal auditory canal histologically resembles to the central nervous system in the rat. In order to confirm the fact in human, the intervening glial cells among nerve fibers were observed in the transverse section of vestibulocochlear and facial nerves. Schwann cells and microglia were observed among nerve fibers, but oligodendroglia. And the number of the glia was counted. The glial ratios related to the transverse nerve areas and the number of axons were calculated, and were examined in relation to aging. We found that there were more Schwann cells than microglia on both vestibulocochlear and facial nerves, facial nerve had more Schwann cells than vestibulocochlear nerve, and the number of Schwann cells per single myelinated fiber increased with age in the facial nerve. A quantitative study has not been included in the literature on the number of glia in the peripheral nervous system. Then, a quantitative study of human normal glial may be essential to elucidate pathogenesis regarding peripheral neuropathies, nerve injury or nerve sheath tumors as distinguished from the normal aging process.

Adult↗

Responses of pokeweed mitogen-stimulated peripheral mononuclear cells to human recombinant interleukins 3 and 4.

Peripheral blood mononuclear cells (PBMC) that had been stimulated with a polyclonal B cell activator, pokeweed mitogen (PWM), were examined for mitogenic responsiveness to interleukins (IL) and colony stimulating factors (CSF) or other cytokines using recombinant preparations from E. coli or Cos cells expressing their cloned cDNAs. PWM-stimulated PBMC (PWM-blasts) were found to be responsive to IL-3 depending upon the concentrations of the agent. Mitogenic response of PWM-blasts in the reaction to IL-3 was suppressed by the addition of a specific monoclonal antibody against IL-3 but not by anti-IL-2 serum, excluding the possibility that the DNA replication induced by IL-3 is a result of the proliferative response of IL-2 responder cells to IL-2, which might be produced during the culture of PWM-blasts in the presence of IL-3. The PWM-blasts were also responsive to IL-2 and IL-4 but not to other interleukins, namely, IL-1, IL-5 and IL-6, nor to granulocyte/macrophage (GM)-, granulocyte (G)- nor macrophage (M)-CSFs. They were also not responsive to interferon gamma. Similar responsiveness to IL-3 and IL-4 was found in the PBMC stimulated with a B-cell mitogen, Staphylococcus aureus Cowan 1 (Sac-1), but not in the PBMC stimulated with T cell mitogens, PHA or ConA. These results suggest that the human PBMC stimulated with B cell mitogens such as PWM or Sac-1 contain activated IL-3- and IL-4- responsive cells in sufficient number to detect these lymphokine activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Temperature-dependent pseudoleukocytopenia and in vitro studies on the underlying mechanism].

Spuriously low electronic white-cell count was obtained on EDTA-anticoagulated blood from a 54-year-old male suffering from liver cell carcinoma. In an attempt to understand better the phenomenon, in vitro studies were performed. The blood smear anticoagulated with EDTA revealed remarkable agglutinations of leukocytes, mainly neutrophils but not lymphocytes. The EDTA-treated blood showed maximal leukocytes-agglutinations at room temperature but no agglutination at 37 degrees C. The agglutinated leukocytes, moreover, were dispersed by incubating the blood at 37 degrees C. Although agglutination occurred in some degree in the blood anticoagulated with Na-heparin or Na3-citrate, it was much less pronounced compared to the EDTA-treated blood. Remarkable leukocytes-agglutinations were induced when EDTA-anticoagulated blood from healthy donor was mixed with serum from the patient at room temperature. These results suggest that the phenomenon of in vitro leukocyte agglutination and consequent pseudoleukocytopenia is due to leukocyte agglutinin in serum from the patient. The mechanisms were discussed comparing with pseudothrombocytopenia caused by platelet agglutinin.

Adolescent↗

[Tissue UFT distribution and histological changes following UFT administration in metastatic liver cancer cases].

For the purpose of assessing the anti-tumor effect of UFT in metastatic liver cancer, blood futraful (FT), 5-fluorouracil (5-FU) and uracil levels and their distribution in tissue (cancer lesion, etc.) following oral UFT administration were examined in 10 surgically treated cases of metastatic liver cancer secondary to cancer of the large intestine and 4 cases of metastatic liver cancer secondary to stomach cancer. Liver tissue 5-FU distribution following UFT treatment was excellent. 5-FU concentration in liver cancer lesion was 0.164 +/- 0.128 micrograms/g, which was markedly higher than the minimal effective tissue concentration for 5-FU (0.050 micrograms/g). 5-FU level in normal tissue of the organ with primary cancer was significantly lower than that in the tumor-affected tissue of the same organ, while no difference in 5-FU level was noted between cancer-affected and normal tissues of the liver. Tissue 5-FU level in both primary and metastatic cancer lesions was significantly higher than the simultaneously determined blood 5-FU level. Histological findings of cancer-affected liver did not differ between different UFT dose levels, but degeneration of cancer cells was severe in some cases given high doses of UFT.

Aged↗

[Application of the Ricketts analysis to children in the primary dentition. Fourth Report: development of lateral cephalogram analysis system and consideration of facial pattern].

A lateral cephalogram analysis system has been developed allowing an extended application of the Ricketts analysis to primary dentition. Using this system, we first examined the growth of facial patterns from the BA-NA ratio profilograms. As samples, we used records of children with normal occlusions stored at Nihon University School of Dentistry Department of Pedodontics. We then used the Fuzzy theory to change Vert's formula and obtained facial types. Lastly, we obtained compositional ratios of facial types within each age group. The results were as follows: 1) Facial patterns tended to show three divisions according to three age groups; from 3 to 5-year olds, from 6 to 7-year olds and from 8 to 10-year olds. 2) The Vert's values of the BA-NA ratio profilograms in each age group based on the data of 9-year olds tended to decrease as age increased. The change was mostly restricted to the range of Mesiofacial type. 3) As for the compositional ratio of facial types in each age group, a nearly normal distribution was observed mainly with the Mesiofacial type. 4) From the lateral cephalogram analysis system which has been developed and the profilograms of the average values for each age group which have been obtained by this system, we obtained the standard values for future evaluation of facial patterns of children with malocclusions.

Age Factors↗

[Immunohistological study on ras and myc oncogene products in pancreatic cancer].

Surgical treatment of the pancreatic cancer is currently unsatisfactory. By using anti-K,H,N-ras monoclonal and anti-myc polyclonal antibodies, paraffin-embedded tissue specimens of the carcinoma in digestive organs were immunohistologically studied. Then, the incidence of expression of these oncogenes and correlative studies of survival rate and disease stage of pancreatic cancer were analyzed. High incidence of expression of ras oncogene in the carcinoma of the pancreas and biliary tract was obtained. Frequency of expression of ras oncogene was correlated to disease stage and T factor for staging the carcinoma of the pancreas. Prognoses of 6 cases of pancreatic cancer without expression of ras oncogene were better than that of pancreatic cancer expressed ras oncogene.

Biliary Tract Neoplasms↗