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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 667 records · Page 37Linked to original sources

Increased production of tumor necrosis factor and prostaglandin E2 by monocytes in cancer patients and its unique modulation by their plasma.

We investigated the role of monocytes in the production of tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) in 77 cancer patients with malignancies of the digestive tract, using 30 normal individuals and 18 noncancer patients as controls. Monocytes were incubated with lipopolysaccharide for 20 h, and TNF production and PGE2 production were analyzed by bioassays. Elevated levels of TNF (greater than 512 U/ml) and PGE2 (greater than 8 ng/ml) production were demonstrated in many cancer patients when these factors were induced in the medium with 10% fetal bovine serum. The elevated level of TNF was seen to be restricted for the most part to patients with malignancies. Thus, 51 out of 59 cancer patients (86%), consisting of 44 primary cancer patients and 15 recurrent cancer patients, showed an increased level of TNF. In contrast, almost all of 18 postoperative cancer patients showed TNF levels comparable to those of normal individuals. Furthermore, 16 primary cancer patients were also demonstrated to have reduced levels of TNF production by monocytes after curative operation. When 10% cancer-patient plasma was added to the induction culture, TNF production by monocytes was drastically suppressed in the cancer patients. Interestingly, the same addition of plasma induced a prominent enhancement of PGE2 production in the cancer patients. The plasma of noncancer patients did not modulate production of these factors. No TNF activity was found in the plasma of cancer patients, but such plasma did contain an increased level of PGE2 (100-300 pg/ml). Although PGE2 (greater than 2 ng/ml) was able to suppress TNF production by monocytes, the addition of 10% plasma PGE2 was not enough to induce suppression. An unknown factor(s) in the plasma of cancer patients may uniquely modulate the elevated TNF and PGE2 production in these patients.

Adolescent↗

Brain abscess with hemorrhage.

A very rare case of brain abscess with hemorrhage in the basal ganglia is reported. We discuss the difficulties in the differential diagnosis and the mechanism of hemorrhage.

Adult↗

Inhibitory effects of pirenzepine on cholecystokinin and secretin stimulation on exocrine and endocrine rat pancreas.

Effects of pirenzepine, a newly developed anticholinergic drug, on exocrine and endocrine pancreatic functions stimulated by cholecystokinin octapeptide and secretin were studied in both isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, pirenzepine did not have any significant effect on cholecystokinin-induced amylase release but caused an inhibition of amylase secretion initiated by secretin and shifted the dose-response curve for amylase secretion to the right. In the isolated perfused pancreas stimulated with 100 pM cholecystokinin octapeptide, addition of 10 microM pirenzepine before as well as after 20 min of perfusion significantly inhibited pancreatic juice flow but not enzyme output. In contrast, pirenzepine caused an inhibition of secretin-stimulated enzyme secretion, but not pancreatic juice flow. The stimulatory effect of both cholecystokinin octapeptide and secretin on insulin secretion was also inhibited by pirenzepine. The present data indicate that pirenzepine may have an influence on pancreatic exocrine and endocrine function by inhibiting endogenous cholinergic activity of the pancreas when a large dose is given.

Amylases↗

Effects of chronic renal failure on the regulation of pyruvate kinase.

The effects of chronic renal failure on the enzyme activity of pyruvate kinase and the mRNA level of this enzyme were studied in 7 out of 8 nephrectomized rats. The mRNA level was measured by RNA-DNA dot blot hybridization, using cloned pyruvate kinase cDNA as hybridized probe. Neither the activity of M1-type pyruvate kinase nor the level of this enzyme in rat gastrocnemius muscle was affected by chronic renal failure, whereas L-type pyruvate kinase enzyme activity in uremic rat liver was lower than that in control at both fasted and refed states. The levels of L-type pyruvate kinase mRNA were not different between two groups at the fasted state. Induction of L-type pyruvate kinase mRNA after high carbohydrate diet refeeding was suppressed proportionally to the severity of chronic renal failure, which was expressed by the serum creatinine concentrations (r = -.876, P less than .005). These results indicate that the suppression of L-type pyruvate kinase activity in uremia was partly reflected by the decreased accumulation of this enzyme mRNA. There was a significantly negative correlation between L-type pyruvate kinase mRNA levels and plasma glucagon/insulin ratios (r = -.719, P less than .05). Hyperglucagonemia in uremia might play a major role in this suppression.

Animals↗

Determination of an immunosuppressive substance in serum by latex particle electrophoresis.

The level of immunosuppressive substance (IS), which increases in the serum of patients with cancer, was determined by an assay based on particle electrophoresis. Polystyrene latex particles (PLP) were coated with IS, which was extracted from the ascitic fluid of patients with cancer. The IS was a glycoprotein with a molecular weight of about 52,000, and an isoelectric point in the range pH 2.7-3.3. When the IS on the surface of the PLP reacted with the anti-IS antibody, the mean electrophoretic mobility of the PLP changed from -3.16 to +0.21 micron.s-1.V-1.cm in the medium of pH 7.2 and ionic strength I = 0.0154. After preincubation of anti-IS antiserum and tested serum, the PLP coated with IS were added to this solution. It was incubated again and then the surface charge of the PLP was measured by an automatic cell-electrophoretic instrument. This method was used to determine the IS concentration in the serum of cancer patients and pregnant women. When compared to healthy controls, the serum IS level was significantly higher in patients with cancer, and lower in pregnant women. The assay based on latex-particle electrophoresis proved to be a sensitive and rapid method for determining the IS level in serum.

Electrophoresis↗

Tumor growth promoting activity of an immunosuppressive substance and its modulation by protein-bound polysaccharide PSK.

The role of an immunosuppressive substance (IS), which is increased in the serum of tumor-bearing animals, was examined in rats. IS isolated from cancerous ascites fluid of rats was administered to Walker 256 tumor-bearing rats to examine changes in the serum level of IS, tumor growth and survival rate. PSK, an immunomodulator, was also administered. Serum IS increased with tumor growth. The administration of IS to tumor-transplanted rats caused the tumor to grow and shortened the animals' survival time. The administration of PSK, however, inhibited the increase in serum level of IS, resulting in the suppression of tumor growth and a prolongation of survival time. The findings suggested that IS is a useful parameter for predicting not only tumor growth but also the therapeutic effect of immunomodulators such as PSK.

Adjuvants, Immunologic↗

Changes in proton T1 in dog brains due to the administration of haloperidol.

Changes in proton T1 in dog brains due to the administration of haloperidol were determined by the intravenous administration of a single dose of 20 mg of haloperidol to mongrel dogs. The MRI used was the Aberdeen type with the static magnetic field of 0.1 T. A coil made exclusively for these animals (bore diameter 120 mm) was used. There was a significant increase in the T1 value in the striate body 30 minutes and more (within two hours) after the administration of haloperidol. Subtraction images were also obtained by subtracting the image of the pre-treatment (control) T1 values from the image of the post-treatment values (2 hours after the injection). The subtraction images also revealed increases in the T1 values of the striate body.

Animals↗

Purification and characterization of immunosuppressive (IS) substance obtained from ascitic fluids of patients with gastrointestinal cancer.

An immunosuppressive substance was isolated from ascitic fluids of patients with advanced colon cancer by means of ammonium sulphate precipitation and preparative isoelectric focusing. This was a glycoprotein with an isoelectric point of pH 2.7-3.3, a molecular weight of about 52,000, and a sedimentation coefficient of 4.0S. The substance showed a single band on ordinary disc electrophoresis, but it was separated into several bands by gel isoelectric focusing, due to the structural variety of the sugar moiety. The results of physicochemical analysis indicate that the amino acid composition of this glycoprotein was indistinguishable from that of alpha 1-acid glycoprotein (alpha 1-AG), but its molecular weight, its carbohydrate content, and composition were distinctly different. Furthermore, this glycoprotein was found to have higher immunosuppressive activity than that of alpha 1-AG in both the in vitro and in vivo assays. This glycoprotein, which we called "IS substance," is a cancer-related substance synthesized in cancer patients.

Amino Acids↗

Actions of neuromedin-B and neuromedin-C on amylase release from isolated rat pancreatic acini.

Neuromedin-B and neuromedin-C are novel decapeptides which have recently been isolated from porcine spinal cord and canine intestinal muscle, and show striking sequence homology with gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin-B and neuromedin-C on exocrine pancreatic function were examined using isolated rat pancreatic acini. Neuromedin-B and neuromedin-C were able to cause full stimulation of amylase release. The relative efficacy of neuromedin-B and neuromedin-C was the same as that of GRP-27. Neuromedin-C was about twofold more potent, whereas, neuromedin-B was about 10-fold less potent than GRP-27. Both neuromedin-B and neuromedin-C potentiated the stimulation of amylase release caused by vasoactive intestinal peptide, secretin, or forskolin. Potentiation of amylase secretion did not occur with neuromedin-B or neuromedin-C plus cholecystokinin (CCK), carbamylcholine, or Ca2+ ionophore A23187. The effects of neuromedin-B and neuromedin-C on enzyme secretion were inhibited neither by dibutyryl cyclic GMP, nor atropine. The present study suggests that neuromedin-B and neuromedin-C act on different receptors than CCK and cholinergic agents, but appear to activate a common intracellular mechanism.

Amylases↗

Prevalence of panic disorder and other subtypes of anxiety disorder and their background.

Two hundred and forty-four patients with various subtypes of DSM-III anxiety disorder were found among 3,059 outpatients who visited our clinic consecutively for evaluation for five years. They included 53 patients with panic disorder comprising an outstanding number of patients, about a quarter of patients with anxiety disorder and 1.7% of the whole outpatient population, and 78 with generalized anxiety disorder. Differentiation between these two groups was difficult to make besides their specific clinical features whether the patient had panic attacks or chronic generalized anxiety. The patients with anxiety disorder were divided into two major groups--panic-generalized anxiety-simple phobia and social phobia-obsessive compulsive-agoraphobia--in respect to their age of onset of the illness, the duration of episode, separation from their parents, psychosocial stressors and response to pharmacotherapy. Social phobia and obsessive compulsive disorder comprised those patients with similar qualities to each other in terms of their demographic data and their social backgrounds, forming a distinct group apparently different from the panic-generalized anxiety group. They consisted predominantly of young male patients with an earlier onset of the illness, less separation experienced and a longer duration of the episode, while without meaningful psychosocial stressors preceding the present episode. These findings indicate that the prevalence of panic disorder in the Japanese population is as high as previously reported, although its discriminant factors from generalized anxiety disorder are ambiguous except for panic attacks.

Adolescent↗

Effects of neuromedin B and neuromedin C on exocrine and endocrine rat pancreas.

Neuromedin B and neuromedin C are novel decapeptides that have recently been isolated from porcine spinal cord and canine intestinal mucosa and show striking sequence homology with bombesin and gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin B and C on exocrine pancreatic function and insulin release have been compared with bombesin and GRP-27 in isolated pancreatic acini and isolated perfused pancreas in rat. Neuromedin B and C as well as bombesin and GRP-27 were able to cause stimulation of amylase release. The relative efficacy of neuromedin B, C, bombesin, and GRP-27 was the same as that of cholecystokinin octapeptide (CCK-8). Bombesin and GRP-27 were equipotent, and both were approximately 15-fold less potent than CCK-8. Neuromedin C was approximately 2-fold more potent, whereas neuromedin B as approximately 10-fold less potent than bombesin and GRP-27. All of these peptides stimulated insulin release that was limited to the first 3 min of a 20-min perfusion. However, GRP-27 and its related peptides were weak stimulants of insulin release compared with their abilities to stimulate exocrine pancreatic secretion. Bombesin and neuromedin B id not stimulate insulin release at doses stimulating pancreatic exocrine secretion. Neuromedin B was also approximately 10-fold less potent than neuromedin C, bombesin, and GRP-27 in eliciting insulin secretion. Because bombesin-like immunoreactivity is found to be present in nerves in the pancreas, neuromedin B and C may be neurotransmitters or neuromodulators and exert a direct local neurocrine action on enzyme secretion by acinar cells and insulin secretion by the islets.

Amylases↗

Suppressing effect of croton oil on intestinal carcinogenesis induced by methylazoxymethanol acetate in rats.

The effect of croton oil on intestinal carcinogenesis by methylazoxymethanol acetate (MAM) was examined in ACI/N rats. Twenty seven male and 28 female ACI/N rats were given a single intragastric intubation of MAM at a dose of 25 mg/kg body weight, followed by croton oil at 0.25 ml/kg body weight, 3 times a week, by gastric intubation until the termination of this experiment (365 days). The animals had diarrhea with administration of the croton oil, but the diarrhea had no effect on their gain in weight. Rats from all groups surviving more than 216 days were counted as effective animals. Seventeen out of 54 effective rats which were treated with MAM and croton oil developed intestinal tumors and the incidence of the intestinal tumors was significantly less than that of the group treated with MAM alone (30 out of 50 rats, P less than 0.01). The average number of tumors per rat in the experimental group which was treated with MAM and croton oil (0.6 +/- 1.1) was also smaller than that in the group which was treated with MAM alone (1.0 +/- 1.8), although the difference was not significant. These results suggest that croton oil may suppress some tumor growth at the proper dose in intestinal carcinogenesis which is initiated by MAM.

Adenoma↗

[Multimodality treatment of nasopharyngeal carcinoma].

In the treatment of nasopharyngeal carcinoma (NPC), radiation has been the treatment of choice, because it is effective for locoregional disease. However, the results of radiotherapy for NPC have revealed that local relapse and/or distant metastases occur frequently, and consequently the five-year survival rate is as low as around 30%. Since 1982, we have adopted chemotherapy initially applied prior to radiotherapy (= pre-radiation chemotherapy) for the treatment of NPC in order to achieve better results. The chemotherapy mainly consists of a combination of cisplatin and peplomycin. Twenty-one previously untreated patients with NPC were evaluable. Three complete and fifteen partial remissions were achieved, with an 86% response rate to the chemotherapy. The treatment involving a combination of pre-radiation chemotherapy and radiotherapy resulted in local relapse in one patient and distant metastases in two patients with an 87.5% survival rate according to the Kaplan-Meier method. Immunotherapy is also indispensable in the treatment of NPC. Our present multimodality treatment for NPC consists of a combination of pre-radiation chemotherapy and radiotherapy followed by long-term administration of a biologics such as OK-432.

Adolescent↗

[Multidisciplinary treatment of carcinoma of the oropharynx].

From 1963 through 1986, we examined 91 patients with carcinoma of the oropharynx. Of these 91 patients, the primary treatment modality was chosen for 75 patients. The patients were divided into 2 groups according to the periods of treatment. In group I (1963-1973), 33% of the patients were applied combined radiotherapy and chemotherapy, and 28% chemotherapy followed by surgery as their initial treatment. In group II (1974-1986), 65% of the patients were applied combined radiotherapy and chemotherapy, and 21% a multimodal treatment consisting of radiotherapy combined with chemotherapy followed by composite resection. Five-year survival rate was 36% in group I and 51% in group II, which indicated a progress in the treatment of carcinoma of the oropharynx. The role of surgical treatment for carcinoma of the oropharynx was discussed. It appears that composite resection and reconstructive surgery produced a great benefit in the treatment of residual diseases after radiotherapy or recurrent diseases. Then our new treatment modality incorporating neo-adjuvant chemotherapy was presented. The literatures in terms of neo-adjuvant chemotherapy were reviewed.

Adult↗

Increased activity of oligo-2',5'-adenylate synthetase in Down's syndrome and epilepsy.

The level of oligo-2',5'-adenylate synthetase activity is a good marker for the response of cells to interferon. This enzyme can polymerize ATP to form oligonucleotides in the presence of double-stranded RNA, i.e. polyinosinate-cytidylate in vitro. The activity of this enzyme in peripheral blood mononuclear leucocytes was significantly increased in Down's syndrome (P less than 0.01) and epilepsy (P less than 0.01) compared with that in healthy controls, but the increase of activity was not significant in multi-infarct dementia (MID) (P greater than 0.05). Although the patients with Down's syndrome showed higher levels of this enzyme activity than the controls, interferon activity was never detected in the circulation. In addition, the serum of patients with Down's syndrome lacked the capacity to induce this enzyme in NC-37 and FL cells, and furthermore it was shown that the inhibitor of interferon activity was not found in the serum of patients. This discrepancy in Down's syndrome may be the result of the hypersensitivity of cells to interferon. On the contrary, interferon activity (32 IU/ml) was detectable in the circulation of one patient with epilepsy, and the serum of this patient had the capacity to induce this enzyme in NC-37 and FL cells.

2',5'-Oligoadenylate Synthetase↗