Biomedical subjects
Publications and source records attributed to F Koizumi.
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We investigated the effect of plasmin on the release of sulfated glycosaminoglycans (GAG) from cultured vascular smooth muscle cells. Confluent cultures of vascular smooth muscle cells from bovine aorta were labelled with [35S]sulfate and incubated at 37 degrees C for principally 60 min in a serum-free medium in the presence of plasmin. Plasmin at 10 mU/ml (approximately 2.7 micrograms/ml) and above significantly increased the release of [35S]sulfate-labeled GAG (35S-GAG) from the cell layer after a 60 min incubation. A time course study showed that plasmin at 10 mU/ml significantly increased the 35S-GAG release after 20 min and longer. However, plasminogen at 100 mU/ml and below did not cause a significant change of the 35S-GAG release after a 90 min incubation. A characterization of 35S-GAG revealed that plasmin increased both dermatan sulfate and the other 35S-GAG in the medium. Plasmin at 100 mU/ml enhanced the cell detachment significantly but only slightly. From these results, it was suggested that a endogenous thrombin inhibitor heparin cofactor II may be activated in the liquid phase by dermatan sulfate released from plasmin-stimulated vascular smooth muscle cells when the vascular is disrupted and plasma is exposed to extravessel.
We investigated the effect of cadmium on the maintenance of the monolayer of vascular endothelial cells to clarify a possible involvement of endothelium injury in cadmium-induced vascular disorders. Endothelial cells from bovine aorta were cultured with cadmium chloride (0.5, 1.0, 2.0 or 5.0 microM) for 24 or 72 h. A histological observation revealed that a de-endothelialized space was formed in the monolayer by cadmium treatment; the number of endothelial cells was significantly decreased by the metal. Cadmium significantly decreased the number of growing endothelial cells with a significant decrease in the [3H]thymidine incorporation, suggesting that cadmium inhibited the cell proliferation. On the other hand, cadmium significantly increased the detachment of [3H]thymidine-labeled endothelial cells from the monolayer with a parallel increase in the lactate dehydrogenase activity in the medium. From these results, it was suggested that cadmium impairs the endothelial cell monolayer; the de-endothelialized space was formed by both an increase in the cell detachment by cadmium cytotoxicity and a retardation of the repair of the space which was due to an inhibition of the cell proliferation caused by the metal.
To investigate the reversibility of rhodamine B inhibition of cell proliferation, human lip fibroblast KD cells were cultured for 3 days in the presence of 25 or 50 micrograms/ml of the dye and the effect of removal of the dye from the culture medium on cell histology and on incorporation of [3H]thymidine into the acid-insoluble fraction of the cell layer was investigated. Removal of rhodamine B on the last 1 or 2 days resulted in an increase in cell number, and incorporation of [3H]thymidine was also restored after removal of the dye; [3H]thymidine incorporation by the cells treated with the dye for only the 1st day was the same as that by the control cells cultured without the dye. In conclusion, it was shown that the decrease in KD cell proliferation caused by rhodamine B can be reversed by removal of the dye.
To clarify a possible involvement of the vasoconstrictive peptide endothelin in the regulation of endothelial cell-mediated fibrinolytic system, confluent cultures of vascular endothelial cells from human umbilical vein were incubated in serum-free medium in the presence of endothelin-1 at 100 nM and below, and tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by enzyme immunoassay. Endothelin-1 at 1 nM and above significantly decreased the release of t-PA:Ag from the endothelial cells after a 24 h incubation. The t-PA:Ag release was also decreased by either endothelin-2 or endothelin-3 at 10 nM. The activity of lactate dehydrogenase in the medium was not changed by endothelin-1 at 100 nM and below, suggesting that the peptide did not cause nonspecific cell damage. The decrease in the t-PA:Ag release induced by endothelin-1 occurred in the presence or absence of 8-bromo cyclic AMP, which is an active congener of cyclic AMP; 3-isobutyl-1-methylxanthine, which is an inhibitor of phosphodiesterase; and forskolin, which is a stimulator of adenylate cyclase. These results strongly indicated that cyclic AMP which is known to down-regulate t-PA:Ag release was not involved in the endothelin-1 effect. However, endothelin-1 failed to decrease the t-PA:Ag release in the presence of either calcium ionophore A23187 or EGTA; the ionophore itself markedly decreased the release. The cytosolic calcium accumulation was significantly increased by endothelin-1. These results suggest that endothelin-1 decreases the release of t-PA:Ag from human endothelial cells through an excess accumulation of intracellular, especially cytosolic which would be mediated by an extracellular, calcium-dependent mechanism.
A 53-year-old male visited our hospital due to nasal obstruction persisting for 6 months and constant rhinorrhea. Pasteurella multocida subsp. multocida was isolated from his nasal discharge and lavage fluid of the maxillary sinus, and also from the oral cavity of the dog he kept. The bacterial strains isolated from the patient and dog were identical in terms of biochemical properties, and drug sensitivity. Although serotype was different, the strain from the patient showed (A:6) and that from his dog showed (A:5). The microorganism is not present in the general environment. The patient had contact with his dog such as he kissed it frequently, gave it food with his chopsticks et al.. From the mouth of the people who kiss one's dog, we detected Pasteurella of the same character of bacteria as from the mouth of the dog. We detected two Pasteurella multocida of different character from only one mouth of a cat. Pasteurella multocida was checked in only one colony for sero type. Sero type A is the popular type for dogs and cats. The above suggest that their was a high possibility that the Pasteurella multocida subsp. multocida found in the patient was from his dog. In Japan, the incidence of Pasteurella multocida subsp. multocida infection has been increasing. In 1969, the Japanese Ministry of Health and Welfare officially communicated this infection as a zoonosis to related institutions. At both medical and surgical departments, wither the patient keeps a pet should be confirmed during interview, and guidance of pet keeping methods is important in some cases from the aspect of clinical bacteriology.(ABSTRACT TRUNCATED AT 250 WORDS)
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The relationship between the molecular structure and insulin releasing action of glucagon remains unknown. In order to investigate the direct action of N-terminal peptides of glucagon, glucagon (1-14), and glucagon (1-21) were studied using an in situ local circulation of the canine pancreas. These glucagon fragments as well as glucagon (1-29) were infused into the superior pancreaticoduodenal artery in a dose of 400 pmol for 10 min during the glucose or arginine infusion, and plasma insulin and glucagon in the superior pancreaticoduodenal vein were determined by radioimmunoassay. During the glucose infusion, glucagon (1-14) elicited a slight increase in plasma insulin, whereas glucagon (1-21) and (1-29) revealed significant changes in plasma insulin. In these experiments plasma glucagon did not change significantly following the administration of glucagon (1-14) or (1-21). During the arginine infusion all of the glucagon fragments studied enhanced insulin secretion markedly, whereas glucagon secretion was not affected. Furthermore, graded doses of glucagon (1-14) (50, 150, and 400 pmol) elicited an increase in plasma insulin in a dose-related manner. It is concluded from the present study that the N-terminal peptides of glucagon stimulate insulin release especially during the arginine infusion.
Controversy persists concerning the pathogenesis of dural arteriovenous malformations (AVM's) and whether they are congenital or acquired. Furthermore, it remains undetermined whether the lesion is located in the sinus itself or within the sinus wall. In order to elucidate the pathogenesis of dural AVM's of the lateral and sigmoid sinuses, histopathological profiles of this disease were studied in serial sections of completely resected lesions from three patients. The essential lesion was histologically confirmed to be a dural arteriovenous fistula within the wall of the venous sinuses. The etiology process of this disease and its progression were evaluated.
Comparative studies in the evaluation of criteria for clinicopathological diagnosis of AGA which was proposed by Japanese Health and Welfare Ministry (JHWM) in 1988 and American College of Rheumatology (ACR) in 1990 were conducted. Twenty seven Japanese patients with AGA and 231 Japanese controlled patients with polyarteritis nodosa (PAN) and Wegener's granulomatosis (WG) were used as material patients who had been provided a second questionnaire in 1984 sponsored by the JHWM. As a result, the JHWM criteria was 85.2% in sensitivity and 96.5% in specificity, which was superior to the ACR criteria being 74.1% in sensitivity and 93.9% in specificity. These results were due to the low sensitivity and low accuracy in paranasal sinus abnormality and pulmonary infiltrates which were included in the ACR criteria. Furthermore, the JHWM criteria could be diagnosed as AGA using not only the histopathological findings but by the clinical symptoms alone. The controlled patients who were overdiagnosed as AGA using ACR criteria were thought to be included as patients with WG. On the other hand, the controlled patients who were overdiagnosed as AGA using JHWM criteria were thought to be included as patients with overlap syndrome of AGA and PAN. Accuracy of polyneuropathy, muscle weakness, melena and pretibial edema were over 60%, indicating that these clinical symptoms were available for vasculitis symptoms of the JHWM criteria.
The following study was conducted in order to investigate the effect of drug therapy on the relapse of peptic ulcers. Acute therapy with pirenzepine (Gastrozepin, CAS 28797-61-7) (100 mg/d) or cimetidine (CAS 51481-61-9) (800 mg/d) was given to 402 patients with peptic ulcers using the envelope method. Subsequently, 1-year maintenance therapy with pirenzepine (75 mg/d) or placebo was carried out in a double-blind study in 251 patients who had been cured within 3 months. During the study period, an endoscopic examination was repeated regularly to study the relapse of ulcers. When the results were stratified and analyzed by Cutler-Ederer's life table method to see changes in relapse over time, it was noted that the acute therapy for active ulcers did have an influence on the course of relapse after the ulcer lesions had been cured. Pirenzepine, a M1 antagonist, was superior to cimetidine, a H2 antagonist, in the prevention of relapse of ulcers after they had been cured. The results suggest that the prevention of relapse of peptic ulcers should be started at the stage of acute therapy for active ulcers and that care should be taken in selecting drugs. The results also suggest that the natural history of peptic ulcers with respect to their relapse can be modified to a certain extent by drug therapy although the period for such cannot be specified.
One-year maintenance therapy with pirenzepine (Gastrozepin, CAS 28797-61-7) (75 mg/d) or placebo was performed in a double-blind fashion in 251 patients to investigate the relapse by means of endoscopic examinations repeated every 3 months. Enrolled were the patients who had been cured within 3 months by acute therapy with either pirenzepine or cimetidine randomly given by the envelope method. When the results were analyzed by Cutler-Ederer's life table method to monitor manifestation of relapse, the maintenance therapy with pirenzepine did not show any significant difference from placebo in all the patients enrolled. However, stratified analysis according to various combinations of background factors revealed that there was significant difference in 1-year cumulative non-relapse rates between the pirenzepine maintenance therapy group and the placebo group, suggesting prophylactic effect of the maintenance therapy with pirenzepine on relapse. An increase of daily dose more than 75 mg in maintenance therapy may be expected to display the prophylactic effect of pirenzepine on ulcer relapse in a definite manner.
Four hundred and two patients with peptic ulcer were selected for acute therapy with either pirenzepine (100 mg/day) or cimetidine (800 mg/day) using the envelope method. Those who achieved healing within 3 months (251 patients) were randomized in a double-blind fashion to maintenance therapy with either pirenzepine (75 mg/day) or placebo. In a preliminary study of 163 patients in which a multiple regression life-table method was employed, 4 out of 15 possible predictors were found to have a significant influence on relapse. These were site of ulcer lesions, psychological stress, endoscopic findings at the time of healing of the original ulcers, and acute therapy. Stratified analysis of the evolution of relapse by the Cutler-Ederer life-table method indicated that several other factors also influenced relapse in certain patient subgroups. Most relapses (93.8%) occurred at the same site as, or close to the site of, the original ulcers, indicating that ulcer scars also play a role in relapse.
In a total of 194 cases, consisting of 86 cases of colorectal cancer undergone operation later, 7 cases of non resectable cancer, 34 cases of recurrence, 43 cases of NED (no evidence of a recurrence after radical surgery for colorectal cancer) and 24 cases of benign colorectal disease, serum CEA, TPA, CA50 and CA72-4 levels were determined. The positivity rate was high for all four markers in stage V cases among 86 cases of colorectal cancer, and in cases of non resectable cancer and cases of recurrence. The highest positive rate was obtained with CEA. On the contrary, in cases of stage I to IV the positivity rates of these four tumor markers were as low as 0 to 34.8%. Out of 127 cases of colorectal cancer excluded of 43 NED cases, 52 cases were negative for all four tumor markers and 14 cases were positive only for CEA. In 49 cases, CEA and at least one of the other three tumor markers gave positive results. In 12 cases, CEA gave negative results and at least one of the other three tumor markers positive results. In conclusion, measurement of blood levels of these tumor markers is limited of its usefulness in early diagnosis of colorectal cancer. However, in the diagnosis of advanced stage and of recurrence during the postoperative follow-up period the measurement of tumor markers provides useful information. CEA is most sensitive among the four tumor markers tested and any combination of these four markers is not advantageous because of an increase in false positivity rate.
Rat cytokine-induced neutrophil chemoattractant (CINC) is a member of the IL-8 family and its human counterpart is MGSA/gro. Rat neutrophil responses in vitro to rat CINC, human IL-8, and human MGSA/gro were studied. CINC concentrations as low as 1 nM induced apparent chemotaxis of rat neutrophils, but human IL-8 and MGSA/gro required concentrations one or two orders higher than that of CINC to attract neutrophils. These data indicate that human IL-8 and MGSA/gro cannot sufficiently substitute for rat counterparts such as CINC in rats. Therefore, the effect of rat CINC on rats was studied. Intradermally injected 10(-10)-10(-7) M CINC dose-dependently caused infiltration of neutrophils. Significant migration of neutrophils appeared by 30 min, and maximum infiltration was observed around 1-2 hr after the injection. CINC induced quick and transient neutrophil accumulation without lymphocyte and monocyte migration or edema formation. CINC, a member of the IL-8 family but a counterpart of human MGSA/gro-related proteins, is a specific neutrophil chemoattractant and can be distinguished from IL-8, which is a chemotactic factor for lymphocytes and neutrophils.
The effect of the cosmetic dye rhodamine B on the proliferation of human lip fibroblasts (KD cells) was investigated in a culture system. Rhodamine B at 25 micrograms/ml and above significantly decreased the number of the cells after a 72 h culture. A time course study revealed that 50 micrograms/ml of rhodamine B-induced decrease in the cell number occurred after 48 h and longer, suggesting that the dye inhibited cell proliferation without a decrease in cell attachment. The detachment of [3H]thymidine-labeled cells from the monolayer was unaffected by rhodamine B at 100 micrograms/ml and below. The incorporation of [3H]thymidine and [14C]leucine into the acid-insoluble fraction of the cell layer was significantly inhibited by 50 micrograms/ml rhodamine B treatment. Histologically, the damage of KD cells was not marked, however, a degenerative change of nuclei and an irregular shape of the cells as well as a decrease in the cell number were caused by 50 micrograms/ml rhodamine B. Rhodamine 6G caused a severe damage of the cells, and rhodamine B significantly decreased the cell number; rhodamine 123 had no significant effect; rhodamine 116 significantly increased the cell number. Furthermore, rhodamine B decreased the number of both vascular endothelial cells from bovine aorta and vascular smooth muscle cells from murine aorta after a 72 h culture. It is concluded that rhodamine B inhibits the proliferation of human lip fibroblasts. This rhodamine B effect may be a warning sign for the dye toxicity.
In order to clarify the relationship between the structure and function of glucagon-like peptide (GLP) 1 in the endocrine function of the pancreas, the response of insulin and glucagon to various synthetic GLP-1-related peptides was investigated in anesthetized dogs. GLP-1-related peptides were administered in a dosage of 400 pmol within 10 min into the pancreatic artery during glucose or arginine infusion and the changes in plasma insulin and glucagon in the pancreatic vein were studied. GLP-1 (7-36) and (7-37), as well as glucagon enhanced insulin release during glucose infusion, whereas neither GLP-1 (1-37), (7-20), (6-37) nor (8-37) stimulated insulin release. The administration of GLP-1 (1-37), (7-36) and (7-37) reduced glucagon release during glucose infusion. When arginine was infused, GLP-1 (7-20), (7-36), (7-37), and glucagon enhanced insulin release. In contrast, glucagon release was increased by the administration of GLP-1 (7-20), (8-37), and (7-37). The present study indicates that histidine at the 7th position of GLP-1 is important in eliciting biological action and that only truncated GLP-1 (7-36), (7-37), and (7-20) showed an insulinotropic action as strong as glucagon in dogs. Furthermore, it is suggested that the response of insulin and glucagon to GLP-1-related peptides is dependent on a background condition.
2'-Deoxypuromycin (2) was synthesized to learn the effect of the 2'-hydroxyl group on the biological activity. Acylated xylose 3 was condensed with silylated 6-chloropurine to give beta-D-xylofuranosyl-6-chloropurine derivative 4, whose 6-dimethylamination, 2'-deoxygenation and deprotection afforded 2'-deoxy-beta-D-xylofuranosyl purine analog 7. The latter was converted to 2'-deoxypuromycin (2) in 8 steps. 2'-Deoxy analog 2 showed only weak antimicrobial activity compared with that of puromycin (1).