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Biomedical subjects

F Koizumi

Publications and source records attributed to F Koizumi.

At least 73 records · Page 4Linked to original sources

Etiological evaluation of dural arteriovenous malformations of the lateral and sigmoid sinuses based on histopathological examinations.

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.

Adult↗

[Studies on criteria for clinicopathological diagnosis of allergic granulomatous angiitis (AGA)].

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.

Churg-Strauss Syndrome↗

Effect of drug therapy on the relapse of peptic ulcers. 1st communication: the effect of acute therapy.

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.

Cimetidine↗

Effect of drug therapy on the relapse of peptic ulcers. 2nd communication: the effect of maintenance therapy.

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.

Cimetidine↗

Predictors of relapse in peptic ulcer.

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.

Adult↗

[Clinical evaluation of four tumor markers (CEA, TPA, CA50 and CA72-4) in colorectal cancer].

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.

Adult↗

Rat CINC, a member of the interleukin-8 family, is a neutrophil-specific chemoattractant in vivo.

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.

Animals↗

Inhibitory effect of rhodamine B on the proliferation of human lip fibroblasts in culture.

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.

Cell Division↗

Interaction between cadmium and copper on ossification of embryonic chick bone in tissue culture.

To investigate the interaction between cadmium and copper in ossification, femurs from 9-day-old chick embryos were cultured for 6 days in the presence of 2 microM cadmium and/or 1 microM copper. It was found that cadmium + copper treatment caused interactively severe damage to osteogenic mesenchymal cells in the periosteum and a severe degenerative change in osteoblasts around the trabecula, resulting in severe impairment of ossification in the diaphysis. Cadmium content was increased by copper; however, copper content was unaffected by cadmium in the diaphysis. It was therefore considered that the copper-induced increase in cadmium content was a primary factor in the interactive toxic effect of the cadmium + copper treatment in ossification.

Animals↗

The structure-function relationship of GLP-1 related peptides in the endocrine function of the canine pancreas.

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.

Animals↗

[Cancer detection and prevention].

Studies were performed on cancer detection and prevention in the high cancer risk group. To improve the screening method in the diagnosis of unspecified cancer, a modified combination assay was devised using a combination of several tumor markers and adding risk factors of malignancies obtainable from blood samples. Five tumor markers, AFP, CEA, CA 19-9, DUPAN-2 and CA 125 were determined simultaneously in each serum sample obtained from 54 patients with various cancer diseases. A modified combination assay was also examined using the risk factors of malignancies, pepsinogen I/II ratio together with 5 tumor markers. Detection rate was elevated to 68.5% by a combination assay using 5 tumor markers. Detection rate by modified combination assay using the risk factor (pepsinogen I/II ratio) together with 5 tumor markers was further improved to 88.8% without decreasing the specificity. The modified combination assay is easy in practice and expected to contribute in the screening of unspecified cancer diseases.

Aged↗

A suitable culture medium for ossification of embryonic chick femur in organ culture.

To establish a culture medium which allows ossification in organ culture, 9-day-old embryonic chick femurs were cultured in variously supplemented BGJb-HW2 media. Changes of Ca and Pi concentrations in the BGJb-HW2 medium or the 10% addition of chick embryo extract (CEE) did not induce ossification. Furthermore, combinations of the 10% CEE with a high Ca x Pi product or with 5 mM beta-glycerophosphate (beta-GP) or with 10% horse serum plus a high Ca x Pi product often caused pathological abnormalities in the periosteum. On the other hand, BGJb-HW2 medium supplemented with 5 mM beta-GP induced development of ossification. The Ca content of femurs and the diaphysial hydroxyproline content were markedly increased. Histological observation showed a formation of a thick and active periosteum, numerous osteoblastic cells, a sufficient amount of osteoid tissue and well developed calcified trabeculae without any pathological changes. Thus, the organ culture system using this medium was considered to be an appropriate one for studies on osteogenesis in vitro.

Animals↗

Role of autonomic nervous system in the response of plasma pancreatic polypeptide to glycopenia in dogs.

The effect of cholinergic and adrenergic influences on pancreatic polypeptide (PP) release was studied in dogs. Administration of acetylcholine resulted in an elevation of plasma PP, whereas epinephrine induced no increase. Insulin-induced hypoglycemia increased plasma PP in a conscious state but not in anesthetized dogs. The infusion of phentolamine or propranolol did not affect the response of plasma PP to insulin-induced hypoglycemia, whereas atropine markedly inhibited the increase in plasma PP. Likewise, atropine reduced the rise of plasma PP during the intravenous administration of 2-deoxy-D-glucose (2-DG). We conclude from the present experiments that cholinergic mechanisms are of major importance in the response of PP to insulin- and 2-DG-induced glucoprivation, while the major role of the adrenergic mechanism was not proved.

Acetylcholine↗

Synthesis and antimicrobial activity of 2'-deoxypuromycin.

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).

Anti-Bacterial Agents↗

[The field of endocrinology-gastrointestinal hormones: radioimmunoassay and regulation of plasma levels].

Radioimmunoassay is still by far the most reliable tool for the measurement of plasma gastrointestinal hormones. However, various factors in plasma, without proper control, can give rise to erroneous results in radioimmunoassay. It contains 1) proteolytic enzymes which degradation the peptide 2) plasma nonspecific interference 3) cross reaction of various peptides of similar structure 4) molecular species which the antibody recognizes, and so on. We reviewed the mechanism of increase in plasma levels of pancreatic polypeptide (PP) measured by radioimmunoassay. Its secretion in the basal state as well as after meals in normal humans and dogs is governed mainly by vagal cholinergic mechanism. However, bile acid and other gastrointestinal hormones (Insulin and CCK) play a part in the postprandial PP response in experimentally induced diabetic and total biliary diversion dogs. The production of hydrochloric acid or secretin is not requisite for plasma PP response to an ingested meal.

Animals↗

Response of gut glucagon-like immunoreactivity to hypoglycemia in dogs.

Previous studies demonstrated that insulin-induced hypoglycemia enhances glicentin secretion in piglets and prompted us to investigate the response of glucagon-like immunoreactivity (GLI) to hypoglycemia in dogs. Insulin hypoglycemia did not induce any rise of plasma total immunoreactive glucagon (IRG) measured by nonspecific antiserum to glucagon in normal or pancreatectomized dogs under anesthesia. In contrast, insulin-induced hypoglycemia clearly increased plasma total IRG in both normal and pancreatectomized dogs in a conscious state. Administration of acetylcholine resulted in an elevation of plasma total IRG, whereas epinephrine induced a slight increase in plasma total IRG. The infusion of alpha- or beta-adrenergic blockers did not affect the response of plasma total IRG to hypoglycemia, whereas atropine completely blunted the increase in plasma total IRG during insulin hypoglycemia. Similarly atropine abolished the rise of plasma total IRG during intravenous administration of 2-deoxy-D-glucose. It is concluded that hypoglycemia clearly enhances the secretion of GLI from the gut in dogs and that GLI secretion during hypoglycemia is modulated, at least in part, by the autonomic nervous system.

Acetylcholine↗

Effect of porcine pancreastatin on endocrine function of canine pancreas.

Controversial results concerning the modulation of insulin release with pancreastatin prompted us to investigate the effect of this peptide upon the endocrine function of the pancreas using an in situ perfusion method in dogs. Administration of porcine pancreastatin into the pancreaticoduodenal artery in a dosage of 0.34 micrograms/kg of body weight during arginine infusion increased slightly plasma insulin and lowered minimally plasma glucagon in the pancreaticoduodenal vein. Pancreastatin infusion in a dosage of 500 ng/min did not modify glucose-induced insulin release and glucagon suppression by glucose. Theophylline infusion induced a slight increase in plasma insulin and glucagon in the pancreaticoduodenal vein. Pancreastatin infusion accelerated slightly these changes in plasma insulin and glucagon following theophylline infusion. From the present experiment it is concluded that porcine pancreastatin did not inhibit glucose-induced insulin release from the canine pancreas, inconsistent with the first report on insulin release from the rat pancreas. Alternatively, porcine pancreastatin rather stimulated insulin release during arginine infusion or following theophylline administration.

Animals↗

[Effect of ursodeoxycholic acid on water immersion restraint stress ulcer of rats].

Ursodeoxycholic acid (UDCA) has been used in the medical treatment of various gastrointestinal diseases. In this study, UDCA-supplemented rats were investigated to elucidate the role of UDCA in the pathogenesis of gastric mucosal lesions induced by water immersion restraint stress. In UDCA-administered rats, the increase of gastric mucosal lipid peroxide (LOP) and ulcer index after 2 hour's stress were prevented as compared with the rats fed on standard diet to serve as the control. In addition, the increase of serum and gastric mucosal catalase after the stress were also suppressed. These results suggested that antioxidant effect of UDCA on the lipid peroxidation may play a role in prevention of gastric lesions induced by water immersion restraint stress.

Animals↗