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Biomedical subjects

M Koizumi

Publications and source records attributed to M Koizumi.

At least 109 records · Page 6Linked to original sources
PubMed1998

Cloning and characterization of a cDNA fragment coding beta-casein-like protein preferentially expressed in cervical adenocarcinoma cell line CAC-1.

We generated new murine monoclonal antibodies against bovine beta-casein. One of eight new monoclonal antibodies generated, 12G2, specifically reacted not only with beta-casein, but also with human cervical adenocarcinoma cell line CAC-1. To identify the gene encoding the putative protein (BCLP) defined by monoclonal antibody (mAb) 12G2, a complementary DNA library was constructed. We obtained the inserted cDNA fragment that showed high homology to reported DNA sequences of unknown function in normal human placenta. We think that BCLP was overexpressed or changed its structure by carcinogenesis.

Adenocarcinoma↗
PubMed1998

Duodenal gastrinoma--clinical features and usefulness of selective arterial secretin injection test.

Duodenal gastrinoma is recognized as a relatively common cause of Zollinger-Ellison syndrome, but its clinical and biological features are not well known. Here we report a case of duodenal gastrinoma with lymph node metastasis which was confirmed by pathology examinations. Hypergastrinemia and gastric acid hypersecretion were documented, but the secretin test showed negative results. An enlarged peripancreatic lymph node lying close to the pancreas head was the only positive finding on preoperative imaging studies. The results of the selective arterial secretin injection (SASI) test suggested that the primary tumor was located in the gastrinoma triangle. Finally, surgical exploration was carried out and a submucosal tumor, approximately 15 mm in size, was detected by intraoperative palpation at the posterior wall of the proximal portion of the duodenum. Intraoperative pathology examination demonstrated metastases to regional lymph nodes. The present case calls attention to the unique features of duodenal gastrinomas, which differ from those of pancreatic origin: a highly malignant potential for its small size, and submucosal location in the proximal duodenum. The SASI test is recommended for assessing the location of a primary lesion if it cannot be identified by various conventional imaging studies.

Diagnosis, Differential↗
PubMed1998

Detection of cracks in polyethylene components of retrieved knee joint prostheses.

Subsurface cracks that had formed in polyethylene artificial knee components were observed nondestructively with a new method, scanning acoustic tomography (SAT). Standardization of the SAT observation was done by in-vitro rolling fatigue testing on an unimplanted ultra high molecular weight polyethylene (UHMWPE) knee component. Retrieved knee components were of two types; KOM (Kyocera, Kyoto, Japan) sterilized with ethylene oxide gas, and MG (Zimmer, IN, USA) sterilized with gamma-irradiation. The SAT images revealed cracks in all the retrieved components, and these existed mainly 0. 3-1.0 mm from the surface. Comparison of crack formation in each portion of the contact area of the polyethylene components showed that the middle portion of the MG type had the highest concentration of cracks. When the distribution of compressive stress on the polyethylene components was assessed by mechanical testing, the strongest compressive stress was seen in the middle portion of MG type components.

Acoustics↗
PubMed1998

Endogenous glucocorticoids decrease the acinar cell sensitivity to apoptosis during cerulein pancreatitis in rats.

BACKGROUND & AIMS: We recently showed that activation of the hypothalamus-pituitary-adrenal axis may mitigate the progress of acute pancreatitis. To clarify the mechanism, the role of endogenous glucocorticoids in pancreatic acinar cell death was examined. METHODS: The occurrence of apoptosis was studied in adrenalectomized or sham-operated rats with or without cerulein-induced pancreatitis. The effects of RU38486, a glucocorticoid-receptor antagonist, on the survival of cultured acinar cells (AR42J) were also examined. RESULTS: Adrenalectomy caused increases in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) of acinar nuclei depending on the time after adrenalectomy but not of other cell types in the pancreas and in other digestive organs. Electron microscopy showed the characteristic features of apoptosis in the TUNEL-labeled acinar cells. In cerulein pancreatitis of adrenalectomized rats, the TUNEL-labeled acinar nuclei increased remarkably depending on the time after cerulein infusion. Replacement of glucocorticoids blocked the occurrence of apoptosis in these experiments. RU38486 induced dose dependently the apoptosis of AR42J cells. CONCLUSIONS: These results provide evidence that endogenous glucocorticoids are an important factor for acinar cell survival. Endogenous glucocorticoids may protect acinar cells by decreasing their sensitivity to the induction of cell death during acute pancreatitis.

Acute Disease↗
PubMed1998

Biologically active oligodeoxyribonucleotides. Part 11: The least phosphate-modification of quadruplex-forming hexadeoxyribonucleotide TGGGAG, bearing 3-and 5-end-modification, with anti-HIV-1 activity.

We have found that a hexadeoxyribonucleotide (5'TGGGAG3', R-95288), Koizumi, M. et al. Bioorganic & Medicinal Chemistry, 1997, 5, 2235, bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5'-end and a 2-hydroxyethylphosphate at the 3'-end, has high anti-HIV-1 activity and the least cytotoxicity in vitro and in vivo. In order to synthesize more potent hexadeoxyribonucleotides, we substituted phosphodiester (P-O) bonds in the 6-mer with the least phosphorothioate (P-S), phosphoramidate (P-N), or methylphosphonate (P-Me) bonds. When more than two P-N or P-Me bonds were introduced into a 6-mer, the phosphate-modified 6-mers had weak or no anti-HIV- activity, in spite of quadruplex structure formation. However, when P-S bonds were substituted for P-O bonds, anti-HIV-1 activity of their 6-mers did not dramatically decrease, compared with compounds substituted with P-N or P-Me bonds. The results suggest that the formation of a quadruplex structure is not always sufficient for anti-HIV-1 activity of the 6-mer, and that net negative charges derived from P-O or P-S bonds in the quadruplex are important for anti-HIV-1 activity. Moreover, among various phosphate-modified ODNs, we found that the anti-HIV-1 activity of ODN PS7 with only one P-S bond was the same as that of R-95288, both having a high stability in human plasma.

Anti-HIV Agents↗
PubMed1998

Increased plasma levels of substance P and disturbed water excretion in patients with liver cirrhosis.

BACKGROUND: The pathogenesis of impaired water excretion in liver cirrhosis has not been fully elucidated. METHODS: We induced an intravenous water overload of 20 ml/kg body weight in 10 cirrhotics without ascites (CLC), 11 cirrhotics with ascites (DLC), and 10 normal subjects (N) and investigated the relationship of plasma levels of substance P (SP), norepinephrine (NE), and antidiuretic hormone (ADH) to impaired water excretion. RESULTS: Free water clearance (CH2O) was lower in DLC (mean, 2.7 ml/min) than in N (8.3 ml/min; P < 0.001) and CLC (6.9 ml/min; P < 0.001). In DLC the creatinine clearance (CCr), maximal urine flow rate/CCr, (CH2O + CNa)/CCr, and mean arterial pressure (MAP) were significantly lower than in N and CLC. There was a progressive increase in basal SP, from lowest in N to CLC, to highest in DLC. Basal NE increased in CLC and DLC. Basal ADH did not differ among N, CLC, and DLC. In cirrhotics CH2O was correlated positively with serum albumin and cholinesterase and negatively with the retention rate of indocyanine green at 15 min. Basal SP was negatively correlated with CH2O (r= -0.71: P < 0.001) and MAP (r= -0.56; P < 0.005). Basal NE was correlated positively with basal SP (r= 0.67, P < 0.01 ). CONCLUSIONS: Decreased CH2O is closely related to the severity of the liver disturbance. Decreased CCr and reduced delivery of filtrate to the ascending limb of the loop of Henle secondary to an increased sodium reabsorption in the proximal tubule may play an important role in the impairment of water excretion. The increase in SP, which has a potent vasodilatory action, and the associated enhanced activity of the sympathetic nervous system may be responsible for the mild or moderate impairment of water excretion in the absence of nonosmotic hypersecretion of ADH in cirrhotics with ascites.

Adult↗
PubMed1998

Influences of cardiopulmonary bypass and fentanyl anesthesia on hepatic circulation and oxygen metabolism in beagles.

UNLABELLED: Decreases in hepatic blood flow (HBF) have been reported in patients and in animal experiments during cardiopulmonary bypass (CPB). We examined changes in HBF and hepatic oxygen metabolism during CPB in 16 beagles anesthetized with fentanyl. Hepatic arterial blood flow (HABF) and portal venous blood flow (PVBF) were measured by using an electromagnetic flowmeter before and during normothermic and hypothermic CPB with 10 microg x kg(-1) x h(-1) (F-10 group; n = 8) or 50 microg x kg(-1) x h(-1) (F-50 group; n = 8) of fentanyl anesthesia. CPB was conducted with membrane oxygenation and a nonpulsatile pump flow of 2.4 L x m(-2) x min(-1). Hepatic oxygen delivery (HDO2) and consumption (HVO2) were calculated from HBF and oxygen content in arterial, portal venous, and hepatic venous blood. HABF did not change during normothermic CPB in the F-10 group, but it decreased significantly during hypothermic CPB in both groups, especially the F-50 group. During CPB, PVBF and total HBF decreased significantly in both groups-more so with the larger dose of fentanyl--whereas HDO2 decreased significantly because the arterial and portal venous blood oxygen levels decreased. The HVO2 was stable in the F-10 group but was significantly depressed during CPB in the F-50 group. Our results indicate that during hypothermic nonpulsatile CPB larger doses of fentanyl are associated with reduced HBF and impaired HDO2 and HVO2. IMPLICATIONS: Hepatic dysfunction after cardiopulmonary bypass (CPB) has been frequently reported and could be partly attributed to hepatic circulatory disturbance during CPB. We found that, in beagles, large doses of fentanyl were associated with greater decreases in hepatic blood flow and hepatic oxygen metabolism during hypothermic CPB than smaller doses of fentanyl.

Analysis of Variance↗
PubMed1998

Pancreatic diabetes in Japan.

Pancreatic diabetes is usually a complication of other pancreatic disorders. Diabetes was a complication in 55.5% of 2,774 patients with chronic pancreatitis (CP) in Japan. More than half of alcoholic patients with CP in our clinic showed diabetes, and approximately 50% of those patients with diabetes were treated with insulin injections. On the other hand, cases of nonalcoholic CP showed mild endocrine dysfunction in terms of diabetic frequency and severity. Epidemiologic studies suggest that diabetes resulting from chronic pancreatitis accounts for <0.8% of all Japanese patients with diabetes. In patients with CP, B-cell dysfunction occurred first, followed by disturbances in A-cell function. Decreased insulin secretion during postprandial periods plays an important role in pancreatic diabetes. The fasting level of blood glucose is not useful for the diagnosis of the early stage of pancreatic diabetes. The glucose-tolerance test should be performed to diagnose early-stage diabetes in patients with CP with normal fasting blood glucose levels. For control of blood glucose in diabetic patients with CP, multiple injections of short-acting effective insulin before the meal are necessary. The incidence of long-term diabetic complications, diabetic retinopathy, nephropathy and neuropathy, in patients with CP with diabetes are not less than those in patients with primary diabetes.

Chronic Disease↗
PubMed1998

Expression of transforming growth factor beta1 (TGFbeta1) and its receptors in pancreatic duct cell carcinoma and in chronic pancreatitis.

Transforming growth factor beta1 (TGF beta1) is a multifunctional factor that regulates many aspects of cellular functions such as epithelial cell growth and synthesis of extracellular matrices. TGFbeta transduces signaling through a heterodimeric complex of type I and type II TGFbeta receptors (TbetaRI and TbetaRII). Recently, it has been shown that enhanced expression of TGFbeta1 is associated with the progress of pancreatic duct cell carcinoma (PDC) and chronic pancreatitis (CP). In this study, the expression of TGFbeta1 and its receptors, TbetaRI and TbetaRII, is examined in 21 cases of PDC by immunohistochemistry using specific antibodies, and the results are compared with those for 13 cases of CP. In the epithelial cells of PDC and CP, there are no significant differences in the expression of TGFbeta1, TbetaRI, and TbetaRII. In contrast, stromal expression of this cytokine and its receptors tends to be stronger in PDC than in CP; especially, the expression of TbetaRII is significantly stronger in PDC (p < 0.05). These findings suggest that there are some pathological differences in the properties of stromal reactions between PDC and CP, although the morphologies of their stroma resemble each other.

Aged↗
PubMed1998

Lipopolysaccharide-induced desensitization to pancreatic edema formation in rat cerulein pancreatitis.

Previously we reported that prior administration of lipopolysaccharide (LPS) mitigates subsequently produced cerulein (Cn) pancreatitis. To clarify the mechanism further, the pathological features of Cn pancreatitis were examined in detail after treating rats with very low doses of LPS. LPS pretreatment reduced the formation of pancreatic edema during Cn pancreatitis in a dose- and time-dependent manner. In contrast, the elevation of serum amylase and the histological findings, including acinar cell vacuolization and infiltration of inflammatory cells, were not affected. The lowest dose of LPS, 500 ng/kg, was sufficient to inhibit pancreatic edema formation completely. LPS at a dose of 5 microg/kg was fully effective when it was given from 30 min to 12 h before the induction of pancreatitis. Pretreatment with tumor necrosis factor-alpha (TNF-alpha) inhibited the pancreatic edema in a manner similar to that of LPS. Moreover, the inhibitory effect of LPS was partially attenuated by the administration of anti-TNF-alpha antibody before the injection of LPS. Actinomycin D (0.5 mg/kg) abolished the effect of LPS, whereas cycloheximide (0.5 mg/kg) given alone reduced pancreatic edema formation during pancreatitis. From these results, it was concluded that very low doses of LPS can induce, partially via TNF-alpha, a state refractory to pancreatic edema formation during Cn pancreatitis, and this phenomenon seems to be regulated at the transcriptional level.

Animals↗
PubMed1998

Low doses of lipopolysaccharide upregulate acinar cell apoptosis in cerulein pancreatitis.

We have reported previously that administration of a sublethal low dose of lipopolysaccharide (LPS; 50 microg/kg) prior to the induction of cerulein (Cn) pancreatitis mitigates the pathological course. To clarify the mechanism, we examined apoptosis in the pancreas using the same model. Apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) and transitional electron microscopy. LPS pretreatment at a dose of 50 microg/kg increased remarkably the incidence of acinar cell apoptosis in Cn pancreatitis rats compared with LPS-untreated Cn pancreatitis rats. Apoptosis was observed selectively in acinar cells but was not shown in endocrine cells or ductal epithelial cells. Infiltration of inflammatory cells was scarcely observed. These acinar cells showed the characteristic morphological features of apoptosis by electron microscopy. Administration of LPS at a dose of 50 microg/kg alone caused acinar cell apoptosis but the incidence was much lower than that in the LPS-pretreated Cn pancreatitis rats. The TUNEL labeling was significantly increased depending on the dose of LPS and on the interval between the administration of LPS and that of Cn. These results suggest that the pathological features of acute pancreatitis might be modified by the presence of nonfatal endotoxemia through the induction of acinar cell apoptosis.

Animals↗
PubMed1998

Nitric oxide is overproduced by peritoneal macrophages in rat taurocholate pancreatitis: the mechanism of inducible nitric oxide synthase expression.

To investigate the pathobiology of severe acute pancreatitis, we studied the expression of inducible nitric oxide synthase (iNOS) in peritoneal macrophages of experimental pancreatitis. Taurocholate (TCA) pancreatitis and cerulein (CE) pancreatitis were used as models of lethal and self-limited pancreatitis, respectively, and the mechanism of iNOS expression in peritoneal macrophages was studied. Serum nitrate and nitrite (NOx) concentrations increased during the course of TCA pancreatitis, and iNOS-immunoreactivity was detected in the peritoneal macrophages 12 h after the induction of TCA pancreatitis, but these phenomena were not observed in CE pancreatitis. Despite the difference in the iNOS expression, the iNOS messenger RNA (mRNA) and the activation of nuclear factor-kappa B (NF-kappa B) were detected in the peritoneal macrophages of both pancreatitis models. The supernatant of TCA pancreatitis ascites could induce iNOS in the peritoneal macrophages of normal rats in vitro, but the peritoneal lavage fluid of CE pancreatitis rats could not. The results indicated that there may be qualitative or quantitative differences in the macrophage activation between the two types of experimental pancreatitis and suggested that the ascites of rats with lethal acute pancreatitis contains some soluble factors that activate the macrophage/monocyte system and cause an overproduction of NO by the iNOS expression.

Acute Disease↗
PubMed1998

Solitary fibrous tumor of the pleura causing recurrent hypoglycemia by secretion of insulin-like growth factor II.

A case of malignant solitary fibrous tumor (SFT) is reported, occurring in a 61-year-old man with frequent hypoglycemia. Endocrinological analyses showed high serum levels of insulin-like growth factor II (IGF-II) and suppressed secretion of insulin. After the removal of a pleural tumor, which weighed 3150 g, serum IGF-II levels returned to normal and hypoglycemic attacks ceased. The tumor was composed of uniform spindle cells arranged in bundles, and fascicles with varying amounts of collagen and reticulin fibers. Mitotic figures at the rate of 6/10 high-power fields, and frequent foci of necrosis and hemorrhage were seen. Almost all of the tumor cells were immunohistochemically positive for vimentin and CD34. Electron microscopy revealed the immature mesenchymal or myofibroblastic nature of the tumor cells. These findings are consistent with malignant SFT of the pleura. Moreover, the tumor produced IGF-II mRNA as demonstrated by northern blot analysis. Thus, hypoglycemia of this patient was induced by SFT through the production and secretion of IGF-II.

Antigens, CD34↗
PubMed1998

A marked increase in free copper levels in the plasma and liver of LEC rats: an animal model for Wilson disease and liver cancer.

Most of copper present in rat plasma and liver binds to caeruloplasmin and metallothionein, respectively, and is not redox active. However, free forms of copper including loosely bound forms to other molecules are redox active. We assessed the free copper in Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease and liver cancer. Compared to those of control rats, the liver and plasma of LEC rats showed a marked elevation of free copper, especially at the stage of acute hepatitis, in parallel with an increase of total copper levels in the livers and a decrease of plasma caeruloplasmin (ferroxidase I) activity. At the onset of jaundice, the total copper levels, however, decreased in liver, but increased in plasma, while free copper levels in both liver and plasma remained higher. Free iron levels in both liver and plasma were also determined and did not change significantly, except for the case of plasma in jaundiced rats. The data are consistent with a proposal in which increased levels of redox active free copper in the liver of LEC rats catalyze Fenton-type reactions, producing a large flux of hydroxyl radicals that would play an important role in the observed liver dysfunction, leading to acute hepatitis, and finally, hepatocarcinoma. This is the first demonstration that the free copper may participate in the pathophysiology of the LEC rats and Wilson disease.

Animals↗
PubMed1998

[Effects of cardiopulmonary bypass on hepatic circulation and hepatic oxygen metabolism under fentanyl anesthesia in beagles].

Disturbances of hepatic blood flow (HBF) and hepatic oxygen metabolism (HMO) have been reported in patients and animals undergoing cardiopulmonary bypass (CPB). In the present study, we examined changes of HBF and HMO during CPB in eight beagles (13.5 +/- 2.4 kg). Hepatic arterial blood flow (HABF) and portal venous blood flow (PVBF) were measured with an electromagnetic flowmeter before CPB, during normothermic CPB, during hypothermic CPB under 10 micrograms.kg-1.h-1 of fentanyl anesthesia. CPB was conducted with membrane oxygenation and a non-pulsatile pump flow of 2.4 l.min-1.m-2. Hepatic oxygen delivery (HDO2) and consumption (HVO2) were calculated from HBF and oxygen content in arterial, portal venous and hepatic venous blood. Hepatic energy charge (HEC) was also assessed by measuring the arterial ketone body ratio (AKBR). HABF was unchanged during CPB, but PVBF decreased during normothermic CPB. Total hepatic blood flow decreased during normothermic and hypothermic CPB. HDO2 decreased during CPB because the oxygen content in the arterial and portal venous blood decreased. However, HVO2 was well maintained by spontaneous rises in oxygen uptake ratio despite the decrease in HDO2. The AKBR remained above 0.8 during CPB. Our results indicate that the CPB technique in the present study decreased HBF, but did not cause any adverse effects on HOM or HEC.

Anesthesia, Intravenous↗
PubMed1998

[Some considerations on the avoidance of excess body burden in case of high dose 131I treatment: with special reference to the urination frequency].

In case of the treatment of metastatic thyroid cancer with radioiodine (131I), 3.7 GBq (100 mCi) or more is often repeatedly administered to the patient. Therefore, we must be aware of avoiding unnecessary exposure to the radioiodine except for the lesions to be treated. The administered radioiodine is excreted mainly through urinary system, resulting in an accumulation of the urine in the bladder for a certain period, which is highly concentrated with it. Based on this fact, we set one case having a particular pattern of the whole body retention curve. Then, two different modes of urination were considered; mode A indicates every 2 hour-urination x 6 times followed by every 6 hour-urination x 2 times, and mode B indicates every 6 hour-urination x 4 times. Focusing on the different amounts of urine in the bladder upon the different modes of urination, the radiation exposures from the urine to the neighboring organs, such as bladder wall, uterus, ovary and testis, and also to the whole body were calculated. As the results, it was found that the urination mode B would cause radiation exposure from the urine in the bladder twice as much as the urination mode A to the neighboring organs as well as to the whole body. This study will supply arguments for the necessity of frequent urination in the cases receiving radioiodine treatment for metastatic thyroid cancer.

Body Burden↗