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Biomedical subjects

M Koizumi

Publications and source records attributed to M Koizumi.

At least 127 records · Page 7Linked to original sources
PubMed1997

Transgenic copper/zinc-superoxide dismutase ameliorates caerulein-induced pancreatitis in mice.

The role of oxidative stress in acute pancreatitis was investigated by comparing the pathological features of caerulein pancreatitis between transgenic mice that overexpress human Cu/Zn-superoxide dismutase (SOD) and nontransgenic littermates. Both the elevation of serum amylase and the formation of pancreatic edema during the pancreatitis were significantly reduced in the transgenic mice compared with the nontransgenic littermates. In the transgenic mice, the pancreatitis-associated reduction of Cu/Zn-SOD activity in the pancreatic tissues was significantly smaller than that in the nontransgenic mice. These results provide direct evidence that the elevation of intracellular oxygen radicals is an important factor for the progress of acute edematous pancreatitis.

Animals↗
PubMed1997

Ultrastructural and confocal laser scanning microscopic examination of TUNEL-positive cells.

TdT-mediated dUTP-biotin nick end labelling (TUNEL) has been widely used for detecting cells with DNA fragmentation or apoptotic cells. However, since the concept of apoptosis is based on cellular ultrastructure, it is important to identify the morphological features of TUNEL-positive cells. In this study, we performed TUNEL and electron microscopic observation on serial semithin and ultrathin sections of pancreas from bilaterally adrenalectomized rats with caerulein-induced pancreatitis. TUNEL-positive cells were identified with two different ultrastructural patterns. One was characteristic of apoptosis, with condensed nuclei, intact mitochondria, and zymogen granules. The other pattern was one of marked cellular degeneration, possibly representing the end stage of cell death. Cells which did not demonstrate these ultrastructural patterns were not labelled by the TUNEL method. The three-dimensional structure of TUNEL-positive cells was also investigated by confocal laser scanning microscopy (CLSM), which showed the apoptotic nuclei exhibited various three-dimensional structures. These results confirm the utility of the TUNEL method in detecting apoptosis; application of the technique reported in this study will contribute to the further characterization of individual TUNEL-positive cells.

Acute Disease↗
PubMed1997

Gallbladder emptying and cholecystokinin and pancreatic polypeptide responses to a liquid meal in patients with diabetes mellitus.

To investigate gallbladder motility and its regulation in patients with diabetes mellitus (DM), we examined the gallbladder response to an intraduodenal test meal by measuring the temporal course of plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels. Eighteen patients with type 2 DM and 7 healthy subjects (controls) were enrolled. The gallbladder volume was calculated by the sum-of-cylinders method from ultrasonographic images, and plasma CCK and PP were measured by radioimmunoassays. No significant difference was found in either the gallbladder response or in the CCK response between patients with DM and controls. However, the fasting plasma PP level of patients with DM was more than tenfold higher than that of controls. The integrated PP response (IPPR) of patients with DM to the test meal was 8.3-fold higher than that of controls. When patients with DM were grouped according to whether they had been treated with insulin or not, the fasting plasma PP of patients with DM without insulin treatment was significantly higher than the level in those treated with insulin. These results suggest that overproduction of PP-like immunoreactive substance(s) may occur in patients with DM, but the high plasma PP immunoreactivity does not appear to be related to the fasting gallbladder volume or to gallbladder emptying and filling.

Adult↗
PubMed1997

An easy and reproducible semi-automatic method for the evaluation of 99mTc-galactosyl human serum albumin.

99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy is a new method for evaluating liver function. This scintigraphy is useful for evaluating the severity of liver diseases. The indices evaluating hepatic function include the receptor index (LHL15) and the index of blood clearance (HH15). These indices are calculated on the basis of the regions of interest (ROIs) for both whole liver and heart, and are susceptible to the ROIs over heart and liver. At present, there is no standard method for determining ROIs. We attempted to establish a standard method which shall not be subject to inter and/or intra operator variation. A computer program to determine heart and liver ROIs semi-automatically was developed. Ten patients (12 instances) were studied with 99mTc-GSA, and HH15 and LHL15 were calculated on the basis of the ROIs obtained manually and semi-automatically by 3 different operators independently. Blood sampling and gamma-counting yielded blood clearance data. The ICG R15 was compared with each index in 34 patients. The time needed for ROI determination was reduced from 2-3 minutes for the manual method to 0.5-0.8 minutes for the semi-automatic method. The % coefficients of variation (% CVs) of HH15 and LHL15 were improved in the order manual-inter observer (M-inter), manual-intra observer (M-intra) and semi-automated-inter observer (SA-inter); % CVs of HH15 were 2.26% for M-inter, 1.55% for M-intra and 0.07% for SA-inter, and % CVs of LHL15 were 2.29% for M-inter, 0.46% for M-intra and 0.07% for SA-inter. The correlation of HH15 and LHL15 among M-inter, M-intra and SA-inter was good. Comparison of indices obtained by manual and semi-automatic methods with blood clearance data obtained by blood sampling and gamma-counting showed good correlations and no significant differences. The comparison with ICG R15 showed that HH15 and LHL15 by the semi-automated method gave better correlation that that by the manual method. A newly developed semi-automated method improved data processing time and deviation of indices in 99mTc-GSA studies. This method should substitute for manual ROI determination.

Automation↗
PubMed1997

Lack of correlation between gallbladder opacification in delayed CT and contrast-associated nephropathy.

The objective of our study was to determine the correlation between gallbladder opacification by delayed CT and contrast-associated nephropathy (CAN). Delayed CT after angiography was performed in 269 patients. Gallbladder opacification was defined when the CT value in gallbladder was more than 30 HU. Positive renal dysfunction was recognized as CAN which defined as an increase in serum creatinine level > 0.3 mg/dl and > 20 % on days 1, 3, or 7. Gallbladder opacification appeared in 154 of 269 (57 %) patients and CAN in 35 (13 %) patients. Of 117 patients without gallbladder opacification, 17 CAN (14 %) were recognized, and of 152 patients with gallbladder opacification, 18 CAN (12 %) were recognized. No significant correlation existed between delayed gallbladder opacification and CAN.

Angiography↗
PubMed1997

Protection of hu-PBL-SCID/beige mice from HIV-1 infection by a 6-mer modified oligonucleotide, R-95288.

We analyzed the anti-HIV-1 activity of an oligonucleotide derivative, R-95288, in severe combined immunodeficient (SCID/beige) mice transplanted with normal human peripheral blood leukocytes (PBLs), designated hu-PBL-SCID/beige mice. The human chimeric mice were inoculated with HIV-1(CC1) 3 weeks after the transplantation and sacrificed 2 weeks later. Virus infection was determined by coculture of splenocytes with fresh human PBLs and also by detection of HIV- specific DNA sequences using the polymerase chain reaction. No evidence of infection was observed in mice treated with R-95288 (100 mg/kg/day) using intraperitoneal delivery by osmotic minipumps starting 1 day before virus challenge. In contrast, virus infection was observed in over 80% of the saline-treated control mice. In addition, partial inhibition of HIV-1 infection was obtained in mice treated subcutaneously with R-95288 (100 mg/kg/day). Toxicity towards the engrafted human cells was not observed by flow cytometric analysis. Moreover, R-95288 failed to inhibit lymphocyte proliferation (CC50 > 400 microg/ml), while 90% inhibition of HIV-1 replication was achieved at 3.1 microg/ml in vitro. These results suggest the ability of R-95288 to protect the human chimeric mice against HIV-1 infection.

Animals↗
PubMed1997

Biologically active oligodeoxyribonucleotides--IX. Synthesis and anti-HIV-1 activity of hexadeoxyribonucleotides, TGGGAG, bearing 3'- and 5'-end-modification.

We have determined that hexadeoxyribonucleotides (5'TGGGAG3'), with modified aromatic groups such as a trityl group at the 5'-end, have anti-HIV-1 activity in vitro. The 6-mer bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5'-end had the most potent activity and the least cytotoxicity. When the 3'-end of the 5'-(3,4-DBB)-modified 6-mer was substituted with a 2-hydroxyethylphosphate, a 2-hydroxyethylthiophosphate, or a methylphosphate group at the 3'-end, anti-HIV-1 activity increased. Moreover, among various 3'- and 5'-end-modified 6-mers that were tested, the 6-mer (R-95288) bearing a 3,4-DBB group at the 5'-end and a 2-hydroxyethylphosphate group at the 3'-end was the most stable, when incubated with mouse, rat, or human plasma. Therefore, R-95288 was chosen as the best candidate for possible use in therapy on the basis of its anti-HIV-1 activity.

Animals↗
PubMed1997

Dissociation of bone formation markers in bone metastasis of prostate cancer.

To clarify the meaning and clinical value of bone formation markers in bone metastasis from prostate cancer, we investigated the bone formation markers carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BA1-p) and osteocalcin, so-called bone gla protein (BGP) in 43 prostate cancer patients with and 46 patients without overt bone metastasis. Patients with bone metastasis were evaluated repeatedly by bone scan at intervals of 3-6 months. The expression patterns of bone formation markers in patients with progression of bone metastasis became dissociated; BA1-p and PICP were elevated in patients with progression of bone metastasis but BGP was not. Instead, BGP showed slight elevation in patients with improvement and complete remission of bone metastasis. PICP, BA1-p and BGP are all bone formation markers, but each marker appears in a different phase of bone formation: PICP appears in proliferation phase, BA1-p appears in matrix maturation phase and BGP appears in late bone formation phase. Our findings that BGP was not elevated in progression of bone metastasis and that it increased slightly with improvement and complete remission of bone metastasis may imply that the bone formation that occurs in blastic bone metastasis is different from normal bone formation.

Aged↗
PubMed1997

Comparison of radiobiological effective depths in 65-MeV modulated proton beams.

To assess the achievement of uniformity of radiobiological effectiveness at different depths in the proton spread-out Bragg peak (SOBP), Chinese hamster ovary (CHO) cells were exposed to 65-MeV modulated proton beams at the Research Center for Nuclear Physics (RCNP) of Osaka University. We selected four different irradiation positions: 2 mm depth, corresponding to the entrance, and 10, 18 and 23 mm depths, corresponding to different positions in the SOBP. Cell survival curves were generated with the in vitro colony formation method and fitted to the linear-quadratic model. With 137Cs gamma-rays as the reference irradiation, the relative biological effectiveness (RBE) values for a surviving fraction (SF) level of 0.1 are 1.05, 1.10, 1.12 and 1.19 for depths of 2, 10, 18 and 23 mm respectively. A significant difference was found between the survival curves at 10 and 23 mm (P < 0.05), but not between 18 and 10 mm or between 18 and 23 mm. There was a significant dependence of RBE on depths in modulated proton beams at the 0.1 surviving fraction level (P < 0.05). Moreover, the rise of RBEs significantly depended on increasing SF level or decreased approximately in correspondence with irradiation dose (P = 0.0001). To maintain uniformity of radiobiological effectiveness for the target volume, careful attention should be paid to the influence of depth of beam and irradiation dose.

Animals↗
PubMed1997

Usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastasis from lung cancer.

Ninety-one lung cancer patients were evaluated to determine the usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastases and also to investigate their clinical usefulness as an adjunct to bone scintigraphy. Both bone resorption markers, ICTP and fDPD, and bone formation markers, Al-p, BAL, PICP and BGP, were evaluated in 47 patients with and 44 without bone metastasis. The patients with bone metastasis were classified according to the bone metastatic burden, and they were also separately classified into groups according to the course of the bone metastasis. ICTP, fDPD, Al-p and BAL were significantly elevated (P < 0.001) in patients with bone metastasis, but PICP and BGP were not. Receiver-operating characteristic (ROC) curves of these markers revealed that ICTP was most highly correlated with the diagnosis of bone metastasis. The sensitivity of ICTP (71.4%) and fDPD (61.0%) were good with high specificity. T scores of ICTP, fDPD and BAL tended to be higher at higher grades of bone metastasis. T-scores of ICTP, fDPD and BAL were elevated in the newly diagnosed cases and progressed cases, but the T-scores of ICTP and fDPD in those cases were higher than that of BAL. In the follow-up study, ICTP was well correlated with uncontrolled or controlled bone metastasis. Thus, bone resorption markers, especially ICTP, could be a good indicator of the progression and multiplicity of disease, and it could help in the follow-up and in the monitoring of therapy for bone metastasis from lung cancer.

Adult↗
PubMed1997

On the morphology of the brachial plexus of the platypus (Ornithorhynchus anatinus) and the echidna (Tachyglossus aculeatus).

Four forelimbs of 3 platypuses and 3 forelimbs of 2 echidnas were examined to study the precise form of the brachial plexus and to clarify the structural characteristics of the brachial plexus in phylogeny. The spinal components contributing to the plexus (C4-T2) and the formation patterns of the 3 trunks of the plexus were the same as those generally observed in mammals. In the cranial half of the brachial plexus from C4, 5 and 6 in monotremes, division into the ventral bundle (lateral cord) and dorsal bundle (axillary nerve) is clear, as in other mammals. However, for monotremes, in the caudal half of the plexus from C7 and T1 (+T2) and the nerves arising from the caudal plexus there is no definite division into the ventral and dorsal bundles, which distribute to the flexor and extensor parts of the forelimbs, respectively. The lower trunk of the monotreme brachial plexus forms a cord which contains both ventral and dorsal components. This characteristic diverges from the generally accepted idea that the tetrapod limb plexus is divided clearly into 2 layers: a dorsal layer for extensors and a ventral layer for flexors of the limb. Considering the incomplete dorsoventral division of forelimb nerves in some reptiles and urodeles, the caudal half of the monotreme brachial plexus has characteristics in common with those of lower tetrapods.

Animals↗
PubMed1997

Role of histidine 46 in the hydrolysis and the reverse transphosphorylation reaction of RNase Rh from Rhizopus niveus.

In order to study the reaction mechanism of RNase Rh from Rhizopus niveus, the rates of cleavage of four 2',3'-cyclic nucleotides by mutant enzymes of RNase Rh, H46F, H109F, E105Q, and K108L were measured. H46F is virtually inactive towards cyclic nucleotides, but H109F hydrolyzed these substrates at 0.7-4.5% of the rates of the native RNase Rh. The other mutants hydrolyzed 2',3'-cyclic nucleotides at 15-20% of the rates of the native enzyme. Relative enzymatic activities towards four cyclic nucleotides of H109F in the hydrolysis reaction (2nd step) were much higher than in the transphosphorylation reaction (the 1st step). In the presence of a 13-fold excess of uridine, H109F catalyzed the transphosphorylation reaction of 2',3'-cyclic AMP (A>p) to ApU. However, this reaction was not catalyzed by H46F mutant or native RNase Rh. These results showed that His46 is crucial to the hydrolysis reaction, and to the reversed reaction of the transphosphorylation reaction. We suggest that His46 in RNase Rh plays a major role in these reactions by acting as a base catalyst to activate water and the 5'-hydroxyl group of nucleosides, respectively.

Binding Sites↗
PubMed1997

The lobular architecture of the normal human pancreas: a computer-assisted three-dimensional reconstruction study.

Tissue specimens of the normal pancreata from three adult patients were subjected to serial sectioning and computer-assisted three-dimensional reconstruction of the lobules, blood vessels, pancreatic ducts, and islets, to establish the anatomical relation among these structures. Most lobules, although more or less imperfectly demarcated by septa, were found to receive a single duct (lobular duct), justifying their definition as "glandular lobules." However, there were also lobules receiving not only a lobular duct of their own but a small accessory duct from a neighboring lobule. On the other hand, these lobules were shown not to correspond to the territories of arterial supply, leaving no ground for defining them as "vascular lobules."

Adult↗
PubMed1997

Effects of glycyrrhizin on immune-mediated cytotoxicity.

Intravenous administration of glycyrrhizin is known to decrease elevated plasma transaminase levels in patients with chronic viral hepatitis, in which immune-mediated cytotoxicity by cytotoxic T lymphocytes and tumour necrosis factor (TNF)-alpha is considered to play an important pathogenic role. However, the immunological interpretation of the transaminase-lowering action of glycyrrhizin is not known. Studies were performed to elucidate this action immunologically by assessing the effects of glycyrrhizin on immune-mediated cytotoxicity using an antigen-specific murine CD4+ T hybridoma line, which exhibits cytotoxicity against antigen-presenting cells after stimulation with specific antigen, and a murine TNF-alpha-sensitive fibroblast line. Glycyrrhizin inhibited the cytotoxic activity of the T cells against antigen-presenting cells and also suppressed TNF-alpha-induced cytotoxicity in the TNF-alpha-sensitive cell line in vitro. These results suggest that the decrease of elevated transaminase levels by glycyrrhizin in patients with chronic viral hepatitis is mediated in part by inhibition of immune-mediated cytotoxicity against hepatocytes.

Animals↗
PubMed1997

Persistent primitive sciatic artery associated with other various anomalies of vessels.

A left persistent primitive sciatic artery was observed in a Japanese male cadaver. The sciatic artery arose from the internal iliac artery and perforated the ventral division of the sacral plexus. The sciatic artery did not anastomose with the perforating arteries nor the popliteal artery. The left femoral artery was incompletely developed, attenuating and terminating as the saphenous artery. Instead of the femoral artery, direct continuation of the profunda femoris artery, which probably corresponded to the fourth perforating artery, became the popliteal artery. Other vessel anomalies were observed in various regions. They included; (1) the retroesophageal right subclavian artery; (2) the left vertebral artery entering the transverse foramen of the 4th cervical vertebra; (3) bilateral occurrence of the superficial brachial artery; (4) the left gastric artery independently arising from the abdominal aorta; (5) a hepatolienomesenteric trunk; (6) three accessory renal arteries; (7) double testicular arteries; (8) the arteria intermesenterica; (9) a venous ring termed the 'renal collar', and (10) paired thoracic ducts. The present cadaver was considered to be a very rare case in which many primitive vascular systems had extensively persisted in various parts of the body.

Abnormalities, Multiple↗
PubMed1997

Effect of thoracic irradiation on hepatocyte growth factor in rats lung and in bronchoalveolar lavage fluid of patients with thoracic malignancies.

This study aimed to examine the physiological role of hepatocyte growth factor (HGF) after thoracic irradiation. We analysed the changes of HGF protein levels in rat lung following 12 Gy of whole thoracic irradiation. Bronchoalveolar lavage fluid (BALF) was then collected from 11 patients (10 lung cancer and one oesophageal cancer) after completion of radiation therapy. One month after irradiation, the HGF protein level in the lungs of irradiated rats decreased (p<0.05), followed by a remarkable elevation in HGF protein levels 2 (p<0.05) and 3 months (nonsignificant) after irradiation accompanied by the clinical appearance of radiation pneumonitis. Finally, HGF protein levels in the lung returned to their original level 6 months after thoracic irradiation. In humans, HGF protein levels in the BALF in the limited irradiated area were lower than those obtained from unirradiated areas (p<0.05). In conclusion, hepatocyte growth factor production is transiently suppressed in the irradiated area after irradiation.

Aged↗