Biomedical subjects

K Sugimura

Publications and source records attributed to K Sugimura.

At least 73 records · Page 4Linked to original sources

PubMed1999

Augmentation of antitumor activity of 5'-deoxy-5-fluorouridine by thymosin fraction 5 in mouse bladder cancer cells in vitro and in vivo.

5'-Deoxy-5-fluorouridine (5'-dFUrd) is a prodrug of 5-fluorouracil (5-FUra) activated by pyrimidine nucleoside phosphorylase (PyN Pase), mainly by uridine phosphorylase (Urd Pase) in rodents and by thymidine phosphorylase (TdR Pase) in humans, which is preferentially located in tumor tissues compared to normal tissues. It has been reported that PyN Pase is induced by cytokines such as tumor necrosis factor (TNF), interleukin-1alpha (IL-1alpha) and interferon (IFN). Thymosin is a glycoprotein extract obtained from the calf thymus and is a potent immunopotentiating preparation. In this study, the antiproliferative activity of 5'-dFUrd used in combination with thymosin fraction 5 (TF5) was investigated in mouse bladder cancer cell line MBT-2 in vitro and in vivo. In vitro TF5 enhanced the activity of 5'-dFUrd by up to 4.11-fold, whereas the activity of other cytostatics such as 5-FUra, mitomycin C, adriamycin, cis-platinum, etoposide, vinblastine and methotrexate was not changed. In vivo when the effects of combination therapy with 5'-dFUrd and TF5 in C3H/HeN mice implanted with MBT2 were studied, tumor growth was not suppressed by TF5 alone while tumor growth was suppressed to some degree by 5'-dFUrd alone. However, tumor growth suppression was enhanced when 5'-dFUrd was used in combination with TF5. In order to investigate this mechanism, Urd Pase in MB2 was measured, and it was found that TF5 increased enzyme activity by up to 1.8-fold in MBT2. This increased susceptibility might be a result of the induction of Urd Pase, which is the essential enzyme for the conversion of 5'-dFUrd to 5-FUra. These results suggested that the therapeutic benefit of 5'-dFUrd would be improved by its use in combination with TF5 and the modulation of converting enzymes for antitumor prodrugs could be a novel therapeutic strategy for treating human cancers.

Animals↗

PubMed1999

"Decoy" of androgen-responsive element induces apoptosis in LNCaP cells.

BACKGROUND: In an androgen-dependent manner, the androgen receptor (AR) binds to the androgen-responsive element (ARE) in the regulatory region of target genes. We hypothesize that an "ARE decoy, " a double-stranded oligonucleotide containing the same DNA sequence as ARE, can inhibit prostatic proliferation by competitive inhibition of AR transcriptional activity. METHODS: We synthesized a 23-mer ARE decoy based on the deduced ARE sequence at the promoter region of the human prostate-specific antigen (PSA) gene. The nuclear extract was prepared from LNCaP cells, and DNA-protein interactions were examined by gel shift assay. Then the antiandrogen effect of the ARE decoy was studied in LNCaP cells transfected with the ARE decoy by lipofection. After 24-hr incubation with 10(-9) M dihydrotestosterone (DHT), induction of apoptosis was examined by DNA fragmentation. RESULTS: The gel shift assay demonstrated specific binding of the ARE decoy to the LNCaP nuclear protein which is most likely AR. The transfection experiment showed DNA fragmentation in the ARE decoy-transfected cells despite the presence of DHT, though not in the cells transfected with the control decoy. CONCLUSIONS: The ARE decoy had an antiandrogen effect and induced apoptosis in LNCaP cells. This ARE decoy may become a potential therapeutic tool for prostate cancers when combined with a highly efficient transfection method.

Amino Acid Sequence↗

PubMed1999

Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein.

We have isolated a cDNA clone coding for CYP3A5 from a human prostate cDNA library. The human prostate CYP3A5 cDNA had a unique 5'-untranslated sequence, suggesting that the prostate specific regulation of CYP3A5 is different from liver. Hybridization screening using a human genomic BAC library yielded four positive clones, two of which were shown to contain the unique 5'-untranslated sequence by Southern blot analysis. The CYP3A5 recombinant protein expressed in Escherichia coli using the pCWOri expression vector was purified to an almost electrophoretically homogeneous state with a specific content of 4.4 nmol of P450/mg of protein. This P450 exhibited 6beta-hydroxylation activity toward both testosterone and progesterone. No polar metabolite of 5alpha-dihydrotestosterone (DHT) was detected. The apparent K(m) values for testosterone and progesterone 6beta-hydroxylation were 143 and 114 microM, respectively, with V(max) values of 0.48 and 0. 21 nmol/min/nmol of P450, respectively. This is the first report that a particular form of P450, CYP3A5, has been isolated from human prostate and that the purified recombinant protein of CYP3A5 has been shown to be active in the metabolism of sex hormones.

5' Untranslated Regions↗

PubMed1999

The contributory role of interstitial water in Gd-DTPA-enhanced MRI in myocardial infarction.

We studied the mechanism underlying regional enhancement of myocardial infarction using T1-weighted MRI with gadolinium (Gd)-DTPA. Anterior myocardial infarction (MI) was produced by left anterior descending coronary artery ligation in three groups of rats as follows: 60 minutes occlusion (occlusion group, N = 6), 60 minutes occlusion plus 120 minutes reperfusion (reperfusion group, N = 8), and sham-operated (control, N = 6). In Gd-DTPA-enhanced MRI, MI was demarcated as a hypoenhanced region in the occlusion group and as a homogeneous hyperenhanced region in the reperfusion group. Both Gd-DTPA tissue concentration and tissue water content in the anterior wall were highest in the reperfusion group (P<0.05), a finding suggestive of microscopically observed interstitial edema. The data suggest that regional accumulation of Gd-DTPA in the reperfused group can be explained by increased interstitial water content, contributing to the delayed washout of the water-soluble contrast medium.

Animals↗

PubMed1999

Thermal distribution of radio-frequency inductive hyperthermia using an inductive aperture-type applicator: evaluation of the effect of tumour size and depth.

A new radio-frequency (RF) inductive hyperthermia device using an inductive aperture-type applicator (IATA) is proposed. This paper reports the evaluation of the heating characteristics of the IATA using a computer simulation and clinical thermal parameters obtained during treatment of superficial and subsurface-seated tumours. The configuration of the IATA is a one-turn square column-like coil whose bottom plate is set to face the heating target. The IATA has advantages over RF capacitive-type heating, such as: generating less heat in the subcutaneous fat layer; less convergency of electric line of force at the edge of the applicator; and no physical contact with the target lesion. The induced magnetic fields and electrical currents within the heating substance are simulated using computer-assisted design software for electro-magnetic analysis. A total of 40 superficial and subsurface tumours are treated with the IATA. Invasive thermometry is performed continuously for 110 sessions using multi-sensor probes of an optical thermometer. Thermal parameters (Tmax, Tmin, Tave) are assessed based on the tumour size and depth. The treated tumours are categorised into three groups according to tumour depth: group 1 (< 3 cm, n = 28), group 2 (3-5 cm, n = 35) and group 3 (> 5 cm, n = 47). The computer simulation shows that induced electrical currents run without convergency, parallel to the surface of the heating material. All thermal parameters of group 3 are significantly higher than those of group 1 and 2 (p < 0.05), indicating that the larger lesions tend to abtain a higher temperature distribution. In conclusion, RF inductive hyperthermia using the IATA results in effective temperature distributions in superficial and subsurface tumours, with large tumours being most effectively heated.

Aged↗

PubMed1999

p16(INK4) is inactivated by extensive CpG methylation in human hepatocellular carcinoma.

BACKGROUND & AIMS: The molecular status of the p16(INK4) tumor-suppressor gene has not been fully elucidated in hepatocellular carcinoma. The aim of this study was to clarify the mechanism that gives rise to inactivation of p16(INK4) in hepatocellular carcinoma. METHODS: The status of p16(INK4) was evaluated in 60 hepatocellular carcinomas by immunohistochemical staining, differential polymerase chain reaction, single-strand conformational polymorphism, methylation-specific polymerase chain reaction, and methylation-sensitive single nucleotide primer extension. RESULTS: Immunohistochemical staining showed that 29 of the 60 tumors exhibited complete loss of p16(INK4) expression. High levels of DNA methylation were detected in 24 of 29 cases of hepatocellular carcinoma with negative p16(INK4) expression, with methylation of 60%-85% of the CpG islands. In contrast, the level of methylation was <25% in tumors with faint p16(INK4) staining, and no methylation was detected in tumors with positive immunostaining. Intragenic alteration of p16(INK4) was detected in 4 cases. CONCLUSIONS: A strong correlation was found between the extent of methylation and the degree of expression of p16(INK4) in tumor tissues, indicating that epigenetic change due to extensive CpG methylation is the main cause of inactivation of p16(INK4) in hepatocellular carcinoma.

Adult↗

PubMed1999

Inhibition of M-tropic HIV-1 infection by the fd phage-gene 3 protein with MIP-1alpha-binding activity.

CCR5 is a chemokine receptor with seven transmembrane-domains. It is expressed on T cells and macrophages and functions as the principal co-receptor for macrophage (M)-tropic strains of HIV-1. The anti-CCR5 monoclonal antibody (mAb) 2D7 inhibits the binding and chemotaxis of the three natural beta-chemokine ligands of CCR5, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES, to CCR5(+) cells. The mAb also efficiently blocks the infectivity of several M-tropic and dual-tropic HIV-1 strains in vitro. In this study, we attempted to determine the peptide motif recognized with the 2D7 mAb. We isolated phage clones by panning a phage display library using 2D7 and identified three peptide motifs. One of these phage clones (M23) showed a marked inhibitory activity on HIV-1 infection. The unique sequence of 15 amino acids with an internal disulfide bond was inserted in the g3p of the M23 phage clone (M23-g3p). The M23-g3p was purified by fast-performance liquid chromatography (FPLC). We show here that (1) M23-g3p was specifically recognized with anti-CCR5 mAb; (2) M23-g3p showed inhibitory activity on the infectivity of M-tropic but not T-tropic HIV-1 strains; (3) M23-g3p bound to MIP-1alpha, MIP-1beta, and RANTES but not MCP-1. These results suggested that the M23-g3p might mimic the CCR5-binding domain shared by beta-chemokines, MIP-1alpha, MIP-1beta, and RANTES as well as the HIV-1 infection.

Amino Acid Motifs↗

PubMed1999

Abnormal uterine cavity: differential diagnosis with MR imaging.

The objective of the study was to assess the usefulness of magnetic resonance (MR) imaging in distinguishing malignant from benign conditions in patients with an abnormal uterine cavity. Fifty-four patients that were suspected of having abnormal uterine cavities were retrospectively evaluated by using MR imaging. The diagnosis of an abnormal uterine cavity included a thickened endometrium, and/or a endometrial mass, and/or a submucosal mass. Threshold values to classify the uterine cavity as abnormal on sagittal T2-weighted images were >10 mm for premenopausal women and >5 mm for postmenopausal women. Malignancy was diagnosed when lesions invaded the myometrial/junctional zone, and/or lesion enhancement was lower than that of the adjacent myometrium. The results found that histology confirmed 18 malignant and 37 benign lesions. Twelve of 15 endometrial carcinomas and 3 malignant mixed mesodermal tumors (MMMT) were correctly characterized as malignant on enhanced T1-weighted images; whereas 6 of 15 endometrial carcinomas and 3 MMMT were correctly characterized on T2-weighted images. Thirty-four of 37 benign cases were correctly characterized as not malignant on enhanced T1-weighted images. One of 14 submucosal leiomyomas, one endometrial stromal metaplasia, and one of ten pathologically normal endometria were misdiagnosed on enhanced T1-weighted images but were correctly diagnosed on T2-weighted images. The overall sensitivity, specificity, and accuracy for distinguishing malignant from benign central uterine masses were 83%, 92%, and 89% for enhanced T1-weighted image, and 50%, 97%, and 82% for T2-weighted image, respectively. We came to the conclusion that in diagnosing patients with abnormal uterine cavity, MR imaging may help differentiate malignant from benign disorders.

Adult↗

PubMed1999

Regional differences on production of chemokines in gastric mucosa between Helicobacter pylori-positive duodenal ulcer and gastric ulcer.

It is well known that antrum-predominant gastritis and pan-gastritis occurs in the patients with Helicobacter pylori-positive duodenal ulcer (DU) and gastric ulcer (GU), respectively. However, the role of chemokines in the pathogenesis of these pathologies is unclear. We examined the regional differences in mucosal chemokine production in patients with DU and GU. The production of interleukin-8 (IL-8), growth-related gene (GRO) alpha, and macrophage inflammatory protein (MIP)-1alpha was greater in the antrum than in the corpus in DU patients. In the patients with GU, monocyte chemoattractant protein (MCP)-1 levels in the mucosa adjacent to ulcer were greater than those away for the ulcer in the corpus. The reduction in chemokine production occurring in association with the eradication of H. pylori differed between DU and GU patients in the antrum (IL-8, P = 0.0394; GROalpha, P = 0.0149; MIP-1alpha, P = 0.0246; MCP-1, P = 0.0087). The data imply a different pathogenesis may exist for the gastritis present in patients with DU and GU occurring in H. pylori-positive individuals.

Adult↗

PubMed1999

Amino acid sequences of lysozymes newly purified from invertebrates imply wide distribution of a novel class in the lysozyme family.

Lysozymes were purified from three invertebrates: a marine bivalve, a marine conch, and an earthworm. The purified lysozymes all showed a similar molecular weight of 13 kDa on SDS/PAGE. Their N-terminal sequences up to the 33rd residue determined here were apparently homologous among them; in addition, they had a homology with a partial sequence of a starfish lysozyme which had been reported before. The complete sequence of the bivalve lysozyme was determined by peptide mapping and subsequent sequence analysis. This was composed of 123 amino acids including as many as 14 cysteine residues and did not show a clear homology with the known types of lysozymes. However, the homology search of this protein on the protein or nucleic acid database revealed two homologous proteins. One of them was a gene product, CELF22 A3.6 of C. elegans, which was a functionally unknown protein. The other was an isopeptidase of a medicinal leech, named destabilase. Thus, a new type of lysozyme found in at least four species across the three classes of the invertebrates demonstrates a novel class of protein/lysozyme family in invertebrates. The bivalve lysozyme, first characterized here, showed extremely high protein stability and hen lysozyme-like enzymatic features.

Amino Acid Sequence↗

PubMed1999

Renin-angiotensin system stimulates cardiac and renal disorders in Tsukuba hypertensive mice.

1. The role of the renin-angiotensin system (RAS) in cardiac hypertrophy and nephropathy was examined in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. 2. Tsukuba hypertensive mice were treated with 20 mg/kg per day lisinopril, 30 mg/kg per day hydralazine or nothing. Administration of drugs was performed for 6 months from 12 weeks of age; water intake and urine volume were measured and urine albumin excretion, heart to bodyweight ratio and the glomerulosclerosis index were examined. 3. Systolic blood pressure was significantly lowered by treatment with lisinopril and hydralazine. Urine volume, water intake and urinary albumin excretion were significantly decreased by lisinopril. When hydralazine was administered to THM, these parameters were transiently decreased, but eventually reached almost the same levels as those in the untreated group. The heart to bodyweight ratio was significantly decreased by lisinopril, but not by hydralazine. The glomerulosclerosis index was significantly lowered by lisinopril, but the index in the hydralazine group was not significantly different from that in the untreated group. 4. These results suggest that the RAS plays an important role in the progression of cardiac hypertrophy in THM. In addition, the RAS may also play an important role in the progression of nephropathy; however, this may also be partially regulated by elevated blood pressure in the short term.

Angiotensin II↗

PubMed1999

Telomerase activity in human renal cell carcinoma.

OBJECTIVE: To determine if telomerase activity plays an important role in the progression of renal cell carcinoma (RCC). MATERIALS AND METHODS: Telomerase activity was measured in 53 tissue samples of RCC (52 patients), 11 samples of normal renal tissue and six tissue samples from benign renal disease using a fluorescence-based telomeric repeat amplification protocol. The activity was assessed for associations with clinical and pathological variables of RCC. To examine the influence of telomerase activity on cell immortalization in vitro, primary cultures of RCC cells were produced; the maximum passage number beyond which cell culture could not be continued was compared with the associated telomerase activity. RESULTS: Among the tissue samples of benign renal disease, one from a patient with a hydronephrotic nonfunctioning kidney had detectable telomerase activity, whereas none of the normal renal tissues had. In 32 of the 53 RCC tissue samples (60%), telomerase activity was detectable, varying from 1.8 to 100.0 TPG units, but was not associated with any clinical or pathological variable such as clinical stage, tumour size, grade or pathological subtype. Telomerase activity also had no association with the maximum passage number of primary cell cultures. CONCLUSIONS: Telomerase activity may not be a prognostic marker for RCC. Alternative mechanism(s) which lengthen telomeres should be considered if maintaining telomere length is considered essential to tumour progression.

Carcinoma, Renal Cell↗

PubMed1999

Reduced expression of the CDK inhibitor p27(KIP1) in rat two-stage bladder carcinogenesis and its association with expression profiles of p21(WAF1/Cip1) and p53.

The cyclin-dependent kinase (CDK) inhibitor p27(KIP1) exerts its growth suppressive effects by targeting the cyclin-CDK complexes. Reduced protein levels of p27(KIP1) have been reported in numerous human cancers and this has been attributed to increased degradation. However, few reports have addressed the significance of p27(KIP1) expression in chemical carcinogenesis of rodents. In a rat two-stage urinary bladder carcinogenesis model, with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) initiation followed by promotion with sodium L-ascorbate (Na-AsA), we evaluated the expression of p27(KIP1) protein using immunohistochemistry during various stages of urinary bladder carcinogenesis. In addition, we evaluated the mRNA expression profiles for p27(KIP1), p21(WAF1/Cip1) and p53 in tumors. Fisher 344 rats were initiated with 0.05% BBN in the drinking water for 4 weeks and then administered 5% Na-AsA in the diet. Immunohistochemical examination revealed p27(KIP1) protein to be constitutively expressed in normal urothelium, simple hyperplasia and in most papillary and nodular (PN) hyperplasias and small papillomas, but diminished or absent in large papillomas and in transitional cell carcinomas. An inverse correlation between expression of p27(KIP1) and cell proliferation was generally observed. Quantitation of mRNA by multiplex reverse transcription-PCR showed a significant downregulaton of p27(KIP1), p21(WAF1/Cip1) and p53 mRNA in tumors. More than 50% reduction in p27(KIP1) mRNA expression was observed in 42 and 47% of tumors at weeks 18 and 24, respectively; similar reduction in p21(WAF1/Cip1) mRNA expression was observed in 58 and 73% of tumors at weeks 18 and 24, and in p53 mRNA expression in 50 and 73% of tumors at weeks 18 and 24, respectively. None of the 25 tumors we examined by PCR-single-strand conformational polymorphism analysis had p53 mutations. These data imply that abnormal down-regulation of p27(KIP1), p21(WAF1/Cip1) and/or p53 in tumor cells may contribute to the malignant progression of tumors during rat two-stage bladder carcinogenesis.

Animals↗

PubMed1999

Analysis of a catalytic pathway via a covalent adduct of D52E hen egg white mutant lysozyme by further mutation.

We previously demonstrated by X-ray crystallography and electrospray mass spectrometry that D52E mutant hen lysozyme formed a covalent enzyme-substrate adduct on reaction with N-acetylglucosamine oligomer. This observation indicates that D52E lysozyme may acquire a catalytic pathway via a covalent adduct. To explain this pathway, the formation and hydrolysis reactions of the covalent adduct were investigated. Kinetic analysis indicated that the hydrolysis step was the rate-limiting step, 60-fold slower than the formation reaction. In the formation reaction, the pH dependence was bell-shaped, which was plausibly explained by the functions of the two catalytic pKas of Glu35 and Glu52. On the other hand, the pH dependence in the hydrolysis was sigmoidal with a transition at pH 4. 5, which was identical with the experimentally determined pKa of Glu35 in the covalent adduct, indicating that Glu35 functions as a general base to hydrolyze the adduct. To improve the turnover rate of D52E lysozyme, the mutation of N46D was designed and introduced to D52E lysozyme. This mutation reduced the activation energy in the hydrolysis reaction of the covalent adduct by 1.8 kcal/mol at pH 5.0 and 40 degrees C but did not affect the formation reaction. Our data may provide a useful approach to understanding the precise mechanism of the function of natural glycosidases, which catalyze via a covalent adduct.

Animals↗

PubMed1999

Genetically engineered brain drug delivery vectors: cloning, expression and in vivo application of an anti-transferrin receptor single chain antibody-streptavidin fusion gene and protein.

A single chain Fv antibody-streptavidin fusion protein was expressed and purified from bacterial inclusion bodies following cloning of the genes encoding the variable region of the heavy chain and light chain of the murine OX26 monoclonal antibody to the rat transferrin receptor. The latter undergoes receptor mediated transcytosis through the brain capillary endothelial wall in vivo, which makes up the blood-brain barrier (BBB); therefore, the OX26 monoclonal antibody and its single chain Fv analog may act as brain drug delivery vectors in vivo. Attachment of biotinylated drugs to the antibody vector is facilitated by production of the streptavidin fusion protein. The bi-functionality of the OX26 single chain Fv antibody-streptavidin fusion protein was retained, as the product both bound biotin and the rat transferrin receptor in vitro and in vivo, based on pharmacokinetic and brain uptake analyses in anesthetized rats. The attachment of biotin-polyethyleneglycol-fluorescein to the OX26 single chain Fv antibody-streptavidin fusion protein resulted in illumination of isolated rat brain capillaries in confocal fluorescent microscopy. In conclusion, these studies demonstrate that genetically engineered single chain Fv antibody-streptavidin fusion proteins may be used for non-invasive neurotherapeutic delivery to the brain using endogenous BBB transport systems such as the transferrin receptor.

Animals↗

PubMed1999

Elevated plasma immunoreactive neuropeptide Y concentrations and its increased urinary excretion in patients with advanced diabetic nephropathy.

Neuropeptide Y (NPY) is a potent vasoconstrictor peptide that is abundant in the brain and the peripheral sympathetic nervous system. In the present study we investigated possible changes in plasma immunoreactive (IR)-NPY concentrations and urinary IR-NPY excretion in patients with non-insulin dependent diabetes mellitus (NIDDM) and the relationship to diabetic complications, such as nephropathy and neuropathy. IR-NPY in plasma and urine was measured by radioimmunoassay in 69 patients with NIDDM. Plasma IR-NPY concentrations in patients with advanced nephropathy (creatinine clearance <30 ml/min) (100.5 +/- 10.3 pmol/l, n=9, mean +/- SEM) were higher than in the control subjects (55.0 +/- 6.8 pmol/l, n=15) (P<0.02). Urinary excretion of IR-NPY and fractional excretion of NPY were also increased in the patients with advanced nephropathy. Sephadex G-50 column chromatography of the urine extracts obtained from healthy subjects, diabetic patients with renal failure and non-diabetic patients with renal failure showed an immunoreactive peak eluting in the NPY position. On the other hand, neither plasma nor urinary IR-NPY was high in patients with retinopathy, or in patients with peripheral neuropathy. The present study has, for the first time, shown high plasma IR-NPY concentrations and urinary IR-NPY excretion in NIDDM patients with advanced nephropathy.

Adolescent↗

PubMed1999

Hemorrhagic myocardial infarction after coronary reperfusion detected in vivo by magnetic resonance imaging in humans: prevalence and clinical implications.

With the advent of thrombolytic therapy, hemorrhagic myocardial infarction (HMI) has been observed in experimental and human autopsy studies. However, its clinical implications remain undetermined, because of the absence of a reliable method to detect its presence in vivo. This study was designed to evaluate the clinical implications of HMI detected by magnetic resonance (MR) imaging in vivo after coronary reperfusion. Thirty-nine patients with acute myocardial infarction (AMI) were studied. Percutaneous transluminal coronary angioplasty (PTCA) was used to reopen the occluded coronary artery. Electrocardiogram (ECG)-gated T2*-weighted gradient-echo MR imaging was performed to detect intramyocardial hemorrhage, using a 1.5-T magnet within 2 weeks after coronary reperfusion (average, 5.7 days). Thirteen patients (33%) showed intramyocardial hemorrhage as a distinct hypointense zone by gradient-echo MR imaging and 26 patients showed homogeneous intensity consistent with absence of intramyocardial hemorrhage. Coronary angiograms showed lesser development of collateral flow in the patients with HMI than in those without (81% vs. 37%). Infarct size, estimated 1 month after coronary reperfusion by thallium-201 scintigraphy, was larger among patients with HMI than in those without (37 +/- 14% vs. 21 +/- 14%, respectively, p < 0.05). Left ventricular ejection fraction at 1 month follow-up showed less recovery in patients with HMI than in those without (47 +/- 9 to 51 +/- 10%; p = 0.47, vs. 53 +/- 10 to 60 +/- 9%, respectively, p < 0.05). ECG-gated T2*-weighted gradient-echo MR imaging offers a noninvasive means of detection of intramyocardial hemorrhage in patients with reperfused AMI. HMI occurred even after primary PTCA and may be a common finding associated with severely injured myocardium.

Aged↗

PubMed1999

[Present states of development in new drugs and treatment of inflammatory bowel disease].

With recent elucidation of pathophysiology and inflammatory process on inflammatory bowel disease(IBD), new drugs and treatments for IBD have developed rapidly. In addition to it, mechanisms of salicylazosulfapyridine, 5-aminosalicylic acid, and glucocorticoid have been clarified at molecular levels as cell transcription factors of NF-kappa B. This paper described the following recent therapy performed in IBD patients; 1)leukocytapheresis by G-column, LCAP and centrifugal separator. 2)cytokine and anti-cytokine therapy with anti-TNF-alpha chimeric monoclonal antibody and IL-10 for treatment of Crohn' disease. 3)therapy with antisense oligonucleotide against ICAM-1 in Crohn's disease, and against p65 subunit of NF-kappa B in TNBS induced colitis in mice. 4)therapy modulating receptor function of target cells. 5)therapy with antibody against cell adhesion molecules. 6)radical scavenger therapy with lipo-SOD. And, 7)treatment with low molecular heparin.

Animals↗