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Biomedical subjects

Y Abe

Publications and source records attributed to Y Abe.

At least 289 records · Page 16Linked to original sources
PubMed1999

Detection of hepatocellular carcinoma arising in cirrhotic livers: comparison of gadolinium- and ferumoxides-enhanced MR imaging.

OBJECTIVE: We prospectively compared the detectability of hepatocellular carcinoma (HCC) arising in cirrhotic livers using dynamic gadolinium-enhanced fast low-angle shot (FLASH), ferumoxides-enhanced T2-weighted turbo spin-echo, and ferumoxides-enhanced T2*-weighted FLASH MR imaging. SUBJECTS AND METHODS: Fifty-three patients with HCC (32 men and 21 women) who were 33-86 years old (mean, 63 years old) were enrolled in a prospective MR study to assess hepatic lesions using both gadopentetate dimeglumine and ferumoxides. Dynamic gadolinium-enhanced imaging was obtained before and 30, 60, and 180 sec after rapid bolus injection of gadopentetate dimeglumine (0.1 mmol/kg). Ferumoxides-enhanced T2-weighted turbo spin-echo imaging and ferumoxides-enhanced T2*-weighted FLASH imaging were performed between 30 min and 2 hr after i.v. infusion of ferumoxides (10 micromol/kg). Images were analyzed qualitatively and quantitatively. A receiver operating characteristic curve study was performed to compare the diagnostic value of gadolinium-enhanced imaging with that of ferumoxides-enhanced imaging for the detection of HCC. RESULTS: Quantitative analysis revealed a significantly higher percentage of signal-intensity loss and higher liver-lesion contrast-to-noise ratio on ferumoxides-enhanced T2*-weighted FLASH imaging than on ferumoxides-enhanced T2-weighted turbo spin-echo imaging. The percentage of signal-intensity loss and liver-lesion contrast-to-noise ratio on ferumoxides-enhanced images was significantly higher in patients with mild liver cirrhosis (Child's class A) than in patients with severe liver cirrhosis (Child's class C). Qualitative analysis showed that dynamic gadolinium-enhanced images revealed significantly higher lesion conspicuity than did ferumoxides-enhanced T2-weighted turbo spin-echo images. According to receiver operating characteristic analysis, dynamic gadolinium-enhanced FLASH imaging achieved the highest sensitivity, and ferumoxides-enhanced T2*-weighted FLASH imaging was the second most sensitive. We found that ferumoxides-enhanced turbo spin-echo imaging was the least valuable technique for revealing HCC lesions. Gadolinium-enhanced imaging revealed more HCC lesions than did ferumoxides-enhanced imaging, particularly for lesions smaller than 2 cm in diameter. CONCLUSION: Ferumoxides-enhanced imaging revealed fewer findings, such as lesion conspicuity of HCCs arising in cirrhotic livers, than did gadolinium-enhanced FLASH imaging.

Adult↗
PubMed1999

[Acute empyema caused by Streptococcus milleri in early pregnancy].

A 40-year-old woman was admitted to our department complaining of left lateral chest pain and fever. She smoked 10 cigarettes per day. Chest radiographs revealed increased density in the upper left lung field and air-fluid level in the lower left lung field. A diagnosis of acute empyema was made, because pus was aspirated by thoracentesis. Streptococcus intermedius (Streptococcus milleri group) was isolated from samples of pleural effusion. The patient was successfully treated with a combination of antibiotics and surgical drainage. It became clear after discharge that she was in her 6th week of pregnancy. Laboratory findings showed decreased lymphocyte transformation in the PHA and Con-A tests. We reasoned, therefore, that smoking and decreased cellular immunity due to pregnancy might be causes of bacterial infections such as empyema.

Acute Disease↗
PubMed1999

Optimum threshold values of 201Tl SPET in the determination of the left ventricular border and extent of myocardial infarction.

The aim of this study was to determine the optimum threshold value of the left ventricular border and the extent of myocardial infarction using quantitative 201Tl single photon emission tomography (SPET). We used the unfolded map method to determine the size of the left ventricle and the extent of myocardial infarction in 10 patients, because it has been shown to be superior to the conventional polar map method. The relative differences in the size of the left ventricle and extent of infarction between 201Tl SPET and post-mortem examination were calculated. The optimum threshold value was determined when the relative difference = 0%. There was an excellent correlation between scintigraphic and post-mortem left ventricular size at a threshold value of 53% (r = 0.91, P < 0.001); an excellent correlation was also observed between scintigraphic and post-mortem infarct size at a threshold value of 55% (r = 0.93, P < 0.03). The optimum threshold value in determining left ventricular size using 201Tl SPET is 53% and that in determining infarct size is 55%.

Adult↗
PubMed1999

[Detection of t(3 ; 21) (q26 ; q22) with AML1/EVI1 mRNA during progression of myelodysplastic syndrome to acute myeloid leukemia].

A 74-year-old woman had myelodysplastic syndrome (MDS) in 1986. In June 1994, she suffered exacerbation of pancytopenia with no chromosomal abnormalities, but AML1/EVI1 chimeric mRNA was detected by RT-PCR. Two months later, an increase in bone marrow blasts (5%) was noted, and chromosomal analysis detected t(3 ; 21) (q26 ; 22), del(7) (q22), del(11) (q23). In 1995, the marrow blasts increased to 30% and the patient died of disease progression. The AML1/EVI1 gene has been shown to cause blast crisis in chronic myelogenous leukemia. This case suggested that the AML1/EVI1 gene may be involved in the progression of MDS together with del(7) (q22) and del(11) (q23).

Acute Disease↗
PubMed1999

[The frequency profile of tuberculin skin testing among students in nursing school].

The frequency profile of tuberculin skin testing (TST) among students in nursing school was studied. Students received a TST upon matriculation. The TST was done by the method of Mantoux, in which 0.1 ml of PPDs was administered intradermally, and the diameters of skin rash and induration were read by the medical doctor at 48 hours. When TST results are negative--that is, the diameter of skin rash is below 10 mm (in Japan, the TST results are judged by skin rash diameter rather than that of induration)-BCG vaccination is given. Those receiving the BCG vaccination are retested with a TST one year later. When the second TST was also negative both the BCG vaccination and TST were followed for two more years. Those students testing TST-negative are not permitted to take clinical training in the tuberculosis ward. Student's mean age on entrance was 18.6 +/- 2.1 years old, and all but three were female. About 70% of students entering in 1996 to 1998 had a history of previous BCG vaccination. In 14% their positive TSTs could be attributed to probable infection with tuberculosis in childhood. In the remaining 16%, details as to TST and BCG vaccination status are unknown. The frequency distribution of TST results was bimodal, showing one peak at 6 mm and another at 12 mm (skin rash diameter). The percentage of negative and positive reactors are 47.1% and 52.9%, respectively. The TST-negative students entering in 1994 to 1996 were given the BCG vaccination. Twenty-four of 134 students (17.9%) remained negative at the second TST, and 6 students (4.5%) at the third year, even after two repeated BCG vaccinations. The TST results were chronologically observed in the above 6 students after BCG vaccination. The TST results of two students showed positive in September, 1996 and June, 1997. While four students showed positive in September, 1996, all ultimately reverted to negative when retested in June, 1997. Those students had negative results for TST at the initial test in 1998 had the two step-tuberculin skin testing. All eight students with negative TST had the history of BCG vaccination. The second TST showed positive except one student whose scar after BCG vaccination was not observed on the arm. The TST is currently recommended in hospital tuberculosis-control programs. If TST-negative, medical staff and students may not work in the tuberculosis ward. However, after BCG vaccinations is given, and subsequent TST conversion is confirmed, they are then able to work or to have training in the ward. From our results, there is 4.5% non-convertors even after 2 years of repeated BCG vaccinations. However, these non-converters turned positive four months after BCG vaccination, only to revert to negative nine months later. These students are considered to have delayed hypersensitivity to PPD after BCG vaccination. However, their reactivity waned in the short period of nine months after the conversion of their TST's. Therefore, it is concluded that non converters after repeated BCG vaccinations are able to have clinical training in the tuberculosis ward as long as their BCG vaccinations are correctly administered and any immunological deficiencies are ruled out.

Adolescent↗
PubMed1999

[Apoptosis in the pathogenesis of autoimmune thyroid disease].

Apoptosis is a physiological process of cell death that occurs as part of normal development and in response to a variety of physiological and pathophysiological stimuli. The effector mechanisms, which carry out the death program, are well preserved across species and evolution. This article summarizes the recent studies on apoptosis in view of its molecular mechanism and the relation to autoimmune thyroid diseases. In Hashimoto's thyroiditis, which is a typical organ-specific autoimmune disease, Fas-FasL-mediated apoptosis has been demonstrated as the mechanism of follicular epithelial cell death. In Graves' disease, Anti TSH receptor antibody inhibits Fas antigen-mediated apoptosis of thyrocytes through the inhibitory effect of Fas antigen expression, resulting in the promotion of growth of the thyroid gland.

Apoptosis↗
PubMed1999

[A case of subarachnoid hemorrhage verified as cerebral vasospasm by using three-dimensional CT angiography (3 D-CTA): reference to comparison with conventional angiography].

The authors present a case of aneurysmal subarachnoid hemorrhage that were verified as cerebral vasospasm by using both three-dimensional CT angioraphy (3 D-CTA) and conventional angiography. A 45-year-old man was referred to our department 4th day after sudden onset of a severe headache. On admission, emergency 3 D-CTA showed the cerebral vasospasm involving M 1 segment. Conventional angiography performed at the same day of the left internal carotid artery confirmed the cerebral vasospasm of the same vessel as 3 D-CTA, and furthermore demonstrated the left middle cerebral artery (MCA) and anterior cerebral artery (ACA) genu aneurysms. The former was seen as a ruptured aneurysm from brain CT findings (Fisher group 3). On the 10th day after the onset, 3 D-CTA demonstrated the remaining severe cerebral vasospasm of the supraclinoid portion of left ICA and M 1 segment. Findings at the conventional angiography subsequently performed were concordant with those of 3 D-CTA. The patient was successfully treated with delayed surgical clipping for both aneurysms without the symptoms related to the cerebral vasospasm and discharged without neurological abnormality. We consider that 3 D-CTA shows promise as a minimally invasive method of evaluating the cerebral vasospasm and would take the place of the conventional angiography.

Cerebral Angiography↗
PubMed1999

[Diagnostic utility of positron emission tomography for parkinsonism after chronic manganese exposure].

Positron emission tomography (PET) with [18F] 6-fluoro-L-dopa (18F-FDOPA) was performed in three South Korean patients with parkinsonism who developed after chronic manganese exposure. A 51-year-old man (patient 1) suffered from masked face, marked postural tremor of hands, dystonia in the neck and the upper extremities, severe retropulsion and lateropulsion which were typical for chronic manganese intoxication. 18F-FDOPA scan was normal. Other two patients, a 46-year-old man (patient 2) and a 47-year-old man (patient 3), showed tremor at rest and rigidity predominantly on the right side, bradykinesia, stooped posture and postural instability; all of these were typical for Parkinson's disease (PD). There was reduced uptake of 18F-FDOPA in the striatum, particularly in the posterior putamen predominant on the left side, in both patient 2 and 3. From these results, patient 1 was diagnosed as pure manganism, while patient 2 and 3 were primarily as PD, because loss of nigrostriatal fibers was obvious with asymmetry of affection in the putamen. PET with 18F-FDOPA provides valuable information for differentiation between PD and manganism, although it is not clear whether development of parkinsonian symptoms in patient 2 and 3 was modified by excessive manganese exposure.

Diagnosis, Differential↗
PubMed1999

Adenosine A(1) receptor antagonist KW-3902 prevents hypoxia-induced renal vasoconstriction.

Studies were carried out to determine the intrarenal adenosine production during hypoxia, and the protective effects of a selective adenosine A(1) receptor antagonist 8-(noradamantan-3-yl)-1, 3-dipropylxanthine (KW-3902) on hypoxia-induced renal hemodynamic changes. We used an in vivo microdialysis method and measured the renal interstitial concentration of adenosine in response to hypoxic exposure in anesthetized mechanically ventilated rabbits. Normocapnic systemic hypoxia (PaO(2) = 32 +/- 6 mm Hg) caused a significant decrease in renal blood flow and increase in renal vascular resistance, indicating a renal vasoconstriction. The basal interstitial concentration of adenosine in the cortex was 293 +/- 70 nM, which was significantly higher than that in the medulla (170 +/- 23 nM). Five minutes after beginning hypoxia, the renal interstitial concentration of adenosine approximately tripled in the cortex and doubled in the medulla. During treatment with KW-3902, hypoxemia caused a similar increase in the adenosine concentration compared with that in the absence of KW-3902. The administration of KW-3902, however, significantly attenuated hypoxia-induced reduction in renal blood flow. These results suggest that adenosine was involved in hypoxia-induced renal vasoconstriction via its effects on adenosine A(1) receptors, and that KW-3902 had a partial protective effect against renal vasoconstriction during hypoxemia.

Adenosine↗
PubMed1999

[Compartment analysis of 123I-iomazenil brain SPECT in patients with moyamoya disease].

We investigated 11 patients with moyamoya disease about 123I-Iomazenil kinetics in the brain using three-compartment, two-parameter model. The transition rate constant (K1) from the blood to the brain and the binding potential (BP) of the benzodiazepine to the receptors were calculated for every ROI (right and left side of cerebellum, frontal lobe, parietal lobe, occipital lobe and temporal lobe; 10 ROIs a case). The K1 value correlated with BP value significantly, but not so closely (r = 0.639). And there is no significant difference in BP value among low-K1 group (mean (of K1) -S.D. < or = K1 < or = mean) and high-K1 group (mean < K1 < or = mean + S.D.). This means that CBF and BP do not correlate closely in the average Moyamoya disease patients. And we showed a case with IMP/IMZ discrepancy. The nerve cell in the hypoperfused area which has almost normal BP value is ischemic but viable. IMZ-SPECT presents an important information about the viability of the hypoperfused area in Moyamoya disease patients' brain.

Adult↗
PubMed1999

Expression of the thrombospondin 1 receptor CD36 is correlated with decreased stromal vascularisation in colon cancer.

Vascularisation is determined by the balance between various angiogenic and angio-inhibitory factors in cancer stroma. CD36 is a cell adhesion receptor shown to interact with the ligand thrombospondin 1 (TSP1). It has not been determined whether the interaction of TSP1 and its receptor CD36 is correlated with vascularisation or clinical outcome of malignant tumours in vivo. We studied the correlations between expression of TSP1, CD36 and vascularisation and prognosis in 65 colon cancers. Various levels of TSP1 gene expression were observed in 27 of 65 colon cancers. CD36 expression was detected in 33 of 65 cancers, and was significantly correlated with decreased stromal vascularisation (P<0.001). The colon cancers expressing CD36 showed better prognosis (P<0.01). TSP1 expression levels did not affect CD36 expression. These results suggested that CD36 expression which decreased stromal vascularisation is correlated with better prognosis of colon cancer.

CD36 Antigens↗
PubMed1998

Hammerhead ribozyme specifically inhibits mutant K-ras mRNA of human pancreatic cancer cells.

We have evaluated the efficacy of an anti-K-ras hammerhead ribozyme targeted against GUU-mutated codon 12 of the K-ras gene in a cell-free system as well as in cultured pancreatic carcinoma cell lines. In the cell-free system, the anti-K-ras ribozyme specifically cleaved K-ras RNA with GUU-mutation at codon 12, but not other triplet sequences at codon 12 of K-ras RNA. In the cell culture system, the anti-K-ras ribozyme significantly reduced K-ras mRNA level (GUU-mutated codon 12) in Capan-1 pancreatic carcinoma cells, but less significantly suppressed K-ras mRNA in Capan-2 (GUU/GGU heterozygous-mutation at codon 12) or MIA PaCa-2 (UGU-mutated codon 12) pancreatic carcinoma cells. The ribozyme inhibited proliferation of transfected Capan-1 cells. These results suggest that this ribozyme selectively recognizes single-base mutation of K-ras mRNA and is able to reverse the malignant phenotype in human pancreatic carcinoma cells.

Adenocarcinoma↗
PubMed1998

A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 4. Discovery of novel frameworks mimicking the active conformation.

In recent articles we reported the identification of a series of 8-[[2, 6-dichloro-3-[N-methyl-N-[(E)-(substituted)acryloylglycyl]amino]++ +benzy l]oxy]-2-methylimidazo[1,2-a]pyridines as the first orally active non-peptide bradykinin (BK) B2 receptor antagonists. Optimization of the terminal glycine part and the imidazo[1,2-a]pyridine moiety led to the discovery of a clinical candidate (5, FR173657). With the aim of completion of the structure-activity relationship (SAR) study, we next investigated the roles of the substituents on the central phenyl ring. The results suggested that the 2,6-dichloro or 2, 6-dimethyl groups may play important roles in regulating the conformations of the 1- and 3-substituents and also may interact with hydrophobic pockets of the B2 receptors. Furthermore, according to the results of a molecular modeling study reported in part 1 of this series, we designed and synthesized a series of sterically constrained analogues by replacing the N-methylamide group with cis-amide-like rigid moieties. We discovered several bioisosteres and chemically proved that the N-methylamide moiety adopts the cis-amide form in the active conformation. Extensive chemical modification led to the identification of a novel class of highly potent and orally active non-peptide B2 antagonists represented by a pyrrole derivative (52a, FR193517). Compound 52a inhibited the specific binding of [3H]BK to recombinant human B2 receptors expressed in Chinese hamster ovary (CHO) cells and guinea pig ileum membrane preparations expressing B2 receptors with IC50s of 0.37 and 0.56 nM, respectively. This compound also displayed excellent in vivo functional antagonistic activity against BK-induced bronchoconstriction in guinea pigs at 1 mg/kg by oral administration.

Administration, Oral↗
PubMed1998

A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 2. Overcoming the species difference between guinea pig and man.

Recently we reported the identification of a series of 8-[[3-(N-acylglycyl-N-methylamino)-2, 6-dichlorobenzyl]oxy]-3-halo-2-methylimidazo[1,2-a]pyridines as the first orally active non-peptide bradykinin (BK) B2 receptor antagonists (1-3). These compounds inhibited the specific binding of [3H]BK to guinea pig ileum membrane preparations expressing B2 receptors with nanomolar IC50's and also displayed in vivo functional antagonistic activities against BK-induced bronchoconstriction in guinea pigs at 1 mg/kg by oral administration. However, it was found that their affinities for the B2 receptors in human A-431 cells (human epidermoid carcinoma) were much lower. Intensive modifications of the terminal substituents at the glycine moiety elucidated the structure-activity relationships (SAR) for human B2 receptors, leading to an extended basic framework which incorporated a novel key pharmacophore. Thus, we overcame the species difference and identified the first clinical candidate 18c (FR167344) with IC50's of 0.66 and 1.4 nM for guinea pig ileum and human A-431 cells, respectively. This compound displayed in vivo functional antagonistic activity against BK-induced bronchoconstriction in guinea pigs with an ED50 value of 0.17 mg/kg by oral administration. This novel non-peptide B2 antagonist is extremely potent both in vitro and in vivo by oral administration and is expected to be the first member of a new class of drug for the treatment of various inflammatory diseases.

Administration, Oral↗
PubMed1998

A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 3. Discovering bioisosteres of the imidazo[1,2-a] pyridine moiety.

Recently we reported on overcoming the species difference of our first orally active non-peptide bradykinin (BK) B2 receptor antagonists, incorporating an 8-[[3-(N-acylglycyl-N-methylamino)-2, 6-dichlorobenzyl]oxy]-3-halo-2-methylimidazo[1,2-a]pyridine skeleton, leading to identification of the first clinical candidate 4a (FR167344). With this potent new lead compound in hand, we then investigated further refinement of the basic framework by replacement of the imidazo[1,2-a]pyridine moiety and discovered several bioisosteric heterocycles. Extensive optimization of these new heteroaromatic derivatives revealed the detailed structure-activity relationships (SAR) around the imidazo[1, 2-a]pyridine ring and the 2,6-dichlorobenzyl moiety, leading to the discovery of our second clinical candidate 87b (FR173657) which inhibited the specific binding of [3H]BK to recombinant human B2 receptors expressed in Chinese hamster ovary (CHO) cells and guinea pig ileum membrane preparations expressing B2 receptors with IC50's of 1.4 and 0.46 nM, respectively. This compound also displayed excellent in vivo functional antagonistic activity against BK-induced bronchoconstriction in guinea pigs with an ED50 value of 0.075 mg/kg by oral administration. Further modifications of the terminal substituents on the pyridine moiety led to a novel pharmacophore and resulted in the identification of 99 (FR184280), whose IC50 value for human B2 receptors (0.51 nM) was comparable to that of the second-generation peptide B2 antagonist Icatibant.

Administration, Oral↗
PubMed1998

Investigation of the structural basis for thermostability of DNA-binding protein HU from Bacillus stearothermophilus.

Site-directed mutagenesis was used to identify amino acid residues essential for the thermostability of the DNA-binding protein HU from the thermophile Bacillus stearothermophilus (BstHU). Two mutants, BstHU-A27S and BstHU-V42I, in which Ala27 and Val42 in BstHU were replaced by the corresponding amino acids Ser27 and Ile42, respectively, in the homologue from a mesophile B. subtilis (BsuHU), were less stable than the wild-type BstHU (63.9 degreesC), showing Tm values of 58.4 degreesC and 60.1 degreesC, respectively, as estimated by circular dichroism (CD) analysis at pH 7.0. The denaturation of two mutants was further characterized using differential scanning calorimetry; the Tm values obtained by calorimetric analysis were in good agreement with those estimated by CD analysis. The results suggest that Ala27 and Val42 are partly responsible for enhancing the thermostability of BstHU. When considered together with previous results, it is revealed that Gly15, Ala27, Glu34, Lys38, and Val42 are essential for the thermostability of thermophilic protein BstHU. Moreover, five thermostabilizing mutations were simultaneously introduced into BsuHU, which resulted in a quintuple mutant with a Tm value of 71.3 degreesC, which is higher than that of BstHU, and also resulted in insusceptibility to proteinase digestion.

Bacterial Proteins↗